1.Role of tumor necrosis factor-α in coronavirus disease 2019-associated kidney injury
Roshan PANDIT ; Junyao LU ; Liheng HE ; Yujie BAO ; Ping JI ; Yingying CHEN ; Jie XU ; Ying WANG
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(1):1-10
Objective·To identify relevant biomarkers for patients with coronavirus disease 2019-associated kidney injury(COVID-19-associated KI)and explore the mechanisms underlying the involvement of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)proteins in infection-related KI by affecting the interactions between renal cells and macrophages.Methods·A retrospective analysis was conducted on the clinical characteristics of COVID-19 patients with KI treated in Shanghai Ninth,People's,hospital from December 2022 to February 2023.Serum levels of inflammatory factors and chemokines were measured by using enzyme-linked immunosorbent assay(ELISA).In vitro,human macrophage cell line THP-1 cells were stimulated with recombinant S1 subunit protein derived from SARS-CoV-2 spike protein.The cells and culture supernatants were collected to detect the levels of inflammatory factors and chemokines by using quantitative real-time PCR(qRT-PCR)and ELISA.Conditioned medium was prepared from the cell culture supernatants of S1-stimulated THP-1 cells and used to stimulate human renal epithelial cells(HK-2)in vitro to assess cytokine secretion.Antibody blocking experiments were performed to analyze the effects of the conditioned medium on the production of cytokines in HK-2 cells.Results·Among 39 patients with COVID-19,8(20.50%)had creatinine levels above the reference interval,which indicated the occurrence of KI.The levels of peripheral tumor necrosis factor-α(TNF-α)in the COVID-19 patient with KI group[(18.33±8.20)pg/mL]were significantly higher than those in the non-KI group[(11.88±6.50)pg/mL](P=0.015).In vitro assay has shown that S1-spike protein stimulation promoted the level of gene transcription and production of TNF-α,interleukin-1β(IL-1β)and chemokine C-X-C motif ligand 10(CXCL10)in THP-1 macrophage cells(P<0.001).Furthermore,the conditioned medium from S1-stimulated THP-1 cells promoted the secretion of TNF-α,IL-1β and CXCL10 by HK-2 cells(P=0.005).When anti-TNF-α antibody(Infliximab)was used to block TNF-α in the culture supernatants from S1-stimulated THP-1 cells,the secretion level of TNF-α by HK-2 cells decreased dramatically(P<0.001).Conclusion·TNF-α levels increase significantly in COVID-19 patients with KI,implying the significance of TNF-α in the occurrence of COVID-19-associated KI.In vitro experiments confirm that the S1 protein induces TNF-α secretion from THP-1 cells,leading to increased inflammatory responses in renal cells,which may contribute to the development of COVID-19-associated KI.Therefore,targeting TNF-α may become an alternative strategy to reduce the occurrence of COVID-19-associated KI.
2.Role of tumor necrosis factor-α in coronavirus disease 2019-associated kidney injury
Roshan PANDIT ; Junyao LU ; Liheng HE ; Yujie BAO ; Ping JI ; Yingying CHEN ; Jie XU ; Ying WANG
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(1):1-10
Objective·To identify relevant biomarkers for patients with coronavirus disease 2019-associated kidney injury(COVID-19-associated KI)and explore the mechanisms underlying the involvement of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)proteins in infection-related KI by affecting the interactions between renal cells and macrophages.Methods·A retrospective analysis was conducted on the clinical characteristics of COVID-19 patients with KI treated in Shanghai Ninth,People's,hospital from December 2022 to February 2023.Serum levels of inflammatory factors and chemokines were measured by using enzyme-linked immunosorbent assay(ELISA).In vitro,human macrophage cell line THP-1 cells were stimulated with recombinant S1 subunit protein derived from SARS-CoV-2 spike protein.The cells and culture supernatants were collected to detect the levels of inflammatory factors and chemokines by using quantitative real-time PCR(qRT-PCR)and ELISA.Conditioned medium was prepared from the cell culture supernatants of S1-stimulated THP-1 cells and used to stimulate human renal epithelial cells(HK-2)in vitro to assess cytokine secretion.Antibody blocking experiments were performed to analyze the effects of the conditioned medium on the production of cytokines in HK-2 cells.Results·Among 39 patients with COVID-19,8(20.50%)had creatinine levels above the reference interval,which indicated the occurrence of KI.The levels of peripheral tumor necrosis factor-α(TNF-α)in the COVID-19 patient with KI group[(18.33±8.20)pg/mL]were significantly higher than those in the non-KI group[(11.88±6.50)pg/mL](P=0.015).In vitro assay has shown that S1-spike protein stimulation promoted the level of gene transcription and production of TNF-α,interleukin-1β(IL-1β)and chemokine C-X-C motif ligand 10(CXCL10)in THP-1 macrophage cells(P<0.001).Furthermore,the conditioned medium from S1-stimulated THP-1 cells promoted the secretion of TNF-α,IL-1β and CXCL10 by HK-2 cells(P=0.005).When anti-TNF-α antibody(Infliximab)was used to block TNF-α in the culture supernatants from S1-stimulated THP-1 cells,the secretion level of TNF-α by HK-2 cells decreased dramatically(P<0.001).Conclusion·TNF-α levels increase significantly in COVID-19 patients with KI,implying the significance of TNF-α in the occurrence of COVID-19-associated KI.In vitro experiments confirm that the S1 protein induces TNF-α secretion from THP-1 cells,leading to increased inflammatory responses in renal cells,which may contribute to the development of COVID-19-associated KI.Therefore,targeting TNF-α may become an alternative strategy to reduce the occurrence of COVID-19-associated KI.
3.Genomic Shift in Population Dynamics of mcr-1-positive Escherichia coli in Human Carriage
Shen YINGBO ; Zhang RONG ; Shao DONGYAN ; Yang LU ; Lu JIAYUE ; Liu CONGCONG ; Wang XUEYANG ; Jiang JUNYAO ; Wang BOXUAN ; Wu CONGMING ; Parkhill JULIAN ; Wang YANG ; R.Walsh TIMOTHY ; F.Gao GEORGE ; Shen ZHANGQI
Genomics, Proteomics & Bioinformatics 2022;(6):1168-1179
Emergence of the colistin resistance gene,mcr-1,has attracted worldwide attention.Despite the prevalence of mcr-1-positive Escherichia coli(MCRPEC)strains in human carriage showing a significant decrease between 2016 and 2019,genetic differences in MCRPEC strains remain largely unknown.We therefore conducted a comparative genomic study on MCRPEC strains from fecal samples of healthy human subjects in 2016 and 2019.We identified three major differences in MCRPEC strains between these two time points.First,the insertion sequenceISApll1 was often deleted and the percentage of mcr-1-carrying IncI2 plasmids was increased in MCRPEC strains in 2019.Second,the antibiotic resistance genes(ARGs),aac(3)-Ⅳa and blaCTX-M-1,emerged and coexisted with mcr-1 in 2019.Third,MCRPEC strains in 2019 contained more viru-lence genes,resulting in an increased proportion of extraintestinal pathogenic E.coli(ExPEC)strains(36.1%)in MCRPEC strains in 2019 compared to that in 2016(10.5%),implying that these strains could occupy intestinal ecological niches by competing with other commensal bacteria.Our results suggest that despite the significant reduction in the prevalence of MCRPEC strains in humans from 2016 to 2019,MCRPEC exhibits increased resistance to other clinically important ARGs and contains more virulence genes,which may pose a potential public health threat.
4.Impact Factors on Nosocomial Respiratory Tract Infections after Operations under General Anesthesia with Tracheal Intubation
Dan YE ; Ciyong LU ; Lianna LI ; Junyao HUANG ; Hongyan LIN
Chinese Journal of Nosocomiology 2009;0(19):-
OBJECTIVE To probe into the impact factors of the nosocomial respiratory tract infections after the operations with tracheal intubation under general anesthesia in order to establish the prevention and treatment strategies and provide the scientific basis.METHODS By descriptive epidemiological method and case-control study method,80 cases with nosocomial respiratory tract infections in nearly 3 years who had tracheal intubation under general anesthesia were selected,and another 180 patients with non-nosocomial respiratory tract infections with tracheal intubation under general anesthesia were selected as the control.RESULTS The incidence of the nosocomial infections from 5923 patients of the operation with tracheal intubation under general anesthesia from 2005 to 2007 accounted for 10.1%.The incidence of the respiratory tract infections of operations under general anesthesia accounted for 5.25%.The nosocomial respiratory tract infection from the tracheal intubation under general anesthesia toped the list and accounted for 52.0%.It showed seven impact factors on the nosocomial respiratory tract infection after the operation with tracheal intubation under general anesthesia by the multi-factorial Logistic regression,respectively,with significant differences(P1).CONCLUSIONS There are many impact factors that the nosocomial respiratory tract infection(especially lower respiratory tract infection) resulting from the operation with tracheal intubation under general anesthesia.The study shows the main risk factors: age,the complications of the disease,surgical condition,the ventilation time of tracheal intubationunder the anesthesia,post-operative recovery time,smoking status,the time that the operated patients start coughing after the operation.Therefore,the prevention is especially important.
5.Measuring volume and density of human organs and its significance in medicine and forensic medicine: brain and heart part.
Xiaojun YU ; Maoyang LIU ; Yubo FAN ; Wen YU ; Jinchuan LI ; Dian WANG ; Junyao LU
Journal of Biomedical Engineering 2007;24(1):210-214
The exact scales of volume and density of human internal organs were measured synchronously with the intelligentized volum-densimeter, which was made. by ourself. These primary values of normal and diffuse pathologic changes can refer easily and used for the diagnosis in human autopsy of pathology and forensic pathology. It is expectated to be co-operated widely in that the basic values of volume and density will be obtained from all organs of the human body with the population of different races. But up to now, we are still lack these primary values in anthropology and medicine.
Anthropometry
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instrumentation
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methods
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Brain
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anatomy & histology
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Forensic Medicine
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Heart
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anatomy & histology
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Humans
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Organ Size
6.Expression and Significance of Telomerase Activity in Cervical Cancer
Wenjing SHEN ; Xiufen LI ; Jiafei YAO ; Shuyue REN ; Dan LU ; Junyao DU
Journal of China Medical University 2001;30(2):112-113,116
Objective: Our aim was to study the role of telomerase activation in the course of cervical carcinogenesis and progression.Methods:Telomeric repeat amplification protocol(TRAP) assay was used to measure telomerase activity in tissue samples with various cervical conditions:40 with cervical cancer, 50 with cervical intraepithelial neoplasia(CIN), 20 with normal cervice. Results:The positive rate of telomerase activity was 95.0%,44.0%, and 10.0% in cervical cancer, CIN, and normal cervices, respectively, which was significantly higher in cervical cancer than that in CIN and normal cervices, so was that in CIN than that in normal cervices (P<0.01) . The positive rate was 22.2%, 37.5%, and 75.0% in CINⅠ,Ⅱ, and Ⅲ, respectively, which was significantly higher in CINⅢ than that in CIN Ⅱand CINⅠ (P<0.01).Conclusion:Telomerase activation may relate to cervical carcinogenesis, which correlates well with the grade of cervical lesions.

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