BACKGROUND Recent advancements in biliary tract cancer(BTC)treatment have expanded beyond surgery to include adjuvant therapy,yet the prognosis remains poor.Identifying prognostic biomarkers could enhance the assessme...BACKGROUND Recent advancements in biliary tract cancer(BTC)treatment have expanded beyond surgery to include adjuvant therapy,yet the prognosis remains poor.Identifying prognostic biomarkers could enhance the assessment of patients who have undergone radical resection for BTC.AIM To determine transmembrane serine protease 4(TMPRSS4)utility as a prognostic biomarker of radical resection for BTC.METHODS Medical records of patients who underwent radical resection for BTC,excluding intrahepatic cholangiocarcinoma,were retrospectively reviewed.The associations between TMPRSS4 expression and clinicopathological factors,overall survival,and recurrence-free survival were analyzed.RESULTS Among the 85 patients undergoing radical resection for BTC,46(54%)were TMPRSS4-positive.The TMPRSS4-positive group exhibited significantly higher preoperative carbohydrate antigen 19-9(CA19-9)values and greater lymphatic invasion than the TMPRSS4-negative group(P=0.019 and 0.039,respectively).Postoperative overall survival and recurrence-free survival were significantly worse in the TMPRSS4-positive group(median survival time:25.3 months vs not reached,P<0.001;median survival time:28.7 months vs not reached,P=0.043,respectively).Multivariate overall survival analysis indicated TMPRSS4 positivity,pT3/T4,and resection status R1 were independently associated with poor prognosis(P=0.032,0.035 and 0.030,respectively).TMPRSS4 positivity correlated with preoperative CA19-9 values≥37 U/mL and pathological tumor size≥30 mm(P=0.016 and 0.038,respectively).CONCLUSION TMPRSS4 is a potential prognostic biomarker of radical resection for BTC.展开更多
Objective:The novel coronavirus(severe acute respiratory syndrome coronavirus 2)has been spreading worldwide since December 2019,posing a serious danger to human health and socioeconomic development.A large number of ...Objective:The novel coronavirus(severe acute respiratory syndrome coronavirus 2)has been spreading worldwide since December 2019,posing a serious danger to human health and socioeconomic development.A large number of clinical trials have revealed that coronavirus disease 2019(COVID-19)results in multi-organ damage including the urogenital system.This study aimed to explore the potential mechanisms of genitourinary damage associated with COVID-19 infection through bioinformatics and molecular simulation analysis.Methods:We used multiple publicly available databases to explore the expression patterns of angiotensin-converting enzyme 2(ACE2),transmembrane serine protease 2(TMPRSS2),and CD147 in major organs in the healthy and disease-specific populations,particularly the genitourinary organs.Single-cell RNA sequencing was used to analyze the cell-specific expression patterns of ACE2,TMPRSS2,CD147,cytokine receptors,and cytokine interacting proteins in genitourinary organs,such as the bladder,kidney,prostate,and testis.Additionally,gene set enrichmentanalysis was used to investigate the relationship between testosterone levels and COVID-19 vulnerability in patients with prostate cancer.Results:The results revealed that ACE2,TMPRSS2,and CD147 were highly expressed in normal urogenital organs.Then,they were also highly expressed in multiple tumors and chronic kidney diseases.Additionally,ACE2,TMPRSS2,and CD147 were significantly expressed in a range of cells in urogenital organs according to single-cell RNA sequencing.Cytokine receptors and cytokine interacting proteins,especially CCL2,JUN,and TIMP1,were commonly highly expressed in urogenital organs.Finally,gene set enrichment analysis results showed that high testosterone levels in prostate cancer patients were significantly related to the JAK-STAT signaling pathway and the Toll-like receptor signaling pathway which were associated with COVID-19.Conclusion:Our study provides new insights into the potential mechanisms of severe acute respiratory syndrome coronavirus 2展开更多
Coronavirus disease 2019(COVID-19),caused by infection with the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),has escalated into a global tragedy afflicting human health,life,and social governance.Throug...Coronavirus disease 2019(COVID-19),caused by infection with the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),has escalated into a global tragedy afflicting human health,life,and social governance.Through the increasing depth of research and a better understanding of this disease,it has been ascertained that,in addition to the lungs,SARS-CoV-2 can also induce injuries to other organs including the liver.Liver injury is a common clinical manifestation of COVID-19,particularly in severe cases,and is often associated with a poorer prognosis and higher severity of COVID-19.This review focuses on the general existing information on liver injury caused by COVID-19,including risk factors and subpopulations of liver injury in COVID-19,the association between preexisting liver diseases and the severity of COVID-19,and the potential mechanisms by which SARS-CoV-2 affects the liver.This review may provide some useful information for the development of therapeutic and preventive strategies for COVID-19-associated liver injury.展开更多
Object:Corona virus disease 2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which leads to acute respiratory infection symptoms.SARS-CoV-2 infection is not always limited to the ...Object:Corona virus disease 2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which leads to acute respiratory infection symptoms.SARS-CoV-2 infection is not always limited to the respiratory tract,and renal infection and dysfunction have been shown to be specific risk factors for death.In addition,COVID-19 has a higher incidence,severity and mortality in men than women.This disparity is due to biological rather than comorbid or behavioral sex differences.Because the male reproductive system is unique,the function of sex hormones in COVID-19 infection may explain the differences between males and females.Understanding these factors will provide appropriate prevention measures and adequate triage strategies and guide the drug discovery process.Methods:An electronic search was completed in PubMed,ARXIV,MEDRXIV and BIORXIV.The most relevant articles were systematically reviewed.In addition,single cell RNA sequencing analysis of tissue samples from human cell landscape was conducted.Results:The influence of SARS-CoV-2 on the urogenital system,the possibility of urinary tract transmission and the functions of sex hormones were discussed in this review.Conclusion:Corona viruses can invade the genitourinary system,causing urological symptoms.Identifying the potential genitourinary organ impairments and protecting them from damage are necessary.Since sex hormones have potential as specific drugs,the gonadal hormones substitution therapy should be considered in both sexes in the COVID-19 pandemic.展开更多
The global coronavirus disease 2019(COVID-19)has become one of the biggest threats to the world since 2019.The respiratory and gastrointestinal tracts are the main targets for severe acute respiratory syndrome coronav...The global coronavirus disease 2019(COVID-19)has become one of the biggest threats to the world since 2019.The respiratory and gastrointestinal tracts are the main targets for severe acute respiratory syndrome coronavirus 2 infection for they highly express angiotensin-converting enzyme-2 and transmembrane protease serine 2.In patients suffering from COVID-19,gastrointestinal symptoms have ranged from 12%to 61%.Anorexia,nausea and/or vomiting,diarrhea,and abdominal pain are considered to be the main gastrointestinal symptoms of COVID-19.It has been reported that the direct damage of intestinal mucosal epithelial cells,malnutrition,and intestinal flora disorders are involved in COVID-19.However,the underlying mechanisms remain unclear.Thus,in this study,we reviewed and discussed the correlated mechanisms that cause gastrointestinal symptoms in order to help to develop the treatment strategy and build an appropriate guideline for medical workers.展开更多
long-term,and relapsing inflammatory disorders.IBD may spontaneously grow in the colon,and in severe cases may result in tumor lesions such as invasive carcinoma in inflamed regions of the intestine.Recent epidemiolog...long-term,and relapsing inflammatory disorders.IBD may spontaneously grow in the colon,and in severe cases may result in tumor lesions such as invasive carcinoma in inflamed regions of the intestine.Recent epidemiological reports indicate that old age and underlying diseases such as IBD contribute to severity and mortality in patients with coronavirus disease 2019(COVID-19).Currently,the ongoing COVID-19 pandemic caused serious morbidity and mortality worldwide.It has also been shown that the transmembrane serine protease 2 is an essential factor for viral activation and viral engulfment.Generally,viral entry causes a'cytokine storm'that induces excessive generation of proinflammatory cytokines/chemokines including interleukin(IL)-6,IL-2,IL-7,tumor necrosis factor-α,and interferon-γ.Future research could concentrate on developing inflammatory immunological responses that are efficient to encounter COVID-19.Current analysis elucidates the role of inflammation and immune responses during IBD infection with COVID-19 and provides a list of possible targets for IBD-regulated therapies in particular.Data from clinical,in vitro,and in vivo studies were collected in English from PubMed,Google Scholar,Scopus,and the Cochrane library until May 2021.展开更多
目的研究蝙蝠来源的重症急性呼吸综合征(SARS)样冠状病毒WIV1刺突蛋白利用浣熊狗血管紧张素转换酶Ⅱ(ACE2)受体侵入细胞的能力,并探究SARS样冠状病毒WIV1潜在的跨宿主传播风险。方法构建来自浣熊狗、果子狸、中华菊头蝠和人等不同动物...目的研究蝙蝠来源的重症急性呼吸综合征(SARS)样冠状病毒WIV1刺突蛋白利用浣熊狗血管紧张素转换酶Ⅱ(ACE2)受体侵入细胞的能力,并探究SARS样冠状病毒WIV1潜在的跨宿主传播风险。方法构建来自浣熊狗、果子狸、中华菊头蝠和人等不同动物来源的ACE2表达质粒,转染至293T细胞并利用免疫印迹方法检测其在293T细胞中的表达水平;建立SARS冠状病毒(Tor2株系)及蝙蝠SARS样冠状病毒(WIV1株系)假病毒感染系统,并进行假病毒感染实验;利用假病毒感染系统及荧光素酶报告基因检测WIV1刺突蛋白对浣熊狗等不同动物来源ACE2受体利用能力;构建跨膜丝氨酸蛋白酶2(TMPRSS2)质粒,并转染至T Rex 293细胞,借助假病毒感染系统检测TMPRSS2对WIV1侵入能力的影响。结果本研究所获赠及构建的不同动物来源的ACE2质粒可经瞬时转染至细胞进行表达;与pc DNA3.1载体相比,浣熊狗、中华菊头蝠、果子狸和人的ACE2均可使蝙蝠SARS样冠状病毒WIV1侵入细胞的能力增加上万倍,上述ACE2组与载体组的荧光素酶活性差异均具有统计学意义(t=27.744、P<0.001,t=18.740、P<0.001,t=32.297、P<0.001,t=15.902、P<0.001);与TMPRSS2阴性组相比,TMPRSS2在靶细胞的表达可使WIV1假病毒的感染能力增加10倍以上,两组荧光素酶活性差异具有统计学意义(t=29.460、P<0.001)。结论蝙蝠SARS样冠状病毒WIV1的刺突蛋白除了利用人类、果子狸及中华菊头蝠的ACE2受体感染细胞,还可利用浣熊狗的ACE2受体侵入细胞,且TMPRSS2可显著促进其侵入能力,提示WIV1可能存在多种跨宿主传播的风险。展开更多
目的:探寻银翘散治疗新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)的活性化合物。方法:应用中药系统药理学分析平台(Traditional Chinese Medicine System Pharmacological,TCMSP)、PubChem数据库、SwissTargetPrediction数据...目的:探寻银翘散治疗新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)的活性化合物。方法:应用中药系统药理学分析平台(Traditional Chinese Medicine System Pharmacological,TCMSP)、PubChem数据库、SwissTargetPrediction数据库挖掘获取银翘散中金银花、连翘、桔梗、薄荷、牛蒡子、竹叶、荆芥穗、淡豆豉、甘草、芦根的活性成分和作用靶点;应用Cytoscape 3.7.2软件构建银翘散成分-靶点网络;利用String数据库构建银翘散作用靶标的PPI网络;通过WebGestalt数据库和KOBAS 3.0数据库对银翘散作用靶点进行GO分析和KEGG富集分析,筛选出潜在通路并分析其作用机制。结果:共筛选出153个银翘散生物活性成分和580个靶点,核心靶点为PTGS2、HSP90AA1、AR、PCP4、F7,主要涉及PI3K-Akt信号通路、MAPK信号通路、细胞凋亡途径、细胞衰老通路、非小细胞肺癌通路等信号通路。分子对接结果显示类黄酮、山柰酚等核心化合物与COVID-19推荐用药的亲和力相似。结论:初步揭示了银翘散可能通过血管紧张素Ⅱ(angiotensin converting enzyme 2,ACE2)和丝氨酸蛋白酶(recombinant transmembrane protease serine 2,TMPRSS2)等结合,作用于PTGS2、HSP90AA1、AR、PCP4、F7等靶点调节多条信号通路,从而发挥其整体调节效应而治疗COVID-19。展开更多
文摘BACKGROUND Recent advancements in biliary tract cancer(BTC)treatment have expanded beyond surgery to include adjuvant therapy,yet the prognosis remains poor.Identifying prognostic biomarkers could enhance the assessment of patients who have undergone radical resection for BTC.AIM To determine transmembrane serine protease 4(TMPRSS4)utility as a prognostic biomarker of radical resection for BTC.METHODS Medical records of patients who underwent radical resection for BTC,excluding intrahepatic cholangiocarcinoma,were retrospectively reviewed.The associations between TMPRSS4 expression and clinicopathological factors,overall survival,and recurrence-free survival were analyzed.RESULTS Among the 85 patients undergoing radical resection for BTC,46(54%)were TMPRSS4-positive.The TMPRSS4-positive group exhibited significantly higher preoperative carbohydrate antigen 19-9(CA19-9)values and greater lymphatic invasion than the TMPRSS4-negative group(P=0.019 and 0.039,respectively).Postoperative overall survival and recurrence-free survival were significantly worse in the TMPRSS4-positive group(median survival time:25.3 months vs not reached,P<0.001;median survival time:28.7 months vs not reached,P=0.043,respectively).Multivariate overall survival analysis indicated TMPRSS4 positivity,pT3/T4,and resection status R1 were independently associated with poor prognosis(P=0.032,0.035 and 0.030,respectively).TMPRSS4 positivity correlated with preoperative CA19-9 values≥37 U/mL and pathological tumor size≥30 mm(P=0.016 and 0.038,respectively).CONCLUSION TMPRSS4 is a potential prognostic biomarker of radical resection for BTC.
文摘Objective:The novel coronavirus(severe acute respiratory syndrome coronavirus 2)has been spreading worldwide since December 2019,posing a serious danger to human health and socioeconomic development.A large number of clinical trials have revealed that coronavirus disease 2019(COVID-19)results in multi-organ damage including the urogenital system.This study aimed to explore the potential mechanisms of genitourinary damage associated with COVID-19 infection through bioinformatics and molecular simulation analysis.Methods:We used multiple publicly available databases to explore the expression patterns of angiotensin-converting enzyme 2(ACE2),transmembrane serine protease 2(TMPRSS2),and CD147 in major organs in the healthy and disease-specific populations,particularly the genitourinary organs.Single-cell RNA sequencing was used to analyze the cell-specific expression patterns of ACE2,TMPRSS2,CD147,cytokine receptors,and cytokine interacting proteins in genitourinary organs,such as the bladder,kidney,prostate,and testis.Additionally,gene set enrichmentanalysis was used to investigate the relationship between testosterone levels and COVID-19 vulnerability in patients with prostate cancer.Results:The results revealed that ACE2,TMPRSS2,and CD147 were highly expressed in normal urogenital organs.Then,they were also highly expressed in multiple tumors and chronic kidney diseases.Additionally,ACE2,TMPRSS2,and CD147 were significantly expressed in a range of cells in urogenital organs according to single-cell RNA sequencing.Cytokine receptors and cytokine interacting proteins,especially CCL2,JUN,and TIMP1,were commonly highly expressed in urogenital organs.Finally,gene set enrichment analysis results showed that high testosterone levels in prostate cancer patients were significantly related to the JAK-STAT signaling pathway and the Toll-like receptor signaling pathway which were associated with COVID-19.Conclusion:Our study provides new insights into the potential mechanisms of severe acute respiratory syndrome coronavirus 2
基金the Key Medical Science and Technology Program of Shanxi Province,No.2020XM01Shanxi“1331”Project Quality and Efficiency Improvement Plan,No.1331KFC+1 种基金Applied Basic Research Program of Shanxi Province,No.202103021224234National Natural Science Foundation of China,No.82170523.
文摘Coronavirus disease 2019(COVID-19),caused by infection with the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),has escalated into a global tragedy afflicting human health,life,and social governance.Through the increasing depth of research and a better understanding of this disease,it has been ascertained that,in addition to the lungs,SARS-CoV-2 can also induce injuries to other organs including the liver.Liver injury is a common clinical manifestation of COVID-19,particularly in severe cases,and is often associated with a poorer prognosis and higher severity of COVID-19.This review focuses on the general existing information on liver injury caused by COVID-19,including risk factors and subpopulations of liver injury in COVID-19,the association between preexisting liver diseases and the severity of COVID-19,and the potential mechanisms by which SARS-CoV-2 affects the liver.This review may provide some useful information for the development of therapeutic and preventive strategies for COVID-19-associated liver injury.
文摘Object:Corona virus disease 2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which leads to acute respiratory infection symptoms.SARS-CoV-2 infection is not always limited to the respiratory tract,and renal infection and dysfunction have been shown to be specific risk factors for death.In addition,COVID-19 has a higher incidence,severity and mortality in men than women.This disparity is due to biological rather than comorbid or behavioral sex differences.Because the male reproductive system is unique,the function of sex hormones in COVID-19 infection may explain the differences between males and females.Understanding these factors will provide appropriate prevention measures and adequate triage strategies and guide the drug discovery process.Methods:An electronic search was completed in PubMed,ARXIV,MEDRXIV and BIORXIV.The most relevant articles were systematically reviewed.In addition,single cell RNA sequencing analysis of tissue samples from human cell landscape was conducted.Results:The influence of SARS-CoV-2 on the urogenital system,the possibility of urinary tract transmission and the functions of sex hormones were discussed in this review.Conclusion:Corona viruses can invade the genitourinary system,causing urological symptoms.Identifying the potential genitourinary organ impairments and protecting them from damage are necessary.Since sex hormones have potential as specific drugs,the gonadal hormones substitution therapy should be considered in both sexes in the COVID-19 pandemic.
基金the Commission,No.KJZD-K202002701General Project of Chongqing Natural Science Foundation,No.cstc2019jcyj msxmX0299+3 种基金Key Project of Chongqing Three Gorges Medical College,No.XJ2021000101Chongqing Natural Drug Anti-Tumor Innovation Research Group,No.CXQT20030Special Fund for Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area,No.Sys20210002the Open Project in 2022 of Chongqing Key Laboratory for the Development and Utilization of Authentic Medicinal Materials in the Three Gorges Reservoir Area,No.KFKT2022004.
文摘The global coronavirus disease 2019(COVID-19)has become one of the biggest threats to the world since 2019.The respiratory and gastrointestinal tracts are the main targets for severe acute respiratory syndrome coronavirus 2 infection for they highly express angiotensin-converting enzyme-2 and transmembrane protease serine 2.In patients suffering from COVID-19,gastrointestinal symptoms have ranged from 12%to 61%.Anorexia,nausea and/or vomiting,diarrhea,and abdominal pain are considered to be the main gastrointestinal symptoms of COVID-19.It has been reported that the direct damage of intestinal mucosal epithelial cells,malnutrition,and intestinal flora disorders are involved in COVID-19.However,the underlying mechanisms remain unclear.Thus,in this study,we reviewed and discussed the correlated mechanisms that cause gastrointestinal symptoms in order to help to develop the treatment strategy and build an appropriate guideline for medical workers.
文摘long-term,and relapsing inflammatory disorders.IBD may spontaneously grow in the colon,and in severe cases may result in tumor lesions such as invasive carcinoma in inflamed regions of the intestine.Recent epidemiological reports indicate that old age and underlying diseases such as IBD contribute to severity and mortality in patients with coronavirus disease 2019(COVID-19).Currently,the ongoing COVID-19 pandemic caused serious morbidity and mortality worldwide.It has also been shown that the transmembrane serine protease 2 is an essential factor for viral activation and viral engulfment.Generally,viral entry causes a'cytokine storm'that induces excessive generation of proinflammatory cytokines/chemokines including interleukin(IL)-6,IL-2,IL-7,tumor necrosis factor-α,and interferon-γ.Future research could concentrate on developing inflammatory immunological responses that are efficient to encounter COVID-19.Current analysis elucidates the role of inflammation and immune responses during IBD infection with COVID-19 and provides a list of possible targets for IBD-regulated therapies in particular.Data from clinical,in vitro,and in vivo studies were collected in English from PubMed,Google Scholar,Scopus,and the Cochrane library until May 2021.
文摘目的研究蝙蝠来源的重症急性呼吸综合征(SARS)样冠状病毒WIV1刺突蛋白利用浣熊狗血管紧张素转换酶Ⅱ(ACE2)受体侵入细胞的能力,并探究SARS样冠状病毒WIV1潜在的跨宿主传播风险。方法构建来自浣熊狗、果子狸、中华菊头蝠和人等不同动物来源的ACE2表达质粒,转染至293T细胞并利用免疫印迹方法检测其在293T细胞中的表达水平;建立SARS冠状病毒(Tor2株系)及蝙蝠SARS样冠状病毒(WIV1株系)假病毒感染系统,并进行假病毒感染实验;利用假病毒感染系统及荧光素酶报告基因检测WIV1刺突蛋白对浣熊狗等不同动物来源ACE2受体利用能力;构建跨膜丝氨酸蛋白酶2(TMPRSS2)质粒,并转染至T Rex 293细胞,借助假病毒感染系统检测TMPRSS2对WIV1侵入能力的影响。结果本研究所获赠及构建的不同动物来源的ACE2质粒可经瞬时转染至细胞进行表达;与pc DNA3.1载体相比,浣熊狗、中华菊头蝠、果子狸和人的ACE2均可使蝙蝠SARS样冠状病毒WIV1侵入细胞的能力增加上万倍,上述ACE2组与载体组的荧光素酶活性差异均具有统计学意义(t=27.744、P<0.001,t=18.740、P<0.001,t=32.297、P<0.001,t=15.902、P<0.001);与TMPRSS2阴性组相比,TMPRSS2在靶细胞的表达可使WIV1假病毒的感染能力增加10倍以上,两组荧光素酶活性差异具有统计学意义(t=29.460、P<0.001)。结论蝙蝠SARS样冠状病毒WIV1的刺突蛋白除了利用人类、果子狸及中华菊头蝠的ACE2受体感染细胞,还可利用浣熊狗的ACE2受体侵入细胞,且TMPRSS2可显著促进其侵入能力,提示WIV1可能存在多种跨宿主传播的风险。
