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In recent years, the prevalence of myopia in children and adolescents has continued to rise in China, followed by an increasing incidence of pathological myopia. Pathological myopia results from excessive axial elongation, with posterior scleral staphyloma and various fundus changes as the main characteristics. It has become a leading cause of blindness in China, causing a serious social burden. However, the attention on pathological myopia is still limited. The prevention and treatment of pathological myopia is difficult since it has plenty of risk factors and many complications with lifelong progress. Pathological myopia, as the key and difficult point in myopia prevention and control, deserves great attention from the whole society.

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Objective To investigate the effects of RO or incubation with cholesterol(CH) on the differentiation and apoptosis of KCs. Methods Ca2+(1.8 mmol/L) was added to KCs for 1 day after co-culture of RO alone or combined with CH in KCs for different time. The expression of Involucrin(INV) and Loricrin in KCs was analyzed by Western blot. After co-culture of RO alone or combination with CH in KCs for different time, the apoptotic changes of KCs cells were detected by flow cytometry and the expression of apoptotic proteins Bax and Bcl-2 were verified by Western blot.Results RO down-regulated the expression of Ca2+induced differentiation marker protein INV, but weakly inhibited the expression of Loricrin, while CH showed no antagonistic effect on RO. RO induced apoptosis of KCs cells in a time dependent manner. CH could antagonize the apoptotic effect of RO on KCs; the expression of Bcl-2 and Bax was inhibited when RO was applied alone,CH could partially antagonize the inhibition effect of RO on Bcl-2 expression, but had no significant effect on Bax; however, RO reduced the ratio of Bcl-2/Bax in a time-dependent manner, and CH partially weakened the effect of RO on the ratio of Bcl-2/Bax.Conclusion RO may inhibit KCs differentiation and induce KCs cell apoptosis by down-regulating the expression of Loricrin and Bcl-2.

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Objective To investigate the role of iron uptake-related geneiucAin the pathogenesis of UropathogenicE.coli(UPEC),UPEC CFT073 strain was used to construct theiucAgene deletion strain ΔiucAby λ Red homologous recombination technology, and the complemented strain C-iucAwas also constructed. Methods The proliferation rates of CFT073, ΔiucAand C-iucAin Luria-Bertani liquid medium and sterile urine were determined by measuring the absorbance at 600 nm. Cultured 5637 human bladder cancer epithelial cells confluent monolayers were incubated with CFT073, ΔiucAand C-iucAfor adhesion and invasion ability assay. C57 BL/6 mouse urinary tract infection model was constructed to assess colonization ability of CFT073, ΔiucAand C-iucAin murine bladder tissues. Results Data showed that CFT073, ΔiucAand C-iucAdisplayed the similar proliferation curves in Luria-Bertani liquid medium(P=0.153). The proliferation rate of △iucAin sterile urine was lower than that of CFT073(P=0.001), while the proliferation rate of C-iucAin sterile urine was significantly higher than that of ΔiucA(P=0.005). △iucAdemonstrated much lower adhesion and invasion ability compared with CFT073(P=0.007, 0.002), and C-iucAshowed significantly higher adhesion and invasion ability than △iucA(P=0.046, 0.037). The colonization ability of △iucAin murine bladder tissues was much lower than that of CFT073 and C-iucA(P=0.002, 0.017). Conclusion The results indicateiucAgene may contribute to the proliferation, adhesion, invasion and colonization ability of UPEC.

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Objective To detect the changes of autophagic flux at different stages after oxygen-glucose deprivation-reoxygenation(OGD/R) with several highly sensitive methods. Methods Primary cortical neurons after oxygen deprivation of sugar after reoxygenation(OGD/R) were divided into the experimental OGD/R group and OGD/R+bafilomycinA1(BafA1) group, using an RFP-GFP series fluorescent tags LC3 gene transfection detection cytolysosome and fusion of lysosomes, transmission electron microscope(TEM) observation the ultrastructure of autophagy, p62/SQSTM1 combining LC3 protein to flip the experimental testing p62 and LC3 protein quantitative, p62 immune staining observing the distribution and content. Results Under fluorescence microscope, the ratio of autophagy lysosome to autophagosome increased significantly in OGD/R group, and the changes of autophagy structure in different stages could be observed in TEM. The ratio of soluble p62 and LC3Ⅱ/Ⅰ reflected the activation of autophagic flux, and p62 was mainly distributed in BafA1 group after fluorescence staining. Conclusion Each method has its own advantages, and different methods and indicators can accurately reflect the specific changes of autophagic flux in different stages after neuronal OGD/R. Mastering and applying these methods can effectively explore central nervous system diseases from the perspective of autophagy.

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Objective To investigate the effect and mechanism of Urolithin B(UB) on proliferation, migration, invasion, apoptosis and cell cycle of glioblastoma cells. Methods The effects of UB on the proliferation, migration and invasion of glioblastoma U251 cells were detected by CCK-8, clone formation assay, scratch healing assay, Transwell invasion assay respectively. The regulation effect of UB on cell cycle and apoptosis was detected by flow cytometry. Western blot was used to detect the effects of UB on the phosphorylation levels of downstream signaling pathway proteins ERK, AKT, p38 and JNK. Results Compared with the control group, at 24 h and 48 h, the absorbance value of U251 cells was decreased by UB(P<0.01) in a dose dependent manner. UB reduced the percentage of cell clone formation(P<0.01). The percentage of the scratch healing area was reduced by UB(P<0.05 orP<0.01). The percentage of the number of invaded cells was reduced by UB(P<0.01). UB could induce apoptosis(P<0.01) and cause the cells to stagnate in G2/M phase(P<0.01). UB could significantly inhibit the phosphorylation of ERK(P<0.05 orP<0.01) and AKT(P<0.05 orP<0.01). Conclusion UB can inhibit proliferation, migration, invasion, apoptosis and cell cycle of glioblastoma cells, and regulate the phosphorylation levels of ERK and AKT.

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Objective To determine expression profile of VISTA on lymphocyte and the potential regulatory effects on immune response in a murine model of sepsis. Methods Expression profile of VISTA on T lymphocytes in the spleen and peripheral blood was examined. Mice wereintravenously injected with an agonistic VISTA mAb(MH5 A) or isotype control, and then the survival rate, cytokine expression, bacterial burden and lymphocyte apoptosiswere determined. Results VISTA was substantially expressed on T cell from the spleen and peripheral blood, septic peritonitis did not induce significant changes in the expression profiles at 24 h post surgery(P>0.05 in each comparison). Treatment with MH5 A improved the survival of septic mice(8/12vs2/12,P=0.01), accompanied by reduced lymphocyte apoptosis [(30 123±6 400)vs(45 482±8 652),P=0.03], decreased bacterial burden and lessened cytokines expression, such as TNF-α, IL-6, IL-1β and IFN-γ(P<0.05 in each comparison). Conclusion The present study identified VISTA as a novel immune checkpoint in the regulation of T cell apoptosis and inflammatory response during sepsis. VISTA agonism might offer a promising approach in the immunotherapy for sepsis.

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Objective To explore the epicardial adipose tissue(EAT) of patients with coronary heart disease, KLF7 stimulates macrophages to secrete inflammatory factors and promotes the differentiation and maturation of adipocytes through the NF-κB signaling pathway, and to clarify the mechanism of KLF7 in the occurrence and development of CAD. Methods 30 patients with coronary heart disease(CAD group) and 30 patients without coronary heart disease(non-CAD group) were collected, and general data and biochemical indicators were collected. qRT-PCR was used to detect the expression levels of KLF7, APN, IL-6, and TNF-α mRNA in EAT. Human THP-1 cells were cultured in vitro and induced into M1 type macrophages and 3 T3-L1 preadipocytes. The cells were divided into 3 groups: KLF7 up-regulated group(transfected with KLF7 mimic), KLF7 down-regulated group(transfected with siRNA knockdown KLF7), NC group(transfected oligopeptide sequence), transfected two kinds of cells. qRT-PCR was used to detect the expression of APN, MCP-1, IL-6 and TNF-α mRNA in M1 type macrophages, and the protein expression levels of key factors in the NF-κB signaling pathway were detected by Westren blot. The qRT-PCR method was used to detect APN, KLF4, IL-6, MCP-1 mRNA and adipocyte differentiation marker peroxisome proliferator-activated receptor-γ(PPARγ) in 3 T3-L1 preadipocytes 24 h after transfection. CCAAT/enhancer binding protein α(C/EBPα), fatty acid binding protein 4(FABP4) mRNA relative expression levels, and Westren blot was used to detect protein expression levels. Results Compared with the non-CAD group, the expression of CAD group decreased, APN decreased, IL-6 and TNF-α increased significantly, and the difference was statistically significant(P<0.01). KLF7 was highly expressed in human THP-1 derived M1 macrophages induced by inflammatory stimuli(LPS). In M1 macrophages derived from human THP-1, knocking down KLF7 could inhibit the release of inflammatory factors. Transfection with KLF7-siRNA could significantly inhibit LPS-induced phosphorylation of JNK-MAPKs, the level of p-p65 and the activation of p-IκBa(P<0.05). In 3 T3-L1 preadipocytes, upregulation of KLF7 increased the expression of adipocyte differentiation markers PPARγ, C/EBPa, FABP4 mRNA, and promoted the differentiation of 3 T3-L1 preadipocytes into adipocytes(P<0.05). Conclusion The expression of KLF7 in EAT in CAD patients increases. KLF7 activates the activation of macrophages mediated by the JNK-NF-KB signaling pathway in EAT, promotes inflammation in EAT in CAD patients, and promotes the differentiation and maturation of adipocytes, thereby promoting the development of CAD. It indicates that KLF7 may be a potential therapeutic target for cardiovascular diseases(such as CAD).

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Objective To investigate the inhibitory effect and molecular mechanism of ribosomal translation factor inhibitor Avilamycin on hepatitis B virus replication. Methods Liver cancer Hep3 B cells were treated with different concentrations of Avilamycin. Cell activity was detected by CCK-8; the apoptosis was detected by flow cytometry, and HBV-DNA、pgRNA、MTIF2、RPL10 gene expression level was detected by qPCR method. The HBsAg and HBeAg was detected by ELISA. The AFP was detected by chemiluminescence. Aspartate aminotransferase(AST), alanine aminotransferase(ALT), and alkaline phosphatase(ALP) proteins was detected by Biochemistry method. Results Avilamycin had no inhibitory effect on Hep3 B cell proliferation and apoptosis. However, it could promote cellular AST secretion, reduce AFP levels, and have less effect on ALP secretion. In Hep3 B cells, Avilamycin promotes accumulation of pgRNA expression by intervening with MTIF2 and feedback upregulates mRNA expression of host RPL10 and MTIF2 genes. It can effectively reduce the HBsAg, HBeAg, and HBV-DNA levels. Conclusion Avilamycin can inhibit MTIF2 translation initiation, regulate the translation process of viral assembly protein by affecting translation initiation, and then inhibit hepatitis B virus replication.

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Objective To investigate the effect of lansterol synthase(LSS) gene knockout on reproductive function in male mice. Methods 30 male and female 8-week-old LSS+/+(WT) and LSS+/-(KO) mice were selected,and respectively according to ♂WT × ♀WT, ♂WT × ♀KO, ♂KO × ♀WT, ♂KO × ♀KO carries out 1 ∶ 1 cages for four months, and the number of litters per litter and reproductive cycle were counted. The serum of LSS+/+（WT） and LSS+/-（KO） mice was taken for sex hormone testing. The apoptosis of spermatogenic cells in the testis was observed by TUNEL staining. Western blot was used to detect the expression of Tubulin, LSS and apoptosis-related protein(GPX4/Bax/Bcl-2) in testis tissue.Results The breeding results showed that there was a statistically difference in the number of litters per litter between ♂WT × ♀WT and ♂KO × ♀KO, and there was no difference in the other groups. There was no statistically difference in the four groups in the reproductive cycle. There was no statistically difference between the sex hormone test results of WT and KO mice. TUNEL staining results showed that there was an increase in spermatogenic cell apoptosis in the testis tissue of the knockout mice. In the results of Western blot, there was no difference in the expression of apoptosis-related proteins(GPX4/Bax/Bcl-2)in KO mice compared with WT mice.Conclusion Loss of LSS gene function can lead to increased apoptosis of mouse spermatogenic cells, which may affect the fertility of mice.

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Objective To investigate the effect of Brigatinib on radiation sensitivity of colorectal cancer LOVO cells by treating colorectal cancer LOVO cells with a combination of radiation and brigatinib. Methods Western blot and immunofluorescence detection were used to detect the amount of epidermal growth factor receptor(EGFR), p-EGFR expression in colorectal cancer cells after treatment with different irradiation doses. The expression levels of EGFR, p-EGFR, γ-H2 AX, cleaved caspase-3, cleaved caspase-7 and cleaved caspase-9 in LOVO cells were determined by Western blot, the levels of Non-homologous End Joining-NHEJ were detected by DR-GFP plasmid system, cell viability was detected by CCK-8 and apoptosis was detected by annexinv FITC/PI double labeling. Results Radiation treatment significantly increased EGFR phosphorylation in LOVO cells, which was inhibited in a dose-dependent manner after treatment with Brigatinib. Non-homologous End Joining repair was inhibited following Brigatinib treatment, and a significant increase in apoptosis was observed in LOVO cells treated with combined Brigatinib and radiation. Conclusion Brigatinib inhibited non homologous end joining repair and promoted apoptosis in LOVO cells by inhibiting EGFR phosphorylation, which eventually increased the radiation sensitivity of LOVO cells.

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Objective To explore the role and molecular mechanism ofSupervillinin zebrafish embryo development. Methods Clustal Omega and DNAman software were used to analyze and compare the homology of amino acid sequences of Svil and SVIL in zebrafish and human. The expression pattern ofSvila(subtype of Svil protein in zebrafish) during early embryonic development was analyzed by RT-PCR and in situ hybridization.Svilaexpression in zebrafish was inhibited by injecting morphinos(MO), and morphological changes of embryos were observed. The expression and nuclear localization of β-catenin protein were detected by Western blot, and the expression ofWnt/β-catenintarget gene was detected by RT-PCR. Results During the early embryonic development of zebrafish,Svilawas maternally expressed and showed an upward trend with the development process. The expression ofSvilawas reduced by MO, and the development of zebrafish embryos was distorted and the body axis was bent, which might be related to the blocked movement of concentrated extension of embryos. Further studies showed thatSvilaexpression affectedβ-cateninnuclear transport andWnt/β-cateninsignaling pathway activation. Conclusion Svilaregulates the concentrated extension movement of zebrafish embryos by activating theWnt/β-cateninsignaling pathway.

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Objective To study the relationship between lncRNA SIL and proliferation and migration of alveolar epithelial cell during pulmonary fibrosis. Methods The expression level of lncRNA SIL in A549 cells induced by transforming growth factor(TGF-β1) was detected by RNA fish. The eukaryotic expression vector of lncRNA SIL was built and transfected into A549 cells, the proliferation and migration of the cells after overexpressing lncRNA SIL were studied by RT-PCR, MTT, Western blot, cell damage repair experiments and immunofluorescence. Results The migration and proliferation of A549 cells were significantly reduced compared with the control group after transfected by lncRNA SIL. When lncRNA SIL was overexpressed in A549 cells, cell proliferation, migration and expression of proliferation-related proteins PCNA and Ki67 were decreased compared with the control group. Analysis of the expression of cellular marker proteins showed that, the expression levels of interstitial cell marker proteins α-SMA and Collagen-1 were significantly reduced, while the expression level of alveolar epithelial marker protein E.cad significantly increased. Conclusion LncRNA SIL can inhibit the proliferation and migration of A549 cells, and also can inhibit EMT induced by TGF-β1.

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Objective To screen the mRNA core genes of naringin in the treatment of colorectal cancer(CRC) by bioinformatics analysis, and to verify the predictive effect of mRNA core genes on CRC by survival analysis. Methods The HCT116 cells of CRC were treated with DMSO solvent and naringin for 48 h and then RNA sequencing was conducted. The sequencing results were preprocessed and their differentially expressed genes were analyzed. The key lncRNAs were screened from differentially expressed genes, and the corresponding lncRNA-miRNA-mRNA regulatory network was established. With gene ontology(GO) analysis, Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis and Protein-Protein Interaction(PPI) network analysis, the core mRNAs were obtained and verified by survival analysis method. Results Ultimately, 197 differentially expressed lncRNAs, 128 differentially expressed miRNAs and 1 938 differentially expressed mRNAs were screened. Based on lncRNA-miRNA-mRNA regulatory network, 5 key lncRNAs and 117 key mRNAs were screened. The results of GO analysis and KEGG pathway analysis showed that they were mainly enriched in the functions and pathways closely related to CRC. In the end, 6 mRNA core genes were obtained by PPI network analysis, and 3 core mRNAs(FOS,CCND2,MXD1) were gained by survival analysis, which closely resembled CRC. Conclusion The molecular mechanism of naringin in the treatment of CRC is analyzed by means of bioinformatics, 3 core mRNAs with significant differences are screened out and they all have an important impact on the prognoses of patients, and the study will provide new ideas for the diagnosis, treatment and prognosis of CRC.

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Objective To investigate the effect and mechanism of prenatal hypoxia on pulmonary artery vascular function in adult male offspring. Methods Sprague-Dawley pregnant rats were randomly divided into hypoxia group and control group. Pregnant rats in the hypoxia group were housed in the hypoxia chamber(a mixture of 89.5% nitrogen gas and 10.5% oxygen) from gestational day 10 th to 20 th. Pregnant rats in the control group were fed under normal oxygen. All animals were fed with standard rat food and tap water, and allowed to give birth naturally. After weaning, the male offspring were raised to 4 months old. Male offspring rats were anesthetized with chloral hydrate, and pulmonary artery was isolated for vascular function and molecular experiments. Results Compared with the control group, phenylephrine(PE)-induced contraction response in prenatal hypoxic pulmonary artery was decreased(P<0.001). There was no difference in acetyl choline(ACH)-and sodium nitrate(SNP)-induced diastolic responses between the two groups. Compared with control group, Cav1.2 protein(P<0.01) and mRNA levels(P<0.001) in hypoxia group were reduced. Conclusion Prenatal hypoxia can lead to a decreased PE-induced vasoconstriction response in adult male offspring, which is related to the down-regulation of Cav1.2 expression in pulmonary artery.

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Objective To explore the regulatory mechanism of the long noncoding FGD5-AS1(LncRNA FGD5-AS1) on hepatocellular carcinoma(HCC)progression. Methods The expression level of FGD5-AS1 was measured in tumor tissues and cell lines by RT-qPCR. CCK-8, EdU, flow cytometry, wound healing and transwell chamber assays were performed to investigate the role of FGD5-AS1 in HCC cell proliferation, apoptosis, migration and invasionin vitro. At the molecular level, dual luciferase reporter and RNA pull down assays were performed to identify the interaction among FGD5-AS1, miR-873-5 p and GTPBP4.Results FGD5-AS1 was upregulated in HCC tissues and cells. Moreover, FGD5-AS1 knockdown suppressed HCC cell proliferation, migration and invasion, and induced apoptosisin vitro. Mechanistically, FGD5-AS1 directly bound to miR-873-5 p and competitively inhibit its expression to increase the expression level of GTPBP4 in HCC cells. Finally, our findings indicated that the role of FGD5-AS1 was mediated by miR-873-5 p GTPBP4 axis.Conclusion FGD5-AS1 promotes the proliferation, migration and invasion of HCC cells and inhibits apoptosis by regulating the miR-873-5 p/GTPBP4 axis.

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Objective To develop an extracellular vesicles(EVs) co-loading system by synergistically deliver tumor necrosis factor related apoptosis inducing ligand(TRAIL)/verteporfin(VPF) combination to induce apoptosis and inhibit proliferation of OSCC cells. Methods TRAIL/VPF co-loaded EVs(MSCT-EVs/VPF) was purified and collected though ultracentrifugation and dialysis. The expression of CD63, CD9 and TRAIL was detected by BCA to confirm the origin of EVs. High performance liquid chromatography(HPLC) was used to detect the drug loading of VPF and draw the release curve in vitro. Cytotoxicity and half inhibitory concentration(IC50) were detected by MTT assay. The apoptosis rate was detected by flow cytometry. Finally, Western blot was used to detect the effects of MSCT-EVs/VPF on the expression of apoptosis related proteins and Yap in SCC25 cells. Results MSCT-EVs/VPF particles were round and well dispersed with a diameter of about 100 nm. The drug loading of the nano system was about(15.43 ± 0.44)%, 57.8% of VPF was released in 10 h and 82.5% in 45 h; MSCT-EVs and VPF could inhibit the growth of SCC25 tumor cells in a dose-dependent manner, showing good synergistic effect in the ratio of 10:1-5:1(CI<1, wt%). At the ratio of 100:5～100:15(Mass ratio of MSCT-EVs to VPF, wt%), the IC50of MSCT-EVs/VPF was significantly lower than that of free MSCT-EVs + free VPF group(P<0.05), and showed a more effective inhibition. The high inhibitory effect of MSCT-EVs/VPF on squamous cell carcinoma cells was partly due to the regulation of Caspase-3, Bax, BCL-2, mTOR, p-mTOR and YAP. Conclusion EVs delivery of a fixed proportion of TRAIL/VPF shows high inhibitory effect on oral squamous cell carcinoma cells, which provides a new idea for the treatment of multidrug-resistant tumors.

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Objective To explore a new MEK 1/2 inhibitor 3-(2,3-dihydroxypropyl)-6-fluor-5-((2-fluor-4-iodophenyl) amido)-8-methylpyridine[2,3-d] pyrimidine-4, 7(3 H, 8 H)-diketone(TAK-733) affects the biological behavior of human papillary thyroid carcinoma(PTC) TPC-1 cells. Methods TPC-1 cells with good growth and logarithmic growth were randomly divided into 2.5、5、10 μmol/L groups and control group, the proliferation ability of each group was detected by MTT assay after 24、48、72 h, respectively. The cell cycle and apoptosis of each group were detected by flow cytometry at 24、48 h, respectively. The migration of TPC-1 cells in each group after 24 h of action was detected by scratch healing test. Results Compared with the control group, TPC-1 cells treated with TAK-733 showed higher inhibition rate of proliferation in a time and dose dependent manner(P<0.05);the apoptosis rate of TPC-1 cells and the proportion of TPC-1 cell G1/G0in each group were higher than those in the control group(P<0.05) and the proportion of S and G2/M cells decreased(P<0.05),which showed an increase in time and dose dependence; the degree of scratch healing decreased in a concentration dependent manner(P<0.05). Conclusion TAK-733 can inhibit the proliferation and migration of human papillary thyroid carcinoma TPC-1 cells, block cell cycle and induce cell apoptosis.

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Objective To explore the potential active compounds and effect targets of Gehua Jiejiu Dizhi Decoction(GJDD) for treatment of alcoholic fatty liver disease(AFLD) based on the network pharmacology. Methods The GJDD drug-compound data set, compound-target data set and AFLD target data set were established, the "TCM-compound-target" interactive network diagram of GJDD anti-AFLD was constructed, and the network was analyzed through Cytoscape to explore GJDD potentially active compounds of anti-AFLD and their possible targets. Results GJDD might act onPIK3CA,PIK3R1,MAPK1,APPand other targets, and achieve its therapeutic purpose through multiple pathways such as inflammation-related signaling pathways, hormone-related pathways, and apoptosis-related signaling pathways. Conclusion Through network pharmacology, this study confirms the effectiveness of GJDD in the treatment of AFLD, and provides important guidance for improving the occurrence of AFLD and the research on the intervention mechanism of GJDD.

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Objective To investigate the effects of dexmedetomidine on inflammatory factors and endoplasmic reticulum stress in myocardial ischemia reperfusion induced brain injury. Methods Twenty-four SPF-grade healthy male SD rats, weighing(200～220)g and aged(6～8) weeks, were divided into three groups(n=8) by random number table method: sham operation group(S group), myocardial ischemia reperfusion group(IR group) and myocardial ischemia/reperfusion+Dex group(IR+Dex group). After the rats were adapted to the feeding environment, the myocardial ischemia reperfusion injury model was established by ligating the anterior descending branch of the left coronary artery for 30 min and reperfusion for 120 min. At the beginning of reperfusion, IR+Dex group was given 25 μg/kg dexmedetomidine, S group and IR group were injected with equal volume normal saline. Rats were sacrificed by decapitation and brain tissue was taken and the changes of hippocampal cell structure of rats stained by HE were observed under light microscope. Serum inflammatory factors IL-6, IL-8 and IL-10 were detected by ELISA. The expressions of Chop, Bip, p-eif-2α and p-perk in rat hippocampal tissues were determined by Western blot. Results Compared with the S group, the IR group and the IR+Dex group showed aggravation of brain lesions, increased expression of inflammatory cytokines IL-6 and IL-8(P<0.05), and decreased expression of IL-10(P<0.05). Hippocampal Chop, Bip, p-eif-2α and p-perk proteins were up-regulated(P<0.05). Compared with IR group, IR+Dex group showed reduced pathological injury, decreased expression of IL-6 and IL-8(P<0.05), increased expression of IL-10(P<0.05), and down-regulated expressions of Chop, Bip, p-eif-2α and p-perk in hippocampal tissues(P<0.05). Conclusion Dexmedetomidine preconditioning can reduce the brain injury caused by myocardial ischemia reperfusion, and its mechanism may be related to the inhibition of systemic inflammatory response and endoplasmic reticulum stress.

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Objective To investigate the influencing factors of the diffusion and utilization of technology for liver cancer screening among clinicians based on the technology acceptance model. Methods A multi-stage sampling method was applied to select the respondents. The des-γ-carboxy prothrombin(DCP) detection technology was taken as an example to conduct a structured questionnaire survey, and structural equation modeling was used for data analysis. Results Perceived ease of use positively affected perceived usefulness(β=0.899, P<0.001) and usage attitude(β=0.223, P<0.05); perceived usefulness positively affected usage attitude(β=0.652, P<0. 001) and behavioral intentions （β = 0. 413,P<0. 001）; usage attitude positively affected behavioral intentions（β = 0. 511,P<0. 001）; behavioral intention positively affected the behavior of using DCP （ β = 0. 237,P<0. 01）. There was a partial mediating effect between perceived ease of use and usage attitude, and a partial mediating effect between perceived usefulness and behavioral intention.Conclusion Usage attitudes are important factors influencing the diffusion of DCP detection technologies, and usage attitudes are determined by both perceived usefulness and perceived ease of use. It is recommended that technology manufacture and utilization organizations should focus on technology performance, allocate technical advisers for promoting new technologies, and reduce barriers to their use.

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Objective To investigate the roles of transient receptor potentia1 vanilloid 1(TRPV 1) and oxytocin receptor(OTR) in the mechanism of dysmenorrhea in adenomyosis. Methods The ectopic endometrium(EC) and the homologous eutopic endometrium(EU) were selected from 60 patients with adenomyosis surgery, and the control endometrium(CE) of patients without endometriosis was used as control. Streptavidin-Peroxidase immunohistochemistry staining(SP) was used to detect the localization of TRPV 1 and OTR in the tissues, and the expression of TRPV 1 and OTR was detected by Western blot. The degree of dysmenorrhea was scored by visual analogue scale/score(VAS), and its correlation with the TRPV 1 and OTR was analyzed. Results The expression of TRPV 1 and OTR in EC was higher than that in EU and CE(P<0.05), but there was no statistically significant difference between EU and CE. In EC, the expression of TRPV 1 and OTR in the severe dysmenorrhea group was higher than that in the mild and moderate groups(P<0.05), but there was no statistically significant difference between the mild dysmenorrhea group and the moderate group. The expression of TRPV 1 and OTR was positively correlated with the severity of dysmenorrhea(rs=0.280,P<0.05;rs=0.318,P<0.05); the expression of TRPV 1 and OTR was positively correlated(rs=0.287,P<0.05). Conclusion TRPV 1 and OTR may play a synergistic role in the pathogenesis of dysmenorrhea in patients with adenomyosis, which are important predictors of dysmenorrhea severity and potential therapeutic targets.

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Objective To investigate the relationship between vitamin D receptor(VDR) gene polymorphisms and the clinical prognosis of acute pancreatitis(AP), and to provide a genetic basis for early identification of critically ill patients.Methods A total of fourteen single nucleotide polymorphisms(SNPs) on the VDR gene were detected in 508 AP patients by using improved ligase detection reaction(imLDR) technology. Unconditional Logistic regression analysis was used to explore the association of VDR gene polymorphisms with outcome( sepsis/severe AP/death) of AP patients after adjusting for age, sex, body mass index(BMI), smoking and drinking status and APACHE II score under different genetic models.Results Rs12721375 GA/AA genotype had a lower risk of sepsis than GG(P= 0. 02) and the A allele had a lower risk of sepsis than G(P= 0. 009). Rs2853559 GA and GA/AA had higher risks of sepsis than GG(P= 0. 022 and 0. 026 respectively). Rs11168287 AA had a higher risk of severe AP than GG and GG/GA(P= 0. 030 and 0. 022 respectively). Rs2853559 AA genotype had a higher risk of severe AP than GG and GG/GA(P= 0. 022 and 0. 021 respectively). The risk of death of rs11168283 CT/TT genotype was lower than that of CC(P= 0. 046).Conclusion VDR gene polymorphisms are related to the clinical outcome of AP patients in Chinese Han population. VDR gene is involved in the progression of AP.

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Objective To investigate the predictive value of platelet volume distribution width(PDW), mean platelet volume(MPV), and D-dimer(D-D) on early shunt dysfunction in patients with decompensated cirrhosis treated with transjugular intrahepatic portosystemic shunt(TIPS). Methods A total of 28 patients with decompensated cirrhosis who developed shunt dysfunction within 6 months after TIPS were selected as the case group, and a 1 ∶2 matched control study was conducted. 56 patients matched by age(±2) and gender who did not develop shunt dysfunction within 6 months after TIPS were selected as the control group. Spss23.00 software was used to conduct univariate analysis to obtain statistically significant variables, and then conditional Logistic regression analysis was conducted with paired design, withP<0.05 being statistically significant. Results Patients with a history of splenectomy, portal vein thrombosis, and those with poor liver function grade were more likely to have functional dysfunction after TIPS. Platelet count(PLT), platelet volume distribution width(PDW), mean platelet volume(MPV), D-dimer(D-D) and Fibrinogen monomer(FDPI) had statistically significant differences between the case group and the control group. The values of D-D、PDW、MPV and FDPI in the case group were higher than those in the control group, while the value of PLT in the case group was lower than that in the control group. TheORvalues of PDW, MPV and D-D were 2.164, 3.826 and 1.382, respectively. ROC analysis results showed that the areas under PDW, MPV and D-D curves were 0.746, 0.773 and 0.690, respectively. Conclusion Compared with ultrasound, D-D, PLT and PDW could predict shunt dysfunction earlier after TIPS. Patients with normal shunt function indicated by color Doppler ultrasonography in postoperative follow-up of TIPS should be closely observed for indicators such as D-D, PLT and PDW, which is of important significance for clinical indication of shunt dysfunction in TIPS.

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Objective To investigate the effects of circulating tumor cells(CTCs) on the survival of different chemoradiotherapy modes for locally advanced esophageal squamous cell carcinoma(ESCC). Methods A total of 124 patients with ESCC undergoing CTCs examination were included before concurrent chemoradiotherapy(CRT), and these patients were divided into two groups(i.e., IC +CRT group and CRT group) according to whether they received induction chemotherapy(IC). The effects of CTCs on the survival between the two groups were compared. Results CTCs were related to T, N, stage, recurrence after treatment and distant metastasis. The objective remission rates(ORR) of IC+CRT group and CRT group were 72.6% and 58.1%, respectively(P=0.089). In the CTCs(+) subgroup, the ORR in the IC+CRT group was higher than that in the CRT group(P=0.046), but there was no significant difference between the two groups in the CTCs(-) subgroup(P=0.693). The median survival time(MST) of IC+CRT group and CRT group were 23 months and 15 months, respectively(P= 0.021). In the CTCs(+) subgroup, MST in the IC+CRT group was higher than that in the CRT group(P=0.008), but there was no difference between the two groups in the CTCs(-) subgroup(P=0.286). Cox regression analysis showed that tumor stage and CTCs were risk factors of overall survival(OS), while the mode of chemoradiotherapy was a protective factor for OS. Conclusion CTCs index has an influence on the survival between the two chemoradiotherapy therapies, which may have some reference values for the selection of them.

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Objective To analyze the correlation between Ki-67 expression and EGFR mutations in lung adenocarcinoma and reveal their prognostic roles. Methods This study retrospectively screened lung adenocarcinoma patients who underwent surgical treatment between 2014 and 2020 in our department. Clinicopathological characteristics, Ki-67 expression and EGFR mutations were collected. The chi-square, Student's t-test and ANOVA were used for the comparison of Ki-67 expression and EGFR mutations among the groups. The Spearman's rho was adopted to evaluate the correlation between Ki-67 expression and EGFR mutations. Finally, the Log-rank test was used to reveal the prognostic roles of Ki-67 expression and EGFR mutations in lung adenocarcinoma. Results A total of 673 lung adenocarcinoma samples were enrolled in this study. The mean expression of Ki-67 was 21.37±20.43 [Median: 15(6～30)]. Among these subjects, 462 samples harbored EGFR mutations(68.65%). The expression of Ki-67 was much higher in males and smokers, and was positively correlated with tumor size and lymph node metastasis. The frequency of EGFR mutations was higher in females and non-smokers, and was negatively correlated with tumor size and lymph node metastasis. Samples with EGFR mutations had a lower Ki-67 expression level than those without EGFR mutations(18.82±17.75vs26.97±24.45,P<0.001). Consistently, the frequency of EGFR mutations in samples with a lower expression level of Ki-67 was significantly higher than that in patients with a higher Ki-67 expression(74.1%vs57.0%,P<0.001). The Spearman's rho analysis indicated that the rho was-0.129(P<0.001) between Ki-67 expression and EGFR mutations. Survival analysis suggested that a higher Ki-67 expression and EGFR wild type were significantly associated with a poorer prognosis of lung adenocarcinoma(P<0.05). The combined analysis of Ki-67 expression and EGFR mutations indicated that EGFR wild type patients with Ki-67>10 had a poorer prognosis than subjects with Ki-67 ≤10 and EGFR mutations. What's more, the HR value was 4.46(95%CI: 1.91～10.73,P<0.001). Conclusion Ki-67 expression was significantly negatively correlated with EGFR mutations in lung adenocarcinoma. Ki-67 expression and EGFR mutations might have a combined effect on the prognosis of lung adenocarcinoma.

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Objective To analyze the risk factors for endophthalmitis requiring evisceration or enucleation. Methods The charts of 121 eyes of 121 inpatients with endophthalmitis were retrospectively reviewed, and the group that required evisceration or enucleation(24 patients) with those that received salvaging therapies(97 patients)were compared. Age, sex, medication history, past medical history, clinical manifestation, Leukocyte counts and treatment progression were retrospectively analyzed.Results Twenty four eyes(19. 8%)underwent enucleation or evisceration. The proportion of corneal ulcerative endophthalmitis( 33. 3%) and endogenous endophthalmitis(25. 0%) in evisceration or enucleation group was greater than that in the salvaging group(1. 0%, 4. 1%)(P<0. 001). The group of eviscerated or enucleated eyes was older(P<0. 05], had poorer initial visual acuity [(2. 9± 0. 2) LogMARvs(2. 3 ± 0. 5) LogMAR,P<0. 001], had longer duration before intervention(15. 8 dvs4. 6 d,P<0. 05), and had more Leukocyte counts [(12. 8 ± 5. 6) × 109/Lvs(9. 1 ± 3. 3) × 109/L,P<0. 005].With Logistic regression analysis, corneal ulcer, endogenous endophthalmitis, initial vision, leukocyte counts, duration before intervention were the risk factor for evisceration or enucleation(OR= 343. 283,OR= 22. 608,OR=1 920. 384,OR= 1. 341,OR= 1. 167).Conclusion The most common cause of evisceration or enucleation caused by infectious endophthalmitis are infections from corneal ulcer and from endogenous source. The risk factors for endophthalmitis requiring evisceration or enucleation would be considered to be corneal ulcer endophthalmitis,endogenous endophthalmitis, initial vision, leukocyte counts, and duration before intervention.

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Objective To investigate the metabolic changes of early hepatocellular carcinoma in patients with cirrhosis caused by viral hepatitis and its relationship with aging and enzyme activity. Methods According to the diagnosis results, a total of 140 patients were divided into liver cirrhosis group(LC group),hepatocellular carcinoma with liver cirrhosis group(CLH group),early hepatocellular carcinoma group(HCC group) and control group, with 35 cases in each group.The proton magnetic resonance spectroscopy(1H-MRS) was used to measure liver cell metabolite levels, and the generalized estimating equation was used to analyze potential risk factors for changes in metabolite levels. Results Serum alkaline phosphatase(ALP) levels in the LC group, serum aspartate aminotransferase(AST),lactate dehydrogenase(LDH),ALP,and glucose levels in the CLH group were higher than those in the control group(P<0.05),and the serum AST and glucose levels in the CLH group were higher than those in the LC group(P<0.05).The levels of lactic acid and triglycerides(Lac+TG)(1.3 ppm) in LC group and CLH group were lower than those in control group and HCC group(P<0.05).The level of choline(Cho)(3.2 ppm) in the CLH group was higher than that in the control group(P<0.05),and the level of Cho(3.2 ppm) in the HCC group was higher than that in the control, LC and CLH groups(P<0.05).The levels of triglycerides(TG)(0.9 ppm) and TG(2.1 ppm) in the LC,CLH and HCC groups were lower than those in the control group(P<0.05).In the LC,CLH and HCC groups, the Lac+TG(1.3 ppm) level was positively correlated with age, LDH,and the Cho(3.2 ppm) level was positively correlated with ALP(r=0.340,P=0.002).The related risk factors for changes in Lac+TG and Cho metabolism were age 60-80 years.The results of interaction analysis showed that Lac+TG levels were related to HCC in men or women aged 40 to 50,and LC,CLH,HCC in men or women aged 60 to 80(P<0.05).The Cho level was related to HCC in men or women aged 60 to 80(P<0.05). Conclusion The high levels of Lac+TG and Cho may be related to the metabolic changes of early hepatocellular carcinoma in patients with cirrhosis caused by viral hepatitis.In addition, the level of Lac+TG in hepatocellular carcinoma is positively correlated with older age and LDH.

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Objective To investigate the changes of intestinal flora in patients with rheumatoid arthritis(RA)before and after treatment with technetium[99 Tc] methylenediphosphonate injection(99 Tc-MDP).Methods Thirty-two patients with RA were collected the fresh fecal specimens before and after they treated with99 Tc-MDP. The genome DNA of fecal specimens was extracted and the V3-V4 regions of 16 S rRNA were sequenced by Illumina Miseq platform. The sequencing results were analyzed by bioinformatics methodology.Results The Chao, observed species, Shannon and Simpson index between the two groups in Alpha diversity analysis had no statistical difference(P>0. 05), but the value in post-treatment group were increased compared with the pre-treatment group. Compared with the pre-treatment of RA, there was no statistical difference in the higher proportion relative abundance on Phylum level of the intestinal microbes of RA patients, and the relative abundance of Tenericutes decreased(P<0. 05). At the genus level, the relative abundance of Ruminococcaceae,Butyricicoccus, Christensenellaceae＿R-7＿group,Holdemaniadecreased after treatment(P<0. 05). And the relative abundances of Pasteurella,Lachnoanaerobaculum and Stomatobaculum increased(P<0. 05).Conclusion The abundance and species of gut microbiota in RA patients have some changes after treatment with 99 Tc-MDP, and the diversity increases after treatment.

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Objective To explore the role and its clinical significance of P300 in biphasic differentiation and epithelial mesenchymal transition(EMT) process in synovial sarcoma(SS) by detecting the expression of histone acetyltransferase P300 and EMT related molecules. Methods 40 cases of SS paraffin embedded tissue samples were collected, and the SYT-SSX fusion gene subtype was detected by RT-PCR. Immunohistochemistry was used to detect the expression of P300 and EMT-related molecules. Results (1)The positivity of SYT-SSX fusion gene was 92.5%(37/40), including 90%(27/30) of BSS(66.7% SYT-SSX1, 33.3% SYT-SSX2) and 100%(10/10) of MFSS(SYT-SSX1 80%, SYT-SSX2 20%), there was no correlation between histological subtype and fusion gene subtype in SS.(2)The rate of positive expression of P300 was 95%(38/40), including 93.3%(28/30) of BSS and 100%(10/10) of MFSS, and there was no significance difference between the expression P300 and histological subtype.(3)The expression of P300 was not statistically correlated with clinicopathological parameters of SS, however, COX regression analysis showed that tumour metastasis(P=0.019) and TNM stage(Ⅲ～Ⅳ)(P=0.003) were independent risk factors for overall survival of patient.(4)The expression of P300 was significantly related with EMT-associated protein β-catenin in the BSS(P=0.027) and Slug in the MFSS(P=0.048), which suggested P300 was closely related to EMT. Conclusion P300 may be involved in the biphasic differentiation and the EMT process of SS, suggesting that P300 plays a certain role in SS invasion and migration.

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To investigate the curative effects of modified submucosal tunnel endoscopic resection(STER) and endoscopic submucosal resection(ESE) in the treatment of paracardial submucosal tumors. Eighty-four patients with paracardial submucosal tumors diagnosed through digestive endoscopy and endoscopic ultrasonography signed informed consent forms, and they were randomly divided into observation group(n=42) and control group(n=42) with the help of the table of random numbers. Patients in the control group received ESE treatment. Patients in the observation group received modified STER surgery.The operation time, average hospitalization time and treatment cost of patients in STER group were(61.32±32.01) min,(8.11±2.42) d and(21.7±3.4) thousand Chinese Yuan respectively, which were better than those in ESE group(87.63±34.09) min,(10.05±2.84) d and(25.9±3.9) thousand Chinese Yuan. The difference was statistically significant(P<0.05). The average number of titanium clips used in the observation group was(5.00±1.37), and in the control group the average number was(4.68±1.25). The difference was not statistically significant. In the STER group, there were 2 cases of intraoperative perforation and 1 case of delayed bleeding. In the ESE group, there were 4 cases of intraoperative perforation and 3 cases of intraoperative uncontrollable bleeding. The incidence of postoperative complications in the STER group was lower than that in the ESE group. The postoperative pathological examination revealed that in both groups the tumors were mostly stromal tumor and leiomyoma. A few of the patients were suffering from lipomas and schwannomas. There was no significant difference in terms of the pathological composition of the patients between the two groups.

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This prospective observational study included 361 benign and malignant breast nodules from 258 women who had underwent breast grayscale ultrasound and had been confirmed pathologically. A total of 396 image features of lesion areas in ultrasonic images were extracted. The radiomic signature was developed using least absolute shrinkage and selection operator algorithms after feature selection using the minimum redundancy maximum relevance method. Receiver operating characteristic curve(ROC)and calibration curve were used to test the performance of the model. The area under the ROC curve(AUC), accuracy, sensitivity, specificity, Youden index for the training cohort were 0.84,0.761,0.840,0.715,0.603. And the AUC, accuracy, sensitivity, specificity, Youden index for the validation cohort were 0.84,0.716, 0.823, 0.654, 0.536. The diagnostic results of data from the radiomics model were basically consistent with the actual situation. Radiomics based on grayscale ultrasound performs well in the differentiation of malignant from benign breast nodules which effectively avoids the subjective diagnosis, and has good clinical application value.

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Genetic diagnosis and etiological analysis were performed on a patient with hypoxic-ischemic encephalopathy at birth. MRI technology was used to examine the brain of the child. G-band karyotype analysis technology was used to analyze the karyotype of the child and her parents. Chromosomal microarray analysis(CMA) was used to analyze the entire genome of the child and her parents for chromosomal copy number variation(CNV) and to identify the small supernumerary marker chromosomes. The results of MRI supported the diagnosis of hypoxic-ischemic encephalopathy of the child and found the appearance of Dandy-Walker malformation. Karyotype analysis showed that the mother's karyotype was 46, XX, t(10; 13)(p11. 1; q11)[11]/46, XX[19]. The karyotype of the father was normal. The karyotype of the child was 47, XX, + mar. The CMA results showed that there was no CNVs above 200 kb in the parents. The CMA results of the child showed that the chromosome 10 was repeated in p15. 3 p11. 1, and the fragment size was 38. 39 Mb. In conclusion, this study found a rare small supernumerary marker chromosome(sSMC) on chromosome 10. Its genetic pattern and pathogenicity were analyzed. It is considered that sSMC(10) is the cause of the patient.