KEAP1 inhibitor-scutellarin-based liposomes serve as an antioxidant switch foroxidative stress induced by ischemic stroke injury

Background:Ischemic stroke is a disease characterized by the damage of brain tissue due to insufficient blood supply.The neuronal necrosis caused by oxidative stress during the acute phase of ischemic stroke leads to serious consequences,including blood-brain barrier disruption and vascular aging.The Kelch-like ECH-associated protein 1(KEAP1),is a key switch of antioxidative system in human body.Until now,there is still a lack of effective treatment to ischemic stroke.Methods:We developed scutellarin-based liposomes for treating ischemic stroke injury caused neuronal damage.Results:The results showed that scutellarin could directly bind to KEAP1 protein,and the Kd was 26.1μM.The scutellarin-based liposomes significantly reduced cellular reactive oxygen species(ROS)levels.It could also upregulate the protein expression level of nuclear factor E2-related factor 2(NRF2),which is the substrate protein of KEAP1.Next,both the mRNA and protein expression level of the NRF2 downstream anti-oxidative element,heme oxygenase 1(HO-1)and NAD(P)H quinone dehydrogenase 1(NQO1)were promoted.Furthermore,the coimmunoprecipitation(Co-IP)and hydrogen-deuterium exchange mass spectrometry(HDX-MS)revealed that scutellarin directly bound to KEAP1’s Kelch domain,interrupting the interaction between KEAP1 and NRF2.Conclusion:Our work indicates that the scutellarin-based liposomes might be a promising therapeutic approach for ischemic stroke induced neuronal necrosis.

Dendrobium officinale extract exerts antioxidant effects against skin photoaging through MMP9-TNF pathway

Background:Skin photoaging is a physiological or pathological process caused by multiple factors.Developing anti-skin photoaging drugs is a hot topic in cosmetology research fields.The purpose of this study was to explore the therapeutic effect of Dendrobium officinale(D.officinale)on skin aging.Methods:The ingredients of D.officinale were detected by UHPLC-Q-TOF/MS.The targets of D.officinale were screened by Swiss Target Prediction database.GeneCards,NCBI,and OMIM databases were utilized to find out the targets associated with skin photoaging.Overlapping targets of D.officinale and skin photoaging were obtained by Venn analysis.The ingredient-disease target network and protein-protein interaction network were constructed by using the STRING database and Cytoscape software.The key compounds and hub genes were obtained by analyzing networks.The DAVID database was applied for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the overlapping targets.Autodock Vina software was used to simulate molecular docking and the results were visualized using Pymol.Finally,the skin photoaging models of cells and mice were established to validate the results predicted by network pharmacology.Results:In D.officinale,a total of 59 compounds and 595 targets were detected,of which 59 proteins were intersectional with skin photoaging targets.The top 10 active ingredients(Dendrophenol,Herbacetin,Lyoniresinol,Trans-ferulaldehyde,Naringenin,and so on)and 8 hub genes(AKT1,TNF,VEGFA,MAPK3,CASP3,MMP9,CTNNB1,and EGFR)were identified.All the key active compounds could bind well with core protein targets(binding energy<-5 kcal/mol).The potential therapeutic targets were related to the response to reactive oxygen species,collagen catabolic process,extracellular matrix organization,and apoptotic process,mainly.We also found that D.officinale could enhance the cell viability and activity of anti-oxidases,reduce reactive oxygen species and MMP9 levels,and stable mitochondrial membrane potential.Furthermore,D.officinale could alleviate skin photoaging injury and reduce malondialdehyde level in mice.Conclusion:D.officinale alleviated skin photoaging via regulating oxidative stress,apoptosis,and collagen catabolic process.

Pancreatic cancer stroma:understanding biology leads to new therapeutic strategies

Pancreatic ductal adenocarcinoma(PDA)is among the deadliest cancers in the United States and in the world.Late diagnosis,early metastasis and lack of effective therapy are among the reasons why only 6%of patients diagnosed with PDA survive past 5 years.Despite development of targeted therapy against other cancers,little progression has been made in the treatment of PDA.Therefore,there is an urgent need for the development of new treatments.However,in order to proceed with treatments,the complicated biology of PDA needs to be understood first.Interestingly,majority of the tumor volume is not made of malignant epithelial cells but of stroma.In recent years,it has become evident that there is an important interaction between the stromal compartment and the less prevalent malignant cells,leading to cancer progression.The stroma not only serves as a growth promoting source of signals but it is also a physical barrier to drug delivery.Understanding the tumor-stroma signaling leading to development of desmoplastic reaction and tumor progression can lead to the development of therapies to decrease stromal activity and improve drug delivery.In this review,we focus on how the current understanding of biology of the pancreatic tumor microenvironment can be translated into the development of targeted therapy.

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.

Higher body mass index deteriorates postoperative outcomes of pancreaticoduodenectomy

Background:Previous studies presented controversies in impact of body mass index(BMI)on perioper-ative complications in pancreatectomy,and mainly focused on Western population.This study aimed to explore the impact of BMI on perioperative outcomes in Chinese patients undergoing pancreaticoduo-denectomy.Methods:Seven hundred and seven adult patients undergoing open pancreaticoduodenectomy between January 2005 and December 2016 at Ruijin Hospital were studied retrospectively and categorized as obese(BMI≥25 kg/m^2),overweight(BMI≥23 kg/m^2 and<25 kg/m^2),or normal weight(BMI≥18.5 kg/m^2 and<23 kg/m^2).Associations of these BMI groups with perioperative outcomes were evaluated.Results:The overweight and obese groups experienced higher risk of clinically related postoperative pan-creatic fistula(CR-POPF)(7.6%vs.9.9%vs.17.6%,P=0.002)and re-operation(1.1%vs.2.5%vs.5.1%,P=0.017),and longer systemic inflammation response syndrome(SIRS)duration[2(1–9)d vs.2(1–7)d vs.3(1–10)d,P=0.003]and postoperative hospital stay[19(2–84)d vs.19(7–158)d vs.23(8–121)d,P=0.023]than the normal weight group did.The multiple logistic regression models showed obese as an independent risk factor for CR-POPF(P=0.013).The multiple linear regression analysis confirmed BMI as a predictor for prolonged postoperative hospital stay(P=0.005).Conclusions:Higher BMI results in higher morbidity of Chinese patients undergoing open pancreaticoduo-denectomy.Pancreaticoduodenectomy is still a safe surgery procedure for overweight and obese patients,with intensive perioperative management.

1-MT Enhances Potency of Tumor Cell Lysate-pulsed Dendritic Cells against Pancreatic Adenocarcinoma by Downregulating the Percentage of Tregs

This study examined whether 1-methyl-tryptophan [1-MT,an indoleamine 2,3-dioxygenase(IDO) inhibitor] could reduce CD4+CD25+ regulatory T cells(Tregs) proliferation and improve the anti-tumor efficacy of dendritic cells(DCs) pulsed with tumor cell lysate in the mice bearing pancreatic adenocarcinoma.The models of pancreatic adenocarcinoma were established in C57BL/6 mice by subcutaneous injection of Pan02 cells.Eight mice which were subcutaneously injected with PBS served as control.The expression of IDO was determined in tumor draining lymph nodes(TDLNs) and spleens of the murine pancreatic adenocarcinoma models.The prevalence of Tregs was measured in the TDLNs and spleens before and after 1-MT administration.The dendritic cells were pulsed with tumor cell lysate for preparing DC vaccine.The DC vaccine,as a single agent or in combination with 1-MT,was administered to pancreatic adenocarcinoma mice.The anti-tumor efficacy was determined after different treatments by regular observation of tumor size.The results showed that the levels of IDO mRNA and protein in tumor-bearing mice were significantly higher than those in the normal control mice.The percentage of Tregs in the spleen and TDLNs was also higer in tumor-bearing mice than in normal control mice(P<0.05).Foxp3 expression was significantly lower in the TDLNs and spleens of tumor-bearing mice administrated with 1-MT than that in normal control mice.Furthemore,in the mice that were administered 1-MT plus DC vaccine,the tumor was increased more slowly than in mice treated with DC vaccine or 1-MT alone,or PBS on day 36(P<0.01).Our results indicated that 1-MT may enhance anti-tumor efficacy of dendritic cells pulsed with tumor cell lysate by downregulating the percentage of Tregs.

Down-regulation of STAT3 expression by vector-based small interfering RNA inhibits pancreatic cancer growth

AIM:To evaluate the effect of RNA interference (RNAi) mediated silence of signal transduction and activation of transcription (STAT)3 on the growth of human pancreatic cancer cells both in vitro and in vivo.METHODS:STAT3 specific shRNA was used to silence the expression of STAT3 in pancreatic cancer cell line SW1990.The anti-growth effects of RNAi against STAT3 were studied in vitro and in experimental cancer xenografts in nude mice.The potential pathways involved in STAT3 signaling were detected using reverse transcription polymerase chain reaction and western blotting.RESULTS:The expression of the STAT3 was inhibited using RNAi in SW1990 cells.RNAi against STAT3 inhibited cell proliferation,induced cell apoptosis and significantly reduced the levels of CyclinD1 and Bcl-xL when compared with parental and control vector-transfected cells.In vivo experiments showed that RNAi against STAT3 inhibited the tumorigenicity of SW1990 cells and significantly suppressed tumor growth when it was directly injected into tumors.CONCLUSION:STAT3 signaling pathway plays an important role in the progression of pancreatic cancer,and silence of STAT3 gene using RNAi technique may be a novel therapeutic option for treatment of pancreatic cancer.

Implication of EMT Induced by TGF-β1 in Pancreatic Cancer

This study examined the implication of EMT induced by TGF-β1 in pancreatic cancer invasion. TGF-β1 expression was determined in 29 cases of human pancreatic carcinoma （PC） by immunohistochemistry and the results were compared with those of pathological examination. Moreover, the effects of TGF-β1 on the phenotype and invasion of pancreatic cancer cell line Panc-1 were also investigated. TGF-β1 was detected in 12 cases （41.4 %） of PC. Significant correlation was found between the expression of TGF-β1 and lymph node involvement （P=0.047） and the depth of invasion （P=0.035）. TGF-β1 obviously promoted EMT of Panc-1 cell lines and their invasion ability was substantially enhanced. TGF-β1 may promote the malignancy of pancreatic cancer by triggering EMT.

The crown jewelry of the surgeries for pancreatic cancer

We are very pleased to organize this issue of Chinese Journal of Cancer Research.Authors come from the most distinguished groups of pancreatic cancer surgeons and oncologists in China and in USA.The first two articles make overviews on the historic and contemporary progresses in surgical management of pancreatic cancer.

Dose-response relationship between risk factors and incidence of COVID-19 in 325 hospitalized patients:A multicenter retrospective cohort study

BACKGROUND The epidemiological and clinical characteristics of coronavirus disease 2019(COVID-19)patients have been widely reported,but the assessment of doseresponse relationships and risk factors for mortality and severe cases and clinical outcomes remain unclear.AIM To determine the dose-response relationship between risk factors and incidence of COVID-19.METHODS In this retrospective,multicenter cohort study,we included patients with confirmed COVID-19 infection who had been discharged or had died by February 6,2020.We used multivariable logistic regression and Cox proportional hazard models to determine the dose-response relationship between risk factors and incidence of COVID-19.RESULTS It clarified that increasing risk of in-hospital death were associated with older age(HR:1.04,95%CI:1.01-1.09),higher lactate dehydrogenase[HR:1.04,95%confidence interval(CI):1.01-1.10],C-reactive protein(HR:1.10,95%CI:1.01-1.23),and procalcitonin(natural log-transformed HR:1.88,95%CI:1.22-2.88),and D-dimer greater than 1μg/m L at admission(natural log transformed HR:1.63,95%CI:1.03-2.58)by multivariable regression.D-dimer and procalcitonin were logarithmically correlated with COVID-19 mortality risk,while there was a linear dose-response correlation between age,lactate dehydrogenase,D-dimer and procalcitonin,independent of established risk factors.CONCLUSION Higher lactate dehydrogenase,D-dimer,and procalcitonin levels were independently associated with a dose-response increased risk of COVID-19 mortality.

Endoscopic-ultrasound-guided biliary drainage with placement of electrocautery-enhanced lumen-apposing metal stent for palliation of malignant biliary obstruction:Updated meta-analysis

BACKGROUND Endoscopic ultrasound-guided biliary drainage using electrocautery-enhanced(ECE)delivery of lumen-apposing metal stent(LAMS)is gradually being re-cognized as a viable palliative technique for malignant biliary obstruction after endoscopic retrograde cholangiopancreatography(ERCP)failure.However,most of the studies that have assessed its efficacy and safety were small and hetero-geneous.Prior meta-analyses of six or fewer studies that were published 2 years ago were therefore underpowered to yield convincing evidence.AIM To update the efficacy and safety of ECE-LAMS for treatment of biliary ob-struction after ERCP failure.METHODS We searched PubMed,EMBASE,and Scopus databases from the inception of the ECE technique to May 13,2022.Primary outcome measure was pooled technical success rate,and secondary outcomes were pooled rates of clinical success,re-intervention,and adverse events.Meta-analysis was performed using a random-effects model following Freeman-Tukey double-arcsine transformation in R soft-ware(version 4.1.3).RESULTS Fourteen eligible studies involving 620 participants were ultimately included.The pooled rate of technical success was 96.7%,and clinical success was 91.0%.Adverse events were reported in 17.5%of patients.Overall reinter-vention rate was 7.3%.Subgroup analyses showed results were generally consistent.CONCLUSION ECE-LAMS has favorable success with acceptable adverse events in relieving biliary obstruction when ERCP is impossible.The consistency of results across most subgroups suggested that this is a generalizable approach.

Predicting the prognosis of hepatic arterial infusion chemotherapy in hepatocellular carcinoma

Hepatic artery infusion chemotherapy(HAIC)has good clinical efficacy in the treatment of advanced hepatocellular carcinoma(HCC);however,its efficacy varies.This review summarized the ability of various markers to predict the efficacy of HAIC and provided a reference for clinical applications.As of October 25,2023,51 articles have been retrieved based on keyword predictions and HAIC.Sixteen eligible articles were selected for inclusion in this study.Comprehensive literature analysis found that methods used to predict the efficacy of HAIC include serological testing,gene testing,and imaging testing.The above indicators and their combined forms showed excellent predictive effects in retrospective studies.This review summarized the strategies currently used to predict the efficacy of HAIC in middle and advanced HCC,analyzed each marker's ability to predict HAIC efficacy,and provided a reference for the clinical application of the prediction system.

Perceptions of pancreatic surgeons and the current status of palliative care for pancreatic cancer in China:a multi-center online questionnaire survey

Objective:To investigate the perceptions of pancreatic surgeons regarding palliative care for pancreatic cancer and the current status of palliative care for pancreatic cancer patients in China.Methods:An online questionnaire consisting of 35 questions in 5 domains,including basic information of the respondents,personal interest,training and experiences of palliative care,recognition of the importance of palliative care,palliative care in the hospital of the respondents,and advice to improve the service of palliative care for pancreatic cancer,was distributed to pancreatic surgeons by the WeChat APP.All the data were automatically recorded and can be downloaded.The respondents’perceptions of palliative care and the current status of palliative care were depicted,and the factors influencing the perceptions of the respondents and palliative care in hospitals were further analyzed.Results:Responses from 429 pancreatic surgeons were validated.81.4%were from tertiary hospitals,and 18.6%were from secondary hospitals.94.2%were from general hospitals,and 5.8%were from cancer hospitals.Most surgeons have worked for over 5 years(93%),72%had senior titles,and 54.5%held administrative positions.49%have not read papers on palliative care before.73.4%of the hospitals did not have a palliative care team,77.9%did not have specific ward or bed for palliative care,76.2%of the surgeons thought palliative care needed more attention in their hospitals.97.4%of the surgeons thought palliative care was important for pancreatic cancer patients,and 94.9%were willing to join the palliative team.46.6%of the surgeons thought palliative care should be conducted once pancreatic cancer was diagnosed.Most surgeons thought palliative care was helpful and should be involved in the multidisciplinary team.Regarding the geographical differences,surgeons and hospitals in North China performed better than in other regions.Surgeons with experience in clinical trials of pancreatic cancer performed better.The top 3 advice from the surgeons to promote palliative care were more education and training,seminars,and public broadcasting.69.9%of the surgeons have concerns about the legal issue of implementation of palliative care.Conclusion:In general,the majority of pancreatic surgeons in China lack training and experience in palliative care for pancreatic cancer,and the current status of palliative care in most hospitals needs to be further improved.Prevalence of the participants think that palliative care is very important for pancreatic cancer patients.Palliative care should be provided once pancreatic cancer is diagnosed,and palliative care should be involved in the multidisciplinary team.More seminars,education and training,and public broadcasting are practical ways to improve palliative care for pancreatic cancer patients.

Preoperative biliary drainage in patients with hilar cholangiocarcinoma undergoing major hepatectomy

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=0.040)were independent risk factors for postoperative complications.CONCLUSION:Overall postoperative morbidity and mortality rates after major liver resection are not improved by PBD in HCCA patients with jaundice.Preoperative TBIL>170μmol/L,Bismuth-Corlette classification and extended liver resection are independent risk factors linked to postoperative complications.

Pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction in the liver of rats with severe acute pancreatitis

AIM To explore the pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction (DCQD) in the liver of rats with severe acute pancreatitis (SAP) based on an herbal recipe tissue pharmacology hypothesis. METHODS Healthy male Sprague-Dawley rats were randomly divided into a sham operation group (SOG); a model group (MG); and low-, median- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Different dosages (6, 12 and 24 g/kg for the LDG, MDG, and HDG, respectively) of DCQD were administered to the rats with SAP. The tissue concentrations of aloeemodin, rhein, emodin, chrysophanol, honokiol, rheo chrysophanol, magnolol, hesperidin, naringenin and naringin in the liver of the treated rats were detected by high-performance liquid chromatography tandem mass spectrometry. Alanine transaminase (ALT) and aspartate transaminase (AST) in serum, inflammatory mediators in the liver and pathological scores were evaluated. RESULTS The major components of DCQD were detected in the liver, and their concentrations increased dose-dependently. The high dose of DCQD showed a maximal effect in ameliorating the pathological damages, decreasing the pro-inflammatory mediators tumor necrosis factor-a and interleukin (IL)-6 and increasing anti-inflammatory mediators IL-4 and IL-10 in the liver. The pathological scores in the pancreas for the MG were significantly higher than those for the SOG (P < 0.05). DCQD could reduce the pathological scores in the pancreas and liver of the rats with SAP, especially in the HDG. Compared to the SOG, the ALT and AST levels in serum were higher in the MG (P < 0.05), while there was no statistical difference in the MG and HDG. CONCLUSION DCQD could alleviate liver damage by altering the inflammatory response in rats with SAP based on the liver distribution of its components.

Pharmacokinetics and pharmacodynamics of Shengjiang decoction in rats with acute pancreatitis for protecting against multiple organ injury

AIM To explore the pharmacokinetics and pharmacodynamics of Shengjiang decoction(SJD) in rats with acute pancreatitis(AP) for protecting against multiple organ injury.METHODS An AP model was established by retrograde perfusion of 3.5% sodium taurocholate into the biliopancreatic duct, and a control group(CG) received 0.9% sodium chloride instead. Twelve male Sprague-Dawley rats were randomly divided into a CG treated with SJD(CG + SJD) and a model group treated with SJD(MG + SJD), both of which were orally administered with SJD(5 g/kg) 2 h after surgery. Blood samples were collected via the tail vein at 10, 20, and 40 min and 1, 2, 3, 4, 6, 8, and 12 h after a single dose of SJD to detect its main components using high-performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters were compared. In the pharmacodynamic experiment, 18 male SpragueDawley rats were randomly divided into a CG, an AP model group(MG), and an SJD treated AP group(SJDG). Serum amylase, lipase, and inflammatory cytokines were measured, and heart, lung, liver, spleen, pancreas, kidney, and intestine tissues were collected for pathological examination.RESULTS The MG + SJD displayed significantly shorter mean residence time(MRT) and higher clearance(CL) for emodin and aloe-emodin; significantly shorter time of maximum concentration and T1/2 and a lower area under curve(AUC) for aloe-emodin; a significantly higher AUC and lower CL for rhein; and longer MRT and lower CL for chrysophanol than the CG + SJD. In the pharmacodynamic experiment, the amylase, interleukin(IL)-6, IL-10, and tumor necrosis factor(TNF)-α levels in the MG were higher than those in the CG(P < 0.05). After the herbal decoction treatment, the SJDG had higher IL-10 and lower TNF-α levels than the MG(P < 0.05). The MG had the highest pathological scores, and the pathological scores of the lung, pancreas, kidney, and intestine in the SJDG were significantly lower than those in the MG(P < 0.05).CONCLUSION AP may have varying effects on the pharmacokinetics of the major SJD components in rats. SJD might alleviate pathological injuries of the lung, pancreas, kidney, and intestine in rats with AP via regulating pro-and antiinflammatory responses, which might guide the clinical application of SJD for AP treatment.

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.

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.

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.