Objective To investigate the relationship between single nucleotide polymorphism (SNP) of BARD 1 gene and BRCA1 gene in epithelial ovarian cancer (EOC).Methods Nineteen EOC patients with BRCA1 gene mutation and 50 EOC cases without BRCA1 gene mutation between January 2016 and October 2016 were collected,and all EOC were diagnosed by pathological method.BARD1 gene variants were detected by next generation sequencing (NGS).The SNP of BARD1 gene was analyzed by Pearson linear correlation.Logistic regression analysis was used to research the clinicopathologic features and BRCA1 gene mutation associated with BARD1 gene SNP.Pearson's chi-square test was used to analyze the association between BARD1 gene Val507Met,Arg378Ser and Pro24Ser with different clinicopathologic features and BRCA1 gene mutation risk.Results (1) Eight BARD1 gene variants were found in 69 ovarian cancer patients,in which Val507Met,Arg378Ser and Pro24Ser were common variants,and the rate of mutation were all 54％ (37/69).(2) There was a significant linear correlation among Val507Met,Arg378Ser and Pro24Ser (all P＜0.01).(3) Obvious differences were found in Val507Met,Arg378Ser and Pro24Ser of BARD1 gene between BRCA1+ and BRCA1 (all P＜0.05).(4) No differences were found between BARD1 gene Val507Met,Arg378Ser and Pro24Ser and the clinicopathologic features (all P＞0.05),while obvious differences were found in BRCA1 gene mutation compared to the controls group.The risk of BRCA1 mutation in Val507Met and Arg378Ser were more evident in subjects with negative family history,positive menopause history,negative tubal ligation,onset age (≤60 years old) and sensitivity to platinum-based chemotherapy in EOC (all P＜0.05),while Pro24Ser was only more evident in positive menopause history of EOC (P＜0.05).Conclusions BARD1 Val507Met,Arg378Ser and Pro24Ser are the common genotypes,which are associated with BRCA1 mutation in EOC.The family history,menopause history,tubal ligation,onset age and sensitivity to platinum-based chemotherapy have effects on BARD1 SNP in the risk of BRCA1 gene mutation.

Objective To investigate the mutations of BRCA genes in sporadic high grade serous ovarian cancer (HGSOC) and study its clinical significance. Methods Sixty-eight patients between January 2015 and January 2016 from the Affiliated Cancer Hospital of Zhengzhou University were collected who were based on pathological diagnosis of ovarian cancer and had no reported family history, and all patients firstly hospitalized were untreated in other hospitals before. (1)The BRCA genes were detected by next-generation sequencing (NGS) method. (2)The serum tumor markers included carcinoembryonic antigen (CEA), CA125, CA199, and human epididymis protein 4 (HE4) were detected by the chemiluminescence methods, and their correlation was analyzed by Pearson linear correlation. Descriptive statistics and comparisons were performed using two-tailed t-tests, Pearson′s chi square test, Fisher′s exact tests or logistic regression analysis as appropriate to research the clinicopathologic features associated with BRCA mutations, including age, International Federation of Gynecology and Obstetrics(FIGO)stage, platinum-based chemotherapy sensitivity, distant metastases, serum tumor markers (STM). Results (1) Fifteen cases (22%, 15/68) BRCA mutations were identified (BRCA1: 11 cases; BRCA2: 4 cases), and four novel mutations were observed. (2) The levels of CEA, CA199, and HE4 were lower in BRCA mutations compared to that in control group, while no significant differences were found (P>0.05), but the level of CA125 was much higher in BRCA mutation group than that in controls (t=-3.536,P=0.003). Further linear regression analysis found that there was a significant linear correlation between CA125 and HE4 group (r=0.494,P<0.01), and the same correlation as CEA and CA199 group (r=0.897,P<0.01). (3) Single factor analysis showed that no significant differences were observed in onset age, FIGO stage, distant metastasis, and STM between BRCA+and BRCA- group (P>0.05), while significant differences were found in CA125 and sensitivity to platinum-based chemotherapy between the patients with BRCA mutation and wild type (P<0.05). The multiple factors analysis showed that the high level of CA125 was a independent risk factor of BRCA mutations in sporadic HGSOC (P=0.007). Conclusion The combination of CA125 with BRCA have great clinical significance, the mutation of BRCA gene could guild the clinical chemotherapy regiments.

Objective: To perform an epidemiological survey of the first case with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Pinghu City of Jiaxing City, Zhejiang Province on March 13, 2022, so as to provide insights into the management of coronavirus disease (COVID-19) epidemics. Methods: According to the requirements of the Protocol on Prevention and Control of COVID-19 (8th Edition), epidemiological investigations were performed among 39 cases with SARS-CoV-2 infections in Pinghu City from March 13 to 20, 2022. Cases' demographics, clinical symptoms, history of immunization and exposure were collected, and close contacts were identified. Pharyngeal swabs were sampled from infected cases for detection of SARS-CoV-2 nucleic acid and whole-genome sequencing, and the source of infection and transmission route were investigated. Results: The index case for this COVID-19 epidemic was an imported case from Shanghai Municipality, who infected 6 persons via aerosol transmission when playing in the badminton venue of Pinghu National Fitness Center on March 9; subsequently, one of these infected cases infected another 18 persons when playing in the badminton venue of Jiadian Village Resident's Fitness Center in Zhapu Township on March 12. Sixteen confirmed cases were reported, and all cases were mild; another 23 asymptomatic cases were diagnosed, with no death reported. This epidemic occurred from March 11 to 20, with 3 generations of spread and a median incubation period of 3 days. The SARS-CoV-2 infected cases had a median age of 33.5 (interquartile range, 12.0) years and included 36 cases with a history of COVID-19 vaccination. There were 16 cases with fever, cough, runny nose and sore throat, and 13 cases with imaging features of pneumonia. The effective reproductive number (Rt) of the COVID-19 epidemic was 7.73 at early stage, and was less than 1 since March 21. Whole-genome sequencing identified Omicron BA.2 variant among 33 cases, which had high homology with the index cases. Conclusion This epidemic was a cluster of COVID-19 caused by imported Omicron BA.2 variant infection from Shanghai Municipality, and the COVID-19 transmission was mainly caused by indoor aerosols.

Objective To investigate the role and mechanism of zinc finger protein 281(ZNF281)in high glucose(HG)-induced epithelial-mesenchymal transition(EMT)and extracellular matrix(ECM)synthesis in renal tubular epithelial cells(RTECs).Methods HG induced RTECs were used to construct a diabetic kidney disease cell model,and cells were divided into the control group,the HG group and the mannitol group.Cell proliferation viability was detected by CCK-8.The expression of ZNF281 was knocked down in HG-treated RTECs using small interfering RNA(siRNA).HG-induced RTECs after knockdown of ZNF281 were divided into the control group,the HG group,the HG+ZNF281 siRNA group and the HG+ZNF281 vector group.Adenosine monophosphate-activated protein kinase(AMPK)was activated using AMPK agonist,acadexin(AICAR),and then cells were divided into the control group,the HG group,the HG+AICAR group and the HG+dimethyl sulfoxide group.The expression levels of ZNF281,EMT and ECM synthesis-related indexes were detected by qPCR and Western blot assay.Results Compared with the control group,the protein and mRNA expression levels of vimentin,α-smooth muscle actin(α-SMA),fibronectin(FN)and collagen Ⅰ(Col Ⅰ)were significantly higher,and the expression of E-cadherin was significantly lower in the HG group.Compared with the HG group,the protein and mRNA expression levels of EMT and ECM synthesis-related indexes were significantly changed in the HG+ZNF281 siRNA group and the HG+AICAR group.The protein and mRNA expression levels of ZNF281 were significantly reduced in the HG+AICAR group compared with the HG group.In cells co-treated with AICAR and transfected with ZNF281 plasmid,the expression levels of vimentin,α-SMA,FN and Col Ⅰ were significantly higher in the AICAR+ZNF281 group,and E-cadherin was significantly lower compared with that of the vector group.Conclusion AMPK inhibits EMT and ECM synthesis in HG-treated RTECs by negatively regulating the expression level of ZNF281.