Background:Human infections with zoonotic coronaviruses(CoVs),including severe acute respiratory syndrome(SARS)-CoV and Middle East respiratory syndrome(MERS)-CoV,have raised great public health concern globally.Here,...Background:Human infections with zoonotic coronaviruses(CoVs),including severe acute respiratory syndrome(SARS)-CoV and Middle East respiratory syndrome(MERS)-CoV,have raised great public health concern globally.Here,we report a novel batorigin CoV causing severe and fatal pneumonia in humans.Methods:We collected clinical data and bronchoalveolar lavage(BAL)specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital,Hubei province,China.Nucleic acids of the BAL were extracted and subjected to next-generation sequencing.Virus isolation was carried out,and maximum-likelihood phylogenetic trees were constructed.Results:Five patients hospitalized from December 18 to December 29,2019 presented with fever,cough,and dyspnea accompanied by complications of acute respiratory distress syndrome.Chest radiography revealed diffuse opacities and consolidation.One of these patients died.Sequence results revealed the presence of a previously unknownβ-CoV strain in all five patients,with 99.8%to 99.9%nucleotide identities among the isolates.These isolates showed 79.0%nucleotide identity with the sequence of SARS-CoV(GenBank NC_004718)and 51.8%identity with the sequence of MERS-CoV(GenBank NC_019843).The virus is phylogenetically closest to a bat SARS-like CoV(SL-ZC45,GenBank MG772933)with 87.6%to 87.7%nucleotide identity,but is in a separate clade.Moreover,these viruses have a single intact open reading frame gene 8,as a further indicator of bat-origin CoVs.However,the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV,indicating that these viruses might use the same receptor.Conclusion:A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.展开更多
AIM:To investigate the effects of early enteral nutrition (EEN) on the immune function and clinical outcome of patients with severe acute pancreatitis (SAP).METHODS:Patients were randomly allocated to receive EEN or d...AIM:To investigate the effects of early enteral nutrition (EEN) on the immune function and clinical outcome of patients with severe acute pancreatitis (SAP).METHODS:Patients were randomly allocated to receive EEN or delayed enteral nutrition (DEN).Enteral nutrition was started within 48 h after admission in EEN group,whereas from the 8 th day in DEN group.All the immunologic parameters and C-reactive protein (CRP) levels were collected on days 1,3,7 and 14 after admission.The clinical outcome variables were also recorded.RESULTS:Sixty SAP patients were enrolled to this study.The CD4+ T-lymphocyte percentage,CD4+/CD8+ ratio,and the CRP levels in EEN group became significantly lower than in DEN group from the 7 th day after admission.In contrast,the immunoglobulin G(IgG) levels and human leukocyte antigen-DR expression in EEN group became significantly higher than in DEN group from the 7 th day after admission.No difference of CD8+ T-lymphocyte percentage,IgM and IgA levels was found between the two groups.The incidences of multiple organ dysfunction syndrome,systemic inflammatory response syndrome,and pancreatic infection as well as the duration of intensive care unit stay were significantly lower in EEN group than in DEN group.However,there was no difference of hospital mortality between the two groups.CONCLUSION:EEN moderates the excessive immune response during the early stage of SAP without leading to subsequent immunosuppression.EEN can improve the clinical outcome,but not decrease the hospital mortality of SAP patients.展开更多
Background No-reflow after emergency percutaneous coronary intervention （PCI） for acute ST segment elevation myocardial infarction （STEMI） is related to the severe prognosis. The aim of this study was to evaluate ...Background No-reflow after emergency percutaneous coronary intervention （PCI） for acute ST segment elevation myocardial infarction （STEMI） is related to the severe prognosis. The aim of this study was to evaluate the efficacy of Tongxinluo, a traditional Chinese medicine, on no-reflow and the infarction area after emergency PCI for STEMI.Methods A total of 219 patients （female 31, 14%） undergoing emergency PCI for STEMI from nine clinical centers were consecutively enrolled in this randomized, double-blind, placebo-controlled, multicenter clinical trial from January 2007 to May 2009. All patients were randomly divided into Tongxinluo group （n=108） and control group （n=111）, given Tongxinluo or placebo in loading dose 2.08 g respectively before emergency PCI with asprin 300 mg and clopidogrel 300 mg together, then 1.04 g three times daily for six months after PCI. The ST segment elevation was recorded by electrocardiogram at hospitalization and 1, 2, 6, 12, 24 hours after coronary balloon dilation to evaluate the myocardial no-flow; myocardial perfusion scores of 17 segments were evaluated on day 7 and day 180 after STEMI with static single-photon emission computed tomography （SPECT） to determine the infarct area.Results There was no statistical significance in sex, age, past history, chest pain, onset-to-reperfusion time, Killip classification, TIMI flow grade just before and after PCI, either in the medication treatment during the follow up such as statin, β-blocker, angiotensin converting enzyme inhibitor （ACEI） or angiotensin receptor blocker （ARB） between two groups. There was significant ST segment restoration in Tongxinluo group compared to the control group at 6 hours （（-0.22±0.18） mV vs. （-0.18±0.16） mV, P=0.0394）, 12 hours （（-0.24 ± 0.18） mV vs. （-0.18±0.15） mV, P=0.0158） and 24 hours （（-0.27±0.16） mV vs. （-0.20±0.16） mV, P=0.0021） reperfusion; and the incidence of myocardial no-reflow was also reduced significantly at 24-hour rep展开更多
Acute pancreatitis is an inflammatory disease of the pancreas.The etiology and pathogenesis of acute pancreatitis have been intensively investigated for centuries worldwide.Many causes of acute pancreatitis have been ...Acute pancreatitis is an inflammatory disease of the pancreas.The etiology and pathogenesis of acute pancreatitis have been intensively investigated for centuries worldwide.Many causes of acute pancreatitis have been discovered,but the pathogenetic theories are controversial.The most common cause of acute pancreatitis is gallstone impacting the distal common bile-pancreatic duct.The majority ofinvestigators accept that the main factors for acute billiary pancreatitis are pancreatic hyperstimulation and bile-pancreatic duct obstruction which increase pancreatic duct pressure and active trypsin reflux.Acute pancreatitis occurs when intracellular protective mechanisms to prevent trypsinogen activation or reduce trypsin activity are overwhelmed.However,little is known about the other acute pancreatitis.We hypothesize that acute biliary pancreatitis and other causes of acute pancreatitis possess a common pathogenesis.Pancreatic hyperstimulation and pancreatic duct obstruction increase pancreatic duct pressure,active trypsin reflux,and subsequent unregulated activation of trypsin within pancreatic acinar cells.Enzyme activation within the pancreas leads to auto-digestion of the gland and local inflammation.Once the hypothesis is confirmed,traditional therapeutic strategies against acute pancreatitis may be improved.Decompression of pancreatic duct pressure should be advocated in the treatment of acute pancreatitits which may greatly improve its outcome.展开更多
The seed germination and seedling growth of pakchoi （Brassica campestris ssp. chinensis var. communis Tsen et Lee cv. Hanxiao） were not significantly inhibited until the concentration of NaCl was increased to 150 mm...The seed germination and seedling growth of pakchoi （Brassica campestris ssp. chinensis var. communis Tsen et Lee cv. Hanxiao） were not significantly inhibited until the concentration of NaCl was increased to 150 mmol/L. Treatment of pakchoi seeds with exogenous 5-aminolevulinic acid （ALA）, at concentrations ranging from 0.01 to 10.00 mg/L, promoted seed germination when seeds were stressed by salinity, whereas levulinic acid （LA）, an inhibitor of ALA dehydrase, significantly inhibited seed germination and seedling growth, suggesting that metabolism of ALA into porphyrin compounds was necessary for seed germination and seedling growth. Determination of respiratory rate during seed germination showed that ALA increased seed respiration under both normal conditions and salt stress. Furthermore, salt stress decreased levels of endogenous ALA, as well as heme, in etiolated seedlings. More salt-tolerant cultivars of pakchoi contained higher relative levels of endogenous ALA and heme under conditions of salt stress. These results indicate that salt stress may inhibit the biosynthesis of endogenous ALA and then heme, which is necessary for seed germination, and treatment of seeds with exogenous ALA prior to germination may be associated with the biosynthesis of heme.展开更多
INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo ...INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo studies[1-5]. Due to limited effectiveness when any anti-carcinogen is used alone and obviously increased toxicity when the dose is raised, there is no exception for As2O3. Furthermore, combined chemotherapy contributes to improve therapeutic effectiveness, disperse toxicity and surmount drug-resistance,in which the combination of traditional Chinese and modern medicine has more advantages and characteristics. As a result,we made an experimental study on anti-tumor effect of As2O3in combination with cisplantin (PDD) or doxorubicin (ADM)on HCC. to investigate the possibility of AS2O3 in combination with PDD or ADM and nature of interaction between them,and to provide experimental basis for clinical application.展开更多
Background： With the progress ofperinatal medicine and neonatal technology, more and more extremely low birth weight （ELBW） survived all over the world. This study was designed to investigate the short-term ontcome...Background： With the progress ofperinatal medicine and neonatal technology, more and more extremely low birth weight （ELBW） survived all over the world. This study was designed to investigate the short-term ontcomes of ELBW infants during their Neonatal Intensive Care Unit （NICU） stay in the mainland of China. Methods： All infants admitted to 26 NICUs with a birth weight （BW） 〈1000 g were included between January 1,2011 and December 31,2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors. Results： A total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age （GA） was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants （23.3%） died and another 69 infants （26.7%） died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas （53.6% vs. 35.3%, P = 0.019）. BW 〈750 g and GA 〈28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization. Conclusions： Our study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.展开更多
BACKGROUND： Disease recurrence is a main challenge in treatment of hepatocellular carcinoma （HCC）. There is no generally accepted method for preventing recurrence of HCC after resection. OBJECTIVE： To compare the ...BACKGROUND： Disease recurrence is a main challenge in treatment of hepatocellular carcinoma （HCC）. There is no generally accepted method for preventing recurrence of HCC after resection. OBJECTIVE： To compare the efficacy of a traditional herbal medicine （THM） regimen and transarterial chemoembolization （TACE） in preventing recurrence in post-resection patients with small HCC. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： This is a multicenter, open- label, randomized, controlled study, which was undertaken in five centers of China. A total of 379 patients who met the eligibility criteria and underwent randomization were enrolled in this trial. One hundred and eighty-eight patients were assigned to the THM group and received Cinobufacini injection and Jiedu Granule, and the other 191 patients were assigned to the TACE group and received one single course of TACE. MAIN OUTCOME MEASURES： Primary outcome measures were the annual recurrence rate and the time to recurrence. Incidence of adverse events was regarded as the secondary outcome measure. RESULTS： Among the 364 patients who were included in the intention-to-treat analysis, 67 patients of the THM group and 87 of the TACE group had recurrence, with a hazard ratio of 0.695 （P = 0.048）. Median recurrence-free survival of the patients in the THM and TACE groups was 46.89 and 34.49 months, respectively. Recurrence rates at 1, 2 and 3 years were 17.7%, 33.0% and 43.5% for the THM group, and 28.8%, 42.5% and 54.0% for the TACE group, respectively （P = 0.026）. Multivariate analysis indicated that the THM regimen had a big advantage for prolonging the recurrence-free survival. Adverse events were mild and abnormality of laboratory indices of the two groups were similar. CONCLUSION： In comparison with TACE therapy, the THM regimen was associated with diminished risk of recurrence of small-sized HCC after resection, with comparable adverse events. TRIAL REGISTRTION IDENTIFIER： This trial was registered in the Chinese Clinical Trial Re展开更多
The efficacy and safety of bevacizumab with modified irinotecan,leucovorin bolus,and 5-fluorouracil intravenous infusion(mIFL) in the first-line treatment of metastatic colorectal cancer(mCRC) has not been well evalua...The efficacy and safety of bevacizumab with modified irinotecan,leucovorin bolus,and 5-fluorouracil intravenous infusion(mIFL) in the first-line treatment of metastatic colorectal cancer(mCRC) has not been well evaluated in randomized clinical trials in Chinese patients.We conducted a phrase Ⅲ trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan(125 mg/m2),leucovorin(20 mg/m2) bolus,and 5-fluorouracil intravenous infusion(500 mg/m2) weekly for four weeks every six weeks] plus bevacizumab(5 mg/kg every two weeks) group and the mIFL group,respectively.Co-primary objectives were progression-free survival(PFS) and 6-month PFS rate.In total,214 patients were enrolled.Our results showed that addition of bevacizumab to mIFL significantly improved median PFS(4.2 months in the mIFL group vs.8.3 months in the bevacizumab plus mIFL group,P < 0.001),6-month PFS rate(25.0% vs.62.6%,P < 0.001),median overall survival(13.4 months vs.18.7 months,P = 0.014),and response rate(17% vs.35%,P = 0.013).Grades 3 and 4 adverse events included diarrhea(21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia(19% in the mIFL group and 33% in the bevacizumab plus mIFL group).No wound-healing complications or congestive heart failure occurred.Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC.Clinical benefit and safety profiles were consistent with those observed in pivotal phase Ⅲ trials with mainly Caucasian patients.展开更多
Epimedii Folium(EF)combined with Psoraleae Fructus(PF)is a common modern preparation,but liver injury caused by Chinese patent medicine preparations containing EF and PF has been frequently reported in recent years.Zh...Epimedii Folium(EF)combined with Psoraleae Fructus(PF)is a common modern preparation,but liver injury caused by Chinese patent medicine preparations containing EF and PF has been frequently reported in recent years.Zhuangguguanjiewan pills(ZGW),which contain EF and PF,could induce immune idiosyncratic liver injury according to clinical case reports and a nonhepatotoxic dose of lipopolysaccharide(LPS)model.This present study evaluated the liver injury induced by EF or PF alone or in combination and investigated the related mechanism by using the LPS model.Liver function indexes and pathological results showed that either EF or PF alone or in combination led to liver injury in normal rats;however,EF or PF alone could lead to liver injury in LPS-treated rats.Moreover,EF combined with PF could induce a greater degree of injury than that caused by EF or PF alone in LPS-treated rats.Furthermore,EF or PF alone or in combination enhanced the LPS-stimulated inflammatory cytokine production,implying that IL-1β,which is processed and released by activating the NLRP3 inflammasome,is a specific indicator of EF-induced immune idiosyncratic hepatotoxicity.Thus,EF may induce liver injury through enhancing the LPS-mediated proinflammatory cytokine production and activating the NLRP3 inflammasome.In addition,the metabolomics analysis results showed that PF affected more metabolites in glycerophospholipid and sphingolipid metabolic pathways compared with EF in LPS model,suggesting that PF increased the responsiveness of the liver to LPS or other inflammatory mediators via modulation of multiple metabolic pathways.Therefore,EF and PF combination indicates traditional Chinese medicine incompatibility,considering that it induces idiosyncratic hepatotoxicity under immunological stress conditions.展开更多
AIM To investigate effect of losartan,an AT1receptor antagonist,on hepatic fibrosis induced byCCl<sub>;</sub>and to determine whether or not AT1receptors are expressed on hepatic stellate cells,METHODS AND...AIM To investigate effect of losartan,an AT1receptor antagonist,on hepatic fibrosis induced byCCl<sub>;</sub>and to determine whether or not AT1receptors are expressed on hepatic stellate cells,METHODS AND RESULTS Fifty male Sprague-Dawley rats,weighing（180±20）g,wererandomized into five groups（control group,modelgroup,and three losartan treated groups）,inwhich all rats were given the subcutaneousinjection of 40% CCl<sub>4</sub>（every 3 days for 6 weeks）except for rats of control group.Rats of losartan-treated groups were treated with losartan（20 mg/kg,10 mg/kg,5 mg/kg,daily gavage）,After 6weeks liver tissue and serum samples of all ratswere examined.Serum hyaluronic acid（HA）,procollagen typeⅢ（PCⅢ）were detected byradioimmunoassays,van Giesion collagen stainingwas used to evaluate the extracellular matrix of ratswith liver fibrosis.The expression of AT1receptors,transforming growth factor-beta（TGF-β）,and alpha-smooth muscle actin（a-SMA）inliver tissue were determined byimmunohistochemical techniques.Compared withmodel group,serum ALT and AST of losartan-treated groups were significantly reduced（t=4.20,P【0.01 and t=4.57,P【0.01）.Serum HAand PCⅢalso had significant differences（t=3.53,P【0.01 and t=2.20,P【0.05）.Thedegree of fibrosis was improved by losartan and correlated with the expressions of AT1 receptors,TGF-β,and α-SMA in liver tissue.CONCLUSION AT1 receptor antagonist,losartan,could limit the progression of the hepatic fibrosisinduced by CCl<sub>4</sub>.The mechanism may be related tothe decrease in the expression of AT1 receptorsand TGF-β,ameliorating the injury of hepatocytes;activation of local renin-angiotensin system mightrelate to hepatic fibrosis;and during progressionof fibrosis,activated hepatic stellate cells mightexpress AT1 receptors.展开更多
基金This study was supported by grants from the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(No.2016-I2M-1-014)the National Major Science&Technology Project for Control and Prevention of Major Infectious Diseases in China(Nos.2017ZX10103004,2018ZX10305409,2017ZX10204401)the National Natural Science Foundation(No.81930063)
文摘Background:Human infections with zoonotic coronaviruses(CoVs),including severe acute respiratory syndrome(SARS)-CoV and Middle East respiratory syndrome(MERS)-CoV,have raised great public health concern globally.Here,we report a novel batorigin CoV causing severe and fatal pneumonia in humans.Methods:We collected clinical data and bronchoalveolar lavage(BAL)specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital,Hubei province,China.Nucleic acids of the BAL were extracted and subjected to next-generation sequencing.Virus isolation was carried out,and maximum-likelihood phylogenetic trees were constructed.Results:Five patients hospitalized from December 18 to December 29,2019 presented with fever,cough,and dyspnea accompanied by complications of acute respiratory distress syndrome.Chest radiography revealed diffuse opacities and consolidation.One of these patients died.Sequence results revealed the presence of a previously unknownβ-CoV strain in all five patients,with 99.8%to 99.9%nucleotide identities among the isolates.These isolates showed 79.0%nucleotide identity with the sequence of SARS-CoV(GenBank NC_004718)and 51.8%identity with the sequence of MERS-CoV(GenBank NC_019843).The virus is phylogenetically closest to a bat SARS-like CoV(SL-ZC45,GenBank MG772933)with 87.6%to 87.7%nucleotide identity,but is in a separate clade.Moreover,these viruses have a single intact open reading frame gene 8,as a further indicator of bat-origin CoVs.However,the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV,indicating that these viruses might use the same receptor.Conclusion:A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
基金Supported by Grants from the Key Project of the Eleventh Five-Year Plan of People's Liberation Army,No.06G041
文摘AIM:To investigate the effects of early enteral nutrition (EEN) on the immune function and clinical outcome of patients with severe acute pancreatitis (SAP).METHODS:Patients were randomly allocated to receive EEN or delayed enteral nutrition (DEN).Enteral nutrition was started within 48 h after admission in EEN group,whereas from the 8 th day in DEN group.All the immunologic parameters and C-reactive protein (CRP) levels were collected on days 1,3,7 and 14 after admission.The clinical outcome variables were also recorded.RESULTS:Sixty SAP patients were enrolled to this study.The CD4+ T-lymphocyte percentage,CD4+/CD8+ ratio,and the CRP levels in EEN group became significantly lower than in DEN group from the 7 th day after admission.In contrast,the immunoglobulin G(IgG) levels and human leukocyte antigen-DR expression in EEN group became significantly higher than in DEN group from the 7 th day after admission.No difference of CD8+ T-lymphocyte percentage,IgM and IgA levels was found between the two groups.The incidences of multiple organ dysfunction syndrome,systemic inflammatory response syndrome,and pancreatic infection as well as the duration of intensive care unit stay were significantly lower in EEN group than in DEN group.However,there was no difference of hospital mortality between the two groups.CONCLUSION:EEN moderates the excessive immune response during the early stage of SAP without leading to subsequent immunosuppression.EEN can improve the clinical outcome,but not decrease the hospital mortality of SAP patients.
文摘Background No-reflow after emergency percutaneous coronary intervention （PCI） for acute ST segment elevation myocardial infarction （STEMI） is related to the severe prognosis. The aim of this study was to evaluate the efficacy of Tongxinluo, a traditional Chinese medicine, on no-reflow and the infarction area after emergency PCI for STEMI.Methods A total of 219 patients （female 31, 14%） undergoing emergency PCI for STEMI from nine clinical centers were consecutively enrolled in this randomized, double-blind, placebo-controlled, multicenter clinical trial from January 2007 to May 2009. All patients were randomly divided into Tongxinluo group （n=108） and control group （n=111）, given Tongxinluo or placebo in loading dose 2.08 g respectively before emergency PCI with asprin 300 mg and clopidogrel 300 mg together, then 1.04 g three times daily for six months after PCI. The ST segment elevation was recorded by electrocardiogram at hospitalization and 1, 2, 6, 12, 24 hours after coronary balloon dilation to evaluate the myocardial no-flow; myocardial perfusion scores of 17 segments were evaluated on day 7 and day 180 after STEMI with static single-photon emission computed tomography （SPECT） to determine the infarct area.Results There was no statistical significance in sex, age, past history, chest pain, onset-to-reperfusion time, Killip classification, TIMI flow grade just before and after PCI, either in the medication treatment during the follow up such as statin, β-blocker, angiotensin converting enzyme inhibitor （ACEI） or angiotensin receptor blocker （ARB） between two groups. There was significant ST segment restoration in Tongxinluo group compared to the control group at 6 hours （（-0.22±0.18） mV vs. （-0.18±0.16） mV, P=0.0394）, 12 hours （（-0.24 ± 0.18） mV vs. （-0.18±0.15） mV, P=0.0158） and 24 hours （（-0.27±0.16） mV vs. （-0.20±0.16） mV, P=0.0021） reperfusion; and the incidence of myocardial no-reflow was also reduced significantly at 24-hour rep
文摘Acute pancreatitis is an inflammatory disease of the pancreas.The etiology and pathogenesis of acute pancreatitis have been intensively investigated for centuries worldwide.Many causes of acute pancreatitis have been discovered,but the pathogenetic theories are controversial.The most common cause of acute pancreatitis is gallstone impacting the distal common bile-pancreatic duct.The majority ofinvestigators accept that the main factors for acute billiary pancreatitis are pancreatic hyperstimulation and bile-pancreatic duct obstruction which increase pancreatic duct pressure and active trypsin reflux.Acute pancreatitis occurs when intracellular protective mechanisms to prevent trypsinogen activation or reduce trypsin activity are overwhelmed.However,little is known about the other acute pancreatitis.We hypothesize that acute biliary pancreatitis and other causes of acute pancreatitis possess a common pathogenesis.Pancreatic hyperstimulation and pancreatic duct obstruction increase pancreatic duct pressure,active trypsin reflux,and subsequent unregulated activation of trypsin within pancreatic acinar cells.Enzyme activation within the pancreas leads to auto-digestion of the gland and local inflammation.Once the hypothesis is confirmed,traditional therapeutic strategies against acute pancreatitis may be improved.Decompression of pancreatic duct pressure should be advocated in the treatment of acute pancreatitits which may greatly improve its outcome.
基金the Overseas Scholarship Foundation of the Chinese Education Department，国家自然科学基金
文摘The seed germination and seedling growth of pakchoi （Brassica campestris ssp. chinensis var. communis Tsen et Lee cv. Hanxiao） were not significantly inhibited until the concentration of NaCl was increased to 150 mmol/L. Treatment of pakchoi seeds with exogenous 5-aminolevulinic acid （ALA）, at concentrations ranging from 0.01 to 10.00 mg/L, promoted seed germination when seeds were stressed by salinity, whereas levulinic acid （LA）, an inhibitor of ALA dehydrase, significantly inhibited seed germination and seedling growth, suggesting that metabolism of ALA into porphyrin compounds was necessary for seed germination and seedling growth. Determination of respiratory rate during seed germination showed that ALA increased seed respiration under both normal conditions and salt stress. Furthermore, salt stress decreased levels of endogenous ALA, as well as heme, in etiolated seedlings. More salt-tolerant cultivars of pakchoi contained higher relative levels of endogenous ALA and heme under conditions of salt stress. These results indicate that salt stress may inhibit the biosynthesis of endogenous ALA and then heme, which is necessary for seed germination, and treatment of seeds with exogenous ALA prior to germination may be associated with the biosynthesis of heme.
基金Supported by the Youth Science Grant of Jiangshu Province,No.BQ98048.
文摘INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo studies[1-5]. Due to limited effectiveness when any anti-carcinogen is used alone and obviously increased toxicity when the dose is raised, there is no exception for As2O3. Furthermore, combined chemotherapy contributes to improve therapeutic effectiveness, disperse toxicity and surmount drug-resistance,in which the combination of traditional Chinese and modern medicine has more advantages and characteristics. As a result,we made an experimental study on anti-tumor effect of As2O3in combination with cisplantin (PDD) or doxorubicin (ADM)on HCC. to investigate the possibility of AS2O3 in combination with PDD or ADM and nature of interaction between them,and to provide experimental basis for clinical application.
文摘Background： With the progress ofperinatal medicine and neonatal technology, more and more extremely low birth weight （ELBW） survived all over the world. This study was designed to investigate the short-term ontcomes of ELBW infants during their Neonatal Intensive Care Unit （NICU） stay in the mainland of China. Methods： All infants admitted to 26 NICUs with a birth weight （BW） 〈1000 g were included between January 1,2011 and December 31,2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors. Results： A total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age （GA） was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants （23.3%） died and another 69 infants （26.7%） died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas （53.6% vs. 35.3%, P = 0.019）. BW 〈750 g and GA 〈28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization. Conclusions： Our study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.
基金Supported by a grant from the Ministry of Science and Technology of China (National Key Technology Research & Development Program, No. 2006BAI 04A06)
文摘BACKGROUND： Disease recurrence is a main challenge in treatment of hepatocellular carcinoma （HCC）. There is no generally accepted method for preventing recurrence of HCC after resection. OBJECTIVE： To compare the efficacy of a traditional herbal medicine （THM） regimen and transarterial chemoembolization （TACE） in preventing recurrence in post-resection patients with small HCC. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： This is a multicenter, open- label, randomized, controlled study, which was undertaken in five centers of China. A total of 379 patients who met the eligibility criteria and underwent randomization were enrolled in this trial. One hundred and eighty-eight patients were assigned to the THM group and received Cinobufacini injection and Jiedu Granule, and the other 191 patients were assigned to the TACE group and received one single course of TACE. MAIN OUTCOME MEASURES： Primary outcome measures were the annual recurrence rate and the time to recurrence. Incidence of adverse events was regarded as the secondary outcome measure. RESULTS： Among the 364 patients who were included in the intention-to-treat analysis, 67 patients of the THM group and 87 of the TACE group had recurrence, with a hazard ratio of 0.695 （P = 0.048）. Median recurrence-free survival of the patients in the THM and TACE groups was 46.89 and 34.49 months, respectively. Recurrence rates at 1, 2 and 3 years were 17.7%, 33.0% and 43.5% for the THM group, and 28.8%, 42.5% and 54.0% for the TACE group, respectively （P = 0.026）. Multivariate analysis indicated that the THM regimen had a big advantage for prolonging the recurrence-free survival. Adverse events were mild and abnormality of laboratory indices of the two groups were similar. CONCLUSION： In comparison with TACE therapy, the THM regimen was associated with diminished risk of recurrence of small-sized HCC after resection, with comparable adverse events. TRIAL REGISTRTION IDENTIFIER： This trial was registered in the Chinese Clinical Trial Re
文摘The efficacy and safety of bevacizumab with modified irinotecan,leucovorin bolus,and 5-fluorouracil intravenous infusion(mIFL) in the first-line treatment of metastatic colorectal cancer(mCRC) has not been well evaluated in randomized clinical trials in Chinese patients.We conducted a phrase Ⅲ trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan(125 mg/m2),leucovorin(20 mg/m2) bolus,and 5-fluorouracil intravenous infusion(500 mg/m2) weekly for four weeks every six weeks] plus bevacizumab(5 mg/kg every two weeks) group and the mIFL group,respectively.Co-primary objectives were progression-free survival(PFS) and 6-month PFS rate.In total,214 patients were enrolled.Our results showed that addition of bevacizumab to mIFL significantly improved median PFS(4.2 months in the mIFL group vs.8.3 months in the bevacizumab plus mIFL group,P < 0.001),6-month PFS rate(25.0% vs.62.6%,P < 0.001),median overall survival(13.4 months vs.18.7 months,P = 0.014),and response rate(17% vs.35%,P = 0.013).Grades 3 and 4 adverse events included diarrhea(21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia(19% in the mIFL group and 33% in the bevacizumab plus mIFL group).No wound-healing complications or congestive heart failure occurred.Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC.Clinical benefit and safety profiles were consistent with those observed in pivotal phase Ⅲ trials with mainly Caucasian patients.
基金supported by the National Natural Science Foundation of China(Nos.81874368 and 81630100)the Beijing Nova Program(No.Z181100006218001)+2 种基金the National Key Technology R&D Program(No.2015ZX 09501-004-001-008)the National Key R&D Program of China(No.2018YFC1707000)the National TCM Industry Science and Technology Program(No.201507004-4-2).
文摘Epimedii Folium(EF)combined with Psoraleae Fructus(PF)is a common modern preparation,but liver injury caused by Chinese patent medicine preparations containing EF and PF has been frequently reported in recent years.Zhuangguguanjiewan pills(ZGW),which contain EF and PF,could induce immune idiosyncratic liver injury according to clinical case reports and a nonhepatotoxic dose of lipopolysaccharide(LPS)model.This present study evaluated the liver injury induced by EF or PF alone or in combination and investigated the related mechanism by using the LPS model.Liver function indexes and pathological results showed that either EF or PF alone or in combination led to liver injury in normal rats;however,EF or PF alone could lead to liver injury in LPS-treated rats.Moreover,EF combined with PF could induce a greater degree of injury than that caused by EF or PF alone in LPS-treated rats.Furthermore,EF or PF alone or in combination enhanced the LPS-stimulated inflammatory cytokine production,implying that IL-1β,which is processed and released by activating the NLRP3 inflammasome,is a specific indicator of EF-induced immune idiosyncratic hepatotoxicity.Thus,EF may induce liver injury through enhancing the LPS-mediated proinflammatory cytokine production and activating the NLRP3 inflammasome.In addition,the metabolomics analysis results showed that PF affected more metabolites in glycerophospholipid and sphingolipid metabolic pathways compared with EF in LPS model,suggesting that PF increased the responsiveness of the liver to LPS or other inflammatory mediators via modulation of multiple metabolic pathways.Therefore,EF and PF combination indicates traditional Chinese medicine incompatibility,considering that it induces idiosyncratic hepatotoxicity under immunological stress conditions.
文摘AIM To investigate effect of losartan,an AT1receptor antagonist,on hepatic fibrosis induced byCCl<sub>;</sub>and to determine whether or not AT1receptors are expressed on hepatic stellate cells,METHODS AND RESULTS Fifty male Sprague-Dawley rats,weighing（180±20）g,wererandomized into five groups（control group,modelgroup,and three losartan treated groups）,inwhich all rats were given the subcutaneousinjection of 40% CCl<sub>4</sub>（every 3 days for 6 weeks）except for rats of control group.Rats of losartan-treated groups were treated with losartan（20 mg/kg,10 mg/kg,5 mg/kg,daily gavage）,After 6weeks liver tissue and serum samples of all ratswere examined.Serum hyaluronic acid（HA）,procollagen typeⅢ（PCⅢ）were detected byradioimmunoassays,van Giesion collagen stainingwas used to evaluate the extracellular matrix of ratswith liver fibrosis.The expression of AT1receptors,transforming growth factor-beta（TGF-β）,and alpha-smooth muscle actin（a-SMA）inliver tissue were determined byimmunohistochemical techniques.Compared withmodel group,serum ALT and AST of losartan-treated groups were significantly reduced（t=4.20,P【0.01 and t=4.57,P【0.01）.Serum HAand PCⅢalso had significant differences（t=3.53,P【0.01 and t=2.20,P【0.05）.Thedegree of fibrosis was improved by losartan and correlated with the expressions of AT1 receptors,TGF-β,and α-SMA in liver tissue.CONCLUSION AT1 receptor antagonist,losartan,could limit the progression of the hepatic fibrosisinduced by CCl<sub>4</sub>.The mechanism may be related tothe decrease in the expression of AT1 receptorsand TGF-β,ameliorating the injury of hepatocytes;activation of local renin-angiotensin system mightrelate to hepatic fibrosis;and during progressionof fibrosis,activated hepatic stellate cells mightexpress AT1 receptors.
