Nonalcoholic fatty liver disease(NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consu...Nonalcoholic fatty liver disease(NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis(NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma(HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type Ⅱ diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear toexperience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.展开更多
BACKGROUND Type I Helicobacter pylori(H.pylori)infection causes severe gastric inflammation and is a predisposing factor for gastric carcinogenesis.However,its infection status in stepwise gastric disease progression ...BACKGROUND Type I Helicobacter pylori(H.pylori)infection causes severe gastric inflammation and is a predisposing factor for gastric carcinogenesis.However,its infection status in stepwise gastric disease progression in this gastric cancer prevalent area has not been evaluated;it is also not known its impact on commonly used epidemiological gastric cancer risk markers such as gastrin-17(G-17)and pepsinogens(PGs)during clinical practice.AIM To explore the prevalence of type I and type II H.pylori infection status and their impact on G-17 and PG levels in clinical practice.METHODS Thirty-five hundred and seventy-two hospital admitted patients with upper gastrointestinal symptoms were examined,and 523 patients were enrolled in this study.H.pylori infection was confirmed by both 13C-urea breath test and serological assay.Patients were divided into non-atrophic gastritis(NAG),nonatrophic gastritis with erosion(NAGE),chronic atrophic gastritis(CAG),peptic ulcers(PU)and gastric cancer(GC)groups.Their serological G-17,PG I and PG II values and PG I/PG II ratio were also measured.RESULTS A total H.pylori infection rate of 3572 examined patients was 75.9%,the infection rate of 523 enrolled patients was 76.9%,among which type I H.pylori infection accounted for 72.4%(291/402)and type II was 27.6%;88.4%of GC patients were H.pylori positive,and 84.2%of them were type I infection,only 11.6%of GC patients were H.pylori negative.Infection rates of type I H.pylori in NAG,NAGE,CAG,PU and GC groups were 67.9%,62.7%,79.7%,77.6%and 84.2%,respectively.H.pylori infection resulted in significantly higher G-17 and PG II values and decreased PG I/PG II ratio.Both types of H.pylori induced higher G-17 level,but type I strain infection resulted in an increased PG II level and decreased PG I/PG II ratio in NAG,NAGE and CAG groups over uninfected controls.Overall PG I levels showed no difference among all disease groups and in the presence or absence of H.pylori;in stratified analysis,its level was increased in GC and PU patients in H.pylori a展开更多
AIM: To conduct a meta-analysis to compare Roux-en-Y (R-Y) gastrojejunostomy with gastroduodenal Billroth?I?(B-I) anastomosis after distal gastrectomy (DG) for gastric cancer.METHODS: A literature search was performed...AIM: To conduct a meta-analysis to compare Roux-en-Y (R-Y) gastrojejunostomy with gastroduodenal Billroth?I?(B-I) anastomosis after distal gastrectomy (DG) for gastric cancer.METHODS: A literature search was performed to identify studies comparing R-Y with B-I?after DG for gastric cancer from January 1990 to November 2012 in Medline, Embase, Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials in The Cochrane Library. Pooled odds ratios (OR) or weighted mean differences (WMD) with 95%CI were calculated using either ?xed or random effects model. Operative outcomes such as operation time, intraoperative blood loss and postoperative outcomes such as anastomotic leakage and stricture, bile re?ux, remnant gastritis, re?ux esophagitis, dumping symptoms, delayed gastric emptying and hospital stay were the main outcomes assessed. Meta-analyses were performed using RevMan 5.0 software (Cochrane library).RESULTS: Four randomized controlled trials (RCTs) and 9 non-randomized observational clinical studies (OCS) involving 478 and 1402 patients respectively were included. Meta-analysis of RCTs revealed that R-Y reconstruction was associated with a reduced bile re?ux (OR 0.04, 95%CI: 0.01, 0.14; P < 0.00?001) and remnant gastritis (OR 0.43, 95%CI: 0.28, 0.66; P = 0.0001), however needing a longer operation time (WMD 40.02, 95%CI: 13.93, 66.11; P = 0.003). Meta-analysis of OCS also revealed R-Y reconstruction had a lower incidence of bile re?ux (OR 0.21, 95%CI: 0.08, 0.54; P = 0.001), remnant gastritis (OR 0.18, 95%CI: 0.11, 0.29; P < 0.00?001) and re?ux esophagitis (OR 0.48, 95%CI: 0.26, 0.89; P = 0.02). However, this reconstruction method was found to be associated with a longer operation time (WMD 31.30, 95%CI: 12.99, 49.60; P = 0.0008).CONCLUSION: This systematic review point towards some clinical advantages that are rendered by R-Y compared to B-I?reconstruction post DG. However there is a need for further adequately powered, well-designed RCTs comparing the same.展开更多
Hepatocellular carcinoma(HCC)is among the leading causes of cancer-related mortality.The principal treatment is surgical resection or liver transplantation,depending on whether the patient is a suitable transplant can...Hepatocellular carcinoma(HCC)is among the leading causes of cancer-related mortality.The principal treatment is surgical resection or liver transplantation,depending on whether the patient is a suitable transplant candidate.However,in most patients with HCC the diagnosis is often late,thereby excluding the patients from definitive surgical resection.Medical treatment includes sorafenib,which is the most commonly used systemic therapy;although,it has been shown to only minimally impact patient survival by several months.Chemotherapy and radiotherapy are generally ineffective.Due to the poor prognosis of patients with HCC,newer treatments are needed with several being in development,either in preclinical or clinical studies.In this review article,we provide an update on the current and future medical and surgical management of HCC.展开更多
Background: The poultry industry is in need of effective antibiotic alternatives to control outbreaks of necrotic enteritis(NE) due to Clostridium perfringens.Methods: This study was conducted to investigate the effec...Background: The poultry industry is in need of effective antibiotic alternatives to control outbreaks of necrotic enteritis(NE) due to Clostridium perfringens.Methods: This study was conducted to investigate the effects of feeding Bacil us coagulans on the growth performance and gut health of broiler chickens with C. perfringens-induced NE. Two hundred and forty 1-day-old broiler chicks were randomly assigned to a 2 × 2 factorial arrangement with two dietary B. coagulans levels(0 or 4 × 109 CFU/kg of diet) and two disease chal enge statuses(control or NE chal enged).Results: NE-induced reduction in body weight gain was relieved by the addition of B. coagulans into broiler diets compared with the NE-infected birds. NE infection damaged intestinal morphological structure, promoted intestinal C.perfringens growth and liver invasion, and enhanced anti-C. perfringens specific sI gA concentrations in the gut and specific IgG levels in serum compared with the uninfected birds. NE infection significantly(P < 0.05) decreased mucin-2(at 14 d post-infection(DPI), tol-like receptor 2(TLR2, at 7 and 14 DPI), TLR4(at 7 and 14 DPI), tumor necrosis factor super family15(TNFSF15, at 7 and 14 DPI), lysozyme(LYZ, at 14 DPI) and fowlicidin-2(at 7 and 14 DPI) mR NA levels, whereas it dramatical y(P = 0.001) increased IFN-γ mR NA levels at 7 DPI. However, chal enged birds fed diets supplemented with B.coagulans showed a significant(P < 0.01) decrease in gut lesion scores, decreased C. perfringens numbers in the cecum and liver, and an increase in fowlicidin-2 mR NA levels in compared with the uninfected birds. In addition, compared with the non-supplemented group, dietary inclusion of B. coagulans improved intestinal barrier structure, further increased specific sI gA levels and alkaline phosphatase(IAP) activity in the jejunum, enhanced the expression of jejunum lysozyme mR NA, and inhibited the growth, colonization, and invasion of C. perfringens; in contrast, it reduced serum-specific IgG concentrations and jejunum IFN-γ mR NA 展开更多
The recent pandemic of coronavirus disease 2019(COVID-19)caused by SARS-CoV-2 has raised global health concerns.The viral 3-chymotrypsin-like cysteine protease(3CL^pro)enzyme controls coronavirus replication and is es...The recent pandemic of coronavirus disease 2019(COVID-19)caused by SARS-CoV-2 has raised global health concerns.The viral 3-chymotrypsin-like cysteine protease(3CL^pro)enzyme controls coronavirus replication and is essential for its life cycle.3CL^pro is a proven drug discovery target in the case of severe acute respiratory syndrome coronavirus(SARS-CoV)and Middle East respiratory syndrome coronavirus(MERS-CoV).Recent studies revealed that the genome sequence of SARS-CoV-2 is very similar to that of SARS-CoV.Therefore,herein,we analysed the 3CL^pro sequence,constructed its 3D homology model,and screened it against a medicinal plant library containing 32,297 potential anti-viral phytochemicals/traditional Chinese medicinal compounds.Our analyses revealed that the top nine hits might serve as potential anti-SARS-CoV-2 lead molecules for further optimisation and drug development process to combat COVID-19.展开更多
BACKGROUND: Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay ...BACKGROUND: Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay of these inflammatory mediators and switching of immune responses during hepatotoxic, viral, drug-induced and immune cell-mediated hepatitis decide the fate of liver pathology. The present review aimed to describe the mechanisms of liver injury, its relevance to human liver pathology and insights for the future therapeutic interventions.DATA SOURCES: The data of mouse hepatic models and rele- vant human liver diseases presented in this review are system- atically collected from PubMed, ScienceDirect and the Web of Science databases published in English. RESULTS: The hepatotoxic liver injury in mice induced by the metabolites of CC14, acetaminophen or alcohol represent ne- crotic cell death with activation of cytochrome pathway, for- mation of reactive oxygen species (ROS) and mitochondrial damage. The Fas or TNF-a induced apoptotic liver injury was dependent on activation of caspases, release of cytochrome c and apoptosome formation. The ConA-hepatitis demonstrat- ed the involvement of TRAIL-dependent necrotic/necroptotic cell death with activation of RIPK1/3. The a-GalCer-induced liver injury was mediated by TNF-a. The LPS-induced hepatitis involved TNF-a, Fas/FasL, and perforin/granzyme cell death pathways. The MHV3 or Poly(I:C) induced liver injury was mediated by natural killer cells and TNF-a signaling. The necrotic ischemia-reperfusion liver injury was mediated by hypoxia, ROS, and pro-inflammatory cytokines; however, necroptotic cell death was found in partial hepatectomy. The crucial role of immune ceils and cell death mediators in viral hepatitis (HBV, HCV), drug-induced liver injury, non-alcohol- ic fatty liver disease and alcoholic liver disease in human were discussed. CONCLUSIONS: The mouse animal models of hepatitis provide a parallel approach for the study of human展开更多
Maize/peanut intercropping system shows the significant yield advantage. Soil microbes play major roles in soil nutrient cycling and were affected by intercropping plants. This experiment was carried out to evaluate t...Maize/peanut intercropping system shows the significant yield advantage. Soil microbes play major roles in soil nutrient cycling and were affected by intercropping plants. This experiment was carried out to evaluate the changing of rhizosphere microbial community composition, and the relationship between microbial community and soil enzymatic activities, soil nutrients in maize/peanut intercropping system under the following three treatments: maize (Zea mays L.) and peanut (Arachis hypogaea L.) were intercropped without any separation (NS), by half separation (HS) using a nylon net (50 μm) and complete separation (CS) by using a plastic sheet, respectively. The soil microbial communities were assessed by phospholipid fatty acid (PLFA). We found that soil available nutrients (available nitrogen (Avail N) and available phosphorus (Avail P)) and enzymatic activities (soil urase and phosphomonoesterase) in both crops were improved in NS and HS treatments as compared to CS. Both bacterial and fungal biomasses in both crops were increased in NS followed by HS. Furthermore, Gram-positive bacteria (G+) in maize soils were significant higher in NS and HS than CS, while the Gram-negative (G-) was significant higher in peanut soil. The ratio of normal saturated to monounsaturated PLFAs was significantly higher in rhizosphere of peanut under CS treatment than in any other treatments, which is an indicator of nutrient stress. Redundancy analysis and cluster analysis of PLFA showed rhizospheric microbial community of NS and HS of both plants tended to be consistent. The urase and Avail N were higher in NS and HS of both plants and positively correlated with bacteria, fungi (F) and total PLFAs, while negatively correlated with G+/G- and NS/MS. The findings suggest that belowground interactions in maize/peanut intercropping system play important roles in changing the soil microbial composition and the dominant microbial species, which was closely related with the imp展开更多
AIM:To conduct a meta-analysis to determine the safety and efficacy of laparoscopic liver resection(LLR) and open liver resection(OLR) for hepatocellular carcinoma(HCC).METHODS:PubMed(Medline),EMBASE and Science Citat...AIM:To conduct a meta-analysis to determine the safety and efficacy of laparoscopic liver resection(LLR) and open liver resection(OLR) for hepatocellular carcinoma(HCC).METHODS:PubMed(Medline),EMBASE and Science Citation Index Expanded and Cochrane Central Register of Controlled Trials in the Cochrane Library were searched systematically to identify relevant comparative studies reporting outcomes for both LLR and OLR for HCC between January 1992 and February 2012.Two authors independently assessed the trials for inclusion and extracted the data.Meta-analysis was performed using Review Manager Version 5.0 software(The Cochrane Collaboration,Oxford,United Kingdom).Pooled odds ratios(OR) or weighted mean differences(WMD) with 95%CI were calculated using either fixed effects(Mantel-Haenszel method) or random effects models(DerSimonian and Laird method).Evaluated endpoints were operative outcomes(operation time,intraoperative blood loss,blood transfusion requirement),postoperative outcomes(liver failure,cirrhotic decompensation/ascites,bile leakage,postoperative bleeding,pulmonary complications,intraabdominal abscess,mortality,hospital stay and oncologic outcomes(positive resection margins and tumor recurrence).RESULTS:Fifteen eligible non-randomized studies were identified,out of which,9 high-quality studies involving 550 patients were included,with 234 patients in the LLR group and 316 patients in the OLR group.LLR was associated with significantly lower intraoperative blood loss,based on six studies with 333 patients [WMD:-129.48 mL;95%CI:-224.76-(-34.21) mL;P = 0.008].Seven studies involving 416 patients were included to assess blood transfusion requirement between the two groups.The LLR group had lower blood transfusion requirement(OR:0.49;95%CI:0.26-0.91;P = 0.02).While analyzing hospital stay,six studies with 333 patients were included.Patients in the LLR group were found to have shorter hospital stay [WMD:-3.19 d;95%CI:-4.09-(-2.28) d;P < 0.00001] than their OLR counterpart.Seven studies including 416 patients展开更多
文摘Nonalcoholic fatty liver disease(NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis(NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma(HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type Ⅱ diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear toexperience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.
基金Supported by National Natural Science Foundation of China,No.U1604174Henan Provincial Government-Health and Family Planning Commission,No.20170123+1 种基金Henan Provincial Government-Health and Family Planning Commission Research Innovative Talents Project,No.51282Henan Provincial Government-Science and Technology Bureau,No.142300410050.
文摘BACKGROUND Type I Helicobacter pylori(H.pylori)infection causes severe gastric inflammation and is a predisposing factor for gastric carcinogenesis.However,its infection status in stepwise gastric disease progression in this gastric cancer prevalent area has not been evaluated;it is also not known its impact on commonly used epidemiological gastric cancer risk markers such as gastrin-17(G-17)and pepsinogens(PGs)during clinical practice.AIM To explore the prevalence of type I and type II H.pylori infection status and their impact on G-17 and PG levels in clinical practice.METHODS Thirty-five hundred and seventy-two hospital admitted patients with upper gastrointestinal symptoms were examined,and 523 patients were enrolled in this study.H.pylori infection was confirmed by both 13C-urea breath test and serological assay.Patients were divided into non-atrophic gastritis(NAG),nonatrophic gastritis with erosion(NAGE),chronic atrophic gastritis(CAG),peptic ulcers(PU)and gastric cancer(GC)groups.Their serological G-17,PG I and PG II values and PG I/PG II ratio were also measured.RESULTS A total H.pylori infection rate of 3572 examined patients was 75.9%,the infection rate of 523 enrolled patients was 76.9%,among which type I H.pylori infection accounted for 72.4%(291/402)and type II was 27.6%;88.4%of GC patients were H.pylori positive,and 84.2%of them were type I infection,only 11.6%of GC patients were H.pylori negative.Infection rates of type I H.pylori in NAG,NAGE,CAG,PU and GC groups were 67.9%,62.7%,79.7%,77.6%and 84.2%,respectively.H.pylori infection resulted in significantly higher G-17 and PG II values and decreased PG I/PG II ratio.Both types of H.pylori induced higher G-17 level,but type I strain infection resulted in an increased PG II level and decreased PG I/PG II ratio in NAG,NAGE and CAG groups over uninfected controls.Overall PG I levels showed no difference among all disease groups and in the presence or absence of H.pylori;in stratified analysis,its level was increased in GC and PU patients in H.pylori a
文摘AIM: To conduct a meta-analysis to compare Roux-en-Y (R-Y) gastrojejunostomy with gastroduodenal Billroth?I?(B-I) anastomosis after distal gastrectomy (DG) for gastric cancer.METHODS: A literature search was performed to identify studies comparing R-Y with B-I?after DG for gastric cancer from January 1990 to November 2012 in Medline, Embase, Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials in The Cochrane Library. Pooled odds ratios (OR) or weighted mean differences (WMD) with 95%CI were calculated using either ?xed or random effects model. Operative outcomes such as operation time, intraoperative blood loss and postoperative outcomes such as anastomotic leakage and stricture, bile re?ux, remnant gastritis, re?ux esophagitis, dumping symptoms, delayed gastric emptying and hospital stay were the main outcomes assessed. Meta-analyses were performed using RevMan 5.0 software (Cochrane library).RESULTS: Four randomized controlled trials (RCTs) and 9 non-randomized observational clinical studies (OCS) involving 478 and 1402 patients respectively were included. Meta-analysis of RCTs revealed that R-Y reconstruction was associated with a reduced bile re?ux (OR 0.04, 95%CI: 0.01, 0.14; P < 0.00?001) and remnant gastritis (OR 0.43, 95%CI: 0.28, 0.66; P = 0.0001), however needing a longer operation time (WMD 40.02, 95%CI: 13.93, 66.11; P = 0.003). Meta-analysis of OCS also revealed R-Y reconstruction had a lower incidence of bile re?ux (OR 0.21, 95%CI: 0.08, 0.54; P = 0.001), remnant gastritis (OR 0.18, 95%CI: 0.11, 0.29; P < 0.00?001) and re?ux esophagitis (OR 0.48, 95%CI: 0.26, 0.89; P = 0.02). However, this reconstruction method was found to be associated with a longer operation time (WMD 31.30, 95%CI: 12.99, 49.60; P = 0.0008).CONCLUSION: This systematic review point towards some clinical advantages that are rendered by R-Y compared to B-I?reconstruction post DG. However there is a need for further adequately powered, well-designed RCTs comparing the same.
文摘Hepatocellular carcinoma(HCC)is among the leading causes of cancer-related mortality.The principal treatment is surgical resection or liver transplantation,depending on whether the patient is a suitable transplant candidate.However,in most patients with HCC the diagnosis is often late,thereby excluding the patients from definitive surgical resection.Medical treatment includes sorafenib,which is the most commonly used systemic therapy;although,it has been shown to only minimally impact patient survival by several months.Chemotherapy and radiotherapy are generally ineffective.Due to the poor prognosis of patients with HCC,newer treatments are needed with several being in development,either in preclinical or clinical studies.In this review article,we provide an update on the current and future medical and surgical management of HCC.
基金The National Special Fund for Agro-Scientific Research in the Public Interest(20140304–07)the National Broiler Industry Technology Project(No.31072049)supported this study
文摘Background: The poultry industry is in need of effective antibiotic alternatives to control outbreaks of necrotic enteritis(NE) due to Clostridium perfringens.Methods: This study was conducted to investigate the effects of feeding Bacil us coagulans on the growth performance and gut health of broiler chickens with C. perfringens-induced NE. Two hundred and forty 1-day-old broiler chicks were randomly assigned to a 2 × 2 factorial arrangement with two dietary B. coagulans levels(0 or 4 × 109 CFU/kg of diet) and two disease chal enge statuses(control or NE chal enged).Results: NE-induced reduction in body weight gain was relieved by the addition of B. coagulans into broiler diets compared with the NE-infected birds. NE infection damaged intestinal morphological structure, promoted intestinal C.perfringens growth and liver invasion, and enhanced anti-C. perfringens specific sI gA concentrations in the gut and specific IgG levels in serum compared with the uninfected birds. NE infection significantly(P < 0.05) decreased mucin-2(at 14 d post-infection(DPI), tol-like receptor 2(TLR2, at 7 and 14 DPI), TLR4(at 7 and 14 DPI), tumor necrosis factor super family15(TNFSF15, at 7 and 14 DPI), lysozyme(LYZ, at 14 DPI) and fowlicidin-2(at 7 and 14 DPI) mR NA levels, whereas it dramatical y(P = 0.001) increased IFN-γ mR NA levels at 7 DPI. However, chal enged birds fed diets supplemented with B.coagulans showed a significant(P < 0.01) decrease in gut lesion scores, decreased C. perfringens numbers in the cecum and liver, and an increase in fowlicidin-2 mR NA levels in compared with the uninfected birds. In addition, compared with the non-supplemented group, dietary inclusion of B. coagulans improved intestinal barrier structure, further increased specific sI gA levels and alkaline phosphatase(IAP) activity in the jejunum, enhanced the expression of jejunum lysozyme mR NA, and inhibited the growth, colonization, and invasion of C. perfringens; in contrast, it reduced serum-specific IgG concentrations and jejunum IFN-γ mR NA
基金This work was supported by the National Key Research and Development Program of China(2020YFC0845600)the Hubei Provincial Natural Science Foundation of China(2019CFA014)+1 种基金the Starting Research Grant for High-level Talents from Guangxi University,Nanning,ChinaPostdoctoral Research Platform Grant of Guangxi University,Nanning,China.
文摘The recent pandemic of coronavirus disease 2019(COVID-19)caused by SARS-CoV-2 has raised global health concerns.The viral 3-chymotrypsin-like cysteine protease(3CL^pro)enzyme controls coronavirus replication and is essential for its life cycle.3CL^pro is a proven drug discovery target in the case of severe acute respiratory syndrome coronavirus(SARS-CoV)and Middle East respiratory syndrome coronavirus(MERS-CoV).Recent studies revealed that the genome sequence of SARS-CoV-2 is very similar to that of SARS-CoV.Therefore,herein,we analysed the 3CL^pro sequence,constructed its 3D homology model,and screened it against a medicinal plant library containing 32,297 potential anti-viral phytochemicals/traditional Chinese medicinal compounds.Our analyses revealed that the top nine hits might serve as potential anti-SARS-CoV-2 lead molecules for further optimisation and drug development process to combat COVID-19.
基金supported by a grant from Higher Education Commission(HEC)at University of Agriculture,Faisalabad,Pakistan(No.20-4613/NRPU/R&D/HEC/14/45)
文摘BACKGROUND: Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay of these inflammatory mediators and switching of immune responses during hepatotoxic, viral, drug-induced and immune cell-mediated hepatitis decide the fate of liver pathology. The present review aimed to describe the mechanisms of liver injury, its relevance to human liver pathology and insights for the future therapeutic interventions.DATA SOURCES: The data of mouse hepatic models and rele- vant human liver diseases presented in this review are system- atically collected from PubMed, ScienceDirect and the Web of Science databases published in English. RESULTS: The hepatotoxic liver injury in mice induced by the metabolites of CC14, acetaminophen or alcohol represent ne- crotic cell death with activation of cytochrome pathway, for- mation of reactive oxygen species (ROS) and mitochondrial damage. The Fas or TNF-a induced apoptotic liver injury was dependent on activation of caspases, release of cytochrome c and apoptosome formation. The ConA-hepatitis demonstrat- ed the involvement of TRAIL-dependent necrotic/necroptotic cell death with activation of RIPK1/3. The a-GalCer-induced liver injury was mediated by TNF-a. The LPS-induced hepatitis involved TNF-a, Fas/FasL, and perforin/granzyme cell death pathways. The MHV3 or Poly(I:C) induced liver injury was mediated by natural killer cells and TNF-a signaling. The necrotic ischemia-reperfusion liver injury was mediated by hypoxia, ROS, and pro-inflammatory cytokines; however, necroptotic cell death was found in partial hepatectomy. The crucial role of immune ceils and cell death mediators in viral hepatitis (HBV, HCV), drug-induced liver injury, non-alcohol- ic fatty liver disease and alcoholic liver disease in human were discussed. CONCLUSIONS: The mouse animal models of hepatitis provide a parallel approach for the study of human
基金supported by grants from the National Natural Science Foundation of China (81303170, 2012CB126309 and U1205021)the Chinese Postdoctoral Science Foundation (2013M541849)
文摘Maize/peanut intercropping system shows the significant yield advantage. Soil microbes play major roles in soil nutrient cycling and were affected by intercropping plants. This experiment was carried out to evaluate the changing of rhizosphere microbial community composition, and the relationship between microbial community and soil enzymatic activities, soil nutrients in maize/peanut intercropping system under the following three treatments: maize (Zea mays L.) and peanut (Arachis hypogaea L.) were intercropped without any separation (NS), by half separation (HS) using a nylon net (50 μm) and complete separation (CS) by using a plastic sheet, respectively. The soil microbial communities were assessed by phospholipid fatty acid (PLFA). We found that soil available nutrients (available nitrogen (Avail N) and available phosphorus (Avail P)) and enzymatic activities (soil urase and phosphomonoesterase) in both crops were improved in NS and HS treatments as compared to CS. Both bacterial and fungal biomasses in both crops were increased in NS followed by HS. Furthermore, Gram-positive bacteria (G+) in maize soils were significant higher in NS and HS than CS, while the Gram-negative (G-) was significant higher in peanut soil. The ratio of normal saturated to monounsaturated PLFAs was significantly higher in rhizosphere of peanut under CS treatment than in any other treatments, which is an indicator of nutrient stress. Redundancy analysis and cluster analysis of PLFA showed rhizospheric microbial community of NS and HS of both plants tended to be consistent. The urase and Avail N were higher in NS and HS of both plants and positively correlated with bacteria, fungi (F) and total PLFAs, while negatively correlated with G+/G- and NS/MS. The findings suggest that belowground interactions in maize/peanut intercropping system play important roles in changing the soil microbial composition and the dominant microbial species, which was closely related with the imp
文摘AIM:To conduct a meta-analysis to determine the safety and efficacy of laparoscopic liver resection(LLR) and open liver resection(OLR) for hepatocellular carcinoma(HCC).METHODS:PubMed(Medline),EMBASE and Science Citation Index Expanded and Cochrane Central Register of Controlled Trials in the Cochrane Library were searched systematically to identify relevant comparative studies reporting outcomes for both LLR and OLR for HCC between January 1992 and February 2012.Two authors independently assessed the trials for inclusion and extracted the data.Meta-analysis was performed using Review Manager Version 5.0 software(The Cochrane Collaboration,Oxford,United Kingdom).Pooled odds ratios(OR) or weighted mean differences(WMD) with 95%CI were calculated using either fixed effects(Mantel-Haenszel method) or random effects models(DerSimonian and Laird method).Evaluated endpoints were operative outcomes(operation time,intraoperative blood loss,blood transfusion requirement),postoperative outcomes(liver failure,cirrhotic decompensation/ascites,bile leakage,postoperative bleeding,pulmonary complications,intraabdominal abscess,mortality,hospital stay and oncologic outcomes(positive resection margins and tumor recurrence).RESULTS:Fifteen eligible non-randomized studies were identified,out of which,9 high-quality studies involving 550 patients were included,with 234 patients in the LLR group and 316 patients in the OLR group.LLR was associated with significantly lower intraoperative blood loss,based on six studies with 333 patients [WMD:-129.48 mL;95%CI:-224.76-(-34.21) mL;P = 0.008].Seven studies involving 416 patients were included to assess blood transfusion requirement between the two groups.The LLR group had lower blood transfusion requirement(OR:0.49;95%CI:0.26-0.91;P = 0.02).While analyzing hospital stay,six studies with 333 patients were included.Patients in the LLR group were found to have shorter hospital stay [WMD:-3.19 d;95%CI:-4.09-(-2.28) d;P < 0.00001] than their OLR counterpart.Seven studies including 416 patients