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Early versus delayed intervention in necrotizing acute pancreatitis complicated by persistent organ failure

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Hepatobiliary & Pancreatic Diseases International 2022年第1期21卷 63-68页

作者： He Zhang Lin Gao Wen-Jian Mao Jie Yang Jing Zhou Zhi-Hui Tong Lu Ke Wei-Qin Li Medical School of Southeast University 87 DingjiaqiaoNanjing 210009China Center of Severe Acute pancreatitis(CSAP) Department of General SurgeryJinling HospitalMedical School of Southeast UniversityNo.305 Zhongshan East RoadNanjing 210002China

Background:Current guidelines for the treatment of patients with necrotizing acute pancreatitis(NAP)recommend that invasive intervention for pancreatic necrosis should be deferred to 4 or more weeks from disease onset to allow necrotic collections becoming“walled-off”.However,for patients showing signs of clinical deterioration,especially those with persistent organ failure(POF),it is controversial whether this delayed approach should always be adopted.In this study,we aimed to assess the impact of differently timed intervention on clinical outcomes in a group of NAP patients complicated by POF.Methods:All NAP patients admitted to our hospital from January 2013 to December 2017 were screened for potential inclusion.They were divided into two groups based on the timing of initial interven-tion(within 4 weeks and beyond 4 weeks).All the data were extracted from a prospectively collected database.Results:Overall,131 patients were included for analysis.Among them,100(76.3%)patients were in-tervened within 4 weeks and 31(23.7%)underwent delayed interventions.As for organ failure prior to intervention,the incidences of respiratory failure,renal failure and cardiovascular failure were not signifi-cantly different between the two groups(P>0.05).The mortality was not significantly different between the two groups(35.0%vs.32.3%,P=0.83).The incidences of new-onset multiple organ failure(8.0%vs.6.5%,P=1.00),gastrointestinal fistula(29.0%vs.12.9%,P=0.10)and bleeding(35.0%vs.35.5%,P=1.00),and length of ICU(30.0 vs.22.0 days,P=0.61)and hospital stay(42.5 vs.40.0 days,P=0.96)were com-parable between the two groups.Conclusion:Intervention within 4 weeks did not worsen the clinical outcomes in NAP patients compli-cated by POF.

关键词： Necrotizing acute pancreatitis Persistent organ failure Early intervention Delayed intervention Clinical outcomes

Calcineurin Inhibitors in the Treatment of Adult Autoimmune Hepatitis:A Systematic Review

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Journal of Clinical and Translational Hepatology 2022年第6期10卷 1155-1166页

作者： Martine AMC Baven-Pronk Joffre M.Hew,Jr Maaike Biewenga Maarten E.Tushuizen Aad P.van den Berg Gerd Bouma Johannes T.Brouwer Bart van Hoek 无 Department of Gastroenterology and Hepatology Groene Hart HospitalGoudaNetherlands Department of Gastroenterolo-gy and Hepatology Leiden University Medical CenterLeidenNetherlands Department of Gastroenterology and Hepatology University Medical Center GroningenGroningenNetherlands Department of Gastroenterology and Hepatology Amsterdam University Medical Center Location VUAmsterdamNetherlands Reinier de Graaf Medical Center Delft DelftNetherlands dutch Autoimmune Hepatitis study group

Background and Aims:A considerable number of au-toimmune hepatitis(AIH)patients completely or partially fail on first-line treatment.Several studies on the use of calcineurin inhibitors(CNIs)in the treatment of AIH have been published without focusing on indication.The aim was to assess the efficacy of CNIs in the treatment of adult AIH patients,specifically focusing on indication:first-line intolerant and with first-line insufficient response(failure to achieve or maintain remission),and with second versus third-line treatment.Methods:A literature search included studies on the use of CNIs in adult AIH.Patients with past or present use of CNIs from the dutch AIH group cohort were added.The primary endpoint was biochemical remission while using CNIs.Secondary endpoints were biochemical response,treatment failure,and adverse effects.Results:Twenty studies from the literature and nine dutch patients were included describing the use of cyclosporine in 59 and tacrolimus in 219 adult AIH patients.The CNI remission rate was 53%in patients with insufficient response to first-line treatment and 67%in patients intolerant to first-line treat-ment.CNIs were used as second-line treatment in 73%with a remission rate of 52%and as third-line treatment in 22%with a remission rate of 26%.Cyclosporine was discontin-ued in 13%and tacrolimus in 11%of patients because of adverse events.Conclusions:CNIs as rescue treatment in adult AIH patients are reasonably effective and safe both with insufficient response or intolerance to previous treat-ment.Prospective studies are needed.

关键词： Autoimmune hepatitis Cyclosporine Tacrolimus Calcineurin inhibi-tor

Validation of the moderate severity category of acute pancreatitis defined by determinant-based classification

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Hepatobiliary & Pancreatic Diseases International 2014年第3期13卷 323-327页

作者： Tao Jin Wei Huang Xiao-Nan Yang Ping Xue Muhammad A Javed Kiran Altaf Robert Sutton Qing Xia Department of Integrated Traditional Chinese and Western Medicine Sichuan Provincial Pancreatitis Center West China Hospital Sichuan University NIHR Liverpool Pancreas Biomedical Research Unit Royal Liverpool and Broadgreen University Hospitals Trust and University of Liverpool

BACKGROUND: Recent international multidisciplinary consultation proposed the use of local(sterile or infected pancreatic necrosis) and/or systemic determinants(organ failure) in the stratification of acute pancreatitis. The present study was to validate the moderate severity category by international multidisciplinary consultation definitions.METHODS: Ninety-two consecutive patients with severe acute pancreatitis(according to the 1992 Atlanta classification) were classified into(i) moderate acute pancreatitis group with the presence of sterile(peri-) pancreatic necrosis and/or transient organ failure; and(ii) severe/critical acute pancreatitis group with the presence of sterile or infected pancreatic necrosis and/or persistent organ failure. Demographic and clinical outcomes were compared between the two groups.RESULTS: Compared with the severe/critical group(n=59), the moderate group(n=33) had lower clinical and computerized tomographic scores(both Pgroup analysis showed that the moderate group also had significantly lower ICU admission rates, shorter hospital stay and lower rate of infection compared with the severe group(n=51). No patients died in the moderate group but7 patients died in the severe/critical group(4 for severe group).CONCLUSIONS: Our data suggest that the definition of moderate acute pancreatitis, as suggested by the international multidisciplinary consultation as sterile(peri-) pancreatic necrosis and/or transient organ failure, is an accurate category of acute pancreatitis.

关键词： acute pancreatitis pancreatic necrosis organ failure determinant-based classification

Preoperative biliary drainage in patients with hilar cholangiocarcinoma undergoing major hepatectomy

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World Journal of Gastroenterology 2013年第46期19卷 8731-8739页

作者： Jun-Jie Xiong Quentin M Nunes Wei Huang Samir Pathak Ai-Lin Wei Chun-Lu Tan Xu-Bao Liu Department of Hepato-Biliary-Pancreatic Surgery West China HospitalSichuan University NIHR Liverpool Pancreas Biomedical Research Unit Department of Molecular and Clinical Cancer MedicineRoyal Liverpool University HospitalUniversity of Liverpool Sichuan Provincial pancreatitis Center Department of Integrated Traditional Chinese and Western MedicineWest China HospitalSichuan University

AIM:To investigate the effect of preoperative biliary drainage(PBD)in jaundiced patients with hilar cholangiocarcinoma(HCCA)undergoing major liver resections.METHODS:An observational study was carried out by reviewing a prospectively maintained database of HCCA patients who underwent major liver resection for curative therapy from January 2002 to December 2012.Patients were divided into two groups based on whether PBD was performed:a drained group and an undrained group.Patient baseline characteristics,preoperative factors,perioperative and short-term postoperative outcomes were compared between the two groups.Risk factors for postoperative complications were also analyzed by logistic regression test with calculating OR and 95%CI.RESULTS:In total,78 jaundiced patients with HCCA underwent major liver resection:32 had PBD prior to operation while 46 did not have PBD.The two groups were comparable with respect to age,sex,body mass index and co-morbidities.Furthermore,there was no significant difference in the total bilirubin(TBIL)levels between the drained group and the undrained group at admission(294.2±135.7 vs 254.0±63.5,P=0.126).PBD significantly improved liver function,reducing not only the bilirubin levels but also other liver enzymes.The preoperative TBIL level was significantly lower in the drained group as compared to the undrained group(108.1±60.6 vs 265.7±69.1,P=0.000).The rate of overall postoperative complications(53.1%vs 58.7%,P=0.626),reoperation rate(6.3%vs 6.5%,P=1.000),postoperative hospital stay(16.5 vs 15.0,P=0.221)and mortality(9.4%vs 4.3%,P=0.673)were similar between the two groups.In addition,there was no significant difference in infectious complications(40.6%vs 23.9%,P=0.116)and noninfectious complications(31.3%vs 47.8%,P=0.143)between the two groups.Univariate and multivariate analyses revealed that preoperative TBIL>170μmol/L(OR=13.690,95%CI:1.275-147.028,P=0.031),Bismuth-Corlette classification(OR=0.013,95%CI:0.001-0.166,P=0.001)and extended liver resection(OR=14.010,95%CI:1.130-173.646,P

关键词： Obstructive jaundice Hilar cholangiocar-cinoma Preoperative biliary drainage Major hepatec-tomy Surgical outcome

Therapeutic effects of salidroside vs pyrrolidine dithiocarbamate against severe acute pancreatitis in rats

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Journal of Traditional Chinese Medicine 2022年第1期42卷 49-57页

作者： QIAN Jing WANG Xiaohong WEI Benzhong ZHOU Guoxiong ZHU Shunxing LIU Chun Department of General Surgery Yizheng Hospital of Nanjing Drum Tower Hospital GroupYizheng 211900China Department of Gastroenterology Yizheng Hospital of Nanjing Drum Tower Hospital GroupYizheng 211900China Department of Anesthesiology Yizheng Hospital of Nanjing Drum Tower Hospital GroupYizheng 211900China Department of Gastroenterology Affiliated Hospital of Nantong UniversityNantong 226001China Department of Laboratory Animal Center Nantong UniversityNantong 226001China

OBJECTIVE:To evaluate the therapeutic effectiveness of salidroside(Sal)and pyrrolidine dithiocarbamate(PDTC)against severe acute pancreatitis(SAP)in a rat model.METHODS:Rat models of SAP were established by retrograde infusion of sodium taurocholate solution.SAP rats were randomly divided into 6 groups:SAP 3 h group,SAP 24 h group,low-dose Sal treatment group(Sal L+S),middle-dose Sal treatment group(Sal M+S),high-dose Sal treatment group(Sal H+S)and PDTC treatment group(PDTC+S).The serum amylase,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-10(IL-10)levels were determined by optical turbidimetry and enzyme-linked immunosorbent assay.The expression of Beclin-1,microtubule-associated protein light chain 3Ⅱ(LC3Ⅱ),lysosome associated membrane protein 2(LAMP2),interleukin-1 receptor associated kinase 1(IRAK1),inhibitorαof nuclear transcription factor-κB(IκBα),nuclear transcription factor-κB 65(p65)in the pancreas tissues were detected by quantitative real-time polymerase chain reaction and Western blot,while the pIκBαand p-p65 levels were detected by Western blot.Pathological changes of the pancreas and all the other indexes were observed at 3 and 24 h after operation.RESULTS:The serum IL-10 level,IκBαand LAMP2 levels in Sal M+S,Sal H+S and PDTC+S groups were higher than those in SAP 24 h group,while all the other indexes in these three groups were all lower significantly than those in SAP 24 h group.There was no significant difference in all indexes between Sal H+S and PDTC+S groups.CONCLUSION:High-dose Sal has an effectively therapeutic effect on SAP in rats,which was similar to PDTC.

关键词： rhodioloside pyrrolidines ethylenebis(dithiocarbamates) pancreatitis autophagy NF-kappa B signal transduction

Effects of melatonin on the oxidative damage and pancreatic antioxidant defenses in ceruleininduced acute pancreatitis in rats

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Hepatobiliary & Pancreatic Diseases International 2014年第4期13卷 442-446页

作者： Cristina Carrasco Ana Beatriz Rodríguez José A Pariente Department of Physiology Neuroimmunophysiology and Chrononutrition Research Group University of Extremadura

BACKGROUND: Oxidative stress is recognized as a pivotal effector of several pathogenic processes, including acute pancreatitis. Reactive oxygen species not just cause damage on the main cellular components, but also influence the expression of antioxidant system genes. Antioxidant molecules, such as melatonin, could be good candidates for the treatment of this multidimensional disease. The present study was to evaluate the chemopreventive effect of melatonin in a rat model of ceruleininduced acute pancreatitis.METHODS: Four subcutaneous injections of cerulein(20 μg/kg body weight) were given to Wistar rats at two hours intervals;melatonin was injected intraperitoneally(25 mg/kg body weight)30 minutes before each injection of cerulein. Lipid peroxidation,protein oxidation(carbonyl groups), total antioxidant status,and glutathione peroxidase activity were determined in pancreatic tissue using commercial kits.RESULTS: The chemopreventive administration of melatonin caused a reduction in lipid peroxidation and protein oxidation due to injections of cerulein. Additionally, melatonin treatment was also able to revert glutathione peroxidase activity and total antioxidant status near to control levels, suggesting that melatonin could prevent from oxidative phenomena in the pancreas, such as lipid peroxidation and protein oxidation,and could stimulate, directly or indirectly, the expression of antioxidant enzymes.CONCLUSION: Melatonin, a polyvalent antioxidant, protected the pancreatic damage via the decrease of oxidative stress andincrease of the activities of antioxidant enzymes in ceruleininduced acute pancreatitis.

关键词： Wistar大鼠抗氧化防御系统急性胰腺炎氧化损伤褪黑素谷胱甘肽过氧化物酶脂质过氧化褪黑激素

Systems response profiles to two Rehmanniae Radix formulae in metabolic syndrome patients

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World Journal of Traditional Chinese Medicine 2017年第1期3卷 1-10页

作者： Jun-Zeng Fu Herman A.van Wietmarschen Jan van der Greef Yan Schroёn Mei Wang Division of Analytical Biosciences LACDR Leiden University Sino-dutch Center for Preventive and Personalized Medicine Louis Bolk Institute SU Bio Medicine Utrechtseweg Oxrider Education and Research

Objective: To explore the effects of two Rehmanniae Radix formulae in patients with metabolic syndrome(Met S), a randomized controlled study was conducted.Methods: Met S patients were randomly assigned to receive either a classic Rehmanniae Six Formula(R6, or ‘Liu Wei Di Huang Wan') or a novel multi-herbal Rehmanniae Radix containing formula SUB889 for 8 weeks. Western medicine related clinical parameters, Chinese medicine defined symptoms and syndromes as well as metabolomic profiles were evaluated at different time points.Results: R6(n = 20) and SUB889(n = 20) showed similar effects on Met S regarding the improvement of clinical parameters(waist circumference, body mass index, LDL-cholesterol, systolic blood pressure) and Qi/Yin deficiency(p group, while SUB889 formula resulted in increased levels of tricarboxylic acid cycle and glucose metabolism intermediates(malate, fumarate and pyruvate).Conclusions: R6 and SUB889 have similar effects on the treatment of Met S by improving Chinese medicine and Western medicine defined clinical outcomes. R6 is more effective in improving lipid profiles compared to SUB889. The exact mechanisms of the two formulae on Met S remain to be elucidated.

关键词： Systems biology Metabolic syndrome Chinese medicine diagnosis Metabolomics Rehmanniae Radix formula

Identificatio of Quantitative Trait Loci for Fruit Weight, Soluble Solids Content, and Plant Morphology Using an Introgression Line Population of Solanum pennellii in a Fresh Market Tomato Inbred Line

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Horticultural Plant Journal 2016年第1期2卷 26-34页

作者： ZHOU Hui WANG Xiaoxuan HUANG Zejun GAO Jianchang GUO Yanmei DU Yongchen HU Hong Institute of Vegetables and Flowers Chinese Academy of Agricultural Sciences Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture Sino-Dutch Joint Laboratory of Horticultural Genomics

Introgression lines are convenient populations for the identification fine-mapping and functional analysis of genes that are responsible for variations in traits, particularly quantitative trait genes. An introgression line population of Solanum pennellii LA0716 in a fresh market tomato inbred line 1052 was developed by our group. This population was composed of 214 lines. In the present study, fi e quantitative trait loci(QTLs)for fruit weight, two QTLs for soluble solids content(SSC), three QTLs for plant height, and one QTL for leaf size were identifie using this introgression line population. Among these, fw3 a and fw4 a for fruit weight, ssc7 a for SSC, h4t2 a, h4t3 a, and h4t7 a for plant height, and lz12 a for leaf size were determined to be novel loci. These results serve as a foundation for fine-mappin and functional analysis of genes underlying these QTLs.

关键词： tomato introgression line quantitative trait locus fruit weight soluble solids content plant morphology

Space-time prisms in multimodal supernetwork-Part 2:Application for analyses of accessibility and equality

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Communications in Transportation Research 2022年第1期2卷 58-65页

作者： Jing Qin Feixiong Liao Urban Planning and Transportation group Eindhoven University of Technologythe Netherlands

Space-time prism(STP)is a fundamental concept in time geography and has been predominately constructed in unimodal transportation networks.Due to the vast trip chaining options by private vehicles and public transportation,it was challenging to construct STP over multimodal transportation networks.We previously put forward an efficient method to narrow down the action space for trip chaining and construct STPs effectively in a multimodal supernetwork.This study applies multimodal STP modeling to measure space-time accessibility and equality of daily activity opportunities.Two equality measures(Gini coefficient and 20:20 ratio)are derived from two space-time accessibility measures based on delineated STPs.We examine the equality of access to shopping and leisure opportunities in the Rotterdam-The Hague metropolitan area,the Netherlands.The results show the effects of various factors on accessibility and equality.It is found that although the study area has relatively low inequality using single modes,multimodal trip chaining further reduces inequality to access the distributed space-time opportunities.

关键词： Space-time prism Accessibility Equality Multimodal supernetwork