System Reliability Analysis Method Based on T-S FTA and HE-BN

For high-reliability systems in military,aerospace,and railway fields,the challenges of reliability analysis lie in dealing with unclear failure mechanisms,complex fault relationships,lack of fault data,and uncertainty of fault states.To overcome these problems,this paper proposes a reliability analysismethod based on T-S fault tree analysis(T-S FTA)and Hyper-ellipsoidal Bayesian network(HE-BN).The method describes the connection between the various systemfault events by T-S fuzzy gates and translates them into a Bayesian network(BN)model.Combining the advantages of T-S fault tree modeling with the advantages of Bayesian network computation,a reliability modeling method is proposed that can fully reflect the fault characteristics of complex systems.Experts describe the degree of failure of the event in the form of interval numbers.The knowledge and experience of experts are fused with the D-S evidence theory to obtain the initial failure probability interval of the BN root node.Then,the Hyper-ellipsoidal model(HM)constrains the initial failure probability interval and constructs a HE-BN for the system.A reliability analysismethod is proposed to solve the problem of insufficient failure data and uncertainty in the degree of failure.The failure probability of the system is further calculated and the key components that affect the system’s reliability are identified.The proposedmethod accounts for the uncertainty and incompleteness of the failure data in complex multi-state systems and establishes an easily computable reliability model that fully reflects the characteristics of complex faults and accurately identifies system weaknesses.The feasibility and accuracy of the method are further verified by conducting case studies.

The complex roles of m^(6)A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases

N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.

不同测试体位对屈腕、屈指肌群定量肌力的影响及其标准化

目的 探究不同测试体位对手、腕屈曲肌群定量肌力的影响,建立各肌群的标准化肌力检测方案。方法 征集40例健康受试者(男性12例,女性28例),使用MicroFET2TM便携式数字肌力测试仪,分别于腕关节背伸30°位、中立0°位和掌屈30°位测量各手指屈曲及腕关节掌屈肌力,分别于拇指掌侧外展30°位和60°位测量拇指掌侧外展肌力。从40例受试者中随机抽取10例,间隔10~15 d后由同一操作者再次测试各肌群定量肌力。结果 除男性腕关节背伸30°位和中立0°位之间的拇指屈曲肌力、腕关节掌屈肌力差异无统计学意义(P>0.05),各指屈曲及腕掌屈肌力值主要呈现以下特点:腕关节背伸30°位>腕关节中立0°位>腕关节掌屈30°位,拇指掌侧外展30°位>60°位;所有受试者手指屈曲肌力均为拇指>示指>中指>环指>小指;男性各项肌力值均大于女性(P<0.05);所有受试者左、右侧肌力值的差异均无统计学意义(P>0.05)。10例受试者不同时期测量肌力值的可靠性良好。结论 手、腕各肌群定量肌力均受体位影响,鉴定过程中应采取规范、统一的测试体位。MicroFET2TM用于手、腕关节定量肌力测试具有良好的可靠性。腕关节背伸30°位可作为各手指屈曲肌力及腕关节掌屈肌力的最佳标准化检测条件。拇指掌侧外展30°位可作为拇指掌侧外展肌力的最佳标准化检测条件。

Fufang E’jiao Jiang’s effect on immunity,hematopoiesis,and angiogenesis via a systematic“compound-effect-target”analysis

Fufang E’jiao Jiang(FEJ)as a healthy food consisting of medicine food homology materials approved by China’s Ministry of Health has been extensively applied to replenish qi and nourish blood,and it has a positive impact on women’s health.To find out the material basis and mechanism of FEJ,a systematic“compoundeffect-target”analysis including chemical composition resolution,zebrafish,network pharmacology,molecular docking,transcriptome,and bibliometric analysis was adopted.124 chemical components including ginsenosides,and phenylethanoid glycosides in FEJ were discovered,and effects of FEJ on promoting the generation of immune cells,erythropoiesis and angiogenesis in zebrafish were exhibited.Based on network pharmacology,molecular docking and in vivo activity assay,6 compounds including jionoside A1,isoacteoside,echinacoside,acteoside,lobetyolin,and rehmannioside D were identified as active components of FEJ.Transcriptome data showed that several pathways such as complement and coagulation cascades,ECM-receptor interaction,and PI3K-Akt signaling pathway were associated with proangiogenic effect of FEJ.19 common targets were obtained through combined analysis of network pharmacology and transcriptomics,and 5 targets of them were verified by PCR.The bibliometric analysis of these common targets revealed that FEJ was related to energy metabolism,pathway in cancer,etc.,which was consistent with the results of network pharmacology and transcriptome.The studies suggested that FEJ could replenish qi and nourish blood through multi-compound and multi-targets.

Malignancy risk factors and prognostic variables of pancreatic mucinous cystic neoplasms in Chinese patients

BACKGROUND Pancreatic mucinous cystic neoplasms(MCNs)represent one of the precursor lesions of pancreatic ductal adenocarcinoma,and their detection has been facilitated by advances in preoperative imaging.Due primarily to the rarity of MCNs,however,there is limited knowledge regarding the prognostic variables and high-risk factors for malignant transformation.A more comprehensive and nuanced approach is necessary to fill this gap and provide a basis for improved treatment decisions and patient outcomes.AIM To investigate the high-risk factors associated with malignant MCNs and to explore the prognostic factors of MCN with associated invasive carcinoma(MCNAIC).METHODS All cases of resected MCNs from a single high-volume institution between January 2012 and January 2022 were retrospectively reviewed.Only cases with ovarian-type stroma verified by progesterone receptor staining were included.Preoperative features,histological findings and postoperative course were documented.Multivariate logistic regression was employed to investigate variables related to malignancy.Survival analysis was performed using the Kaplan-Meier curve,and the prognostic factors were assessed to evaluate the postoperative course of patients with MCN-AIC.RESULTS Among the 48 patients,36 had benign MCNs,and 12 had malignant MCNs(1 high-grade atypical hyperplasia and 11 MCN-AIC).Age,tumour size,presence of solid components or mural nodules and pancreatic duct dilatation were identified as independent risk factors associated with malignancy.The follow-up period ranged from 12 mo to 120 mo,with a median overall survival of 58.2 mo.Only three patients with MCN-AIC died,and the 5-year survival rate was 70.1%.All 11 cases of MCN-AIC were stage I,and extracapsular invasion was identified as a prognostic factor for poorer outcomes.CONCLUSION The risk factors independently associated with malignant transformation of MCNs included age,tumour size,presence of solid components or mural nodules,and pancreatic duct dilatation.Our study also revealed that encapsulated invasion was a favourable prognostic factor in MCN-AIC patients.

城镇燃气企业法律风险防控体系构建研究

伴随着燃气产业快速发展,天然气行业的法律规范逐步完善,城镇燃气企业在经营管理过程中需准确把握资源获取风险、股权投资风险、固定资产投资风险,使之与法律风险进行有效衔接。为此需在严判城镇燃气企业法律风险防控原则的基础上,综合考虑管理、技术、法律等多个维度,从城镇燃气企业法律风险岗位指引编制、关键节点控制和实施检查考核等具项措施,构建城镇燃气企业法律风险防控体系只有这样,才能使经营管理风险与法律风险有效衔接,提升城镇燃气企业风险防控措施,增强企业市场竞争力。

m6A修饰对中枢神经系统功能及疾病的影响

6-甲基腺嘌呤(N6-methyladenosine,m6A)是一种重要的RNA修饰,参与细胞内mRNA的整个代谢活动,调控基因的表达,调节多种生物过程,在大脑组织中丰度较高。稳定的m6A修饰有助于胚胎大脑发育、记忆力的形成,在维持中枢神经系统的功能中起到重要作用。当m6A修饰水平及相关蛋白表达水平发生改变时,将会引起神经系统功能异常,包括脑组织发育迟缓、轴突再生能力障碍、记忆力改变以及干细胞更新和分化紊乱等。近年来的研究还发现,m6A修饰及其相关蛋白在阿尔茨海默症、帕金森症、脆性X染色体综合征、抑郁症和胶质母细胞瘤等众多神经系统疾病的发展进程中扮演关键角色。本文主要综述了近年来在中枢神经系统中m6A修饰调控机制研究的相关进展,重点介绍了m6A修饰介导的基因表达调控对中枢神经系统生物学功能以及多种相关疾病的影响,以期为中枢神经系统疾病提供新的研究靶点和治疗方向。

Early nasogastric enteral nutrition for severe acute pancreatitis: A systematic review

AIM: To evaluate the effectiveness and safety of early nasogastric enteral nutrition (NGEN) for patients with severe acute pancreatitis (SAP). METHODS: We searched Cochrane Central Register of Controlled Trials (Issue 2, 2006), Pub-Medline (1966-2006), and references from relevant articles. We included randomized controlled trials (RCTs) only, which reported the mortality of SAP patients at least. Two reviewers assessed the quality of each trial and collected data independently. The Cochrane Collaboration’s RevMan 4.2.9 software was used for statistical analysis. RESULTS: Three RCTs were included, involving 131 patients. The baselines of each trial were comparable. Meta-analysis showed no significant differences in mortality rate of SAP patients between nasogastric and conventional routes (RR = 0.76, 95% CI = 0.37 and 1.55, P = 0.45), and in other outcomes, including time of hospital stay (weighted mean difference = -5.87, 95% CI = -20.58 and 8.84, P = 0.43), complication rate of infection (RR = 1.41, 95% CI = 0.62 and 3.23, P = 0.41) or multiple organ defi ciency syndrome (RR = 0.97, 95% CI = 0.27 and 3.47, P = 0.97), rate of admission to ICU (RR = 1.00, 95% CI = 0.48 and 2.09, P = 0.99) or conversion to surgery (RR = 0.66, 95% CI = 0.12 and 3.69, P = 0.64), as well as recurrence of re-feeding pain and adverse events associated with nutrition. CONCLUSION: Early NGEN is a breakthrough in the management of SAP. Based on current studies, early NGEN appears effective and safe. Since the available evidence is poor in quantity, it is hard to make an accurate evaluation of the role of early NGEN in SAP.Before recommendation to clinical practice, further high qualified, large scale, randomized controlled trials are needed.

Effect of Chaiqinchengqi decoction on sarco/endoplasmic reticulum Ca^(2+)-ATPase mRNA expression of pancreatic tissues in acute pancreatitis rats

AIM: To investigate the effect of Chaiqinchengqi decoction (CQCQD) on sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) mRNA expression of pancreatic tissues in acute pancreatitis (AP) rats. METHODS: Thirty Sprague-Dawley (SD) rats were randomized into control group, AP group and CQCQD group (n = 3 × 10). The rats in the CQCQD group were intragastrically administered with CQCQD (10 mL/kg every 2 h) after induction of AP by intraperitoneal injection of caerulein (50 μg/kg.h × 5) within 4 h. At 6 h after the induction of AP model, pancreatic tissues were collected for the pathological observation, mRNA extraction for determination of SERCA1 and SERCA2 mRNA expression or pancreatic acinar cell isolation for measurement of fluorescence intensity (FI) of intracellular calcium ion concentration [Ca2+]i. RESULTS: There was no expression of pancreatic SERCA1 mRNA in the control group and the AP group. The expression of pancreatic SERCA2 mRNA in the AP group was down-regulated (expression ratio = 0.536; P = 0.001) compared with the control group, while that in the CQCQD group was up-regulated (expression ratio= 2.00; P = 0.012) compared with AP group. The FI of intracellular [Ca2+] of pancreatic acinar cells in the AP group (138.2 ± 23.1) was higher than the C group (111.0 ± 18.4) and the CQCQD group (118.7 ± 15.2 ) (P < 0.05) and the pancreatic pathological score in the CQCQD group was lower than that in the AP group (5.7 ± 1.9 vs 9.2 ± 2.7, P < 0.05).CONCLUSION: CQCQD can up-regulate the expression of SERCA2 mRNA of pancreatic tissues, reduce intracellular calcium overload and relieve pancreatic tissue lesions.

Effect of Chaiqinchengqi decoction on serum amyloid A in severe acute pancreatitis patients

Objective:To investigate the effect of Chaiqinchengqi decoction(CQCQD) on serum amyloid A (SAA) in severe acute pancreatitis(SAP) patients.Methods:Thirty-five participants enrolled and were randomly assigned into either a treatment condition(n=17,treated with CQCQD) or a control condition(n=18,treated with placebo) 24 hours following the onset of the disease. No statistical difference was observed in either group at baseline.Upon admission,the Acute Physiology and Chronic Health Evaluation scoreⅡ(APACHEⅡ),SAA,serum C-reactive protein (CRP) and interleukin-6(IL-6) were measured,as well as on the first,3rd and 7lh day and were compared between the two groups.Organ complications,infection,operation rate,mortality and hospital stay were also compared.Results:The duration of acute respiratory distress syndrome, acute hepatitis,acute renal failure,gastrointestinal failure and blood coagulation dysfunction were shorter in the treatment group than in those in the control group(P【0.05).The secondary infection rates and the hospital fees in the treatment group were lower than those in the control group(P【0.05) as well as length of hospital stay(P【0.01).After 3 days of hospitalization,the APACHEⅡ,score SAA levels,serum CRP and IL-6 in the treatment group was lower than those in the control group(P【0.05).SAA was positively correlated with serum CRP(R = 0.346,P = 0.042),Ranson score(R = 0.442,P = 0.008) and serum IL-6(R=0.359,P =0.034).The area under the receiver operating characteristic curve of admission SAA predict pancreatic necrosis(PN) was 0.815(95%CI:0.625-0.954;P =0.006).The best cut-off value of admission SAA was 7.85 mg/L with the sensitivity 84.6%and specificity 68.2%.Conclusions:The CQCQD can reduce the duration of organ damage through lowering the SAA in SAP patients and the SAA can early predict the PN and severity of SAP patients.

Meta-analysis of subtotal stomach-preserving pancreaticoduodenectomy vs pylorus preserving pancreaticoduodenectomy

AIM: To investigate the differences in outcome following pylorus preserving pancreaticoduodenectomy(PPPD) and subtotal stomach-preserving pancreaticoduodenectomy(SSPPD).METHODS: Major databases including Pub Med(Medline), EMBASE and Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials(CENTRAL) in The Cochrane Library were searched for comparative studies between patients with PPPD and SSPPD published between January 1978 and July 2014. Studies were selected based on specific inclusion and exclusion criteria. The primary outcome was delayed gastric emptying(DGE). Secondary outcomes included operation time, intraoperative blood loss, pancreatic fistula, postoperative hemorrhage, intraabdominal abscess, wound infection, time to starting liquid diet, time to starting solid diet, period of nasogastric intubation, reinsertion of nasogastric tube, mortality and hospital stay. The pooled odds ratios(OR) or weighted mean difference(WMD) with 95% confidence intervals(95%CI) were calculated using either a fixed-effects or random-effects model. RESULTS: Eight comparative studies recruiting 650 patients were analyzed, which include two RCTs, one non-randomized prospective and 5 retrospective trial designs. Patients undergoing SSPPD experienced significantly lower rates of DGE(OR = 2.75; 95%CI: 1.75-4.30, P < 0.00001) and a shorter period of nasogastric intubation(OR = 2.68; 95%CI: 0.77-4.58,P < 0.00001), with a tendency towards shorter time to liquid(WMD = 2.97, 95%CI:-0.46-7.83; P = 0.09) and solid diets(WMD = 3.69, 95%CI:-0.46-7.83; P = 0.08) as well as shorter inpatient stay(WMD = 3.92, 95%CI:-0.37-8.22; P = 0.07), although these latter three did not reach statistical significance. PPPD, however, was associated with less intraoperative blood loss than SSPPD [WMD =-217.70, 95%CI:-429.77-(-5.63); P = 0.04]. There were no differences in other parameters between the two approaches, including operative time(WMD =-5.30, 95%CI:-43.44-32.84; P = 0.79), pancreatic fistula(OR = 0.91; 95%CI: 0.56-1.49; P = 0.70), postoperative hemorrhage(OR = 0.51; 95%CI: 0.15-1.74; P = 0.29), intraabdominal abscess(OR = 1.05; 95%CI: 0.54-2.05; P = 0.89), wound infection(OR = 0.88; 95%CI: 0.39-1.97; P = 0.75), reinsertion of nasogastric tube(OR = 1.90; 95%CI: 0.91-3.97; P = 0.09) and mortality(OR = 0.31; 95%CI: 0.05-2.01; P = 0.22).CONCLUSION: SSPPD may improve intraoperative and short-term postoperative outcomes compared to PPPD, especially DGE. However, these findings need to be further ascertained by well-designed randomized controlled trials.

Effect of severe acute pancreatitis on pharmacokinetics of Da-Cheng-Qi Decoction components

AIM:To investigate the effect of severe acute pan- creatitis(SAP)on pharmacokinetics of Da-Cheng-Qi Decoction(DCQD)components in rats. METHODS:Rats were divided into SAP group and sham-operation group as a control group(n=6). Rhein,chrysophanol,rheochrysidin,magnolol,hesperidin and naringin in DCQD were quantified in rat serum by high performance liquid chromatography tandem mass spectrometry for studying their pharmacokinetics. RESULTS:Early absorption of each DCQD component was tended to degrade in SAP group after treatment with DCQD by gavage.The Cmax(chrysophanol,P= 0.0059;rheochrysidin,P=0.0288;magnolol,P= 0.0487;hesperidin,P=0.0277;naringin,P=0.0023) and AUC(rhein,P=0.0186;chrysophanol,P=0.0013; magnolol,P=0.001;hesperidin,P=0.0081;naringin, P=0.0272)of DCQD component were obviously lower in SAP group than in control group.The T1/2α of chrysophanol and rheochrysidin(P=0.0467 and 0.0005,respectively)and Tmax of chrysophanol and rheochrysidin(P=0.0101 and 0.0037,respectively) lasted longer in SAP group than in control group. CONCLUSION:SAP can significantly impact the ab-sorption of DCQD components in rats and their phar-macokinetic parameters.

Continuous regional arterial infusion for the treatment of severe acute pancreatitis: a meta-analysis

BACKGROUND： Continuous regional arterial infusion（CRAI） is a drug delivery system, which dramatically increases the drug concentration in the pancreas. Previous clinical and basic studies have demonstrated the possible therapeutic efficacy of CRAI for severe acute pancreatitis（SAP）. This meta-analysis of all published randomized controlled trials（RCTs） was conducted to assess the efficacy and safety of CRAI for the treatment of SAP. DATA SOURCES： Up to August 10, 2014, RCTs comparing CRAI with intravenous infusion for SAP in PubM ed, Embase, EBSCO, MEDLINE, Science Citation Index Expanded, Cochrane Library, China Academic Journals Full-Text Database, Chinese Biomedical Literature Database, and Chinese Scientific Journals Database were selected by two independent reviewers. The relative risk（RR） and their 95% confidence intervals（CI） for duration of elevated serum amylase and urine amylase, duration of abdominal pain, infection rate, incidence of complication, overall mortality, curative rate, hospital stay and details of subgroup analysis were extracted. Meta-analyses were made using the software Review Manager（RevM an version 5.10）.RESULTS： Six RCTs with 390 patients meeting the inclusion criteria were included in the final analysis. Compared with intravenous infusion route, CRAI significantly shortened the duration of elevated urine amylase（MD=-2.40, 95% CI=-3.20,-1.60; P〈0.00001） and the duration of abdominal pain（MD=-1.46, 95% CI=-1.94,-0.98; P〈0.00001）, decreased the incidence of complication（RR=0.35, 95% CI=0.15, 0.81; P=0.01） and overall mortality（RR=0.25, 95% CI=0.08, 0.78;P=0.02）, shortened the duration of hospital stay（MD=-10.36, 95% CI=-17.05,-3.68; P=0.002）, and increased the curative rate（RR=1.66, 95% CI=1.13, 2.46; P=0.01）. No mortality and catheter-related infections due to CRAI administration was reported in these studies. Subgroup analysis showed that the combination of drug administration via CRAI did not significantly improve the outcomes.CONCLUSION： CRAI is effective for the treatment of SAP, and the combination of drug administration via CRAI did not have a significant effect on the improvement of the outcomes.

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

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 P<0.05). They also had a lower incidence of pancreatic necrosis (45.5% vs 71.2%, P=0.015), infection (9.1% vs 37.3%, P=0.004), ICU admission (0% vs 27.1%, P=0.001), and shorter hospital stay (15 +/- 5 vs 27 +/- 12 days; P<0.001). A subgroup 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 but 7 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 (pen-) pancreatic necrosis and/or transient organ failure, is an accurate category of acute pancreatitis.

Impact of alanyl-glutamine dipeptide on severe acute pancreatitis in early stage

AIM:To evaluate the therapeutic effect of alanyl- glutamine dipeptide (AGD) in the treatment of severe acute pancreatitis (SAP) in early and advanced stage. METHODS: Eighty patients with SAP were randomized and received 100 mL/d of 20% AGD intravenously for 10 d starting either on the day of (early treatment group) or 5 d after (late treatment group) admission. Groups had similar demographics, underlying diseases, Ranson score, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, and Balthazar’s computed tomography (CT) score at the beginning of the study and underwent similar other medical and nutritional management. RESULTS: The duration of acute respiratory distress syndrome (2.7 ± 3.3 d vs 12.7 ± 21.0 d, P < 0.01), renal failure (1.3 ± 0.5 d vs 5.3 ± 7.3 d, P < 0.01), acute hepatitis (3.2 ± 2.3 d vs 7.0 ± 7.1 d, P < 0.01), shock (1.7 ± 0.4 d vs 4.8 ± 3.1 d, P < 0.05), encephalopathy (2.3 ± 1.9 d vs 9.5 ± 11.0 d, P < 0.01) and enteroparalysis (2.2 ± 1.4 d vs 3.5 ± 2.2 d, P < 0.01) and hospital stay (28.8 ± 9.4 d vs 45.2 ± 27.1 d, P < 0.01) were shorter in the early treatment group than in the late treatment group. The 15-d APACHE Ⅱ score was lower in the early treatment group than in the late treatment group (5.0 ± 2.4 vs 8.6 ± 3.6, P < 0.01). The infection rate (7.9% vs 26.3%, P < 0.05), operation rate (13.2% vs 34.2%, P < 0.05) and mortality (5.3% vs 21.1%, P < 0.05) in the early treatment group were lower than in the late treatment group.CONCLUSION: Early treatment with AGD achieved a better clinical outcome in SAP patients.

Prediction of the severity of acute pancreatitis on admission by urinary trypsinogen activation peptide: A meta-analysis

AIM: To undertake a meta-analysis on the value of urinary trypsinogen activation peptide (uTAP) in predicting severity of acute pancreatitis on admission.METHODS: Major databases including Medline, Embase, Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials in the Cochrane Library were searched to identify all relevant studies from January 1990 to January 2013. Pooled sensitivity, specificity and the diagnostic odds ratios (DORs) with 95%CI were calculated for each study and were compared to other systems/biomarkers if mentioned within the same study. Summary receiver-operating curves were conducted and the area under the curve (AUC) was evaluated.RESULTS: In total, six studies of uTAP with a cut-off value of 35 nmol/L were included in this meta-analysis. Overall, the pooled sensitivity and specificity of uTAP for predicting severity of acute pancreatitis, at time of admission, was 71% and 75%, respectively (AUC = 0.83, DOR = 8.67, 95%CI: 3.70-20.33). When uTAP was compared with plasma C-reactive protein, the pooled sensitivity, specificity, AUC and DOR were 0.64 vs 0.67, 0.77 vs 0.75, 0.82 vs 0.79 and 6.27 vs 6.32, respectively. Similarly, the pooled sensitivity, specificity, AUC and DOR of uTAP vs Acute Physiology and Chronic Health Evaluation II within the first 48 h of admission were found to be 0.64 vs 0.69, 0.77 vs 0.61, 0.82 vs 0.73 and 6.27 vs 4.61, respectively.CONCLUSION: uTAP has the potential to act as a stratification marker on admission for differentiating disease severity of acute pancreatitis.

Cost-effectiveness analysis of early veno-venous hemofiltration for severe acute pancreatitis in China

AIM： To determine the most cost-effective hemofiltration modality for early management of severe acute pancreatitis （SAP） in China. METHODS： We carried out a search of Pub-Medline and Chinese Biomedical Disk database. Controlled clinical trials on Chinese population were included in the analysis. The four decision branches that were analyzed were： continuous or long-term veno-venous hemofiltration （CVVH/LVVH）, short-term veno-venous hemofiltration （SVVH）, SVVH plus peritoneal dialysis （PD）, and non-hemofiltration control group. The effectiveness of the technique was determined by survival rate, complications prevention and surgery preservation. The total cost of hospitalization was also assessed. RESULTS： The SVVH only technique was the least costly modality, $5809 （44449 RMB）, and was selected as the baseline treatment modality. SVVH only arm achieved the lowest C/E ratio in terms of overall survival, complications prevention and surgery preservation. In incremental cost-effectiveness analysis, the CWH/ LVVH only and the control arms were inferior to other techniques. Sensitivity analysis showed SVVH only and SVVH plus PD arms overlapped in C/survival ratio. CONCLUSION： The role of early veno-venous hemofiltration as an alternative therapy for SAP remains controversial. However, we propose that early use of short-term high-volume veno-venous hemofiltration would have a beneficial impact on the management of SAP.

Alleviation of acute pancreatitis-associated lung injury by inhibiting the p38 mitogen-activated protein kinase pathway in pulmonary microvascular endothelial cells

BACKGROUND Previous reports have suggested that the p38 mitogen-activated protein kinase signaling pathway is involved in the development of severe acute pancreatitis(SAP)-related acute lung injury(ALI).Inhibition of p38 by SB203580 blocked the inflammatory responses in SAP-ALI.However,the precise mechanism associated with p38 is unclear,particularly in pulmonary microvascular endothelial cell(PMVEC)injury.AIM To determine its role in the tumor necrosis factor-alpha(TNF-α)-induced inflammation and apoptosis of PMVECs in vitro.We then conducted in vivo experiments to confirm the effect of SB203580-mediated p38 inhibition on SAP-ALI.METHODS In vitro,PMVEC were transfected with mitogen-activated protein kinase kinase 6(Glu),which constitutively activates p38,and then stimulated with TNF-α.Flow cytometry and western blotting were performed to detect the cell apoptosis and inflammatory cytokine levels,respectively.In vivo,SAP-ALI was induced by 5%sodium taurocholate and three different doses of SB203580(2.5,5.0 or 10.0 mg/kg)were intraperitoneally injected prior to SAP induction.SAP-ALI was assessed by performing pulmonary histopathology assays,measuring myeloperoxidase activity,conducting arterial blood gas analyses and measuring TNF-α,interleukin(IL)-1βand IL-6 levels.Lung microvascular permeability was measured by determining bronchoalveolar lavage fluid protein concentration,Evans blue pulmonary cells was confirmed by performing a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling analysis and examining the Bcl2,Bax,Bim and cle-caspase3 levels.The proteins levels of P-p38,NFκB,IκB,P-signal transducer and activator of transcription-3,nuclear factor erythroid 2-related factor 2,HO-1 and Myd88 were detected in the lungs to further evaluate the potential mechanism underlying the protective effect of SB203580.RESULTS In vitro,mitogen-activated protein kinase(Glu)transfection resulted in higher apoptotic rates and cytokine(IL-1βand IL-6)levels in TNF-α-treated PMVECs.In vivo,SB2035080 attenuated lung histopathological injury,decreased inflammatory activity(TNF-α,IL-1β,IL-6 and myeloperoxidase)and preserved pulmonary function.Furthermore,SB203580 significantly reversed changes in the bronchoalveolar lavage fluid protein concentration,Evans blue accumulation,terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cell numbers,apoptosis-related proteins(cle-caspase3,Bim and Bax)and endothelial microstructure.Moreover,SB203580 significantly reduced the pulmonary P-p38,NFκB,P-signal transducer and activator of transcription-3 and Myd88 levels but increased the IκB and HO-1 levels.CONCLUSION p38 inhibition may protect against SAP-ALI by alleviating inflammation and the apoptotic death of PMVECs.

Urinary trypsinogen-2 for diagnosing acute pancreatitis:a meta-analysis

BACKGROUND: Currently, serum amylase and lipase are the most popular laboratory markers for early diagnosis of acute pancreatitis with reasonable sensitivity and specificity. Urinary trypsinogen-2 (UT-2) has been increasingly used but its clinical value for the diagnosis of acute pancreatitis and post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis has not yet been systematically assessed. DATA SOURCES: A comprehensive search was carried out using PubMed (MEDLINE), Embase, and Web of Science for clinical trials, which studied the usefulness of UT-2 as a diagnostic marker for acute pancreatitis. Sensitivity, specificity and the diagnostic odds ratios (DORs) with 95% confidence interval (CI) were calculated for each study and were compared with serum amylase and lipase. Summary receiver-operating curves were conducted and the area under the curve (AUC) was evaluated. RESULTS: A total of 18 studies were included. The pooled sensitivity and specificity of UT-2 for the diagnosis of acute pancreatitis were 80% and 92%, respectively (AUC=0.96, DOR=65.63, 95% CI: 31.65-139.09). The diagnostic value of UT-2 was comparable to serum amylase but was weaker than serum lipase. The pooled sensitivity and specificity for the diagnosis of post-ERCP pancreatitis were 86% and 94%, respectively (AUC=0.92, DOR=77.68, 95% CI: 24.99-241.48).CONCLUSIONS: UT-2 as a rapid test could be potentially used for the diagnosis of post-ERCP pancreatitis and to an extent, acute pancreatitis. Further studies are warranted to confirm these results.

Present and future of prophylactic antibiotics for severe acute pancreatitis

AIM: To investigate the role of prophylactic antibiotics in the reduction of mortality of severe acute pancreatitis (SAP) patients, which is highly questioned by more and more randomized controlled trials (RCTs) and metaanalyses. METHODS: An updated meta-analysis was performed. RCTs comparing prophylactic antibiotics for SAP with control or placebo were included for meta-analysis. The mortality outcomes were pooled for estimation, and re-pooled estimation was performed by the sensitivity analysis of an ideal large-scale RCT. RESULTS: Currently available 11 RCTs were included. Subgroup analysis showed that there was significant reduction of mortality rate in the period before 2000, while no significant reduction in the period from 2000 [Risk Ratio, (RR ) = 1.01, P = 0.98]. Funnel plot indi-cated that there might be apparent publication bias in the period before 2000. Sensitivity analysis showed that the RR of mortality rate ranged from 0.77 to 1.00 with a relatively narrow confidence interval (P < 0.05). However, the number needed to treat having a minor lower limit of the range (7-5096 patients) implied that certain SAP patients could still potentially prevent death by antibiotic prophylaxis. CONCLUSION: Current evidences do not support prophylactic antibiotics as a routine treatment for SAP, but the potentially benefited sub-population requires further investigations.