To investigate the clinical feature, risk factors and outcome of treatment in patients with liver failure complicated by invasive fungal infections. Retro-spective analysis of the clinical data and related factors of ...To investigate the clinical feature, risk factors and outcome of treatment in patients with liver failure complicated by invasive fungal infections. Retro-spective analysis of the clinical data and related factors of 27 patients with liver failure com-plicated by invasive fungal infections was per-formed. These patients were admitted from January 2007 to August 2009 in our department. Among them, Candida albicans accounted for 17cases (54.84%), albicans tropicals for 4 cases (12.90%). Fungal infection in respiratory tract and alimentary tract accounted for 58.06% and 11% respectively. 81.25% of them had fever fluctuating from 37.4oC to 40oC. 81.25% had elevated white blood cell counts .All had the usage of broad-spectrum of antibiotics, whereas some of them used corticosteroids and had invasive medical manipulation for the treatment. Most patients deteriorated after invasive fungal infections. 21 cases accepted with the treatment of antifungal drugs and mortality rate was 63.00%. It was found that the invasive fungal infection possibility of patients with liver failure significantly increased. To prevent the occurrence of invasive fungal infection, promptly early treatment of liver failure, proper use of antibiotics, cautious use or disuse of corticosteroids, reduction of invasive medical manipulation should be well done. Early detection and treatment of fungal infection are vital to decrease in mortality rate.展开更多
To screen species-specific DNA probes for identification of Fallopia muhiflora, the genomic DNA (gDNA) suppression subtraction hybridization (SSH) between F. muhiflora and F. muhiflora var. ciliinervis was firstly...To screen species-specific DNA probes for identification of Fallopia muhiflora, the genomic DNA (gDNA) suppression subtraction hybridization (SSH) between F. muhiflora and F. muhiflora var. ciliinervis was firstly performed. The obtained differential gDNA fragments by SSH were then hybridized with gDNA ar- rays consisting of multiple whole genomes of several species (adulterants and/or closely related species of F. muhiflora) and four differential fragments were screened uniquely representing F. muhiflora, which could be used as F. muhiflora species-specific probes. The screened DNA probes were tested by reverse dot blot hybridization and the results demonstrated that these probes could be used reliably to identify F, muhiflora. The species-specific DNA probes obtained in this study exhibited broad application prospects in the preparation of gene chips for identifying Chinese traditional medicines and the authentication of germplasm re- sources and crude drugs of F. muhiflora.展开更多
Idiosyncratic drus-induced liver injury(IDILI)is an intrequent but potentially serious disease that develops the main reason for post-marketing safety warnings and withdrawals of drugs.Epimedii Folium(EF),the widely u...Idiosyncratic drus-induced liver injury(IDILI)is an intrequent but potentially serious disease that develops the main reason for post-marketing safety warnings and withdrawals of drugs.Epimedii Folium(EF),the widely used herbal medicine,has shown to cause idiosyncratic liver injury,but the underlying mechanisms are poorly understood.Increasing evidence has indicated that most cases of IDILI are immune mediated.Here,we report that icarisideⅡ(ICSⅡ),the major active and metabolic constituent of EF,causes idiosyncratic liver injury by promoting NLRP3 inflammasome activation.ICSⅡexacerbates NLRP3 inflammasome activation triggered by adenosine triphosphate(ATP)and nigericin,but not silicon dioxide(SiO2),monosodium urate(MSU)crystal or cytosolic lipopolysaccharide(LPS).Additionally,the activation of NLRC4 and AIM2 inflammasomes is not affected by ICSⅡ.Mechanistically,synergistic induction of mitochondrial reactive oxygen species(mtROS)is a crucial contributor to the enhancing effect of ICSⅡon ATP-or nigericin-induced NLRP3 inflammasome activation.Importantly,in vivo data show that a combination of non-hepatotoxic doses of LPS and ICSⅡcauses the increase of aminotransferase activity,hepatic inflammation and pyroptosis,which is attenuated by Nlrp3 deficiency or pretreatment with MCC950(a specific NLRP3 inflammasome inhibitor).In conclusion,these findings demonstrate that ICSⅡcauses idiosyncratic liver injury through enhancing NLRP3 inflammasome activation and suggest that ICSⅡmay be a risk factor and responsible for EF-induced liver injury.展开更多
Background:Coronavirus disease 2019(COVID-19)has killed over 2.5 million people worldwide,but effective care and therapy have yet to be discovered.We conducted this analysis to better understand tocilizumab treatment ...Background:Coronavirus disease 2019(COVID-19)has killed over 2.5 million people worldwide,but effective care and therapy have yet to be discovered.We conducted this analysis to better understand tocilizumab treatment for COVID-19 patients.Main text:We searched major databases for manuscripts reporting the effects of tocilizumab on COVID-19 patients.A total of 25 publications were analyzed with Revman 5.3 and R for the meta-analysis.Significant better clinical outcomes were found in the tocilizumab treatment group when compared to the standard care group[odds ratio(OR)=0.70,95%confidential interval(CI):0.54-0.90,0.007].Tocilizumab treatment showed a stronger correlation with good prognosis among COVID-19 patients that needed mechanical ventilation(OR=0.59,95%CI:0.37-0.93,P=0.02).展开更多
Background:There have been many studies about coronavirus disease 2019(COVID-19),but the clinical signifi-cance of quantitative serum severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)-specific IgM and IgG le...Background:There have been many studies about coronavirus disease 2019(COVID-19),but the clinical signifi-cance of quantitative serum severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)-specific IgM and IgG levels of COVID-19 patients have not been exhaustively analyzed.We aimed to investigate the time profiles of these IgM/IgG levels in COVID-19 patients and their correlations with clinical features.Methods:A multicenter clinical study was conducted from February 20 to March 52020.It involved 179 COVID-19 patients(108 males and 71 females)from five hospitals in Huangshi in Hubei Province,China.To detect SARS-CoV-2-specific IgM/IgG,quantitative antibody assays(two-step indirect immunoassays with direct chemilu-minescence technology)based on the nucleocapsid protein(NP)and spike protein 1(S1)were used.For normally distributed data,means were compared using the t-test,𝜒2-test,or exact probability method.For categorical data,medians were compared using Mann-Whitney U test.Results:The median age was 57(44-69)years(58[38-69]for males and 57[49-68]for females).The median duration of positive nucleic acid test was 22.32(17.34-27.43)days.The mortality rate was relatively low(3/179,1.68%).Serum SARS-CoV-2-specific IgG was detected around week 1 after illness onset,gradually increased until peaking in weeks 4 and 5,and then declined.Serum IgM peaked in weeks 2 and 3,then gradually declined and returned to its normal range by week 7 in all patients.Notably,children had milder respiratory symptoms with lower SARS-CoV-2-specific IgM/IgG levels.The duration of positive nucleic acid test in the chronic obstructive pulmonary disease(COPD)group was 30.36(18.99-34.76)days,which was significantly longer than that in the non-COPD group(21.52[16.75-26.51]days;P=0.025).The peak serum SARS-CoV-2-specific IgG was sig-nificantly positively correlated with the duration of positive nucleic acid test.The incidence rate of severe and critical cases in the IgM hi group(using the median IgM level of 29.95 AU/mL as the cutofffor grouping)was about 38.0%(19/50),which was twice as much as that in the IgM lo group(18.4%;9/49).The patients with positive chest imaging and lymphocytopenia(<1×10^(9)/L)had a higher SARS-CoV-2-specific IgM level.Conclusions: Quantitative SARS-CoV-2-specific IgM and IgG levels are helpful for the diagnosis, severity classifi- cation, and management of COVID-19 patients, and they should be monitored in each stage of this disease.展开更多
Background:Splenectomy has been reported to improve liver function as well as hypersplenism,but it is still controversial whether splenectomy will further damage the immune function of patients with liver cirrhosis.Th...Background:Splenectomy has been reported to improve liver function as well as hypersplenism,but it is still controversial whether splenectomy will further damage the immune function of patients with liver cirrhosis.This study aims to evaluate the impact of splenectomy on the risk of infection in patients with liver cirrhosis.Methods:A total of 4355 patients with liver cirrhosis admitted to the First Affiliated Hospital of Nanjing Medical University from October 1,2016 to September 30,2020 were enrolled.The patients were first divided into the splenectomy group(SG)and the nonsplenectomy group(NSG).After standardization,patients were further divided according to the stage of cirrhosis.Infection rates in different stages were calculated,respectively.Laboratory results and infection sites of patients with cirrhosis were analyzed in combination with clinical data.Continuous variables conforming to normal distribution were presented as mean±standard deviation,compared by sample t test or paired sample t test.Non-normal variables were presented as the median(interquartile range)and compared by Mann-Whitney U test or Wilcoxon signed rank test.Results:Five hundred and two patients received splenectomy and 3853 patients did not.Bacterial infection was diagnosed in 497 of the 4355(11.41%)hospitalizations of patients with cirrhosis.The infection rate of the compensated cirrhosis SG was higher than that of the NSG(8.06%vs.5.18%,P<0.05).However,the infection rate in the SG with decompensated cirrhosis was lower than that in the NSG(11.35%vs.22.22%,P<0.001).The peak level of leukocytes did not differ significantly between the SG with compensated liver cirrhosis and the NSG[11.97(7.65)109/L vs.12.19(14.04)109/L,P>0.05].The peak value of leukocytes in SG suffering from decompensated liver cirrhosis was significantly higher than that in NSG[12.29(11.52)109/L vs.6.37(8.90)109/L,P=0.004].Patients with decompensated liver cirrhosis had a significantly higher rate of abdominal infection than patients with compensated liver cirrhosis,and splenectomy itself did not affect the sites of infection.Conclusions:Splenectomy increases the risk of infection for patients with compensated liver cirrhosis,but significantly decreases the risk in patients with decompensated liver cirrhosis.展开更多
文摘To investigate the clinical feature, risk factors and outcome of treatment in patients with liver failure complicated by invasive fungal infections. Retro-spective analysis of the clinical data and related factors of 27 patients with liver failure com-plicated by invasive fungal infections was per-formed. These patients were admitted from January 2007 to August 2009 in our department. Among them, Candida albicans accounted for 17cases (54.84%), albicans tropicals for 4 cases (12.90%). Fungal infection in respiratory tract and alimentary tract accounted for 58.06% and 11% respectively. 81.25% of them had fever fluctuating from 37.4oC to 40oC. 81.25% had elevated white blood cell counts .All had the usage of broad-spectrum of antibiotics, whereas some of them used corticosteroids and had invasive medical manipulation for the treatment. Most patients deteriorated after invasive fungal infections. 21 cases accepted with the treatment of antifungal drugs and mortality rate was 63.00%. It was found that the invasive fungal infection possibility of patients with liver failure significantly increased. To prevent the occurrence of invasive fungal infection, promptly early treatment of liver failure, proper use of antibiotics, cautious use or disuse of corticosteroids, reduction of invasive medical manipulation should be well done. Early detection and treatment of fungal infection are vital to decrease in mortality rate.
基金Supported by Fund of Guangdong Provincial Administration of Traditional Chinese Medicine(20111251)
文摘To screen species-specific DNA probes for identification of Fallopia muhiflora, the genomic DNA (gDNA) suppression subtraction hybridization (SSH) between F. muhiflora and F. muhiflora var. ciliinervis was firstly performed. The obtained differential gDNA fragments by SSH were then hybridized with gDNA ar- rays consisting of multiple whole genomes of several species (adulterants and/or closely related species of F. muhiflora) and four differential fragments were screened uniquely representing F. muhiflora, which could be used as F. muhiflora species-specific probes. The screened DNA probes were tested by reverse dot blot hybridization and the results demonstrated that these probes could be used reliably to identify F, muhiflora. The species-specific DNA probes obtained in this study exhibited broad application prospects in the preparation of gene chips for identifying Chinese traditional medicines and the authentication of germplasm re- sources and crude drugs of F. muhiflora.
基金supported by National Natural Science Foundation of China(81874368,81630100,and 81903891)Beijing Nova Program(Z181100006218001,China)+1 种基金National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”(2017ZX09301022 and 2018ZX09101002-001-002,China)the Innovation Groups of the National Natural Science Foundation of China(81721002)
文摘Idiosyncratic drus-induced liver injury(IDILI)is an intrequent but potentially serious disease that develops the main reason for post-marketing safety warnings and withdrawals of drugs.Epimedii Folium(EF),the widely used herbal medicine,has shown to cause idiosyncratic liver injury,but the underlying mechanisms are poorly understood.Increasing evidence has indicated that most cases of IDILI are immune mediated.Here,we report that icarisideⅡ(ICSⅡ),the major active and metabolic constituent of EF,causes idiosyncratic liver injury by promoting NLRP3 inflammasome activation.ICSⅡexacerbates NLRP3 inflammasome activation triggered by adenosine triphosphate(ATP)and nigericin,but not silicon dioxide(SiO2),monosodium urate(MSU)crystal or cytosolic lipopolysaccharide(LPS).Additionally,the activation of NLRC4 and AIM2 inflammasomes is not affected by ICSⅡ.Mechanistically,synergistic induction of mitochondrial reactive oxygen species(mtROS)is a crucial contributor to the enhancing effect of ICSⅡon ATP-or nigericin-induced NLRP3 inflammasome activation.Importantly,in vivo data show that a combination of non-hepatotoxic doses of LPS and ICSⅡcauses the increase of aminotransferase activity,hepatic inflammation and pyroptosis,which is attenuated by Nlrp3 deficiency or pretreatment with MCC950(a specific NLRP3 inflammasome inhibitor).In conclusion,these findings demonstrate that ICSⅡcauses idiosyncratic liver injury through enhancing NLRP3 inflammasome activation and suggest that ICSⅡmay be a risk factor and responsible for EF-induced liver injury.
文摘Background:Coronavirus disease 2019(COVID-19)has killed over 2.5 million people worldwide,but effective care and therapy have yet to be discovered.We conducted this analysis to better understand tocilizumab treatment for COVID-19 patients.Main text:We searched major databases for manuscripts reporting the effects of tocilizumab on COVID-19 patients.A total of 25 publications were analyzed with Revman 5.3 and R for the meta-analysis.Significant better clinical outcomes were found in the tocilizumab treatment group when compared to the standard care group[odds ratio(OR)=0.70,95%confidential interval(CI):0.54-0.90,0.007].Tocilizumab treatment showed a stronger correlation with good prognosis among COVID-19 patients that needed mechanical ventilation(OR=0.59,95%CI:0.37-0.93,P=0.02).
基金the Ministry of Science and Technology of the People’s Republic of China[Grant Number 2020YFC0843700]the fifth round of the Gusu Health Person Training Project[Grant Number GSWS2019050]the Six Talent Peaks Project in Jiangsu Province[Grant Number WSN-058,YY-053,2019].
文摘Background:There have been many studies about coronavirus disease 2019(COVID-19),but the clinical signifi-cance of quantitative serum severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)-specific IgM and IgG levels of COVID-19 patients have not been exhaustively analyzed.We aimed to investigate the time profiles of these IgM/IgG levels in COVID-19 patients and their correlations with clinical features.Methods:A multicenter clinical study was conducted from February 20 to March 52020.It involved 179 COVID-19 patients(108 males and 71 females)from five hospitals in Huangshi in Hubei Province,China.To detect SARS-CoV-2-specific IgM/IgG,quantitative antibody assays(two-step indirect immunoassays with direct chemilu-minescence technology)based on the nucleocapsid protein(NP)and spike protein 1(S1)were used.For normally distributed data,means were compared using the t-test,𝜒2-test,or exact probability method.For categorical data,medians were compared using Mann-Whitney U test.Results:The median age was 57(44-69)years(58[38-69]for males and 57[49-68]for females).The median duration of positive nucleic acid test was 22.32(17.34-27.43)days.The mortality rate was relatively low(3/179,1.68%).Serum SARS-CoV-2-specific IgG was detected around week 1 after illness onset,gradually increased until peaking in weeks 4 and 5,and then declined.Serum IgM peaked in weeks 2 and 3,then gradually declined and returned to its normal range by week 7 in all patients.Notably,children had milder respiratory symptoms with lower SARS-CoV-2-specific IgM/IgG levels.The duration of positive nucleic acid test in the chronic obstructive pulmonary disease(COPD)group was 30.36(18.99-34.76)days,which was significantly longer than that in the non-COPD group(21.52[16.75-26.51]days;P=0.025).The peak serum SARS-CoV-2-specific IgG was sig-nificantly positively correlated with the duration of positive nucleic acid test.The incidence rate of severe and critical cases in the IgM hi group(using the median IgM level of 29.95 AU/mL as the cutofffor grouping)was about 38.0%(19/50),which was twice as much as that in the IgM lo group(18.4%;9/49).The patients with positive chest imaging and lymphocytopenia(<1×10^(9)/L)had a higher SARS-CoV-2-specific IgM level.Conclusions: Quantitative SARS-CoV-2-specific IgM and IgG levels are helpful for the diagnosis, severity classifi- cation, and management of COVID-19 patients, and they should be monitored in each stage of this disease.
基金This work was supported by the National Natural Science Foundation of China(Nos.81770591 and 81800778)Science and Technology Plan of Hainan Province(Clinical Research Center)(LCYX202103)Hainan Province Clinical Medical Center,and the Open Foundation of Key Laboratory of Tropical Translational Medicine of Ministry of Education,Hainan Medical University.
文摘Background:Splenectomy has been reported to improve liver function as well as hypersplenism,but it is still controversial whether splenectomy will further damage the immune function of patients with liver cirrhosis.This study aims to evaluate the impact of splenectomy on the risk of infection in patients with liver cirrhosis.Methods:A total of 4355 patients with liver cirrhosis admitted to the First Affiliated Hospital of Nanjing Medical University from October 1,2016 to September 30,2020 were enrolled.The patients were first divided into the splenectomy group(SG)and the nonsplenectomy group(NSG).After standardization,patients were further divided according to the stage of cirrhosis.Infection rates in different stages were calculated,respectively.Laboratory results and infection sites of patients with cirrhosis were analyzed in combination with clinical data.Continuous variables conforming to normal distribution were presented as mean±standard deviation,compared by sample t test or paired sample t test.Non-normal variables were presented as the median(interquartile range)and compared by Mann-Whitney U test or Wilcoxon signed rank test.Results:Five hundred and two patients received splenectomy and 3853 patients did not.Bacterial infection was diagnosed in 497 of the 4355(11.41%)hospitalizations of patients with cirrhosis.The infection rate of the compensated cirrhosis SG was higher than that of the NSG(8.06%vs.5.18%,P<0.05).However,the infection rate in the SG with decompensated cirrhosis was lower than that in the NSG(11.35%vs.22.22%,P<0.001).The peak level of leukocytes did not differ significantly between the SG with compensated liver cirrhosis and the NSG[11.97(7.65)109/L vs.12.19(14.04)109/L,P>0.05].The peak value of leukocytes in SG suffering from decompensated liver cirrhosis was significantly higher than that in NSG[12.29(11.52)109/L vs.6.37(8.90)109/L,P=0.004].Patients with decompensated liver cirrhosis had a significantly higher rate of abdominal infection than patients with compensated liver cirrhosis,and splenectomy itself did not affect the sites of infection.Conclusions:Splenectomy increases the risk of infection for patients with compensated liver cirrhosis,but significantly decreases the risk in patients with decompensated liver cirrhosis.