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Abstract Objective To enhance the solubility expression of carbonyl reductase ChKRED20 and investigate its enzymatic properties. Methods The ChKRED20 gene was synthesized and transformed into Escherichia coli BL21(DE3) for heterologous expression. The solubility of the protein was evaluated by adding or removing His⁃tag ,changing its position , and adjusting the induction conditions. Further optimization was performed by varying the in⁃duction time , temperature and IPTG concentration. Subsequently , the enzymatic properties of the recombinant en⁃zyme were examined. Results The ChKRED20 was cloned within the Escherichia coli system to achieve soluble protein expression. This was achieved by removing the His⁃tag and optimizing expression conditions. Compared to by 0. 77 and 1. 28 times , respectively. The optimal temperature and pH for enzyme activity were 55 ℃ and 8. 0 ,respectively. Furthermore , the enzyme demonstrated good adaptability in higher temperature and alkaline environ⁃prove the soluble expression of ChKRED20 in Escherichia coli.

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To investigate the potential therapeutic mechanisms of kaempferol , an active component in the traditional Chinese medicine gardenia , for lung cancer treatment using a network pharmacology approach . Methods The main active ingredients and potential targets of Gardenia jasminoides were obtained through the Tra⁃ ditional Chinese Medicine Pharmacology Database and Analysis Platform (TCMSP) , and combined with the lung cancer related target information collected from Gene Cards and OMIM databases , the intersection targets of Garde⁃ nia jasminoides and lung cancer treatment were determined by drawing Venn diagrams . Further screening of core targets was conducted through PPI network analysis , and gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes ( KEGG) pathway enrichment analysis were performed using the Metascape platform . Auto dock software was used to evaluate the binding affinity between the active ingredients of Gardenia jasminoides and target proteins . In terms of experiments , cell proliferation ability was evaluated through CCK⁃8 assay , cell migration and invasion ability were detected through cell scratch healing assay and Transwell assay , and the expression levels of epithelial mesenchymal transition ( EMT) protein and inflammatory factors were detected by Western blot and RT⁃qPCR . Results The active ingredient kaempferol in Gardenia jasminoides exhibited significant binding ability invasion of lung cancer cells . The results of Western blot and RT⁃qPCR further confirmed that kaempferol could promote an increase in E ⁃cadherin , a decrease in N ⁃cadherin and Vimentin , and reduce the expression of inflam⁃ matory factors . Conclusion The active ingredient of Gardenia jasminoides , kaempferol , inhibits the proliferation ,migration and invasion of lung cancer cells by targeting BCL⁃2 , while reversing EMT progression and suppressing the expression levels of inflammatory cytokines in lung cancer cells , thus preventing lung cancer progression .

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To investigate the effect of intraarticular hemorrhage on extending knee joint contracture model in rats . Methods 18 mature male SD rats were divided into 3 groups by random number table method . The control group ( group C) was not immobilized and was killed after 4 weeks of feeding . In the simple fixation group( M1 group) , the left lower limb knee joint was immobilized in straight position for 4 weeks . The blood fixationgroup (M2 group) was injected into the knee cavity with body blood and immobilized in a straight position for 4 weeks . The knee joint motion of each group was measured by the joint motion measuring instrument under a stand⁃ard torque . The contracture degree was calculated by the joint range of motion of the knee joint before and after muscles separation . HE staining and Masson staining were used to detect the number of cells and collagen deposi⁃tion in the anterior joint capsule . The protein expressions of transforming growth factor 1 (TGF⁃ β1) , wingless⁃type MMTV integration site family , member 1 ( Wnt1) and beta⁃catenin ( β⁃catenin) in the anterior articular capsule were detected by Western blotting . Results Compared with group C , total knee contracture and arthrogenic con⁃tracture of rats in M1 and M2 groups increased , and the difference was statistically significant (P < 0. 05) . At the same time , the degree of total contracture and arthrogenic contracture in M2 group was higher than that in M1 group , and the difference was statistically significant (P < 0. 05) . Compared with group C , the number of anterior joint capsule cells and collagen deposition in M1 and M2 groups increased , and the difference was statistically sig⁃group were higher than those in M1 group , and the difference was statistically significant (P < 0. 05) . Compared with group C , the protein expressions of TGF⁃ β1 , Wnt1 and β ⁃catenin in the anterior articular capsule of rats in M1 expressions of TGF⁃ β1 , Wnt1 and β ⁃catenin in the anterior articular capsule of the knee joint in M2 group were sig⁃nificantly higher than those in M1 group , with statistical significance (P < 0. 05) . Conclusion Joint immobiliza⁃ tion can lead to joint contracture , and joint bleeding aggravates the degree of joint capsule fibrosis induced by im⁃mobilization .

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To investigate the effects of different doses of X ⁃rays irradiation combined with allogeneic lymphocyte infusion on the establishment of aplastic anemia in mice. Methods Forty BALB/c mice were randomly divided into four groups : the 3 Gy group (n = 9) , the 4 Gy group (n = 9) , the 5 Gy group (n = 10) , and the con⁃trol group (n = 12) . In the 3 Gy , 4 Gy , and 5 Gy groups , the experimental mice were exposed to corresponding do⁃ses of X ⁃ray and then intravenously infused with 0. 2 mL mixed suspension of the thymus and spleen cells from DBA/2 mice , at a concentration of 1 × 107 cells/mL , within 4 hours after irradiation. The control group did not un⁃dergo X ⁃ray irradiation and infused with an equivalent volume of physiological saline instead. Blood samples were collected from the orbital venous plexus of BALB/c mice and analyzed using an animal automated hematology analy⁃zer to measure peripheral blood parameters , including red blood cells ( RBC) , white blood cells ( WBC) , and platelets (PLT) . The general condition of mice was monitored daily , and survival rates were recorded for each group. At the experimental endpoint , the tibias were harvested for hematoxylin and eosin (HE) staining , while the femurs were used to prepare bone marrow smears for morphological examination. For the 5 Gy group , T ⁃cell subsets(ELISA) at the endpoint. Results In the 3 Gy group , pancytopenia was observed , but platelet recovery occured rapidly , returning to normal levels by day 17 post⁃modeling. No deaths occurred during the observation period. At myeloid⁃to⁃erythroid (M/E) ratio , and no significant morphological abnormalities were noted in cells at any devel⁃with hematopoietic cells. In the 4 Gy group , pancytopenia persisted throughout the observation period. The survival rate was 90% . Endpoint analysis showed hypocellular marrow by morphological examination. HE staining indicated minimal fatty infiltration in the bone marrow tissue. In the 5 Gy group , pancytopenia was observed , though erythro⁃cyte counts returned to normal levels by day 24. The survival rate during the observation period was 50% . End⁃oint analysis revealed vacuolization of marrow particles and reduced hematopoietic cells with predominantly non⁃hematopoietic cells in bone marrow morphology. HE staining demonstrated severe fatty infiltration in the bone mar⁃row tissue , with scarcity of immature cells and hematopoietic precursor cells. Flow cytometry analysis showed a de⁃creased proportion of CD4 + T cells (% ) and an increased proportion of CD8 + T cells (% ) . ELISA confirmed ele⁃vated secretion of negative hematopoietic regulators : interferon⁃gamma ( IFN⁃γ) and tumor necrosis factor⁃alpha (TNF⁃α ) . Conclusion Combined administration of varying radiation doses with allogeneic lymphocyte infusion consistently induced peripheral blood cytopenia in mice , characterized by reductions in RBC , WBC , and PLT counts. Integrated analysis of bone marrow morphology , histopathological assessment via HE staining , and immuno logical parameters confirmed that a mouse model of aplastic anemia can be successfully established using 5 Gy X ⁃ ray irradiation coupled with infusion of 2 × 106 allogeneic lymphocytes.

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Ma Dandan , Zhang Qinquan , Dong Yi , Li Zhonghu , Zhang Zhiyong logical function of DHX32 in pancreatic cancer cell line SW1990. To investigate the clinical significance and prog⁃nostic value of DHX32 in pancreatic cancer, and predict the possible related mechanism. Methods GEPIA data⁃base was used to analyze the expression and prognosis of DHX32 in pancreatic cancer, and TCGA database was used to analyze the relationship between DHX32 mRNA expression level and clinicopathological features and prog⁃nosis of patients with pancreatic cancer. The effects of DHX32 on the proliferation , invasion and migration of SW1990 pancreatic cancer cells were studied by EdU immunofluorescence assay , Transwell assay and scratch as⁃say. GSEA was used to predict DHX32 the possible related signaling pathways involved with DHX32 in pancreatic cancer. Results The results of GEPIA database analysis showed that the expression level of DHX32 in pancreaticcancer tumor tissues was significantly higher than that in normal pancreatic tissues ( P < 0. 05 ) . Meanwhile , the prognosis of pancreatic cancer patients with high DHX32 expression was worse than that of patients with low DHX32 expression (P < 0. 001) . Cox regression analysis showed that DHX32 mRNA expression level and M stage were in⁃dependent risk factors for prognosis of pancreatic cancer patients (all P < 0. 05) . EdU immunofluorescence assay ,Transwell assay and scratch assay confirmed that the overexpression of DHX32 promoted the proliferation , invasion and migration of pancreatic cancer cells (all P < 0. 001) , while silencing DHX32 inhibited the proliferation , inva⁃sion and migration of pancreatic cancer cells ( all P < 0. 001) . The results of GSEA enrichment analysis showed that DHX32 was enriched in four signaling pathways : hematopoietic cell lineage , neuroactive ligand receptor inter⁃action , primary immune deficiency and spliceosome (all P < 0. 05) . Conclusion DHX32 is highly expressed in pancreatic cancer. It promotes the proliferation , invasion and metastasis of pancreatic cancer cells , and is closelyrelated to the poor prognosis of pancreatic cancer patients.

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To investigate the effects of occlusal alterations on masseter muscle atrophy after the applica⁃tion of excessive orthodontic tension , and the role and mechanism of prophylactic nitrate supplementation in the pre⁃vention and treatment of masseter muscle atrophy. Methods Eight⁃week⁃old male SD rats were selected. An ortho⁃dontic appliance was placed in the oral cavity of the rats to obtain a rat model of occlusal alterations , and the mas⁃seter muscles were taken at various times after excessive orthodontic force application for relevant tests. Masseter muscle weighing , HE staining , Western blot and immunohistochemistry assays were used to detect the atrophic state of the masseter muscle. Meanwhile , immunofluorescence staining was used to detect the hypoxic status of the mas⁃[ cluster of differentiation 31 (CD31) , vascular endothelial growth factor (VEGF)] . After 28 days of prophylactic nitrate supplementation and application of orthodontic tension , the status of masseter muscle atrophy , tissue hypoxi⁃ growth factor receptor (EGFR) , protein kinase B (AKT ) , extracellular signal⁃regulated kinases 1/2 (ERK1/2) to detect masseter muscle apoptosis. Results The molar displacement caused by overload traction could lead to masseter muscle atrophy , accompanied by hypoxia in the masseter tissue and decreased expression of angiogenesis⁃related proteins. Preventive nitrate supplementation could prevent masseter muscle atrophy , alleviate tissue hypoxi⁃a , and promote angiogenesis. The anti⁃apoptotic effects of the EGFR⁃AKT/ERK1/2 signaling pathway contributed to the preventive effects of nitrate on masseter muscle atrophy. Conclusion Occlusal alterations brought about by excessive orthodontic tension exertion in rats may lead to masseter muscle atrophy , and prophylactic nitrate supple⁃mentation may resist hypoxia and atrophy of masseter muscle tissues by promoting angiogenesis through the anti⁃ap⁃optotic effects of the EGFR⁃AKT/ERK1/2 pathway.

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To explore the changes in behavior and spatial memory of C57BL/6J female mice of differ- ent ages (youth , middle-aged , and elderly) . Methods C57BL/6J female mice were divided into female youth group (YG group) , female middle-aged group ( MG group) and female elderly group ( OG group) according to age. The Morris water maze test measured spatial memory ability , and the open field and elevated cross maze test observed activity level and anxiety level. Western blot was used to determine the protein expressions of CREB , CaMKⅡ(pan) and CaMKⅡ(p) in the hippocampus of the brain tissues of female mice in each group. Results Compared with the YG group , the weight of the MG group and the OG group significantly increased (P < 0. 01 , P < 0. 001) . Compared with the OG group , the third quadrant escape latency and the number of crossings in the YG group and MG group were shortened , and the difference was not statistically significant. Compared with the OG group , there was a statistically significant difference in the exercise speed in the open field of the YG group (P < 0. 01) , there was no significant difference in the movement speed in the open field of the MG group , the number of entries into the central zone significantly increased in the MG group ( P < 0. 05 ) , and there was no significant difference in the number of entries in the YG group (P > 0. 05) . Compared with the OG group , the YG group had a statistically significant difference in the elevated cross maze (P < 0. 05) , the MG group had no statistically signif- icant difference in the elevated cross maze , and the number of closed arm entries in the YG group and MG group significantly increased (P < 0. 001 , P < 0. 01) . Compared with the YG group , the relative expression level of CaMKⅡ(pan) in the OG group was statistically significant ( P < 0. 05 ) , while the relative expression level of CaMKⅡ(pan) in the MG group was not statistically significant ( P > 0. 05) . Conclusion With the increase of age , the weight of C57BL/6J female mice gradually increased , the activity level and desire to explore gradually de- creased , the spatial memory ability also declined , and the anxiety level and anxiety-like behavior increased. This study helps to reveal the effect of age on the activity level and cognitive function of females , and provides a refer- ence for studying cognitive and memory decline in older females.

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To explore the biocompatibility of hydroxyapatite and dexamethasone composite coatings on the surface of TiO2 nanotubes. Methods A composite coating was constructed by loading hydroxyapatite and dexa⁃copy , and contact angle measurement instrument was used to observe the characteristics of sample substrates , and in vitro biological evaluation was conducted to evaluate the effect of the coating on the adhesion and proliferation of hu⁃modified composite coating had changed. After cytological examination , it could significantly promote the adhesion and proliferation of osteoblasts. Conclusion By simulating the immersion of body fluids and the method of adding dropwise loads , the titanium nanotube⁃hydroxyapatite⁃dexamethasone composite coating is successfully constructed ,which has good biocompatibility.

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To investigate the impact of fecal microbiota transplantation (FMT) on the composition of 15 intestinal-derived estrogens and their metabolites (EMs) and its correlation with non-alcoholic fatty liver disease (NAFLD) . Methods Thirty male C57BL/6J mice were divided into a normal control group (Control) , a high- sugar high-fat diet combined with low-dose CCl4 -induced NAFLD model group ( Model) , and a group of model mice treated with fecal microbiota from normal female mice (FMT) . After 17 weeks of modeling , liver pathology in each group was observed using HE staining , biochemical methods were used to measure serum alanine aminotrans- ferase (ALT) and aspartate aminotransferase (AST) levels , as well as hepatic triglyceride (TG) and total choles- terol (TC) levels. and the content of 15 EMs in portal vein serum was detected using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) . The correlation between disease phenotype and intesti- nal EMs was analyzed using Pearson ′s method. Results The NAFLD model was successfully established , and the FMT group showed improved liver structure and morphology , with significant decreases in liver function and hepatic lipids compared to the Model group. In NAFLD mice , the contents of E1 , E2 , and their 2- and 4-position metabo- lites in portal vein blood serum was reduced compared to normal mice , while the content of most 16- and 17-posi- tion metabolites ( except 16α-OHE1) increased compared to normal mice. Correlation analysis showed that ALT was strongly positively correlated with E3 and 17-epiE3 , and strongly negatively correlated with E1 , E2 , 4- MeOE1 , and 16α-OHE1 . The TC was strongly positively correlated with 17-epiE3 and strongly negatively correla- ted with E1 , 4-MeOE1 , and 16α-OHE1 . Conclusion FMT restores the disrupted composition of intestinal EMs and improves NAFLD.

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To explore the mechanism of action of hepatic leukemia factor (HLF) in diabetes mellitus and to construct a conditional animal model of mice with islet β ⁃cell⁃specific HLF gene knockout. Methods At the cellular level , the effects of HLF inhibition or overexpression on the proliferation of MIN6 cells was verified by the CCK⁃8 assay. The effects of HLF inhibition or overexpression were detected at the mRNA level and protein level by Cre + / - mice (C57BL/6J) to obtain offspring mice. The genotypes of the mice were identified by the PCR method.The differences in the expression levels of the HLF gene at the mRNA and protein levels in islet β ⁃cell knockout mice (HLFflox/flox Cre + / - ) and control mice (HLFflox/flox ) were detected by RT⁃qPCR technology and Western blot technology to verify the knockout effect. At the same time , the islet tissues of the mice in two groups were taken to make paraffin sections and analyzed by hematoxylin⁃eosin (HE) staining. Results HLF gene inhibition or overex⁃pression had no significant effect on the proliferation of MIN6 cells. When the HLF gene was inhibited in MIN6 cells , the mRNA expression level decreased by 74% compared with the control group , and the protein expression level decreased by 60% compared with the control group. After overexpressing the HLF gene , the mRNA expres⁃sion level was 2. 13 times compared with that of the control group , and the protein expression level was 1. 8 times compared with that of the control group. The mRNA expression level of the HLF gene in the knockout mice de⁃creased by 89% compared with the control group , and the protein expression level decreased by 65% compared with the control group. The results of HE staining showed that there was no significant difference in the cell mor⁃phology in the islet tissues between the knockout mice and the control mice. Inhibiting HLF increased the glycogen content in MIN6 cells by approximately 20% . Conclusion The HLF gene knockout mice are successfully con⁃structed , providing an animal model for studying the role of HLF in the pathogenesis of diabetes mellitus.

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To investigate the protective effect of dulaglutide on lipopolysaccharide (LPS)-induced inju- ry in MLE-12 cells. Methods An in vitro model of acute lung injury was established by inducing MLE-12 cells with LPS ( 1 μg/mL) , followed by treatment with dulaglutide for 24 hours. The cells were divided into four groups : CON group , LPS group , LPS + 100 nmol/L dulaglutide group , and LPS + 200 nmol/L dulaglutide group. Protein and RNA were extracted from each group. The mRNA levels of inflammatory factors , including interleukin (IL)-6 , tumor necrosis factor-α (TNF-α ) , IL-1β , monocyte chemotactic protein 1 (CCL2) , C-X-C motif chemokine lig- and (CXCL) 1 and CXCL2 , were detected by qRT-PCR. Cell apoptosis was assessed by TUNEL assay , and the expression levels of phosphorylated protein kinase B (P-Akt) and phosphorylated extracellular signal-regulated ki- nase (P-Erk) were measured by Western blot. Results Compared with the CON group , the LPS group showed in- creased mRNA levels of inflammatory mediators (TNF-α , IL-6 , IL-1β , CCL2 , CXCL1 , and CXCL2) , increased TUNEL-positive cells , and elevated expression of P-Akt and P-Erk proteins. Compared with the LPS group , the LPS + 100 nmol/L dulaglutide treatment group exhibited reduced mRNA levels of TNF-α , IL-6 , IL-1β , CCL2 , CXCL1 , and CXCL2 , decreased TUNEL-positive cells , and downregulated expression of P-Akt and P-Erk pro- teins. However, the LPS + 200 nmol/L dulaglutide treatment group showed less pronounced improvement in inflam- matory factors compared to the LPS + 100 nmol/L dulaglutide group. Conclusion Dulaglutide has a protective effect on LPS-induced injury in MLE-12 cells , potentially through inhibiting Akt and Erk phosphorylation , thereby reducing the expression of inflammatory mediators and alleviating inflammatory damage , ultimately protecting the lungs.

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To compare the transcriptomic profiles between three distinct metabolic dysfunction⁃associat⁃mal murine model that more closely resembles human MASH progression . Methods Forty 8 ⁃week⁃old male C57BL/6J mice were randomly assigned to either a control group fed normal chow diet ( NCD) or one of three MASH model groups receiving high⁃fat high⁃cholesterol diet (HFHCD) , choline⁃deficient high⁃fat diet (CDHFD) ,from three randomly selected mice per group were collected for mRNA sequencing ( mRNA⁃seq) analysis . Mean⁃bases . Overlap of functional profiles was analyzed by gene set enrichment analysis (GSEA) profiles to compare the mouse transcriptome with that of human patients at different stages of the disease . Additionally , Pearson ′s correla⁃tion analysis was used to explore the correlation between gene expression of murine models and human MASH . Re-sults Seven commonly up⁃regulated genes (Col1a1 , Smoc2 , Col6a1 , Gpx3 , Col16a1 , Spp1 and Crtap) were de⁃ways involving steatosis , hepatocellular injury and fibrosis were detected in the three MASH models at the pathway level . HFHCD and MCD might share more common traits . In comparing gene expression and pathway profiles be⁃tween different murine models and patients with different stages of MASH , all three murine MASH models showed a closer resemblance to the human progressive stages of MASH . Notably , the transcriptomic features of the CDHFD model were more consistent with those of human MASH . Conclusion There are certain similarities and differences among the transcriptional profiles of the three MASH models . The MASH models are more similar to the advanced stage of MASH in human patients . Compared to the other two models , the CDHFD model ′ s transcriptome profile more closely resembles human MASH .

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To investigate whether zerumbone ( ZER) has the effect of preventing cisplatin ( Cis) -in- duced acute kidney injury (Cis-AKI) . Methods The MTT method was used to detect the effect of different con- centrations of ZER on the cell viability of Cis-AKI. The in vivo and in vitro models of Cis-AKI mice were estab- lished by dividing into control group , separate administration group , model group , and dose group. Western blot and immunofluorescence experiments were used to detect the expression changes of kidney injury marker-1 ( KIM- 1) , phosphorylated NF-κB p65 ( P-p65 ) , Cleaved casepase3 , receptor interacting protein kinase 1 ( RIPK1) , RIPK3 , and tumor necrosis factor-α (TNF-α) . Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the mRNA expression of KIM-1 , TNF-α , interleukin-6 ( IL-6) , and monocyte chemoattractant protein-1(MCP-1) . Periodic acid-Schiff (PAS) staining confirmed the therapeutic effect of ZER on Cis-AKI. RNA-seq and cell thermal shift (CETSA) were used to explore possible target proteins. Results MTT results showed that ZER could alleviate the decrease in cell viability of Cis-AKI ; in vivo and in vitro studies showed that compared with the model group , after treatment with ZER , its KIM-1 , P-p65 , Cleaved casepased3 , RIPK1 , RIPK3 , TNF -α expres- sion decreased significantly , and the mRNA expression of KIM-1 , TNF-α , IL-6 mRNA , and MCP-1 decreased. PAS staining showed that ZER had a therapeutic effect on Cis-AKI. RNA-seq and CETSA analysis showed that ZER might prevent and treat Cis-AKI by targeting the PIM1 protein. Conclusion ZER may alleviate Cis-AKI and im- prove inflammatory response and necroptosis by regulating PIM1 protein. ZER is expected to be a potential drug for the prevention and treatment of Cis-AKI.

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To investigate the protective effect of total glucosides of paeony ( TGP) on dexamethasone(DEX) ⁃induced liver injury in rats. Methods Thirty SD rats were randomly divided into normal ( N) , DEX ,DEX + TGP (50 mg/kg) , DEX + TGP ( 100 mg/kg) , and DEX + TGP (200 mg/kg) groups , with 6 rats in each group. A rat model of liver injury was established by intraperitoneal injection of DEX ( 17. 5 mg/kg) . Serum levels of alanine aminotransferase ( ALT) , aspartate aminotransferase ( AST) , and alkaline phosphatase ( ALP) were measured , and the liver⁃to⁃body weight ratio was calculated. HE staining was performed to observe histopathological changes in the liver. The contents of malondialdehyde ( MDA) , superoxide dismutase ( SOD) , and glutathione (GSH) in liver tissues were determined. Western blot analysis was conducted to detect the expression levels of NADPH oxidase 4 ( NOX4 ) and endoplasmic reticulum stress⁃related proteins : glucose regulatory protein 94 homologous protein (CHOP) expression level in liver tissues. Results Compared with the normal group , the DEX group exhibited significantly elevated serum levels of ALT , AST , ALP and liver⁃to⁃body weight ratio ( t = 14. 96 ,ing, degeneration , and necrosis ( t = 15. 49 , P < 0. 01) . Compared with the DEX group , there was no significant change in liver function biochemical indexes and liver histopathology in the TGP (50 mg/kg) treatment group. TGP treatment at 100 mg/kg and 200 mg/kg significantly attenuated these effects : both doses reduced ALT , AST , ALP and liver⁃to⁃body weight ratio( t = 3. 30 , 4. 13 , 7. 45 , 2. 97 , P < 0. 05 ; t = 8. 92 , 6. 45 , 8. 65 , 7. 47 , P < 0. 01) ,vealed that DEX administration significantly increased hepatic MDA levels ( t = 7. 06 , P < 0. 01) and NOX4 ex⁃pression ( t = 4. 23 , P < 0. 01) , whereas SOD activity ( t = 7. 78 , P < 0. 01) and GSH content ( t = 7. 92 , P <0. 01) were markedly suppressed. There was no significant change in the TGP (50 mg/kg) treatment group , TGP intervention at 100 mg/kg and 200 mg/kg effectively reversed these changes , lowering MDA and NOX4 levels( t = 3. 35 , 4. 30 , P < 0. 05 ; t = 5. 44 , 7. 44 , P < 0. 01) , while restoring SOD ( t200 mg/kg = 4. 04 , P < 0. 05) and GSH ( t = 4. 70 , P < 0. 05 ; t = 5. 50 , P < 0. 01) . Endoplasmic reticulum stress markers , including GRP94、GRP78、p- elF2α、CHOP ( t = 3. 31 , 6. 53 , 5. 18 , 3. 09 ; P < 0. 05 , 0. 01 , 0. 01 , 0. 05 ) , were significantly upregulated in the DEX group compared to the normal group. However, TGP treatment at 100 mg/kg and 200 mg/kg dose-dependent- ly suppressed the expression of GRP94、GRP78、p-elF2α、CHOP ( t = 3. 14 ,4. 95 , 3. 13 ,4. 25 , P < 0. 05 ; t = 4. 03 , 7. 48 ,4. 68 ,5. 10 ,P < 0. 01) expression levels were significantly reduced compared to the DEX group , and there was no significant change in the TGP (50 mg/kg) treatment group. Conclusion TGP exerts protective effects a- gainst DEX-induced liver injury , and its mechanism is likely mediated by suppressing hepatic oxidative stress and endoplasmic reticulum stress triggered by DEX in rats.

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To investigate the inhibitory effect of Elesclomol (ES) + Cu2 + on the proliferation of human hepatoma cell lines PLC/PRF/5 and Huh-7 and its potential to induce Cuproptosis. Methods Human hepatoma cell lines PLC/PRF/5 and Huh-7 cells were Cultured in vitro. ES solution , Cu2 + solution and copper chelating a- gent ammonium tetrathiomolybdate VI (ATTM) solution was treated separately or in combination. The effect of ES + Cu2 + on the survival rate of human hepatoma cell lines PLC/PRF/5 and Huh-7 cells and the effect of ES + Cu2 + on the survival rate after pretreatment with copper chelating agent ATTM were evaluated using CCK-8 kit. The cell intervention at 100 mg/kg and 200 mg/kg effectively reversed these changes , lowering MDA and NOX4 levels( t = 3. 35 , 4. 30 , P < 0. 05 ; t = 5. 44 , 7. 44 , P < 0. 01) , while restoring SOD ( t200 mg/kg = 4. 04 , P < 0. 05) and GSH ( t = 4. 70 , P < 0. 05 ; t = 5. 50 , P < 0. 01) . Endoplasmic reticulum stress markers , including GRP94、GRP78、p- elF2α、CHOP ( t = 3. 31 , 6. 53 , 5. 18 , 3. 09 ; P < 0. 05 , 0. 01 , 0. 01 , 0. 05 ) , were significantly upregulated in the DEX group compared to the normal group. However, TGP treatment at 100 mg/kg and 200 mg/kg dose-dependent- ly suppressed the expression of GRP94、GRP78、p-elF2α、CHOP ( t = 3. 14 ,4. 95 , 3. 13 ,4. 25 , P < 0. 05 ; t = 4. 03 , 7. 48 ,4. 68 ,5. 10 ,P < 0. 01) expression levels were significantly reduced compared to the DEX group , and there was no significant change in the TGP (50 mg/kg) treatment group. Conclusion TGP exerts protective effects a- gainst DEX-induced liver injury , and its mechanism is likely mediated by suppressing hepatic oxidative stress and endoplasmic reticulum stress triggered by DEX in rats.

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To explore the effects of lipopolysaccharide⁃binding protein (LBP) on the skin reconstruc⁃tion process and to compare the differences in the healing rate and healing quality of scald wounds in C57BL/6J wild⁃type (WT) mice and LBP knockout ( LBP - / - ) mice were compared. Methods Based on WT mice and periodically after scald injury , and images were acquired and weighed. After the scar matured , the material was taken for HE staining , oil red staining and Masson staining , which were used to assess the quality of the newborn skin. Results The wound healing time of WT mice and LBP - / - mice was 18 days and 24 days , respectively. The results of pathological staining of skin tissue showed that compared with WT mice , the skin of LBP - / - mice had thinner new fat layer, fewer hair follicles and dysplasia of accessory glands. The mature scar tissue of LBP - / - mice was thicker and the collagen content was higher. Conclusion After scalding in LBP - / - mice , due to the lack of LBP , the wound healing rate is slowed down and the skin structure reconstruction is impaired.

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To analyze the physical and chemical properties of human gastric factor by bioinformatics method , and to express and purify the protein. Methods Protein online analysis software was used to predict the physical and chemical properties of gastric intrinsic factor and analyze their hydrophilicity and hydrophobicity. The online tool was used to predict and analyze the human gastric factor signal peptide and its subcellular location. The eukaryotic expression recombinant plasmid pcDNA3. 1 ( + ) ⁃human GIF⁃His tag was constructed , and the gastric intrinsic factor was purified by nickel column after expression in HEK293F cells. The purity and activity of purified gastric intrinsic factor were verified by SDS⁃PAGE , Western blot and indirect ELISA. Results Gastric factor con⁃tained 417 amino acids and was a hydrophilic acid stable protein. It was a secreted protein with Sec original signal peptide. pcDNA3. 1( + ) ⁃human GIF⁃His tag recombinant plasmid was successfully constructed and soluble expres⁃sic factor is successfully prepared , and the bioinformatics results show that the protein is a hydrophilic acid stable secreted protein , laying a foundation for the subsequent use of this protein as an immunogen and protein calibrator to construct an immunoassay for gastric factor.

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To investigate the mechanism of action of benvitimod (BVM) in the treatment of atopic der- matitis (AD) . Methods HaCaT cells were stimulated by TNF-α and IFN-γ , and the cells were grouped into NC group , TNF-α/IFN-γ group , TNF-α/IFN-γ BVM group , and TNF-α/IFN-γ BVM ML385 group. The AD model of DNCB-induced Balb/c mice was divided into CON group , DNCB group , DNCB + BVM group , and DNCB + TAC group. The efficacy of BVM and its roles in antioxidant and pyroptosis regulation were evaluated. Results Com- pared with the control group , BVM inhibited the inflammatory response of HaCaT cells stimulated by TNF-α and IFN-γ , and ameliorated the skin lesions and inflammation in the DNCB-induced AD mouse model ; at the same time , it significantly increased the expression of nuclearfactorerythroid-2-relatedfactor2 (NRF2)-related anti-oxida- tive stress proteins , and significantly reduced the expression of cellular reactive oxygen species (ROS) levels and pyroptosis proteins. At the same time , the levels of NRF2-related anti-oxidative stress proteins significantly in- creased , and the levels of ROS and pyroptosis proteins significantly decreased. Conclusion BVM activates the NRF2/ROS/NLRP3 pathway to inhibit pyroptosis , thereby reducing the inflammatory response in AD.

abstract:
To investigate the mechanism of action of benvitimod (BVM) in the treatment of atopic der- matitis (AD) . Methods HaCaT cells were stimulated by TNF-α and IFN-γ , and the cells were grouped into NC group , TNF-α/IFN-γ group , TNF-α/IFN-γ BVM group , and TNF-α/IFN-γ BVM ML385 group . The AD model of DNCB-induced Balb/c mice was divided into CON group , DNCB group , DNCB + BVM group , and DNCB + TAC group . The efficacy of BVM and its roles in antioxidant and pyroptosis regulation were evaluated . Results Com- pared with the control group , BVM inhibited the inflammatory response of HaCaT cells stimulated by TNF-α and IFN-γ , and ameliorated the skin lesions and inflammation in the DNCB-induced AD mouse model ; at the same time , it significantly increased the expression of nuclearfactorerythroid-2-relatedfactor2 (NRF2)-related anti-oxida- tive stress proteins , and significantly reduced the expression of cellular reactive oxygen species (ROS) levels and pyroptosis proteins . At the same time , the levels of NRF2-related anti-oxidative stress proteins significantly in- creased , and the levels of ROS and pyroptosis proteins significantly decreased . Conclusion BVM activates the NRF2/ROS/NLRP3 pathway to inhibit pyroptosis , thereby reducing the inflammatory response in AD .

abstract:
To establish an interleukin-1β (Il-1β) induced inflammatory model of rat articular chondro- cytes (ACs) , and to investigate the relationship between the expression of lysine acetyltransferase 7 (KAT7) under inflammatory stimulation and the senescence of ACs. Methods Primary ACs were obtained by digestion of rat knee cartilage with collagenase type Ⅱ and identified. The inflammatory model of ACs was induced by IL-1β . KAT7 was over-expressed or knocked down in ACs by adeno-associated virus infection or small interfering RNA transfection , respectively. A negative control group was set up. Transwell assay was used to detect cell migration ability. Senes- cent cells were stained with senescence-associated β-galactosidase (SA-β-Gal) . Western blot ( WB) was used to detect the protein expression levels of KAT7 , collagen type II (Col Ⅱ ) , matrix metalloproteinase 13 (MMP13) , tumor protein p53 (p53) and cyclin-dependent kinase inhibitor 1A (p21) . The cells of negative control group and KAT7 over-expression group were performed for RNA sequencing , and WB was used to verify the related signaling pathways obtained by Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. Results Compared with the control group , the SA-β-Gal staining was enhanced , the protein expression of Col Ⅱ decreased , the pro- tein expression of MMP13 and p53 increased , the cell migration ability decreased , and the expression of KAT7 also increased in the ACs of rats after IL-1β stimulation. Compared with the negative control group , the SA-β-Gal stai- ning was enhanced , the protein expression of Col Ⅱ decreased , the protein expression of MMP13 , p53 and p21 in- creased , and the cell migration ability decreased in the KAT7 over-expression group. Compared with the negative control group , the SA-β-Gal staining was weakened , the protein expression of Col Ⅱ increased , the protein expres- sion of MMP13 , p53 and p21 decreased , and the cell migration ability was enhanced in the KAT7 knockdown inflammatory model of ACs. KEGG enrichment analysis showed that phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was activated. Compared with the negative control group , the relative protein ex⁃pression levels of phosphorylated protein kinase B (p⁃AKT)/AKT and phosphorylated mammalian target of rapamy⁃cin (p⁃mTOR)/mTOR in KAT7 over⁃expression group increased. The relative protein expression levels of p ⁃AKT/AKT and p ⁃mTOR/mTOR in KAT7 knockdown cells decreased.

abstract:
To investigate the role and related mechanisms of IgD on the viability , proliferation , apopto⁃healthy controls. The sIgD levels were quantified by ELISA. For in vitro studies , Molm ⁃13 cells were treated with colony formation assays. Apoptosis rates were determined using an Annexin V/PI apoptosis detection kit. Prelimi ⁃nary exploration of the mechanisms related to IgD⁃induced proliferation of Molm ⁃13 were analyzed through differenti⁃al gene analysis. Results Compared with healthy controls , the levels of sIgD in AML patients were significantly el⁃evated (P < 0. 001 ) . IgD treatment dose⁃dependently increased Molm ⁃13 cell viability and proliferation ( P <evated (P < 0. 001 ) . IgD treatment dose⁃dependently increased Molm ⁃13 cell viability and proliferation ( P <0. 05) , inhibited apoptosis rates (P < 0. 001) . Conclusion IgD promotes the viability and proliferation of Molm ⁃13 cells , and reduces apoptosis.

abstract:
To analyze the epidemiological characteristics of tuberculosis in Urumqi and assess the im⁃pact of the national health examination policy , as well as COVID⁃19 prevention and control measures , on tuberculo⁃sis incidence in Xinjiang. Methods The seasonal patterns of pulmonary tuberculosis were examined using the sea⁃sonal index method and circular distribution analysis. An Interrupted Time Series (ITS , Interrupted Time Series) model was employed to investigate how the national health examination policy and COVID⁃19 interventions influ⁃culosis were reported in Urumqi. The peak incidence day occurred on May 25th , indicating a consistently high rate throughout the year, particularly during spring and summer months. The results of the interrupted time series model indicated that the initial monthly incidence rate of pulmonary tuberculosis in Urumqi was 5. 05 per 100 ,000. From January 2013 to September 2016 , the incidence rate of pulmonary tuberculosis showed a slow upward trend , and the upward trend was significant (β1 = 0. 039 ,P < 0. 05) . After the implementation of the universal health check⁃up policy , the incidence rate of pulmonary tuberculosis showed a slow downward trend , and the downward trend was significant(β3 = - 0. 109 ,P < 0. 05) . After the outbreak of the COVID⁃19 epidemic in January 2020 , the inci⁃dence rate of pulmonary tuberculosis in Urumqi first dropped rapidly and then entered a slow upward stage , and the upward trend was significant(β5 = 0. 082 , P < 0. 05) . Conclusion It is recommended that public health authori⁃ties prioritize timely identification of potential TB patients during periods with elevated incidence rates observed in spring and summer months. While significant progress has been made through implementing national health exami ⁃tion. Thus , enhancing surveillance efforts and intervention strategies are essential in adapting to this new normal.

abstract:
To investigate the risk factors for wheezing during infancy in preterm infants after discharge and to develop a nomogram model for predicting wheezing. Methods A total of 329 preterm infants were selected for this study. The data were randomly divided into a training set (n = 232) and a validation set (n = 97) in a 7 ∶3 ratio. The training set was further divided into a wheezing group (n = 73) and a non⁃wheezing group (n = 159) based on the occurrence of wheezing. Logistic regression analysis was used to identify independent risk factors for wheezing , and the R software was used to construct and validate the predictive model. Results Compared with the non⁃wheezing group , the wheezing group had significantly lower gestational age , higher rates of mechanical ventila⁃tion , neonatal pneumonia , patent ductus arteriosus within 1 week , pulmonary hypertension , and prolonged antibiot⁃ic use (P < 0. 05) . The independent risk factors for wheezing in preterm infants during infancy included gestational age ( OR : 0. 96 , 95% CI: 0. 95 - 0. 98) , mechanical ventilation ( OR : 11. 08 , 95% CI: 6. 36 - 19. 31) , duration of antibiotic use ( ≥1 week vs < 1 week , OR : 5. 31 , 95% CI: 3. 19 - 8. 84) , 25% tidal volume expiratory flow 22. 58) , neonatal pneumonia ( OR : 4. 79 , 95% CI: 2. 83 - 8. 10) , and frequency of respiratory infections in the first six months ( ≥3 times vs < 3 times , OR : 5. 18 , 95% CI: 3. 10 - 8. 67) ( P < 0. 05) . The areas under the ROC curve (AUC) for the training and validation sets were 0. 889 (95% CI:0. 844 - 0. 934) and 0. 959 (95% CI: 0. 923 - 0. 995 ) , respectively. The calibration curve showed good agreement with the ideal curve , and decision curve analysis demonstrated high net benefit for predicting wheezing. Conclusion The nomogram model based on independent risk factors for wheezing in preterm infants provides a high level of accuracy and may serve as a useful reference for clinical practice.

abstract:
To evaluate the clinical effectiveness of transcutaneous electrical acupoint stimulation (TEAS) in the treatment of sequelae of inflammatory pelvic diseases in women. Methods A total of 100 patients diagnosed with sequelae of inflammatory pelvic diseases were selected. They were randomly divided into three groups : transcutaneous electrical acupoint stimulation (TEAS) treatment group (40 cases) , drug treatment group (30 cases) and combined treatment group(30 cases) . The three groups received treatment for four weeks : the medication group received Kangfu xiaoyan shuan ; the combination treatment group received TEAS combined with Kangfu xiaoyan shuan ; and the TEAS treatment group received the highest level of electrical stimulation that the hu⁃the uterine acupoints. Prior to and following treatment , the three patient groups ′ local sign score , symptom and sign score (McCormack score) , visual analogue scale ( VAS) score for lower abdomen pain , and SF⁃36 scale score tervention , all three groups ′ local sign score , McCormack score , and VAS score for lower abdomen pain were con⁃ences (P < 0. 05) between the combination treatment group and the TEAS treatment and drug treatment groups.The combined treatment group ′ s scores were lower. The three groups ′ total somatic health score and total mental health score before and after the intervention differed significantly (P < 0. 05) after the period of therapy. Addition⁃ally , the combined treatment group ′s total somatic health score and total mental health score were higher than those of the medication group. In all three groups , there were no notable negative reactions. Conclusion TEAS treat⁃ease , and the combination of medication is better than monotherapy in improving pain symptoms and quality of life.

abstract:
To explore the risk of endometrial polyp (EP) based on lipid metabolism and vaginal micro- ecology combined with uterine volume line drawing model. Methods 143 EP patients treated by hysteroscopic sur- gery were selected as the experimental group , and 113 healthy women were selected as the control group at the same time. The data were randomly divided into training set and validation set according to the ratio of 7 : 3. The clinical data of the two groups were collected and recorded , and t/χ2 test , LASSO regression and multifactorial lo- gistic regression analysis were used to screen the independent risk factors , construct the prediction model , and draw the column line graph. The performance of the model was evaluated by applying subject operating characteristic (ROC) curves , calibration curves , Hosmer-Lemeshow test and clinical decision-making (DCA) curves. Results Multifactorial logistic regression analysis showed that total cholesterol ( TC) , low-density lipoprotein cholesterol (LDL-C) , vaginal microecological balance , and uterine volume were independent risk factors for the development of EP. ROC curve analysis showed that the AUC values of the training and validation sets of the column line graph model were 0. 935 and 0. 887 , respectively , and its sensitivity and specificity were 90. 21% , 83. 46% and 86. 29% , 80. 66% respectively , The Hosmer-Lemeshow test showed that the model fits well ( training set : χ2 = 2. 261 , P = 0. 840 ; validation set : χ2 = 4. 837 , P = 0. 441) and the calibration curves of the training and validation sets were close to the ideal curves , which indicated that the model had good prediction accuracy; the analysis of DCA curves of the training and validation sets both showed that the column-line graph model had a good clinical benefit rate in predicting EP. Conclusion TC , LDL-C , vaginal microecological balance and uterine volume are independent risk factors for EP , and the column-line diagram model constructed by the model has high clinical ben- efit , calibration and accuracy in predicting the risk of EP.

abstract:
To investigate the impact of endometriosis on pregnancy and delivery outcomes in patients undergoing single euploid frozen⁃thawed blastocyst transfer cycles following preimplantation genetic testing. Meth-transfer after preimplantation genetic testing at the reproductive center of The First Affiliated Hospital of Anhui Med⁃ ical University. The endometriosis group comprised 84 treatment cycles. After 1 ∶ 3 propensity score matching , 252 treatment cycles from non⁃endometriosis patients were included as the control group. General characteristics and ences between the two groups in terms of general characteristics , human chorionic gonadotropin ( HCG) positive rate , cycle clinical pregnancy rate per cycle , early miscarriage rate , preterm birth rate , live birth rate per cycle ,cesarean section rate , delivery weeks , cumulative clinical pregnancy rate , and cumulative live birth rate (all P >0. 05) . Conclusion Endometriosis may not reduce the pregnancy rate and live birth rate in single frozen euploid blastocyst transfer cycles.

abstract:
Ferroptosis , a novel , non-apoptotic form of cell death discovered in 2012 , has garnered significant at- tention. It is implicated in the pathogenesis and progression of various intestinal diseases , including colorectal canc- er, intestinal ischemia-reperfusion injury , functional gastrointestinal disorders , and inflammatory bowel disease. These processes involve multiple pathological mechanisms such as inflammation , immune dysregulation , and intesti- nal epithelial dysfunction. By reviewing and summarizing recent literature on ferroptosis-related mechanisms in in- testinal diseases , this article explores the roles and effects of ferroptosis in different intestinal pathologies.

abstract:
Esophageal cancer is one of the most common malignant tumors of the digestive system in China , with e-sophageal squamous cell carcinoma (ESCC) being the predominant pathological type. The exact etiology of ESCC remains incompletely understood. With advances in 16S rRNA gene sequencing and metagenomics , microbial dys- biosis has been suggested to play a significant role in the pathogenesis of ESCC. Currently , research on the rela- tionship between microorganisms and ESCC is still in its early stages. This review summarizes the association be- tween oral and esophageal microbiota and ESCC , factors influencing microbial composition , and microbial commu- nities linked to ESCC prognosis , which may contribute to early detection and optimized treatment strategies for ES- CC.