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Abstract Objective To explore the correlation between uteroglobulin-related protein 1 ( UGRP1) and primary hypothyroidism. Methods Ninety-six patients with primary hypothyroidism were selected , including 66 patients with positive thyroid peroxidase antibodies (TPOAb) or anti-thyroglobulin antibodies (ATG) as the antibody-posi- tive group , 30 patients with negative thyroid autoantibodies as the antibody-negative group , and 96 healthy people as the control group . The general clinical data , thyroid-related indicators and serum UGRP1 levels were compared among these three groups . Human thyroid normal cells (NTHY-ORI 3-1) were transfected with plasmids in vitro , thus establishing the control group as well as the UGRP1 group . Enzyme linked immunosorbent assay (ELISA) was used to detect and compare the T4 level in the cell culture supernatant. Results The differences in thyroid stimu- lating hormone (TSH) , TPOAb and ATG among the three groups were statistically significant ( P < 0. 05) . The serum UGRP1 levels in the antibody-positive (303 . 97 ±156. 00) pg/m Land antibody-negative groups (352. 13 ± 188. 37)pg/m L were higher than those in the control group(237 . 54 ±137 . 20)pg/m L，and the differences between the groups were statistically significant ( P = 0. 005) . Meanwhile , there was no statistically significant difference between the antibody-positive and antibody-negative groups . Multi-factor Logistic regression analysis showed that UGRP1 was the risk factor for the occurrence of primary hypothyroidism (OR = 1 . 004 , 95% CI:1 . 001 - 1 . 007 , P = 0. 007) . The difference between the control group and UGRP1 group in T4 concentration secreted by human thyroid normal cells was not statistically significant. Conclusion Serum UGRP1 levels increase in patients with primary hypothyroidism , and the high expression of UGRP1 may have no direct relation to the function of thyroid cells secre- ting T4 .

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Abstract Objective To investigate the value of decreased carbohydrate antigen 19-9 (CA19-9) kinetics in pre- dicting short-term outcomes and determining prognosis among advanced biliary or pancreatic cancer patients receiv- ing first- or second-line therapy in the real world . Methods Eighty-nine patients were retrospectively collected with advanced biliary or pancreatic cancer , especially on the CA19-9 dynamics and decline rates at different time points . This study evaluated the association of CA19-9 changes with clinicopathological features , short-term re- sponse to antitumor therapy , and survival outcomes . Results The enrolled patients recorded baseline CA19-9 lev- els ranging from 1 . 20 to 65 706. 40 U/ml , with a median of 303 . 11 U/ml . There was no statistical correlation be- tween baseline CA19-9 levels and gender , age , body mass index , primary tumor site , hepatic metastases , pulmo- nary metastases , lymph node metastases , peritoneal metastases , performance status , treatment lines , and combina- tions of drug types . Baseline CA19-9 levels were not associated with systemic immunoinflammatory index , prognos- tic nutritional index , and total bilirubin . A 25% or 50% decrease in CA19-9 after 2 - 3 therapy courses indicated short-term efficacy in reaching tumor objective remission or disease control . Both combinations of multiple drug types and a 25% decline in CA19-9 after one course of treatment were independent prognostic factors that affected the longer progression-free survival of patients receiving first or second line of treatment. Conclusion Decreased CA19-9 kinetics has specific values in predicting the efficacy and prognosis of advanced biliary or pancreatic cancer.

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Alzheimer ′s disease (AD) is a common neurodegenerative disease . It has been found that AD is re- lated to various pathogenic factors such as genetics , cardiovascular and cerebrovascular disease , and excessive phosphorylation of tau protein . However , no definitive conclusions on its pathogenesis have been reached . In this paper , the research progress on the pathogenesis of AD in C. elegans model and the therapeutic effects of traditional Chinese medicine extracts on AD are reviewed , providing a basis for further research on the alleviating effects of Chinese medicine extracts on AD .

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Abstract Objective To evaluate the clinical value of combining low-dose energy spectrum CT with virtual un-en- hanced (VUE) scanning and deep-learning image reconstruction (DLIR) in aortic CT angiography (CTA) . Meth- ods In a prospective study , 94 patients scheduled for aortic CTA were randomized into two groups : a low-dose en- ergy spectrum group and a standard 100 kVp enhancement group , with 47 patients in each . All patients initially underwent a true un-enhanced (TUE) scan at 120 kVp using adaptive statistical iterative reconstruction-V (ASIR- V) at 40% for image reconstruction . The low-dose group received enhanced scans using gemstone spectral imaging (GSI) mode with DLIR-H , producing 60 keV virtual monoenergetic images (VMIs) and VUE images . The stand- ard group was scanned at 100 kVp , with images reconstructed using ASIR-V at 50% . Parameters were measured including CT values , noise (SD) , signal-to-noise ratio (SNR) , and contrast-to-noise ratio (CNR) for key vascu- lar and muscular areas , alongside the effective radiation dose (ED) . Two radiologists evaluated the image quality using a 5-point scale . Results The low-dose group exhibited significantly higher SNR and CNR values in the as- cending aorta , descending aorta , abdominal aorta , and common iliac artery compared to the standard group (P < 0. 05) , with comparable subjective quality scores . The VUE images also demonstrated superior SNR values in the abdominal aorta , common iliac artery , and psoas major muscle , and CNR value in the ascending aorta compared to TUE images , with similar subjective quality. Importantly , the ED in the low-dose group was about 40% lower than that of the standard group . Conclusion Low-dose energy spectrum CT with DLIR in aortic CTA can significantly enhance SNR and CNR , while approximating the image quality of traditional TUE scans , thereby substantially re- ducing radiation exposure .

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Abstract Objective To assess the epidemiological , drug resistance , and their relative risk and prevalence for yielding clinical diseases of Streptococcus mitis group (SMG) bloodstream infections in recent years . Methods A total of 50 blood culture specimens were collected from patients with SMG bloodstream infection . These SMG iso- lates were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry ( MALDI-TOF MS) . The susceptibility to antibiotics was tested by minimal inhibitory concentrations and Kirby-Bauer (K-B) disk diffusion methods . The data were comprehensively analyzed by statistical software combined with clinical data. Re- sults Five strains were identified in SMG bloodstream infection by mass spectrometry , namely Streptococcus oralis/ mitis (S. oralis/mitis) , Streptococcus pneumonia (S. pneumonia) , Streptococcus gordonii (S. gordonii) , Streptococ– cus sanguinis (S. sanguinis) , and Streptococcus parasanguinis. These SMG showed high resistance to erythromycin and clindamycin , but low resistance to penicillin , ampicillin and ceftriaxone . Reduced hemoglobin and albumin , elevated C-reactive protein and procalcitonin were the common hematological changes in patients with SMG blood- stream infections . In SMG bacteremia , S. gordonii , S. sanguinis and S. orals/mitis were the leading group causing infective endocarditis . Patients with myocardial disease factor were more likely to cause infective endocarditis by S. gordonii and S. sanguinis , compared with S. orals/mitis. S. oralis/mitis bacteremia more occurred in patients with renal transplants progressing to pulmonary infection . Conclusion In this area , β- lactam antibiotics are the best choice for treating SMG. SMG species with closely related phylogenetically show different prevalence and risk of clinical disease in bloodstream infection patients . Early prevention and diagnosis of bacteremia caused by SMG are necessary for clinical diagnosis , treatment and effective control of infectious diseases progression .

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Abstract Objective To explore the predictive value of depression severity plasma thyroid-stimulating hormone and thyroid hormones in patients with schizophrenia. Methods The subjects of this study were 203 schizophrenic patients , grouped on the basis of suicidal ideation . Clinical characteristics were assessed using multiple scales . Neutrophil to lymphocyte ratio (NLR) , platelet to lymphocyte ratio (PLR) , monocyte to lymphocyte ratio (MLR) and thyroid hormones were also detected . SPSS 23 . 0 was used for statistical analyses . Results The prevalence of suicidal ideation was 21 . 7% in patients with schizophrenia. Logistic stepwise regression analyses showed that Cal- gary depression scale (CDSS) total score (OR = 1 . 490 , 95% CI = 1 . 287 - 1 . 724 , P < 0. 001) , insomnia severity index scale (ISI) total score (OR = 1 . 096 , 95% CI = 1 . 011 - 1 . 187 , P = 0. 025) , modified overt aggression scale (MOAS) total score (OR = 1 . 111 , 95% CI = 1 . 016 - 1 . 215 , P = 0. 021) , MLR(Ln) (OR = 15 . 123 , 95% CI = 3 . 868 - 59. 125 , P < 0. 001) , and triiodothyronine ( T3) ( OR = 0. 037 , 95% CI = 0. 003 - 0. 388 , P = 0. 006) were the independent influences of suicidal ideation . Additionally , receiver operating characteristic (ROC) curve analyses revealed that the five-item combination of CDSS total score , ISI total score , MOAS total score , MLR (Ln) , and T3 (AUC = 0. 908 , 95% CI = 0. 867 - 0. 949 , P < 0. 001) had better ability to identify suicidal idea- tion . Conclusion The risk of suicidal ideation is relatively high in patients with schizophrenia , and there may be stronger associations between suicidal ideation and depression , insomnia , aggression , MLR , and T3 .

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Abstract Objective To explore the central role of interleukin (IL)-25 in allergy of eosinophil asthma. Methods Forty 4 - 5 week-old C57BL/6 mice were used in this study ( n = 10) . Mice were randomly divided into 4 groups : WT + shRNA NT group , WT + HDM group , IL-25 shRNA + IL-25 group , and IL-25 shRNA + IL-25 + HDM group . According to each group ′s treatment requirement , mice were treated with house dust mite and/or IL- 25 by intranasal infusion . HE staining and PAS staining were used for lung tissue section staining and pathological analysis . The levels of type 2 cytokines in bronchoalveolar lavage fluid (BALF) were determined by ELISA . Flow cytometry (FCM) was used to determine the number of type 2 helper T (Th2) cells , the group 2 innate lymphoid cells (ILC2) and eosinophils in lung tissues . Mice were treated with FITC-labeled DQ-ovalbumin (DQ-OVA) by intranasal infusion to determine the antigen presentation ability of eosinophils infiltrated in the lungs . Results HE staining and PAS staining results showed that , compared with WT + shRNA NT group , a large amount of mucus and a large number of eosinophil infiltration were found in the lungs , and subcutaneous thickening of inflammatory air- way were observed in the pulmonary vessels , alveolar ducts and the whole alveoli in IL-25 shRNA + IL-25 + HDM group . In the IL-25 shRNA + IL-25 group , only a small amount of mucus and a small amount of eosinophil infiltra- tion were found in the lungs , and a small amount of subcutaneous thickening of inflammatory airway were observed in pulmonary vessels , alveolar ducts and the whole alveoli . There was no significant difference in WT + HDM group . Compared with WT + shRNA NT group , the levels of IL-25 , IL-4 , IL-5 , IL-13 , IL-33 and interferon-γ (IFN-γ) in BALF significantly increased; the levels of infiltrated Th2 , ILC2 and eosinophils in the lung signifi- cantly increased; the fluorescence levels of FITC-labeled DQ-OVA in eosinophils infiltrated in lungs significantly increased in IL-25 shRNA + IL-25 + HDM group (P < 0. 05) . IL-25 shRNA + IL-25 group mice also showed an in- crease in the above measurements , but the amplitude were limited (P < 0. 05) . WT + HDM group had no signifi- cant difference . Conclusion IL-25 plays an essential role in the allergy and eosinophil antigen presentation processes in eosinophil asthma mice .

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Abstract Objective To investigate the role of AdipoRon , an adiponectin receptor agonist , in treatment of carbon tetrachloride (CCl4 ) induced liver fibrosis mice model and the mechanisms . Methods Forty mice were randomly divided into control group , model group , L- AdipoRon group and H-AdipoRon group , with 10 mice in each group . Hepatic fibrosis was induced by intraperitoneal injection of CCl4 solution . The mice in L- and H-AdipoRon groups were given 100 mg/kg and 200 mg/kg AdipoRon by gavage , respectively . The activities of serum aspartate amin- otransferase (AST) and alanine aminotransferase (ALT) were detected by biochemical method . Liver histopatho- logical changes and fibrosis were detected by HE staining , Masson staining and Sirius scarlet stain . The protein ex- pression levels of Collagen I , α-smooth muscle actin ( α-SMA) , matrix metalloproteinase 1 (MMP-1) and matrix metalloproteinase inhibitor 1 (TIMP-1) in mice liver were detected by Western blot. Lipid deposition in liver were detected by oil red O staining. The percentage (% ) of CD68 + iNOS + positive M1-type macrophages in the liver were detected by immunofluorescence . The expression levels of fatty acid synthetase (Fasn) , stearoyl-CoA desatu- rase 1 (Scd1) , fatty acid transporter (Cd36) , peroxissome proliferator activated receptor-α(Pparα) and carnitine palmitoyl transferase 1 α (Cpt1α) in mice liver tissues , as well as M1 macrophage-related genes interleukin-6 (IL- 6) and tumor necrosis factor-α(TNF-α) and M2 macrophage-related genes arginase 1 ( Arg1) , Chil3 chitinase- like 3 (Ym-1) were detected by RT-qPCR assay . Results Compared with model group , in low-dose AdipoRon group and high-dose AdipoRon group , serum ALT and AST activities significantly decreased (P < 0. 05) ; liver tis- sues structure were damaged , liver cells degeneration and inflammatory cells infiltration were improved; collagen fi- ber deposition was also significantly reduced; the relative expression levels of Collagen I , α-SMA and TIMP-1 pro- teins were significantly down-regulated (P < 0. 05) , while the relative expression levels of MMP-1 protein were sig- nificantly up-regulated (P < 0. 05) ; the lipid droplets deposition in livers were significantly reduced . The relative Fasn , Scd1 and Cd36 mRNA expression levels in liver tissues were significantly down-regulated (P < 0. 05) , and the relative Pparαand Cpt1 αmRNA expression levels were significantly up-regulated (P < 0. 05) ; the percentage (% ) of CD68 + iNOS + positive M1-type macrophages significantly decreased (P < 0. 05) ; the relative IL-6 and TNF-αmRNA expression levels significantly decreased (P < 0. 05) , the relative Arg1 and Ym-1 mRNA expression levels were significantly up-regulated ( P < 0. 05 ) . In addition , the improvement effects of high-dose AdipoRon group were better than those of low-dose AdipoRon group ( P < 0. 05) . Conclusion AdipoRon can improve the disorder of lipid metabolisms , inhibit the M1 type macrophages polarization , and improve the liver fibrosis in CCl4 - induced liver fibrosis mice model .

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Abstract Objective To investigate the selective activation of 5-hydroxytryptamine neurons ( DRN5-HT) in the dorsal raphe nucleus of rats with insomnia induced by p-chlorophenylalanine (PCPA) using chemical genetics tech-niques , and to explore whether it has a regulatory effect on comorbidities of insomnia and anxiety. Methods 32 male SD rats were randomly divided into control group , PCPA model group ( PCPA group) , chemical activation group (hM3Dq + CNO group) , and chemical control group (hM3Dq + Saline group) . The anxiety level of experi- mental rats was evaluated through open field experiments and elevated cross maze experiments . In vivo electroen- cephalography (EEG) was used to record propofol induced sleep and cortical EEG changes , and immunofluores- cence staining was used to observe changes in c-Fos positive protein expression in 5-HT neurons . Results The be- havioral results showed that compared with the chemical control group , the anxiety level of the chemical activation group was significantly lower (P < 0. 05) , and sleep duration was significantly prolonged (P < 0. 05) . The expres- sion level of c-Fos positive protein in DRN5-HT neurons in the chemical activation group was higher (P < 0. 05) . The EEG results showed that the percentage of δ-band power between the chemical activation group and the chemi- cal control group was higher ( P < 0. 05 ) , the power percentage in the α-band was relatively low ( P < 0. 05 ) . Conclusion Chemical activation of 5-HT neurons in the DRN region can improve anxiety levels and increase sleep duration in PCPA induced insomnia rats .

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Abstract Objective To investigate the effect and mechanism of sex-determining region Y-box transcription factor 4 (SOX4) on autophagy in small cell lung cancer (SCLC) cells . Methods Human SCLC cell line NCI-H446 was transfected with small interfering RNA ( siRNA) to knockdown SOX4 . RT-qPCR and Western blot were used to verify the transfection efficiency . NCI-H446 cells were divided into control group , si-SOX4 group , si-SOX4 + oe- Beclin1 group and oe-Beclin1 group . Western blot analysis was performed to detect the ratio of microtubule-associ- ated protein 1 light chain 3 (LC3)-Ⅱ/LC3 - Ⅰ expression and the expression of Beclin1 and p62 in different groups of cells . The transcriptional regulation of Beclin1 by SOX4 was detected by dual luciferase reporter assay and chro- matin immunoprecipitation PCR ( ChIP-PCR) assay . CCK-8 assay was used to detect the proliferation ability of NCI-H446 cells in different groups . Flow cytometry was used to detect the apoptosis rate of NCI-H446 cells in dif- ferent groups . Transwell assay was performed to determine the cell migration and invasion ability in different groups . Results Compared with the control group or the si-NC group , the relative mRNA and protein expression level of SOX4 in si-SOX4 group were down-regulated (P < 0. 05) , and the ratio of LC3-Ⅱ/LC3 - Ⅰ protein expres- sion and the relative protein expression level of Beclin1 in si-SOX4 group decreased (P < 0. 05) , the relative pro- tein expression of p62 increased (P < 0. 05) . The relative luciferase activity of Beclin1 WT in the si-SOX4 group was lower than that in the si-NC group (P < 0. 05) ; the relative enrichment of Beclin1 promoter in the Anti-SOX4 group was higher than that in the Anti-IgG group (P < 0. 05) . Compared with control group , cell proliferation ac- tivity decreased , cell apoptosis rate increased , migration number and invasion number decreased in si-SOX4 group (P < 0. 05) . Compared with the si-SOX4 group , the ratio of LC3-Ⅱ/LC3 - Ⅰ protein expression and the relative protein expression of Beclin1 increased in si-SOX4 + oe-Beclin1 group , while the relative protein expression of p62 decreased , cell proliferation activity increased , apoptosis rate decreased , migration number and invasion number increased (P < 0. 05) . Conclusion Down-regulation of SOX4 can inhibit autophagy , decrease proliferation activi- ty of NCI-H446 cells , and inhibit cell migration and invasion by inhibiting Beclin1 expression .

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Abstract Objective To investigate the role of enhancer of zeste homolog 2 (EZH2) - trimethylated lysine 27 of niques , and to explore whether it has a regulatory effect on comorbidities of insomnia and anxiety . Methods 32 male SD rats were randomly divided into control group , PCPA model group ( PCPA group) , chemical activation group (hM3Dq + CNO group) , and chemical control group (hM3Dq + Saline group) . The anxiety level of experi- mental rats was evaluated through open field experiments and elevated cross maze experiments . In vivo electroen- cephalography (EEG) was used to record propofol induced sleep and cortical EEG changes , and immunofluores- cence staining was used to observe changes in c-Fos positive protein expression in 5-HT neurons . Results The be- havioral results showed that compared with the chemical control group , the anxiety level of the chemical activation group was significantly lower (P < 0. 05) , and sleep duration was significantly prolonged (P < 0. 05) . The expres- sion level of c-Fos positive protein in DRN5-HT neurons in the chemical activation group was higher (P < 0. 05) . The EEG results showed that the percentage of δ-band power between the chemical activation group and the chemi- cal control group was higher ( P < 0. 05 ) , the power percentage in the α-band was relatively low ( P < 0. 05 ) . Conclusion Chemical activation of 5-HT neurons in the DRN region can improve anxiety levels and increase sleep duration in PCPA induced insomnia rats .

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Abstract Objective To investigate the molecular mechanisms and pathways of action of total flavonoids of Draco- cephalum moldavica L. (TFDM) in treating vascular cognitive impairment ( VCI) based on network pharmacology and in vivo animal experiments . Methods The swiss target prediction database , literature , and PubChem were used to screen the active components and action targets of TFDM . The online mendelian inheritance in man ( OMIM) and GeneCards databases were utilized to screen for possible VCI targets . Venny software was used to ob- tain the intersection target of TFDM and VCI . The search tool for recurring instances of neighbouring genes (String) database and Cytoscape software was used to construct the PPI network . The database for annotation , vi- sualization and integrated discovery (DAVID) database was utilized to screen for the kyoto encyclopedia of genes and genomes (KEGG) pathway and gene ontology (GO) enrichment analyses to explore the molecular mechanism and signaling pathway of TFDM for VCI . 24 rats were divided into Sham , Model , Donepezil , and TFDM groups . Except for the Sham group , the VCI model was created using modified bilateral common carotid artery ligation . Af- ter continuous gavage for 21 days , the Morris water maze test was used to evaluate the spatial learning and memory ability of rats . Hematoxy-lineosin (HE) staining was used to observe the pathological changes in the hippocampal CA1 and cortex region of the animals and immunohistochemistry detection of zonula occludens-1(ZO-1) content in the brains of the rats . Western blot was used to detect nuclear factor kappa-B p65 (NF-κB p65) and tumor necro- sis factor-α(TNF-α) in rat brains . Results A total of 39 active ingredients of TFDM were screened , 209 corre- sponding targets , 10 417 gene targets of VCI , and 193 intersecting targets . According to the results of the GO en- richment of function analysis , TFDM could improve the response of reactive oxygen species and metabolic processes of reactive oxygen species , etc . KEGG pathway enrichment analysis suggested that TFDM might regulate TNF , IL- 17 signing pathway , etc . The results of animal experiments showed that TFDM improved learning and memory while reduced pathological damage in the brains of VCI rats . In addition , TFDM upregulated the positive expression of ZO-1 and downregulated the protein levels of TNF-αand NF-κB p65 ( P < 0. 05 ) . Conclusion TFDM can improve the cognitive function of VCI through multi-components and multi-targets , and its key mechanism may be related to inhibiting TNF-α/NF-κB p65 signaling pathway , reducing neuroinflammation , and improvement of blood- brain barrier permeability.

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Abstract Objective To explore the characteristic of obesity in adolescents with major depressive disorder and its relationship with inflammatory cytokines . Methods One hundred and forty adolescents with major depressive disor- der were enrolled . According to the classification standard of body mass index (BMI) for adolescents in China , the patients were classified into underweight group , normal group , overweight group and obese group . The center for epidemiologic studies depression scale (CES-D) was used to evaluate symptoms of depression in patients , and ul- trasensitive multiplex electrochemiluminescence detection technology was used to measure the levels of plasma in- flammatory cytokines including interleukin(IL)-6 , IL-17A , IL-1β, IL-6 , IL-8 and tumour necrosis factor(TNF) -α. One-way ANOVA or Kruskal-Wallis H test and chi-square test were used for comparison between groups . Binary Logistic regression was used to analyze the influencing factors of obesity in adolescent patients with major depressive disorder. Results Among the 140 adolescent patients with major depressive disorder , wasting were 9. 3% ( 13/ 140) , overweight were 17. 9% (25/140) and obesity were 6. 4% (9/140) respectively . There were statistically significant differences in gender ( χ2 = 8. 301 , P < 0. 05 ) and inflammatory cytokines IL-6 ( H = 16. 217 , P < 0. 01) , IL-8 (H = 10. 926 , P < 0. 05) and TNF-α(H = 7 . 879 , P < 0. 05) among the four groups . Analysis of co- variance showed that the difference in levels of the inflammatory cytokine IL-6 (F = 4. 486 , P < 0. 01) remained statistically significant after controlling for age , gender and antidepressant use . The results of multiple comparisons showed that compared with the wasting group , the plasma IL-6 (Z = - 3 . 843 , P Bonferroni calibrate < 0. 01) were higher in the obese group;compared with the normal group , the obesity rate of males was higher than that of females ( χ2 = 8 . 812 , P Bonferroni calibrate < 0. 01) , and the level of IL-6 in the obese group (Z = - 3 . 023 , P Bonferroni calibrate < 0. 05) was higher. Binary Logistic regression analysis showed that plasma IL-6 (OR = 2. 500 , P < 0. 01) and gender (OR = 11 . 292 , P < 0. 01) were independent influencing factors for obesity in patients with adolescent depressive disor- ders . Conclusion There are gender differences in obesity rates in adolescents with depressive disorders , and obe- sity is associated with elevated levels of inflammatory cytokines .

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Abstract Objective To investigate the distribution of solute carrier organic anion transporter family member 1B1 (SLCO1B1) and apolipoprotein E(ApoE) gene polymorphisms in the patients of Han nationality with cardiovascu- lar and cerebrovascular diseases from Anhui Province , in order to provide the basis for the individualized therapy of statins in clinical practice . Methods 924 Han patients with cardiovascular and cerebrovascular diseases were se- lected . The SLCO1B1 and ApoE genotypes of the patients were detected by polymerase chain reaction-fluorescent probe method , and their distribution was compared among different genders and other regions in China. Results Seven SLCO1B1 gene subtypes were detected in 924 patients , including * 1a/ * 1b (33 . 01% ) , * 1b/ * 1b (41 . 45% ) , *1b/ *15(12. 34% ) , *1a/ *1a(7 . 03% ) , *1a/ *15(5 . 52% ) , *15/ *15(0. 54% ) and * 5/ *5(0. 11% ) , without detection of the two gene subtypes of * 1a/ *5 and *5/ * 15 ; the normal metabolic genotype I of SLCO1B1（ *1a/ *1 a , *1a/ *1b , *1b/ *1b) accounted for the highest proportion in this popu- lation(81 . 49% ) , the intermediate metabolic genotype II and the weak metabolic genotype III of SLCO1B1 accoun- ted for 17. 86% and 0. 65% respectively; six ApoE gene subtypes were detected , including E3/E3 (66. 78% ) , E3/E4(19. 37% ) , E2/E3(9. 63% ) , E4/E4( 1 . 84% ) , E2/E4 (1 . 73% ) and E2/E2(0. 65% ) ; the E3 mass genotype (E2/E4 , E3/E3) accounted for the highest proportion in this population (68 . 51% ) ; there was no sig- nificant difference in the distribution of SLCO1B1 and ApoE genes between different genders; there was no signifi- cant difference in the distribution of SLCO1B1 between the Han population from Anhui and the South China and Central China , but a significant difference was found between the Anhui Han population and the Southwest China ( P < 0. 05) ; the distribution of ApoE in the Anhui Han population demonstrated no statistically significant variation from those in South China and Southwest China , whereas significant differences were observed in comparison with Central China(P < 0. 05) . Conclusion In the Han population with cardiovascular and cerebrovascular diseases in Anhui , the distributions of SLCO1B1 and ApoE gene polymorphisms show no significant gender differences but ex- hibit regional variations . These populations are predominantly characterized by class I normal metabolic genotype (SLCO1B1) and E3 mass genotypes (ApoE) , indicating a higher tolerance to statin dosages and normal therapeu- tic efficacy in this cohort.

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Abstract Objective To explore the polymorphism of endothelial nitric oxide synthase (eNOS) gene in umbilical cord blood of preterm infants and its relationship with major complications in preterm infants . Methods A total of 254 preterm infants ( < 37 weeks) who were hospitalized were selected as the study subjects . Umbilical cord blood was collected at delivery to determine the genotypes and alleles of eNOS gene at three loci : rs61722009 , rs2070744 , and rs1799983 . Clinical data of the preterm infants were recorded , and the relationship between eNOS gene polymorphism and major complications in preterm infants was analyzed . Results ① The TC + CC genotype at locus rs2070744 was an independent risk factor for bronchopulmonary dysplasia (BPD) in preterm infants , with an OR (95% CI) of 1 . 266 ( 1 . 017 - 1 . 577) . ② The GT + TT genotype at locus rs1799983 was an independent risk factor for retinopathy prematurity (ROP) , with an OR (95% CI) of 1 . 184 ( 1 . 008 - 1 . 391) . ③ The AB + AA genotype at locus rs61722009 was also an independent risk factor for ROP , with an OR (95% CI) of 1 . 335(1 . 033 -1 . 726) . ④ There was no significant relationship between gene polymorphism and the occurrence of respiratory dis- tress syndrome (RDS) and periventricular-intraventricular hemorrhage (PIVH) . Conclusion eNOS gene polymor- phism is associated with the occurrence of BPD and ROP in preterm infants . The evaluation of eNOS gene polymor- phism by umbilical cord blood measurement is helpful for the prevention and correct management of some serious complications .

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Abstract Objective To explore the molecular characteristics of four CAMP negative Streptococcus agalactiae (S. agalactiae) in whole genome sequencing. Methods The identification of suspicious bacterial strains was conduc- ted using matrix-assisted laser desorption ionization time-of-flight mass spectrometry ( MALDI-TOF MS) . For the strains confirmed as S. agalactiae through identification , further CAMP experiments were conducted . For CAMP negative strains , whole genome sequencing was performed using MGI DNBSEQ-T7 and MinION Flow Cell sequen- cing platforms . Subsequently , multi-locus sequence typing ( MLST) , virulence genes and resistance genes of the strains were compared and analyzed using various databases . Phoenix M50 fully automatic drug sensitivity analyzer was employed to determine the sensitivity of the bacterial strains to commonly used antibiotics . Results Four CAMP-negative S. agalactiae strains were included . Whole-genome sequencing analysis revealed that all four CAMP-negative S. agalactiae strains belonged to the ST862 type . These strains harbored 22 virulence genes associ- ated with capsular polysaccharides , β-hemolysin , and hyaluronidase , as well as seven resistance genes linked to macrolides , lincosamides , polypeptides , and aminoglycosides . Antimicrobial susceptibility testing revealed that CAMP-negative S. agalactiae was susceptible to penicillin G , cefepime , cefotaxime , and vancomycin . However , three strains exhibited resistance to erythromycin , and one strain demonstrated resistance to clindamycin . Conclu- sion Four CAMP negative S. agalactiae of the ST862 type possess multiple virulence and drug resistance genes , showing high resistance to erythromycin , warranting clinical attention .

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Abstract Objective To investigate the relationship between the risk occurrence of rectal cancer and the single nucleotide polymorphisms (SNP) of zinc finger protein 6(ZBED6) , and to provide the experimental basis for early diagnosis and treatment of rectal cancer. Methods Polymerase chain reaction-restriction fragment length polymor- phism (PCR-RFLP) technology was used to genotype the ZBED6 gene in 109 randomly selected rectal cancer pa- tients and 110 unrelated healthy controls . To evaluate the relationship between alleles , genotypes and the risk of rectal cancer , unconditional Logistic regression analysis was used to OR and 95% CI. Results The SNP rs7552670 of ZBED6 had significant correlation with the risk of rectal cancer. Compared with the population carrying the TT genotype , those carrying the TC genotype had a 2. 653 fold increased risk of rectal cancer (TT vs TC : OR = 2. 635 , 95% CI = 1 . 501 - 4. 690) . Other SNPs had no significant correlation with the risk of rectal cancer. Conclusion There is an interaction between the polymorphisms of ZBED6(rs7552670) and rectal cancer. The population car- ried ZBED6 rs7552670 TC genotype had an growing risk of rectal cancer.

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Abstract Objective To investigate associations of suicidal ideation with clinical features , inflammatory markers ,and thyroid hormones in patients with schizophrenia. Methods The subjects of this study were 203 schizophrenic patients , grouped on the basis of suicidal ideation . Clinical characteristics were assessed using multiple scales . Neutrophil to lymphocyte ratio (NLR) , platelet to lymphocyte ratio (PLR) , monocyte to lymphocyte ratio (MLR) and thyroid hormones were also detected . SPSS 23 . 0 was used for statistical analyses . Results The prevalence of suicidal ideation was 21 . 7% in patients with schizophrenia. Logistic stepwise regression analyses showed that Cal- gary depression scale (CDSS) total score (OR = 1 . 490 , 95% CI = 1 . 287 - 1 . 724 , P < 0. 001) , insomnia severity index scale (ISI) total score (OR = 1 . 096 , 95% CI = 1 . 011 - 1 . 187 , P = 0. 025) , modified overt aggression scale (MOAS) total score (OR = 1 . 111 , 95% CI = 1 . 016 - 1 . 215 , P = 0. 021) , MLR(Ln) (OR = 15 . 123 , 95% CI = 3 . 868 - 59. 125 , P < 0. 001) , and triiodothyronine ( T3) ( OR = 0. 037 , 95% CI = 0. 003 - 0. 388 , P = 0. 006) were the independent influences of suicidal ideation . Additionally , receiver operating characteristic (ROC) curve analyses revealed that the five-item combination of CDSS total score , ISI total score , MOAS total score , MLR (Ln) , and T3 (AUC = 0. 908 , 95% CI = 0. 867 - 0. 949 , P < 0. 001) had better ability to identify suicidal idea- tion . Conclusion The risk of suicidal ideation is relatively high in patients with schizophrenia , and there may be stronger associations between suicidal ideation and depression , insomnia , aggression , MLR , and T3 .

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Abstract Objective To explore the differential lipid metabolites in the plasma of mice with idiopathic pulmonary fibrosis (IPF) . Methods Thirty SPF C57BL/6 male mice were randomly divided into 2 groups with 15 mice in each group . The experimental groups were divided into control group and bleomycin (BLM) group . The model of idiopathic pulmonary fibrosis was induced by one-time intratracheal infusion of BLM ( 1 mg/kg) . Hematoxylin-eo- sin (HE) staining was used to observe the lung histopathology . The collagen fiber deposition in lung tissue was ob- served by Sirius red staining. The differential lipid metabolites in plasma of IPF mice were screened and enriched by lipidomics . Results HE staining showed that the pulmonary tissue structure was disordered , alveolar septum was broken and alveolar wall was destroyed in BLM group . Sirius red staining showed a large amount of collagen fi- ber deposition in the lung interstitium of BLM group . The results of lipidomics analysis showed that the lipid metab- olism profile of BLM group changed , 15 differential lipid metabolites were screened out , of which 11 differential lipid metabolites were up-regulated , and 4 differential lipid metabolites were down-regulated , mainly concentrated in Glycerophosphoglycerophosphates , Glycerophosphocholines , Steroid lactones , etc . Conclusion The lipid me- tabolism profile of BLM group mice changes , differential lipid metabolites such as phosphoglycolate phosphatase (PGP)(18:0/18:0) , PGP( i-12:0/i-24:0) , PGP( i-13:0/a-25:0) , and phosphatidylcholine ( PC) (18:0/14 : 0) , PC(18:3/16:0) , lysophosphatidylcholine (LPC)(16:1) , and LPC(18:3) may play an important role in the progression of IPF . These findings provide a new reference for further study of the molecular mechanism of IPF , and also provide a potential new target for clinical treatment.

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Abstract Objective To investigate the effects of heat shock protein 70 ku protein 1A (HSPA1A) on H9c2 in- flammation and apoptotic injury in rat cardiomyocytes under hypoxia , and to analyze its mechanism . Methods H9c2 cells were treated with normal oxygen (Nor) and hypoxia (Hyp) , and the expression of HSPA1A was detec- ted by RT-qPCR and Western blot. Normal H9c2 cells were divided into Nor group (normoxia culture) , sh-HS- PA1A + Nor group (cells transfected with HSPA1A shRNA , normoxia culture) , Hyp group (hypoxia culture) , sh- HSPA1A + Hyp group (cells transfected with HSPA1A SHRNA , hypoxia culture) , the expression level of HSPA1A in H9c2 cells in each group was detected by RT-qPCR and Western blot , the morphology of H9c2 cells in each group was observed by inverted microscope , and the activity of H9c2 cells in each group was detected by CCK-8 , the contents of inflammatory factors tumor necrosis factor-α(TNF-α) , interleukin(IL)-6 , IL-1βand the activities of myocardial injury markers lactate dehydrogenase (LDH) , creatine kinase (CK) in the supernatant of H9c2 cells were detected by ELISA , apoptosis rate of H9c2 cells in each group was detected by Annexin V-FITC/PI double staining , the expression levels of TNF receptor-associated factor 2 (TRAF2) /nuclear factor κB (NF-κB) pathway- related proteins in H9c2 cells of each group were detected by Western blot. Results Compared with Nor group , the relative expression of HSPA1A mRNA and protein in H9c2 cells in Hyp group after hypoxia induction was sig- nificantly up-regulated (P < 0. 05) . Compared with Nor group , the number of H9c2 cells in Hyp group significant- ly decreased , some cells were wrinkled and disordered , the cell activity significantly decreased ( P < 0. 05) , the contents of TNF-α, IL-6 , IL-1βand the activities of LDH and CK in supernatant significantly increased ( P < 0. 05) , the cell apoptosis rate significantly increased (P < 0. 05) , the relative expressions of TRAF2 protein and the phosphorylation level of p65 and inhibitor of nuclear factor κB alpha (IκBα) were significantly up-regulated (P < 0. 05) ; compared with Hyp group , the morphology of H9c2 cells in sh-HSPA1A + Hyp group was improved , the cell arrangement was more dense , the cell activity significantly increased (P < 0. 05) , the contents of TNF-α, IL- 6 and IL-1βin supernatant decreased , the activities of LDH and CK significantly decreased (P < 0. 05) , the apop- tosis rate significantly decreased ( P < 0. 05) , the relative expressions of TRAF2 protein and the phosphorylation level of p65 and IκBαwere also significantly down-regulated ( P < 0. 05 ) . Conclusion The expression of HS- PA1A in rat cardiomyocytes H9c2 is increased by hypoxia , and inhibition of HSPA1A expression can improve the hypoxia-induced inflammatory response of H9c2 cells and reduce apoptosis damage , which may be related to the regulation of TRAF2/NF-κB pathway .

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Abstract Objective To investigate the effect of Sirtuin 2 (SIRT2) on the proliferation and migration of cardiac forty SPF healthy male C57BL/6J mice were randomly divided into four groups : normal diet group ( ND group) , high fat diet induced obesity group (DIO group) , DIO supplemented with the control virus group (DIO + Scramble group) and DIO supplemented with the interfering virus group (DIO + shPTGES3 group) . The Morris water maze test was conducted to evaluate the cognitive behavior changes of the four groups of mice . The immunofluorescence staining was performed to detect the expression of PTGES3 and HSP90 in the medial prefrontal cortex and the acti- vation of ionized calcium binding adapter molecule 1 (IBA1)-labeled microglia. Results In the case-control stud- y , the cognitive function of obese patients significantly decreased , and the expression of PTGES3 in peripheral blood significantly increased , while the level of PTGES3 was negatively correlated with cognitive function . In ani- mal experiments , compared with ND group , DIO group had significantly prolonged time reaching the target plat- form , otherwise , the residence time in the target quadrant was shortened in the Morris water maze test. Simultane- ously , there were significant increase in the expression of PTGES3 and HSP90 , and the activation of IBA1 in the medial prefrontal cortex . Compared with DIO + Scramble group , mice in the DIO + shPTGES3 group spent less time reaching the target platform , and stayed longer in the target quadrant. The expression and co-localization levels of PTGES3 and HSP90 in medial prefrontal cortex significantly decreased . The activation level of microglia cells was also attenuated by PTGES3 interference . Conclusion Obesity-related cognitive dysfunction may be attributed to PTGES3/HSP90 in the medial prefrontal cortex by mediating neural inflammation .

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Abstract Objective To predict and validate key targets for cisplatin( DDP) resistance in colorectal cancer to provide more options for precision medicine in clinical treatment. Methods Differentially expressed genes (DEGs) between normal colonic mucosa and colorectal cancer(CRC) were screened from the gene expression om- nibus(GEO) database . Key genes were identified using the STRING database and Cytoscape software . DEGs were subjected to enrichment analysis using the gene ontology ( GO) and kyoto encyclopedia of genes and genomes (KEGG) databases . Key targets were validated through RNA-seq , qRT-PCR , and Western blot. The versican (VCAN) gene overexpression vector was transfected into human ileocecal colorectal adenocarcinoma cell line HCT8 , and cell viability was assessed using the CCK-8 assay . Flow cytometry was used to assess apoptosis and cell cycle distribution . qRT-PCR and Western blot were performed to detect mRNA and protein levels of the target genes . Results In this study , 118 upregulated DEGs and 146 downregulated DEGs were identified from the GEO database . DEGs were mainly enriched in extracellular matrix degradation , extracellular matrix organization , and the phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway . Based on protein-protein interaction network analysis , 20 hub genes were identified . By comparing the transcriptome sequencing results of the HCT8 pa- rental strain and DDP-resistant strain , the VCAN gene was further selected . In CRC tissues , the expression level of VCAN was higher than that in normal colonic mucosa , and patients with high VCAN expression had shorter overall survival (OS) and recurrence free survival(RFS) times . Overexpression of VCAN in CRC cells promoted cell pro- liferation (P < 0. 05 ) , increased resistance to DDP , reduced DDP-induced apoptosis ( P < 0. 05 ) , and G0 /G1 phase arrest (P < 0. 05) ; upregulation of VCAN activated the protein kinase B (AKT)-mammalian target of rapam- ycin ( mTOR) signaling pathway . Conclusion Bioinformatics and transcriptome sequencing identified VCAN as a key target gene for DDP resistance in CRC , potentially promoting CRC progression and DDP resistance by regula- ting the AKT-mTOR pathway .

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Abstract Objective To investigate the mechanism of prostaglandin E synthase 3 (PTGES3) / heat shock protein 90 (HSP90) in the medial prefrontal cortex regulating obesity-related cognitive dysfunction . Methods This study consisted of clinical trials and animal experiments . In part one , obese patients scheduled for bariatric surgery , and healthy adults matching gender and age were recruited at the same time to reach 10 cases in each group . The cogni- tive level was assessed with trail making test part A (TMT-A) and victoria stroop tests (VST) . Four-dimensional data-independent acquisition (4D-DIA) was used to screen the proteome changes in peripheral blood . In part two ,forty SPF healthy male C57BL/6J mice were randomly divided into four groups : normal diet group ( ND group) , high fat diet induced obesity group (DIO group) , DIO supplemented with the control virus group (DIO + Scramble group) and DIO supplemented with the interfering virus group (DIO + shPTGES3 group) . The Morris water maze test was conducted to evaluate the cognitive behavior changes of the four groups of mice . The immunofluorescence staining was performed to detect the expression of PTGES3 and HSP90 in the medial prefrontal cortex and the acti- vation of ionized calcium binding adapter molecule 1 (IBA1)-labeled microglia. Results In the case-control stud- y , the cognitive function of obese patients significantly decreased , and the expression of PTGES3 in peripheral blood significantly increased , while the level of PTGES3 was negatively correlated with cognitive function . In ani- mal experiments , compared with ND group , DIO group had significantly prolonged time reaching the target plat- form , otherwise , the residence time in the target quadrant was shortened in the Morris water maze test. Simultane- ously , there were significant increase in the expression of PTGES3 and HSP90 , and the activation of IBA1 in the medial prefrontal cortex. Compared with DIO + Scramble group , mice in the DIO + shPTGES3 group spent less time reaching the target platform , and stayed longer in the target quadrant. The expression and co-localization levels of PTGES3 and HSP90 in medial prefrontal cortex significantly decreased . The activation level of microglia cells was also attenuated by PTGES3 interference . Conclusion Obesity-related cognitive dysfunction may be attributed to PTGES3/HSP90 in the medial prefrontal cortex by mediating neural inflammation .

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Abstract Objective To establish an in vitro model of ferroptosis induced by Erastin and RAS-selective lethal 3 (RSL3) in hepatoma cells , and to provide theoretical basis for the development of novel therapeutic strategies for HCC . Methods Hepatoma cells ( HCCLM3 , HepG2 , Hep3B , Huh7 and PLC/PRF/5 ) in logarithmic growth phase were treated with Erastin (0 - 40 μmol/L) and RSL3 (0 - 10 μmol/L) at double concentrations respective- ly . After 24 h , CCK-8 method was used to detect cell viability , draw growth curve , calculate IC50 , and HCC cells sensitive to inducers were selected for follow-up experiments . The effect of inducer on the state of hepatoma cells was observed under light microscope , and immunoblotting and flow cytometry were used to verify whether the fer- roptotic model in vitro was successfully constructed . Results Huh7 , Hep3B and HepG2 cells were sensitive to Erastin and RSL3 , but HCCLM3 and PLC/PRF/5 were insensitive to Erastin and RSL3 . When the concentration of Erastin and RSL3 reached the maximum , the survival rate was still above 65% . Huh7 , Hep3B and HepG2 cells were selected for subsequent experiments . Compared with the control group , the expression of Glutathione peroxi- dase 4 (GPX4) , a ferroptotic marker , was down-regulated in a concentration-dependent manner. In Huh7 , Hep3B and HepG2 cells , lipid reactive oxygen species ( ROS) levels significantly increased after 24 h treatment with 10 μmol/L and 20 μmol/L Erastin , respectively; in Huh7 cells , lipid ROS levels significantly increased after 24 h treatment with 0. 5 μmol/L and 1 μmol/L RSL3 , respectively; in Hep3B and HepG2 cells , lipid ROS levels sig- nificantly increased after 24 h treatment with 1 μmol/L and 2 μmol/L RSL3 , respectively , compared with control group . Conclusion Huh7 , Hep3B and HepG2 cells are highly sensitive to Erastin and RSL3 . Huh7 , Hep3B and HepG2 cells treated with 10 μmol/L Erastin for 24 h are good models for simulating ferroptosis induced by Erastin in vitro , Huh7 cells treated with 0. 5 μmol/L RSL3 for 24 h and Hep3B and HepG2 cells treated with 1 μmol/L RSL3 for 24 h are good models for simulating ferroptosis induced by RSL3 in vitro .

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Abstract Non-small cell lung cancer (NSCLC) , the most prevalent type of lung cancer , has a poor prognosis in patients with advanced disease . In recent years , immune checkpoint inhibitors (ICIs) have demonstrated promising efficacy in this disease , while bringing a unique set of immune-related adverse events (irAEs) . This article com- prehensively explores the multi-systemic irAEs of programmed death protein-1 ( PD-1) /programmed death protein ligand-1 (PD-L1) inhibitors in the treatment of NSCLC , including but not limited to dermatotoxicity , endocrine toxicity , hepatic toxicity and gastrointestinal toxicity . The occurrence of these adverse reactions not only poses a challenge for clinical treatment , but also correlates with treatment efficacy . In addition , the paper discusses bio- markers for predicting the risk of irAEs , such as gut microbiota , blood biomarkers , etc . , with the aim of providing a potential risk assessment tool for the clinic .

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Asthma is a well-characterized heterogeneous disease marked by airway remodeling and chronic air- way inflammation . Clinically , the treatment of asthma primarily relies on hormonal drugs . However , the long-term use of these medications can lead to significant side effects . Mitophagy is a biological process that selectively trans- ports damaged mitochondria to lysosomes for degradation . Recent research has revealed the crosstalk between mito- phagy and asthma. Accordingly , taking mitophagy as an entry point , summarizing the key molecular mechanisms and regulators of mitophagy in asthma will facilitate the development of novel intervention targets and strategies for asthmatic treatment.

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Abstract Objective To establish a novel autistic juvenile rat model with down-regulation of PTEN gene (PTEN- ASD) , to compare the newly constructed animal model with two traditional autistic animal models of Valproic acid (VPA) and adenovirus (ADV) , and ultimately to prove the advantages of this model in animal model establishment of acupuncture treatment for ASD. Methods Wista rats at 12. 5 days of gestation were randomly divided into 2 groups . VPA rats were given 600 mg/kg of normal saline (NS) intraperitoneally. Weight , eye opening time and tail deformity were recorded . The newborn mice in NS group were randomly divided into three groups ( 10 rats in each group) : normal (NS) group , virus (ADV) group and virus-negative control (ADV-NC) group; VPA group (20 young rats) was randomly divided into 2 groups (10 rats in each group) : valproic acid (VPA) group and val- proic acid-binding virus interference (VPA + ADV) group . The body weight , tail length , curved tail , geotaxis text time and skeletal deformity of 5 groups of young rats after birth , the neurobehavioral behavior of 21-day-old rats , and the myelin structure of brain tissue under electron microscope were observed , the expression levels of PTEN , PI3K , AKT , GSK3 βand MBP were detected by immunohistochemistry , Western blot and q-PCR. Results Com- pared with the NS group , the VPA group had significantly increased malformation rate , slow weight gain , slow tail length growth , and long negative geotaxis reflex time (P < 0. 05) . Compared with the NS group , the weight gain , tail length growth and negative geotaxis reflex time of the three model groups were slower (P < 0. 05) , and the per- formance of model 3 was the most significant. There were significant differences in the time of crossing the central grid , the number of crossing the edge grid , and the time of crossing the edge grid in the open field test between the three groups and the NS group (P < 0. 05) . In the self-grooming experiment , the number of interactions in Model 3 was the least (P < 0. 05) , and the number of digging and self-grooming was the most (P < 0. 05) . The three-box social experiment model 3 had the shortest average number of entries into the social box and the shortest residence time (P < 0. 05) . The longer it took to find the platform in the water maze experiment , the fewer times it crossed the third quadrant (P < 0. 05) . The structure of the myelin sheath layer in the corpus callosum was observed by transmission electron microscopy. The structure of the NS group was clear and complete . Compared with the NS group , the myelin structure of the ADV-NC group was similar , and the myelin structure of the three model groups was stratified and broken , and there were pathological changes and myelin damage in the ASD . Among them , the myelin sheath of the model 3 was thickened , stratified , and severe visible disintegration . The results of immunohis- tochemistry , Western blot and q-PCR showed that the expression of PTEN in model 3 was down-regulated by about 50% , which was the most obvious . The expression of AKT and MBP increased , and the expression of GSK3 βde- creased (P < 0. 05) . However , the results of q-PCR showed that the expression of PI3K-mRNA in the three model groups significantly increased (P < 0. 05) , and the change of model 3 was the most significant. Conclusion The novel PTEN-ASD animal model established by VPA + ADV method is observed to have significant pathological changes that are typical of the manifestation of ASD myelin dysplasia and is determined to have better results than the two traditional autistic animal models .

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Abstract Objective To investigate the expressions of GPR15 and FOXP3 in colorectal carcinoma(CRC) tissues and their clinical prognostic values . Methods A total of 132 patients with CRC underwent radical surgery were collected . The control group selected the normal mucosal tissues more than 5 cm away from the edge of the cancer focus . Immunohistochemistry (Envision two-step method) was used to detect the expression levels of GPR15 and FOXP3 in CRC and adjacent tissues , and analyze their relationships with clinicopathological factors of colorectal cancer . Kaplan-Meier method was used to draw the survival curve to analyze the correlation between the expressions of GPR15 and FOXP3 and the survival prognosis of patients with CRC . The factors influencing prognosis of patients with colorectal cancer were analyzed by Cox regression . Results The immunohistochemistry showed that the ex- pression levels of GPR15 and FOXP3 in CRC were significantly higher than those in normal colorectal mucosal tis- sues (P < 0. 05) . The expression of GPR15 in CRC tissues was correlated with location , nerve invasion and TNM stage; FOXP3 expression was correlated with sex ( P < 0. 05) . Both expressions were not significantly correlated with the clinicopathologic features of age , tumor size , differentiation degree , tissue type , depth of invasion , tumor budding , vascular invasion and lymph node metastasis . Correlation analysis showed that there was no significant correlation between GPR15 and FOXP3 expression ( Kappa = - 0. 019 , P > 0. 05 ) . The survival prognosis of GPR15 positive group was significantly worse than that of negative group(log-rank:χ2 = 4. 3 , P = 0. 039) ;while the survival prognosis of FOXP3 positive group was significantly better than that of negative group(log-rank:χ2 = 7 . 3 , P = 0. 007) . Age ≤55 years , positive GPR15 and negative FOXP3 were independent risk factors for poor prognosis in patients with CRC(P < 0. 05) . Conclusion The expression levels of GPR15 and FOXP3 in CRC are signifi- cantly higher than those in paracancer tissues , GPR15 and FOXP3 are expected to become new tumor markers for early screening , accurate treatment and prognosis assessment of CRC .

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Abstract Objective To investigate the therapeutic effects and underlying mechanisms of cannabidiol (CBD) and its nano-formulations on depression-like behaviors in mice . Methods A murine model of acute anxiety and depres- sion was established by intraperitoneal administration of lipopolysaccharide ( LPS) . A total of 55 mice were ran- domly assigned into several groups : for the long-term study , a control group (Con) , a model group (LPS) , a can- nabidiol group (CBD) , a nano-cannabidiol group (NCBD) , and a sertraline (SER) group , each consisting of 7 mice . In the short-term study , mice were divided into four groups : the Con group , LPS group , CBD group , and NCBD group , with 5 mice in each group . Except for the Con group and LPS group , which were given distilled wa- ter , the remaining groups were administered 25 and 50 mg/kg of cannabidiol and its nano-formulation via oral ga- vage . The open field and forced swimming tests were employed to assess anxiety- and depression-like behaviors in immune cells . The expression of Card9 in the cornea of mice treated with Card9 siRNA was significantly reduced . After inhibiting the expression of Card9 gene , the expressions of Card9 , NF-κB , IL-1β, IL-6 and TNF-αsignifi- cantly decreased and the changes of IL-1βwere most significant. In in vitro studies , Card9 exhibited negligible ex- pression in human corneal epithelial cells , contrasting with its pronounced expression in THP-1 cells . After the in- duction of macrophages , Card9 , NF-κB , IL-1β, IL-6 , and TNF-αwere significantly upregulated under the stimu- lation of A. fumigatus . After inhibiting the expression of Card9 , the stimulated expression of these factors was sig- nificantly reduced , with the most notable change observed in IL-1β. Conclusion Card9 is involved in the inflam- matory development and healing process of A. fumigatus keratitis . Card9 deficiency can cause functional impair- ment of macrophages and inhibit the expression of inflammatory factors to a certain extent , in which IL-1βhas the greatest effect.

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Abstract Objective To explore whether chrysophanol (CHR) affects macrophage polarization by promoting mito- chondrial biosynthesis through AMPK/PGC-1 αpathway. Methods The molecular docking and binding ability of CHR with AMPK and PGC-1 αwere predicted by Autodock vina software . Human monocytes ( THP-1) were in- duced to M0 macrophages by phorbol myristate acetate ( PMA) , and to M1 macrophages by lipopolysaccharide (LPS) combined with interferon-γ(IFN-γ) , which were set as Control group . M1 macrophages treated with CHR were set as CHR group . M1 macrophages treated with CHR combined with AMPK inhibitor ( Compound C) were set as CHR + Compound C group . The mRNA expression levels of M1 macrophage markers (iNOS , CD86) and mi- tochondrial biosynthesis related genes (PGC-1 α, NFR-1 , TFAM) were detected by Quantitative real time polymer- ase chain reaction (qRT-PCR) . The expression level of M1 macrophage marker iNOS was detected by immunofluo- rescence . The protein expression levels of AMPK , p-AMPK and PGC-1 αwere detected by Western blot. Results The docking results showed that the binding energies of CHR with AMPK and PGC-1 αwere - 8. 4 kcal/mol and - 7. 4 kcal/mol , respectively. qRT-PCR results showed that the in vitro model of M1 macrophages was successfully established . Compared with the Control group , CHR treatment significantly increased the mRNA expression of mito- chondrial biosynthesis-related genes PGC-1 α, NFR-1 , and TFAM ( P < 0. 001) . Compared with CHR treatment group , CHR combined with Compound C treatment significantly decreased the mRNA expression levels of mitochon- drial biosynthesis-related genes PGC-1 α, NFR-1 , and TFAM (P < 0. 05) . Immunofluorescence results showed that CHR treatment inhibited the protein expression of iNOS compared with the Control group (P < 0. 001) . Compared with CHR treatment group , CHR combined with Compound C treatment reversed the inhibitory effect of CHR on iN- OS protein expression (P < 0. 05) . Western blot results showed that compared with the Control group , the CHR treatment group had significant increase in the protein expression levels of p-AMPK and PGC-1 α ( P < 0. 001) . Compared with CHR treatment group , CHR combined with Compound C treatment significantly decreased the pro- tein expression levels of p-AMPK and PGC-1 α ( P < 0. 05) . Conclusion Chrysophanol may inhibit macrophage polarization to M1 by activating AMPK/PGC-1 αsignaling pathway to promote mitochondrial biosynthesis .

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Abstract Objective To investigate the effects of usnic acid(UA) on proliferation , cell cycle , apoptosis and au- tophagy of lung cancer cells A549 and NCI-H358 . Methods The CCK-8 method was used to detect the inhibitory effect of UA on two kinds of lung cancer cells proliferation . Flow cytometry was used to detect the cell cycle arrest effect of UA on two types of lung cancer cells . The fluorescence amount of UA-induced reactive oxygen species (ROS) in two kinds of lung cancer cells were detected by DCFH-DA probe assay and flow cytometry. Western blot was used to detect the expression of apoptosis related proteins Bax , Caspase-3 , Cleaved-Caspase-3 , and autophagy related proteins LC3 - Ⅰ and LC3-Ⅱ in two types of lung cancer cells after treatment with UA and UA + ROS inhibi- tion . Result ① Usnic acid reduced the survival rates of two types of cells and had a stronger ability to inhibit the proliferation of A549 cells than NCI-H358 cells . ② Usnic acid blocked A549 cells in the G0 /G1 phase , while NCI- H358 cells in the G2 /M and S phases . ③ Usnic acid induced an increase in ROS content in two types of cells . Compared to A549 , NCI-H358 cells showed a greater increase in ROS , and the ROS inhibitor reduced the intracel- lular ROS increase induced by UA . ④ Usnic acid induced high expression of apoptosis-related proteins Bax and Cleaved Caspase-3 and increased the ratio of autophagy-related proteins LC3-Ⅱ/LC3 - Ⅰ in both lung adenocarcino- ma cells , and its pro-apoptotic and autophagic effects were stronger in A549 than in NCI-H358 . After ROS inhibi- tion , the expression levels of Bax and Cleaved Caspase-3 and the LC3-Ⅱ/LC3 - Ⅰ ratio of both lung adenocarcino- ma cells decreased , and the decrease was greater in NCI-H358 cells . Conclusion Usnic acid inhibits the prolifer- ation of lung cancer A549 and NCI-H358 cells , induces cell cycle arrest , and induces apoptosis and autophagy in cancer cells . The inhibitory and killing effect of UA on A549 cells is stronger than that on NCI-H358 cells . In this case , the induced cell ROS are involved in the action of UA in two types of lung cancer cells . In contrast to A549 cells , ROS might play a more significant role in mediating the apoptosis and autophagy induced by usnic acid in NCI-H358 cells .

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Abstract Objective To investigate the role of caspase recruitment domain-containing protein 9 (Card9) in As- pergillus fumigatus (A. fumigatus) keratitis and the effect of its deficiency on macrophage resistance to fungal in- fection . Methods ① C57BL/7 mice aged 6 - 8 weeks were selected and the mice pretreated Card9 siRNA and Blank siRNA , respectively , and the expression of Card9 in each group was detected by Western blot and RT-PCR. The corneal epithelium of the mice was scraped away 72 hours later , and A. fumigatus spore suspension was injec- ted into the corneal stroma. The corneal scores were recorded at 1d , 3d , 5d and 7d after infection . The expression of Card9 , nuclear factor κB (NF-κB) , interleukin 1β(IL-1β) , interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in each group was detected by RT-PCR and immunohistochemical (IHC) . ② Human corneal epithelial cells (HCECs) and human monocytic-leukemia cells (THP-1) in vitro , RT-PCR was used to examine the expres- sion of Card9 gene in the two cells , and a stable cell line of THP-1 cells was constructed using shRNA vectors . The expression of Card9 in the cell line was detected by Western Blot and RT-PCR. The cells were induced into macro- phages and stimulation by A. fumigatus , and the expression of Card9 , NF-κB , IL-1β, IL-6 and TNF-αwas detec- ted by RT-PCR. Results Card9 expression increased in A. fumigatus keratitis , mainly distributed in cytoplasm of immune cells . The expression of Card9 in the cornea of mice treated with Card9 siRNA was significantly reduced . After inhibiting the expression of Card9 gene , the expressions of Card9 , NF-κB , IL-1β, IL-6 and TNF-αsignifi- cantly decreased and the changes of IL-1βwere most significant. In in vitro studies , Card9 exhibited negligible ex- pression in human corneal epithelial cells , contrasting with its pronounced expression in THP-1 cells . After the in- duction of macrophages , Card9 , NF-κB , IL-1β, IL-6 , and TNF-αwere significantly upregulated under the stimu- lation of A. fumigatus . After inhibiting the expression of Card9 , the stimulated expression of these factors was sig- nificantly reduced , with the most notable change observed in IL-1β. Conclusion Card9 is involved in the inflam- matory development and healing process of A. fumigatus keratitis . Card9 deficiency can cause functional impair- ment of macrophages and inhibit the expression of inflammatory factors to a certain extent , in which IL-1βhas the greatest effect.

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Abstract Objective To construct a human keratinocyte-forming cell line (HaCaT) with stable knockout of the G protein-coupled receptor 107 (GPR107) gene , and to preliminarily investigate the effect of GPR107 deletion on the biological behaviour of HaCaT cells . Methods Using CRISPR/Cas9 gene editing technology , HaCaT cells with knockout of GPR107 gene were constructed and monoclonal cells with GPR107 deletion were obtained by limited di- lution method . Genomic DNA was amplified using Western blot and PCR and sequenced to validate the single-cell clones with knockdown of GPR107 . The cell cycle changes were detected by flow cytometry; cell proliferation was detected by CCK-8 ; apoptosis was detected by flow cytometry; changes in cell differentiation markers were detected by Western blot; cell migration ability was analyzed by cell scratch assay and other methods . Results LentiCas9 - Blast and plenti-guide-RNA-GPR107 plasmids were successfully transfected into HaCaT cells , 21 monoclonal cell lines were obtained by limited dilution , and Western blot showed that the GPR107 expression was significantly re- duced in 8 of them; PCR sequencing of the cellular genome was used , which resulted in the obtainment of C4 and 2D8 GPR107 - / - HaCaT monoclonal cell lines . CCK-8 assay and flow cytometry assay showed that GPR107 gene deletion resulted in G0 G1 phase block , significantly weakened proliferation ability and increased apoptosis level of HaCaT cells . Western blot found that the differentiation of HaCaT cells accelerated after knockdown of GPR107. Additionally the results of the cell scratch assay indicated that the migration ability of HaCaT cells was enhanced af- ter knockdown of GPR107. The results showed that the migration ability of HaCaT cells was enhanced after knock- down of GPR107. Conclusion HaCaT cell line with GPR107 gene deletion is successfully constructed , GPR107 deletion blocks the G0 G1 phase of HaCaT cells , which inhibiting the proliferation of HaCaT cells and promoted ap- optosis , and it was found that the differentiation and migration of HaCaT cells were enhanced after knocking down GPR107.

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Abstract Objective To investigate the effect of laminarin(LAM) on nonproliferative diabetes retinopathy by high throughput sequencing( RNA-seq) . Methods The diabetes model was established by intraperitoneal injection of streptozotocin (STZ) , and the effect of LAM on diabetic mice was observed . C57BL/6 mice were randomly divided into three groups : control group , model group , and LAM group , with 8 mice in each group . After 8 weeks of model- ing , the LAM group received a 4-week intraperitoneal injection of LAM treatment. Changes in blood glucose and body weight of the three groups of mice were recorded , HE staining was performed to examine retinal lesions , and RNA-seq was used to identify differentially expressed genes (DEGs) in DR under the action of STZ and LAM . Re- sults STZ successfully established the model of diabetic retinopathy (DR) , and LAM reduced the blood sugar in diabetic mice to a certain extent and improved the pathological morphology of retinal structural looseness in diabetic mice . After RNA-seq analysis of DEGs , it was found that there were a total of 214 DEGs in the retina of the Model group mice compared to the Control group . Enrichment analysis revealed that DR could exacerbate the lesions through the PI3K Akt signaling pathway . There were a total of 42 DEGs in the retina of the Model group and LAM group mice , and enrichment showed that LAM improved the lesions through the neutrophil extracellular trap path- way . Early growth response factor 1 (EGR1) , FBJ osteosarcoma oncogene (Fos) , nuclear receptor subfamily 4A member 1 (NR4A1) , and salt-induced kinase 1 (SIK1) were regulated by STZ , and LAM significantly regulated their expression , which might be closely related to LAM ′s treatment of diabetic retinopathy . Conclusion DEGs can exacerbate the severity of diabetic retinopathy via the PI3K-Akt signaling pathway . LAM can mitigate diabetic reti- nopathy via the neutrophil extracellular trap pathway . Egr1 , Fos , Nr4a1 , and Sik1 are key genes involved in lami- narin ′s treatment of STZ-induced diabetic retinopathy .

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Abstract Objective To investigate the effects of cinnamaldehyde (CA) on the growth , metastasis and apoptosis of human endometriosis ( EMs) cells and to explore whether the mechanism is related to ribosomal protein S7 (RPS7) expression . Methods Endometriosis cells were divided into control group , CA group , sh-NC group , CA + sh-RPS7 group . Effects of CA on cell growth in human endometriotic cells were determined using Cell Counting Kit-8 (CCK-8) and colony formation assay . Effects of CA on cell metastasis were performed by motility assay and Transwell assay . Effects of CA on cell apoptosis were evaluated by Hoechst 33258 staining and flow cytometry . Meanwhile , the levels of PCNA , E-cadherin , Vimentin , Bax and Bcl-2 were evaluated using Western blot in hu- man endometriotic cells with treatment CA . The expression of RPS7 was detected by qRT-PCR and Western blot as- say . The RPS7 overexpression of human endometriotic cells was established by cell transfection . CA-mediated effects on cell proliferation and apoptosis were determined by CCK-8 assay and flow cytometry in human endometri- otic cells with RPS7 overexpression . Results CA repressed cell growth as well as down-regulated PCNA . The half inhibitory concentration ( IC50 ) value was 53 . 60 μmol/L after 24 h treatment , and colony formation rate was 25 . 32% . Additionally , CA inhibited metastasis which was associated with downregulated Vimentin and upregulated E-cadherin . The relative migration rates were 35% and 29% as well as invasion rate was 40% . Further , CA in- duced apoptosis by cell cycle G2/M phase arrest and cell apoptosis rate was 25 . 1% , which related to the up-regu- lation of of Bax and the down-regulation of Bcl-2 . CA inhibited the expression of RPS7 and overexpression of RPS7 promoted cell proliferation and suppressed apoptosis in CA-mediated 12Z cells . Conclusion CA inhibits cell growth , metastasis , and induces cell apoptosis by downregulating the expression of RPS7 .

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Abstract Objective To explore the expression level of PPFIA4 in hepatocellular carcinoma tissues and HCCLM3 cells and its regulation of the biological behavior of hepatocellular carcinoma. Methods Bioinformatics analysis , Western blot , and immunohistochemistry were employed to detect the expression of PPFIA4 in tumor tissues of pa- tients with hepatocellular carcinoma and analyze the prognosis of these patients . An siRNA plasmid was designed to knock down the expression of PPFIA4 in HCCLM3 cells . The effects of PPFIA4 knockdown on the migration and invasion abilities of HCCLM3 cells were then evaluated using scratch healing and Transwell assays . Furthermore , Western blot was utilized to detect the expression levels of epithelial-mesenchymal transition (EMT)-related protein markers in the HCCLM3 cell line after transfection with the siRNA plasmid . Results PPFIA4 was highly expressed in hepatocellular carcinoma tissues and hepatocellular carcinoma cells ( HCCLM3 , Li-7 , MHCC97H ) ; the high expression of PPFIA4 indicated that the clinical stage of patients was late and the overall survival (OS) was short. After knocking down the expression of PPFIA4 in HCCLM3 cell line , the migration and invasion ability of HCCLM3 cells decreased (P < 0. 001) and the expression of EMT markers changed . The expression of epithelial cell marker E-cadherin increased ( P < 0. 01) , while the expression of mesenchymal markers Vimentin and N-cadherin de- creased(P < 0. 05 , P < 0. 01) . Conclusion PPFIA4 is highly expressed in hepatocellular carcinoma tissues and hepatocellular carcinoma cell lines and is associated with poor prognosis of patients . Silencing PPFIA4 can regulate the biological behavior of hepatocellular carcinoma cells and inhibit the migration and invasion of HCCLM3 cells . The specific mechanism may be related to EMT.

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Abstract Objective To clarify the intrinsic link between a high-fat diet (HFD) and the pathological progression and prognosis of spinal cord injury (SCI) while preliminarily exploring the potential underlying mechanisms . Meth- ods SCI models were established in mice that were fed either a regular diet (RD) or HFD , with injury inflicted specifically on the T9 - T12 segments . Hematoxylin-Eosin (HE) staining , Masson staining , and Nissl staining were used to observe the local histological changes in SCI tissues . The Basso , Beattie , and Bresnahan (BBB) score and footprint analysis were used to evaluate and compare hindlimb functional recovery after SCI in both RD and HFD mice . In vitro experiments were conducted to identify key fatty acids in the HFD that exacerbate neuronal damage , while in vivo experiments assessed the effects of 2-bromopalmitate (2-BP) , a palmitic acid inhibitor , on HFD-fed mice with SCI . Results Compared to RD-fed mice , HFD-fed mice exhibited significantly larger lesion areas , more severe neuronal damage , and poorer hindlimb functional recovery after SCI . Palmitic acid was identified as the key fatty acid aggravating neuronal damage . Further more , inhibition of palmitoylation , mediated by palmitic acid , en- hanced neuronal survival , promoted tissue repair , and improved hindlimb functional recovery in HFD-fed mice post-SCI . Conclusion HFD exacerbates pathological damage following SCI in mice through palmitic acid , impai- ring recovery. Palmitic acid-mediated palmitoylation is likely the main mechanism underlying this effect.

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Abstract Objective To investigate the role of single nucleotide polymorphisms (SNP) of glutathione peroxidase 4 (GPX4) gene in the risk of non-cardia gastric cancer. Methods A total of 1 031 samples were selected , inclu- ding 506 normal examiners and 525 patients with non-cardia gastric cancer. GPX4 rs4807542 , rs713041 , rs2074451 and rs3746162 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) . Unconditional Logistic regression was used to analyze the relationship between each SNP with the risk of non-cardia gastric cancer under the four genetic models . Results The CT + TT genotype of rs713041 re- duced the risk of non-cardia gastric cancer compared with the CC genotype ( OR = 0. 699 , 95% CI: 0. 537 - 0. 910) . The GT + TT genotype of rs2074451 reduced the risk of non-cardia gastric cancer compared with the GG genotype (OR = 0. 681 , 95% CI: 0. 520 - 0. 893 ) . The G-C-G-C haplotype , constructed by the four SNPs of GPX4 , was related to an increased risk of non-cardia gastric cancer ( OR = 1 . 262 , 95% CI: 1. 035 - 1. 539), and G-T-T-C haplotype was related to a decreased risk of non-cardia gastric cancer (OR = 0. 784 , 95% CI: 0. 656 - 0. 937) . The fourth-order interaction of GPX4 rs4807542 , rs713041 , rs2074451 and rs3746162 played a syner- gistic effect in the risk of non-cardia gastric cancer (P < 0. 05) . Conclusion GPX4 rs713041 and rs2074451 are related to non-cardia gastric cancer susceptibility . The G-C-G-C haplotype composed of GPX4 rs4807542 , rs713041 , rs2074451 and rs3746162 is a risk factor for non-cardia gastric cancer , while the G-T-T-C haplotype is a protective factor. The interaction between GPX4 rs4807542 , rs713041 , rs2074451 and rs3746162 is closely con- nected with the occurrence of non-cardia gastric cancer.

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To investigate the prevalence of negative emotions in hospitalized youth patients with type 2 diabetes ( T2DM) and its correlation with coping strategies and psychological resilience . Methods 141 youth T2DM patients who met the research standards were selected . Blood glucose related indicators , blood pressure , body mass index (BMI) , diabetes chronic complications screening results and other data were collected . The basic information and disease related information questionnaire , self-rating depression scale ( SDS) , self-rating anxiety scale (SAS) , diabetes distress scale (DDS) , medical coping modes questionnaire (MCMQ) and Connor-Davidson resilience scale ( CD-RISC) were completed . Results Among 141 hospitalized youth T2DM patients , 37 . 6% were combined with depression , 32. 6% were combined with anxiety , and 35 . 5% were combined with diabetic dis- tress (DD) . Univariate analysis showed that systolic blood pressure (P < 0. 01) , educational level , and the form of hospitalization expenses ( P < 0. 05) were significantly correlated with depression . Marital status ( P < 0. 01) , family residence , blood glucose monitoring methods , and the last fasting blood glucose ( P < 0. 05) were signifi- cantly correlated with anxiety. BMI , whether it was first diagnosed or treated ( P < 0. 01) , gender , occupation , disease course , weekly blood glucose monitoring frequency , and the presence of chronic complications (P < 0. 05) were significantly correlated with DD . In multivariate analysis , systolic blood pressure ( P < 0. 01) , educational level , and the form of hospitalization expenses were significantly correlated with depression , marital status ( P < 0. 05) was significantly correlated with anxiety; BMI and weekly blood glucose monitoring frequency ( P < 0. 01) were significantly correlated with DD . SDS , SAS , total scores and dimensions of DDS were negatively correlated with the total score and dimensions of CD-RISC ( rs = - 0. 182 - - 0. 467 , P < 0. 05 or 0. 01) , and positively correlated with the yielding coping strategies ( rs = 0. 177 - 0. 271 , P < 0. 05 or 0. 01) . SAS , total scores and di- mensions of DDS were positively correlated with avoiding coping strategies ( rs = 0. 237 - 0. 419 , P < 0. 05 or 0. 01) . The total and dimensions of CD-RISC were positively correlated with facing coping strategies ( rs = 0. 215 - 0. 349 , P < 0. 05 or 0. 01) , and negatively correlated with yielding coping strategies ( rs = - 0. 234 - - 0. 325 , P < 0. 01) . Conclusion More than 30% of hospitalized youth T2DM may experience negative emotions such as de- pression , anxiety , and DD . The occurrence of negative emotions in such patients may be related to disease manage- ment or socio-economic issues such as systolic blood pressure , educational level , hospitalization expenses , marital status , BMI , and frequency of blood glucose monitoring , as well as decreased psychological resilience and negative coping strategies .

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Abstract Objective To construct and validate a clinical diagnostic model to differentiate between pulmonary tu- berculosis and non-tuberculous lung diseases . Methods Information was collected from 258 patients with respirato- ry system diseases , and they were divided into a training set of 152 cases and a test set of 106 cases with a ratio of 6:4 using the random number seed method in R software . The training set was further divided into a tuberculosis group of 95 cases and a non-tuberculosis group of 57 cases , and the test set into a tuberculosis group of 65 cases and a non-tuberculosis group of 41 cases based on the diagnosis of pulmonary tuberculosis . A diagnostic model was constructed using multivariate logistic regression analysis to determine the influencing factors of pulmonary tubercu- losis . The diagnostic value and clinical utility of the model were assessed using the Receiver Operating Characteris- tic (ROC) curve , calibration curve , and Decision Curve Analysis (DCA) . Results CD161 + % ( OR = 0. 768 ; 95% CI 0. 697 - 0. 845 ; P < 0. 001) , AST (OR = 0. 961 ; 95% CI 0. 930 - 0. 993 ; P = 0. 019) , and smoking his- tory (OR = 3 . 181 ; 95% CI 1 . 149 - 8. 804 ; P = 0. 026) were identified as independent risk factors for the occur- rence of pulmonary tuberculosis . In both the training and test sets , the area under the ROC curve (AUC) reached 0. 870 (95% CI 0. 816 - 0. 924) and 0. 887 (95% CI 0. 827 - 0. 948) , respectively . The Hosmer-Lemeshow good- ness-of-fit test showed a good fit ( training set χ2 = 6. 213 , P = 0. 623 ; test set χ2 = 6. 197 , P = 0. 625) . DCA indi- cated that the model had good reference significance for the diagnosis of the probability of pulmonary tuberculosis occurrence . Conclusion The diagnostic model constructed using the percentage of CD161 + % , AST levels , and smoking history has certain diagnostic performance , facilitating rapid clinical differentiation between pulmonary tu- berculosis and non-tuberculous lung diseases .

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Abstract Objective To explore the feasibility of machine learning methods in the discrimination of tuberculosis patients . Methods The data of 15 observation indicators of 860 patients were obtained from a tertiary hospital . Through in-depth mining and analysis of the data , support vector machine , random forest and neural network model methods were used to discriminate the diseases of patients . Results The accuracies of the TB suspected patient discrimination models based on support vector machine , random forest and neural network were 90% , 91% and 88% , respectively. Conclusion All three machine learning methods can be used for discriminative analysis of suspected tuberculosis patients . In comparison , random forest performs better in discriminating patients with tuber- culosis from those with pneumonia.

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Abstract Objective To investigate the effects of branched-chain amino acid ( BCAA) on the differentiation of 3T3-L1 preadipocytes and its potential mechanism . Methods 3T3-L1 preadipocytes were divided into the Control , differentiation medium ( DM) , low-concentration BCAA , and high-concentration BCAA groups . A CCK-8 assay was utilized to evaluate pre-adipocyte survival under various BCAA concentrations . Oil-red O staining was used to observe the formation of lipid droplets in adipocytes . Intracellular triglyceride ( TG) and total cholesterol ( TC) were detected by enzymatic method . RT-qPCR and Western blot were used to detect the mRNA and protein expres- sion of Stat3 and adipocyte differentiation-related genes . Results CCK-8 results showed that the viability of 3T3 - L1 cells was not affected when the BCAA concentration was ≤ 10 mmol/L. Compared with the DM group , the low- concentration BCAA groups (0. 5 and 1 . 0 mmol/L) had significantly larger intracellular lipid droplets , increased number of lipid droplets , and elevated levels of the intracellular TC (0. 88 vs 0. 68 mmol/g; 0. 83 vs 0. 68 mmol/ g , P < 0. 01) and TG (0. 77 vs 0. 40 mmol/g; 0. 62 vs 0. 40 mmol/g , P < 0. 01) . Nevertheless , the cell differen- tiation in the high-concentration group (5 . 0 and 10 mmol/L) significantly decreased compared with that in the DM group . Further , levels of PPARγ, C/EBPα, Adiponectin , and FABP4 mRNA and protein expression significantly increased in the low-concentration group , but significantly decreased in the high-concentration group than that in the DM group (P < 0. 01) . In addition , low concentrations of BCAA promoted stat3 phosphorylation , while high concentrations inhibited its phosphorylation ( P < 0. 01) . Conclusion BCAA have a dual role in regulating the differentiation of preadipocytes through Stat3 , i . e . low concentrations of BCAA induce cell differentiation by pro- moting Stat3 phosphorylation; whereas high concentrations of BCAA inhibit Stat3 phosphorylation and cell differen- tiation .

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Abstract Objective To monitor changes in blood pressure during rapid eye movement ( REM) and non-REM (NREM) sleep in patients with obstructive sleep apnea (OSA) , and to analyze the effect of obstructive respiratory events on blood pressure during different sleep stages . Methods A cross-sectional trial was adopted on 1 219 pa- tients diagnosed with OSA in the Department of Otolaryngology of West China Fourth Hospital . The obstructive re- spiratory events and blood pressure of patients during REM and NREM sleep were monitored . Additionally , the symptoms of blood pressure fluctuations in OSA patients during different sleep periods and the effects of obstructive respiratory events on blood pressure fluctuations were analyzed . Results SBP and DBP during REM and NREM sleep both tended to rise as OSA worsened . The differences in SBP , DBP , mean apnea time ( MAT) , mean hy- poventilation time (MHT) , lowest oxygen saturation (LSpO2 ) , and oxygen desaturation index (ODI) in different sleep periods were statistically significant (P < 0. 05) . Multiple linear regression analysis revealed that SBP during REM sleep was negatively correlated with LSpO2 and the apnea-hypopnea index (AHI) (P < 0. 05) , but positively correlated with ODI(P < 0. 05) . DBP during REM sleep was negatively correlated with LSpO2 , AHI , and MHT(P < 0. 05) , but positively correlated with ODI(P < 0. 05) ; SBP and DBP during NREM sleep were negatively corre- lated with LSpO2 (P < 0. 05) . Conclusion As the severity of OSA increases , the blood pressure values during dif- ferent sleep periods rise accordingly. The blood pressure levels during REM sleep in OSA patients are higher than those during NREM sleep . LSpO2 is an important factor causing blood pressure changes in different sleep periods . AHI , ODI , and MHT are important factors causing blood pressure changes during REM sleep .

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Abstract Among women of reproductive age , pelvic inflammatory disease is a prevalent gynecological condition . In its early stages , it may be mild or asymptomatic . If treatment is delayed , there is a high likelihood of recur- rence , which can have a major impact on women ′s reproductive health and raise the financial , emotional , and physical load on the family. Significant advancements in the treatment of chronic pelvic inflammatory disease have been made possible by the thorough investigation of this condition . In an effort to advance the health management of this illness and offer fresh concepts for clinical treatment , this review discusses a number of facets of both Chinese and Western medicine .

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Abstract Alzheimer ′s disease (AD) is a chronic and progressive neurodegenerative disorder. Since there are cur- rently no effective treatment options , early diagnosis is crucial for slowing the progression of the disease . The retina and the brain share a common embryological origin and exhibit similarities in both anatomical structure and vascular system . In the early stages of AD , patients may develop visual symptoms due to changes in the visual cortex circuit- ry and associated retinal alterations . Therefore , in recent years , there has been growing interest in exploring the role of the retinal vascular network in the pathogenesis , early diagnosis , and precision intervention of neurodegener- ative diseases . This review overviews the changes in the visual cortex circuitry and retinal vascular network in AD patients , their underlying mechanisms , the relationship between neural circuits and visual disorders , and introduces novel diagnostic methods in retinal research .

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Abstract Kidney stones are common and frequently occurring diseases in urology. In recent years , the incidence of urinary stones has increased year by year , affecting people ′s quality of life and aggravating the social and eco- nomic burden . The occurrence and development of kidney stones are closely related to metabolic factors . This re- view mainly conducts a systematic overview of the research on the relationship between electrolyte metabolism ab- normalities , dyslipidemias and other metabolic disorder diseases and kidney stones in recent years . By exploring the relationship between various metabolic disorder diseases and kidney stones , this review provides reference for explo- ring the occurrence and development of kidney stones from the perspective of metabolism.

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Abstract Objective To analyze the current status of anti-PD-1 combined with chemotherapy in advanced gastric cancer. Methods The clinical data of 120 patients with advanced gastric cancer treated with chemotherapy or anti - PD-1 plus chemotherapy were retrospectively analyzed . The efficacy [ measures include objective response rate (ORR) , disease control rate (DCR) , and progression-free survival( PFS) ] and the occurrence of adverse reac- tions in patients was monitored . Univariate and multivariate COX were used to analyze the relationship between clinicopathologic data (including age , gender , BMI , differentiation degree , and related hematological indexes) , specific treatment conditions and PFS , and to analyze the influence of treatment plan and line number on the cura- tive effect. Results The PFS of chemotherapy plus immunotherapy was significantly better than that of chemothera- py alone (P < 0. 05) , and the median PFS of the two was 7. 17 months (95% CI , 5 . 85 - 8. 49) and 5 . 33 months (95% CI , 3 . 96 - 5 . 70) , respectively . In the combination group , the overall ORR was 27. 5% and DCR was 94. 8% . In the chemotherapy group alone , the overall ORR was 9. 7% and DCR was 69. 4% . In the chemotherapy plus anti-PD-1 group , a high prognostic nutritional index (PNI) level also provided superior PFS in patients with a 47% reduction in the risk of progression versus a low PNI level [ HR 0. 53 (95% CI 0. 30 - 0. 96) ; P < 0. 05] . The median PFS was 7. 47 months (95% CI 5 . 83 - 9. 11) with a high PNI level versus 6. 00 months (95% CI 4. 45 - 7. 55) with a low PNI level . The overall incidence of adverse reactions of chemotherapy combined with anti-PD - 1 was slightly higher than that of chemotherapy alone , and the incidence of adverse reactions of grade 3 - 4 was similar , within a controllable range , and could be improved after clinical treatment. Conclusion The efficacy of anti-PD-1 combined with chemotherapy in patients with advanced gastric cancer is better than that of chemotherapy , and the adverse reactions are controllable . In the chemotherapy plus anti-PD-1 group , patients with high PNI levels achieved a higher PFS .

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Abstract Objective To investigate the diagnostic value of plasma calprotectin in refractory mycoplasma pneu- moniae pneumonia. Methods A multicenter , prospective cohort study was conducted , enrolling 228 children with mycoplasma pneumoniae pneumonia ( MPP) . Among these , 177 cases were diagnosed with general mycoplasma pneumoniae pneumonia (GMPP) , while the remaining 51 cases were refractory mycoplasma pneumoniae pneumonia (RMPP) . Plasma was collected at the time of admission of the children in both groups , and calprotectin levels were measured . A one-way difference analysis was performed on the blood test indexes of the children in the two groups , and the difference variables with P < 0. 05 between the two groups were included in a multifactorial logistic regression to analyze the risk factors for the progression of GMPP to RMPP. The differential diagnostic value of plas- ma calprotectin for GMPP and RMPP was analyzed by the receiver operating characteristic (ROC) curves . Results Univariate analysis showed that plasma calprotectin levels were significantly higher in the RMPP group than those in the GMPP group , and the difference was statistically significant (P < 0. 05) . Logistic regression analysis showed that plasma calprotectin was an independent risk factor for RMPP (OR = 1 . 323 , P < 0. 001) , ROC curve analysis showed that plasma calprotectin had a higher diagnostic value for the differential diagnosis of GMPP and RMPP (AUC = 0. 839) , and its combination with C-reactive protein and albumin could significantly improve the diagnos- tic efficiency . Conclusion Plasma calprotectin has good clinical value for the diagnosis of RMPP.

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Abstract Objective To analyze the correlation between different laboratory biomarkers and disease activity in an- kylosing spondylitis and to compare their specificity and sensitivity in assessing disease activity . Methods Spearman correlation or Pearson correlation was used to analyze the correlation between disease activity and labora- tory biomarkers . Receiver operating characteristic ( ROC) was used to compare the sensitivity and specificity of each laboratory biomarker in evaluating disease activity . Results Hypersensitive C-reactive protein , fibrinogen , D-dimer , erythrocyte sediment rate , C-reactive protein , immuno-inflammatory index ( platelet count ×neutrophil count/lymphocyte count ) , fibrinogen/albumin ratio , albumin and pro-albumin were correlated with disease activi- ty . The ratio of fibrinogen to albumin , fibrinogen , erythrocyte sedimentation rate , immuno-inflammatory index , C - reactive protein and hypersensitive C-reactive protein had good values in determining the disease activity . Conclu- sion Different laboratory biomarkers are correlated with the disease activity of ankylosing spondylitis , and some of them have better discriminating values for the disease activity .

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Abstract Objective To analyze the correlation between different laboratory biomarkers and disease activity in an- kylosing spondylitis and to compare their specificity and sensitivity in assessing disease activity . Methods Spearman correlation or Pearson correlation was used to analyze the correlation between disease activity and labora- tory biomarkers . Receiver operating characteristic ( ROC) was used to compare the sensitivity and specificity of each laboratory biomarker in evaluating disease activity . Results Hypersensitive C-reactive protein , fibrinogen , D-dimer , erythrocyte sediment rate , C-reactive protein , immuno-inflammatory index ( platelet count ×neutrophil count/lymphocyte count ) , fibrinogen/albumin ratio , albumin and pro-albumin were correlated with disease activi- ty . The ratio of fibrinogen to albumin , fibrinogen , erythrocyte sedimentation rate , immuno-inflammatory index , C - reactive protein and hypersensitive C-reactive protein had good values in determining the disease activity . Conclu- sion Different laboratory biomarkers are correlated with the disease activity of ankylosing spondylitis , and some of them have better discriminating values for the disease activity .

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Abstract Objective To explore the differences in oxidative stress levels between patients with and without non- suicidal self-injury (NSSI) behavior in depressive disorders , and their correlation with depressive symptoms , dis- ease duration , and self-injury frequency. Methods A total of 95 subjects were included in the study , including 65 patients with depression (patient group) . They were divided into NSSI subgroup (31 cases) and Non-NSSI sub- group (34 cases) based on whether they had NSSI . 30 healthy control group cases( HC) . Enzyme linked immu- nosorbent assay (ELISA) was used to detect the levels of superoxide dismutase (SOD) , catalase (CAT) , malond- ialdehyde (MDA) , glutathione peroxidase(GPX) , and oxidized low-density lipoprotein (OxLDL) in the peripheral blood of the subjects . The Hamilton depression rating scale ( HAMD-17) was used to assess the patient /s condi- tion , and the Ottawa self-injury inventory (OSI) was used to quantitatively evaluate the self-injury frequency of NS- SI group patients . Results The levels of SOD , CAT , MDA , GPX and OxLDL in the patient group were significantly higher than those in the control group (P < 0. 05) . The levels of SOD , CAT , MDA , GPX and OxLDL in the Abstract Objective To explore the differences in oxidative stress levels between patients with and without non- suicidal self-injury (NSSI) behavior in depressive disorders , and their correlation with depressive symptoms , dis- ease duration , and self-injury frequency. Methods A total of 95 subjects were included in the study , including 65 patients with depression (patient group) . They were divided into NSSI subgroup (31 cases) and Non-NSSI sub- group (34 cases) based on whether they had NSSI . 30 healthy control group cases( HC) . Enzyme linked immu- nosorbent assay (ELISA) was used to detect the levels of superoxide dismutase (SOD) , catalase (CAT) , malond- ialdehyde (MDA) , glutathione peroxidase(GPX) , and oxidized low-density lipoprotein (OxLDL) in the peripheral blood of the subjects . The Hamilton depression rating scale ( HAMD-17) was used to assess the patient /s condi- tion , and the Ottawa self-injury inventory (OSI) was used to quantitatively evaluate the self-injury frequency of NS- SI group patients . Results The levels of SOD , CAT , MDA , GPX and OxLDL in the patient group were significantly higher than those in the control group (P < 0. 05) . The levels of SOD , CAT , MDA , GPX and OxLDL in the

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Abstract Cholestasis can be seen in many acute and chronic liver diseases . If not intervened in time , persistent cholestasis can further progress to liver fibrosis , liver cirrhosis , liver failure , and even death . The pathogenesis of cholestasis is complex , and there is currently a lack of effective therapeutic drugs . Bile acids ( BAs) , the main component of bile , are synthesized from cholesterol in the liver as primary bile acids . After entering the intestine through the enterohepatic circulation , they are reshaped into secondary bile acids by gut microbiota. BAs can di- rectly or indirectly affect the composition and function of gut microbiota , which in turn can regulate the synthesis and metabolism of BAs . The interaction between BAs and gut microbiota plays an important role in the pathogenesis and treatment of cholestasis . This review elucidates the bidirectional regulatory mechanisms between BAs and gut microbiota and their roles in the pathogenesis and treatment of cholestasis , aiming to provide insights and references for basic research and clinical practice related to cholestasis-associated diseases .