Background:Liver dysfunction was common in coronavirus disease 2019(COVID-19),but its association with clinical features and poor prognosis has not been fully delineated.Our study aimed to determine the role of liver ...Background:Liver dysfunction was common in coronavirus disease 2019(COVID-19),but its association with clinical features and poor prognosis has not been fully delineated.Our study aimed to determine the role of liver dysfunction in COVID-19 and understand the predictors for worse outcomes in patients with liver injury.Methods:We conducted this multicenter,retrospective study in five designated hospitals for COVID-19 manage-ment.Laboratory-confirmed COVID-19 patients were enrolled and classified into the normal live function group and liver dysfunction group according to liver enzymes,bilirubin,and albumin on admission,respectively.Data of baseline,clinical manifestations,and outcomes were collected and compared in the paired groups.Results:Of the 649 included COVID-19 patients,200(30.8%),69(10.6%),and 267(41.1%)patients had elevated liver enzymes,increased bilirubin,and low-level albumin,respectively.Fever,cough,and dyspnea were the most common symptoms and showed an increased proportion in the liver dysfunction group.Compared with patients in the normal liver function group,patients with liver dysfunction manifested decreased lymphocytes,higher level of leukocytes,neutrophils,inflammatory indicators,and cytokines,as well as more severe impairment in kidney function and myocardium.They were more likely to show bilateral involvement and more pulmonary lobes involved according to chest images.With increased proportion of patients who developed severe/critical conditions and needed mechanical ventilation and systemic glucocorticoid therapy,patients with liver dysfunc-tion on admission showed significantly higher in-hospital mortality.Moreover,cardiac troponin I≥1.5 ng/mL was identified as an independent mortality predictor in the elevated liver enzymes group.Conclusion:Patients with liver dysfunction on admission had worse clinical manifestation,and resulted in higher rate of severe/critical type,receiving mechanical ventilation and in-hospital mortality.展开更多
Background:Although examinations and therapies for bronchial lung cancer,also called lung cancer(LC),have become more effective and precise,the morbidity and mortality of LC remain high worldwide.Describing the changi...Background:Although examinations and therapies for bronchial lung cancer,also called lung cancer(LC),have become more effective and precise,the morbidity and mortality of LC remain high worldwide.Describing the changing profile of LC characteristics over time is indispensable.This study aimed to understand the changes in real-world settings of LC and its characteristics in China.Methods:In this study,119,785 patients were enrolled from 2012 to 2020 in the Shanghai Pulmonary Hospital.The patients’medical records were extracted from the hospital’s database.Demographic characteristics,general clinicopathological information,and blood coagulation indices at the initial diagnoses were analyzed using the Kruskal-Wallis,Nemenyi,chi-squared,and Bonferroni tests.Changes in demographic characteristics during the 8-year study period,namely dynamic changes among different stages and different pathological types,were evaluated.Results:The percentages of female(from 38.50%[323/839]in 2012 to 48.29%[5112/10,585]in 2020)and non-smoking LC(from 69.34%[475/685]to 80.48%[8055/10,009])patients increased significantly during the study period,with a trend toward a younger age at diagnosis(from 3.58%[30/839]to 8.99%[952/10,585]).Over the study period,the proportion and absolute number of lung adenocarcinoma cases increased(from 67.97%[433/637]to 76.31%[6606/8657])while the proportion of lung squamous cell carcinoma decreased(from 21.19%[135/637]to 12.08%[1046/8657]).Comprehensive driver gene mutation examination became more common,and epidermal growth factor receptor(EGFR)mutation occurred more frequently in female vs.male(62.03%[12793/20625]vs.29.90%[8207/27,447])and non-smoking vs.smoking(53.54%[17,203/32,134]vs.23.73%[3322/13,997])patients(both P<0.001).The distribution of the common driver genes differed among different stages of LC.EGFR mutation was detected most frequently at each stage,and other driver gene alterations were more common in advanced stages(P<0.001).The combination of chemotherapy,targeted ther-apy,and immunotherapy,as a comprehensive management regimen,gradually became predominant over the study period(P<0.001).A hypercoagulable state was shown in advanced-stage LC patients and patients with the anaplastic lymphoma kinase fusion,indicated by significantly elevated levels of d-dimer,fibrinogen,and fibrinogen degradation products.Conclusions:This study comprehensively depicted the changing characteristics of Chinese LC patients over an 8-year period to provide preliminary insights into LC treatment.Trial registration:ClinicalTrials.gov,NCT05423236.展开更多
Pyroptosis is a type of programed cell death that differs from apoptosis,ferroptosis,or necrosis.Numerous studies have reported that it plays a critical role in tumorigenesis and modification of the tumor microenviron...Pyroptosis is a type of programed cell death that differs from apoptosis,ferroptosis,or necrosis.Numerous studies have reported that it plays a critical role in tumorigenesis and modification of the tumor microenvironment in multiple tumors.In this review,we briefly describe the canonical,non-canonical,and alternative mechanisms of pyroptotic cell death.We also summarize the potential roles of pyroptosis in oncogenesis,tumor development,and lung cancer treatment,including chemotherapy,radiotherapy,targeted therapy,and immunotherapy.Pyrop-tosis has double-edged effects on the modulation of the tumor environment and lung cancer treatment.Further exploration of pyroptosis-based drugs could provide novel therapeutic strategies for lung cancer.展开更多
Immunotherapy that targets checkpoints, especially programmed cell death protein 1 and programmed cell death ligand 1, has revolutionized cancer therapy regimens. The overall response rate to mono-immunotherapy, howev...Immunotherapy that targets checkpoints, especially programmed cell death protein 1 and programmed cell death ligand 1, has revolutionized cancer therapy regimens. The overall response rate to mono-immunotherapy, however, is limited, emphasizing the need to potentiate the efficacy of these regimens. The functions of immune cells are modulated by multiple stimulatory and inhibitory molecules, including lymphocyte activation gene 3 (LAG-3). LAG-3 is co-expressed together with other inhibitory checkpoints and plays key roles in immune suppression. Increasing evidence, particularly in the last 5 years, has shown the potential of LAG-3 blockade in anti-tumor immunity. This review provides an update on the biological properties and clinical applications of LAG-3 in cancers.展开更多
基金This study was supported by the National Natural Science Foun-dation of China(No.81630001)the Shanghai Municipal Key Clini-cal Specialty(No.shslczdzk02202)+2 种基金the Shanghai Top-Priority Clinical Key Disciplines Construction Project(No.2017ZZ02014)the Shanghai Shenkang Hospital Development Center Clinical Science and Technol-ogy Innovation Project(No.SHDC12018102)the Innovative Re-search Team of High-level Local Universities in Shanghai and Zhejiang University special scientific research fund for COVID-19 prevention and control(No.2020XGZX011).
文摘Background:Liver dysfunction was common in coronavirus disease 2019(COVID-19),but its association with clinical features and poor prognosis has not been fully delineated.Our study aimed to determine the role of liver dysfunction in COVID-19 and understand the predictors for worse outcomes in patients with liver injury.Methods:We conducted this multicenter,retrospective study in five designated hospitals for COVID-19 manage-ment.Laboratory-confirmed COVID-19 patients were enrolled and classified into the normal live function group and liver dysfunction group according to liver enzymes,bilirubin,and albumin on admission,respectively.Data of baseline,clinical manifestations,and outcomes were collected and compared in the paired groups.Results:Of the 649 included COVID-19 patients,200(30.8%),69(10.6%),and 267(41.1%)patients had elevated liver enzymes,increased bilirubin,and low-level albumin,respectively.Fever,cough,and dyspnea were the most common symptoms and showed an increased proportion in the liver dysfunction group.Compared with patients in the normal liver function group,patients with liver dysfunction manifested decreased lymphocytes,higher level of leukocytes,neutrophils,inflammatory indicators,and cytokines,as well as more severe impairment in kidney function and myocardium.They were more likely to show bilateral involvement and more pulmonary lobes involved according to chest images.With increased proportion of patients who developed severe/critical conditions and needed mechanical ventilation and systemic glucocorticoid therapy,patients with liver dysfunc-tion on admission showed significantly higher in-hospital mortality.Moreover,cardiac troponin I≥1.5 ng/mL was identified as an independent mortality predictor in the elevated liver enzymes group.Conclusion:Patients with liver dysfunction on admission had worse clinical manifestation,and resulted in higher rate of severe/critical type,receiving mechanical ventilation and in-hospital mortality.
基金This study was supported in part by grants from the National Key Research and Development Program of China(No.2022YFF0705300)National Natural Science Foundation of China(No.52272281)+5 种基金Clinical Research Project of Shanghai Pulmonary Hospital(No.FKLY20010)Young Talents in Shanghai(No.2019 QNBJ)Shang-hai Shuguang Scholars.This study was supported by the Shanghai Mu-nicipal Science and Technology Major Project(No.2021SHZDZX0100)Fundamental Research Funds for the Central Universities(No.22120210562)2021 Science and Technology Think Tank Youth Tal-ent Plan of the China Association for Science and Technology,“Dream Tutor”Outstanding Young Talents Program(No.fkyq1901)the National Key Research and Development Program of China(Nos.2021YFF1201200 and 2021YFF1200900).
文摘Background:Although examinations and therapies for bronchial lung cancer,also called lung cancer(LC),have become more effective and precise,the morbidity and mortality of LC remain high worldwide.Describing the changing profile of LC characteristics over time is indispensable.This study aimed to understand the changes in real-world settings of LC and its characteristics in China.Methods:In this study,119,785 patients were enrolled from 2012 to 2020 in the Shanghai Pulmonary Hospital.The patients’medical records were extracted from the hospital’s database.Demographic characteristics,general clinicopathological information,and blood coagulation indices at the initial diagnoses were analyzed using the Kruskal-Wallis,Nemenyi,chi-squared,and Bonferroni tests.Changes in demographic characteristics during the 8-year study period,namely dynamic changes among different stages and different pathological types,were evaluated.Results:The percentages of female(from 38.50%[323/839]in 2012 to 48.29%[5112/10,585]in 2020)and non-smoking LC(from 69.34%[475/685]to 80.48%[8055/10,009])patients increased significantly during the study period,with a trend toward a younger age at diagnosis(from 3.58%[30/839]to 8.99%[952/10,585]).Over the study period,the proportion and absolute number of lung adenocarcinoma cases increased(from 67.97%[433/637]to 76.31%[6606/8657])while the proportion of lung squamous cell carcinoma decreased(from 21.19%[135/637]to 12.08%[1046/8657]).Comprehensive driver gene mutation examination became more common,and epidermal growth factor receptor(EGFR)mutation occurred more frequently in female vs.male(62.03%[12793/20625]vs.29.90%[8207/27,447])and non-smoking vs.smoking(53.54%[17,203/32,134]vs.23.73%[3322/13,997])patients(both P<0.001).The distribution of the common driver genes differed among different stages of LC.EGFR mutation was detected most frequently at each stage,and other driver gene alterations were more common in advanced stages(P<0.001).The combination of chemotherapy,targeted ther-apy,and immunotherapy,as a comprehensive management regimen,gradually became predominant over the study period(P<0.001).A hypercoagulable state was shown in advanced-stage LC patients and patients with the anaplastic lymphoma kinase fusion,indicated by significantly elevated levels of d-dimer,fibrinogen,and fibrinogen degradation products.Conclusions:This study comprehensively depicted the changing characteristics of Chinese LC patients over an 8-year period to provide preliminary insights into LC treatment.Trial registration:ClinicalTrials.gov,NCT05423236.
基金This study was supported in part by a grant from the Clinical Research Project of Shanghai Pulmonary Hospital(No.FKLY20010)Young Talents in Shanghai(2019 QNBJ)+1 种基金Shanghai Shuguang Scholar,2021 Science and Technology Think Tank Youth Talent Plan of China Association for Science and Technology,“Dream Tutor”Outstand-ing Young Talents Program(No.fkyq1901)National Key Re-search and Development Program of China(Nos.2021YFF1201200 and 2021YFF1200900).
文摘Pyroptosis is a type of programed cell death that differs from apoptosis,ferroptosis,or necrosis.Numerous studies have reported that it plays a critical role in tumorigenesis and modification of the tumor microenvironment in multiple tumors.In this review,we briefly describe the canonical,non-canonical,and alternative mechanisms of pyroptotic cell death.We also summarize the potential roles of pyroptosis in oncogenesis,tumor development,and lung cancer treatment,including chemotherapy,radiotherapy,targeted therapy,and immunotherapy.Pyrop-tosis has double-edged effects on the modulation of the tumor environment and lung cancer treatment.Further exploration of pyroptosis-based drugs could provide novel therapeutic strategies for lung cancer.
基金This study was supported in part by National Natural Science Foundation of China(No. 81802255)Young Talents in Shanghai(No. 2019 QNBJ)+2 种基金"Dream Tutor" Outstanding Young Talents Program(No. fkyq1901)Clinical Research Project of Shanghai Pulmonary Hospital(No. fk18005)Key Discipline in 2019 (oncology), Project of Shanghai Municipal Science and Technology Commission (Project of Municipal Science and Technology Commission), and Scientific Research Project of Shanghai Pulmonary Hospital(No. fkcx1903)。
文摘Immunotherapy that targets checkpoints, especially programmed cell death protein 1 and programmed cell death ligand 1, has revolutionized cancer therapy regimens. The overall response rate to mono-immunotherapy, however, is limited, emphasizing the need to potentiate the efficacy of these regimens. The functions of immune cells are modulated by multiple stimulatory and inhibitory molecules, including lymphocyte activation gene 3 (LAG-3). LAG-3 is co-expressed together with other inhibitory checkpoints and plays key roles in immune suppression. Increasing evidence, particularly in the last 5 years, has shown the potential of LAG-3 blockade in anti-tumor immunity. This review provides an update on the biological properties and clinical applications of LAG-3 in cancers.
