Objective To explore the effects of HPV16 E6 on genes and signaling pathways in cervical epithelial cells and to screen genes associated with oncogenic transformation.Methods HUCEC models infected with HPV16 E6 were constructed,and transcriptome sequencing was performed to screen for differentially expressed genes(DEGs),which were subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment to analyze the differential signaling pathways.RT-qPCR was used to validate major differentially down-regulated expressed genes.After predicting the major differentially expressed proteins by molecular docking analysis,the expression of major differential genes in HUCEC cell model was verified by RT-qPCR and Western blotting.In addition,RT-qPCR and Western blotting were used to further verify the expression of major differential genes in cervical cancer cell lines,SiHa and CaSki.Results A total of 55 genes with more than two-fold differential expression were screened.The results centering on down-regulated genes showed that the negatively regulated differential gene was mainly enriched in redox processes;KEGG enrichment analysis revealed that it was mainly associated with carbohydrate metabolism and cancer.RT-qPCR results showed that the down-regulated differential expression trends of the selected 10 genes were basically consistent with the sequencing results.Molecular docking analysis predicted an interaction between DHRS2 and HPV16 E6,and RT-qPCR and Western blotting confirmed that HPV16 E6 down-regulated DHRS2 mRNA(P＜0.01)and protein(P＜0.05)and ETV5 protein expression(P＜0.01).In SiHa and CaSki cells,compared with the control group,the mRNA and protein expression of DHRS2 was downregulated and positively correlated with the trend of P53 protein expression(P＜0.05).Conclusion HPV16 E6 can mediate oncogenic transformation of cervical cells and promote cervical carcinogenesis through downregulating DHRS2 expression.

Objective:This study aims to explore how technological innovation can promote high-quality development of hospital discipline construction.Methods:The study elucidated the connotation, significance, and current status of high-quality development in discipline construction. Taking the Orthopedic Department of a tertiary hospital in Beijing as an example, it analyzed the problems and deficiencies in hospital discipline construction in China. Additionally, specific suggestions were put forward on how technological innovation can facilitate high-quality development of hospital discipline construction in China.Results:Strengthening technological innovation capacity, actively exploring collaborative technological innovation, optimizing research platform construction, enhancing talent cultivation and recruitment, and strengthening awareness of translating clinical research findings into practice were important approaches to achieving high-quality development of hospital discipline construction. These measures provided solid support for the high-quality development of hospitals.Conclusions:By enhancing the vitality of technological innovation and promoting the integration and coordinated development of disciplinary construction and technological innovation, it can assist in the high-quality development of medical disciplines in our country. Furthermore, it can accelerate the advancement of high-level first-class disciplinary construction, serving as an inexhaustible driving force for the cohesive high-quality development of Chinese hospitals.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective:To explore combined detection of mad2 with anti-nuclear mitotic spindle apparatus antibody(MSA)and anti-centromere antibody(ACA)and their clinical value for the diagnosis of small cell lung cancer(SCLC).Methods:One hundred and twen-ty SCLC patients,110 non-small cell lung cancer(NSCLC)patients,and 115 pulmonary nodule(PN)patients were enrolled in this study. The expression of mad2 was analyzed by qt-PCR.MSA and ACA were detected by indirect immunofluorescence(IIF)staining.Results:mad2 was overexpressed in SCLC and NSCLC samples(P<0.05).There were significant differences between the results obtained for SCLC and NSCLC samples by qt-PCR(P<0.05).AUC in ROC curve for mad2 expression was 0.799 with an intermediate diagnostic value. In the correlative analysis,the odds ratio of MSA and ACA was 6.94 and 5.60,respectively.In the correlation analysis,Kappa value of mad2 with MSA was 0.49,and Kappa value of mad2 with ACA was 0.42.In the parallel analysis,the sensitivity and specificity was 83.31% and 79.34%,respectively,while the Youden Index was 0.62.Moreover,in the serial analysis,the sensitivity and specificity was 65.32% and 93.35%,respectively,and the Youden Index was 0.59.Conclusions:In comparison with the NSCLC and PN samples,mad2 was overexpressed in SCLC samples.Therefore,mad2 ought to play a critical role in the pathology of SCLC.The combined expression of mad2 with MSA and ACA may contribute to enhancing the sensitivity and specificity of detection;this expression may allow early diag-nosis and clinical diagnosis of SLCC and may be a promising treatment for SCLC.

Objective To evaluate the effects of aerobic exercise during dialysis on physical function and life quality among hemodialysis patients.Methods The randomized controlled trials on aerobic exercise during dialysis published in PubMed,Embase,Cochrane Library,WanFang data,China National Knowledge Infrastructure (CNKI) and VIP database were retrieved from setting up the database to 31 December 2017.The RevMan 5.1 was used in statistical analysis.Results A total of 13 documents were included consisting of 11 English articles and 2 Chinese articles.Meta analysis showed that the peak oxygen uptake,times of situp within one minute,the 6-minute walk distance and grip strength of hemodialysis patients in the group of aerobic exercise during dialysis all improved compared with those of control group (P ＜ 0.05) especially in the peak oxygen uptake in long term movement training (＞ 12 weeks).There was no statistical difference in blood pressure and life quality of patients between two groups (P ＞ 0.05).Conclusions Aerobic exercise during dialysis can significantly improve patients' physical function,however,has no significant effects on enhancing patients' life quality.

Objective To investigate the resistance rates of the Candida albicans strains isolated from patients with vulvovaginal candidiasis to 5 antifungal agents and examine the mechanism of azole resistance in these strains.Methods A total of 1 646 C.albicans strains were collected in Obstetrics and Gynecology Hospital of Fudan University from January to December 2015.The resistance rates of these isolates to five antifungal agents were analyzed.Azole-resistant (n=30),dose dependent sensitive (S-DD) (n=13),and susceptible isolates (n=10) were randomly selected from the microbiology laboratories of three obstetrics and gynecology hospitals in Shanghai.The expression levels of drug efflux pump related gene CDR1,CDR2,MDR1 and drug target enzyme gene ERG11 were analyzed by real-time fluorescence quantitative polymerase chain reaction (PCR).At the same time,the ERG11 and ERG3 genes were amplified by PCR and sequenced,and analyzed for resistance-related mutations.Results Of the 1 646 C.albicans strains,5.2％,3.2％,2.5％ and 2.1％ were resistant to itraconazole,voriconazole,fluconazole and 5-fluorocytosine,respectively.All isolates were sensitive to amphotericin B.The expression of ERG11 gene was significantly higher in S-DD group and azole-resistant group than in azole-sensitive group (P＜0.05).The expression of CDR1,CDR2 and MDR1 did not show significant difference among the three groups.There were 13 missense mutations in the ERG11 gene,of which T123I,P98S and Y286D amino acid substitutions were newly discovered.Both T123I and Y132H were identified in 26 resistant isolates,of which 16 gene mutation was detected in two pan-azole-resistant isolates.Conclusions The C.albicans strains isolated from vulvovaginal candidiasis showed higher resistance rates to azole antifumgal agents than that to 5-fluorocytosine and amphotericin B.Mutation and over-expression ofERG11 gene may be one of the prevalent molecular mechanisms underlying azole resistance in C.albicans.were pan-azole-resistant.In addition,the ERG3 heterozygous

Objective To investigate the distribution and molecular epidemiology of Candida strains isolated from vulvovaginal candidiasis in Shanghai,and conduct molecular phylogenetic analysis of the strains.Methods Candida pathogens were collected from the patients with vulvovaginal candidiasis during the period from August 2015 to February 2016 in Obstetrics and Gynecology Hospital of Fudan University,Shanghai First Maternity and Infant Hospital,and Intemational Peace Matemity and Child Health Hospital.All the strains were identified and statistically analyzed.ATB FUNGUS 3 kit was used to determine the minimum inhibitory concentration of antifungal agents against these strains in vitro.Molecular typing was conducted using multilocus sequence typing (MLST) method.Phylogenetic analysis was carried out by eBURST and MEGA 6 software.Results Of the 2 185 strains of Candida,1 988 were identified as Candida albicans,149 Candida glabrata,20 Candida tropicalis and 28 other Candida species.Overall,6.5％ of the Candida albicans strains were resistant to fluconazole.Twenty-six diploid sequence types (DSTs) were identified among the 93 strains of Candida albicans analyzed,including 50 fluconazole-susceptible strains with sporadic genotypes,but 43 fluconazole-resistant strains clustered as one clonal complex (CC 69) on the same branch (MLST Clade 1) of phylogenetic tree.Conclusions Candida albicans was the main pathogen of vulvovaginal candidiasis in the three obstetrics & gynecology hospitals in Shanghai,which showed slightly higher resistance to fluconazole.It is necessary to monitor the spread of fluconazole-resistant Candida albicans in these hospitals,especially clonal dissemination of CC 69 clone.

Objective To study the relationship of the plasma levels of miRNA-491-5p in Han population in Shaanxi Province and the changes of single nucleotide polymorphisms (SNP ) of the target gene matrix metalloproteinases-9 (MMP-9 ) of miRNA-4 9 1-5 p (has-miR-4 9 1-5 p ) with the incidence risk and prognosis of premature coronary artery disease (pCAD)through the case-control design.Methods In this study,we made a consecutive recruitment of 270 pCAD cases in the case group and 300 cases in the control group.Using the polymorphism method of polymerase chain reaction and restriction fragment length (PCR-RFLP),target gene MMP-9 of has-miR-491-5p and rs1056628 genotypes was detected to compare the association between the variant genotypes and pCAD.Results In the changes of rs1056628C-A polymorphisms,compared with that of CC genotypes (the incidence was 42%),the risks of having coronary heart disease in the individuals carrying CA and AA genotypes were 31%,the difference was statistically significant (P=0.045).The risks of developing coronary heart disease in the individuals carrying CA and AA genotypes were reduced more significantly in the population with low total cholesterol (TC),and low low-density lipoprotein cholesterol (LDL-C).Conclusion Target gene MMP-9 of has-miRNA-491-5p rs1056628C-A polymorphism is associated with the reduced incidence risk of pCAD,and carrying C alleles is an independent risk factor for pCAD.

Objective To explore the role and relationship of N-terminal pro-brain natriuretic peptide (NT-proBNP) and matrix metalloproteinase-9 (MMP-9 ) in risk stratification and prognosis assessment of non-ST elevation acute coronary syndrome (NSTE-ACS).Methods We recruited 114 patients with NSTE-ACS and classified them into three groups according to the GRACE risk stratification:high-risk,intermediate-risk and low-risk groups.Another 5 8 patients were recruited as controls.Arterial blood was collected before angiography for the measurement of serum NT-proBNP and MMP-9 .Gensini score was used to evaluate the degree of coronary artery stenosis.All the patients were followed up for 6 months and MACE was observed and recorded.Results ① The levels of lg NT-proBNP and MMP-9 significantly differed between the groups (P<0.05).② ROC curve analysis showed that lg NT-proBNP could predict MACE of NSTE-ACS;area under the curve was 0.795,the cutoff value was 2 .0 6 9 ,corresponding to the NT-proBNP value of 1 1 6 .5 6 ng/L.MMP-9 could predict MACE of NSTE-ACS;area under the curve was 0 .6 9 6 ,the cutoff value was 3 2 .4 9 ng/ml;both of the abnormal indexes could predict MACE with the sensitivity of 80.41%,specificity of 82.19%,and Youden’s index of 0.63.③ Cox regression analysis showed that abnormal MMP-9 and NT-proBNP levels were independently related to the incidence of MACE by the value of OR as 3.751.Conclusion MMP-9 and NT-proBNP may be used as serological indicators in risk stratification of NSTE-ACS. The combined use of NT-proBNP and MMP-9 increases the power of predicting MACE.

Objective To understand the management status quo of migrant workers with chronic hepatitis B (CHB) to ex‐plore the management countermeasures and improve the survival quality for tamping the foundation of the healthy project .Methods Totally 300 migrant workers with CHB were performed the living quality evaluation and investigation on the service needs ,com‐pliance ,economic condition ,categories and proportion of reimbursement by adopting the supplementary revision of SF‐36 living quality scale and general information questionnaire ;the influencing factors of their living quality were performed the univariate anal‐ysis and multivariate stepwise regression analysis .Results The statistical analysis found that whether convenient for outside visit‐ing hospital ,categories and proportion of reimbursement ,whether normalized antiviral therapy ,whether conducting examination and follow up at regular intervals and liver disease specific symptoms were the influencing factors of living quality in the migrant work‐ers with CHB(P<0 .05);the living quality in the patients with outside convenient visiting hospital ,high reimbursement proportion , normalized antiviral therapy and examination and follow up at regular intervals was significantly higher than that in the patients with inconvenient outside visiting hospital ,low reimbursement proportion ,non‐normalized anti‐viral therapy and examination and follow up without regular intervals(P<0 .05);the liver disease specific symptom score showed the positive correlation trend with the living quality score (B=7 .657 ,SD=2 .650 ,t=2 .889 ,P=0 .004) .Conclusion It is necessary to improve the patient′s medical needs ,reimbursement type and proportion ,increase the compliance of patient′s normalized examination and follow‐up at regular in‐tervals and standard antiviral treatment ,thus to realize the standardized examination and treatment in CHB patients ,prevent or de‐lay the disease progression ,avoid liver cirrhosis and decompensated hepatopathy ,reduce the occurrence of HCC ,improve the quality of life and prolong the survival period .