Vitamin D and Pancreatitis: A Narrative Review of Current Evidence.

Emerging research indicates that vitamin D metabolic disorder plays a major role in both acute pancreatitis (AP) and chronic pancreatitis (CP). This has been demonstrated by studies showing that vitamin D deficiency is associated with pancreatitis and its anti-inflammatory and anti-fibrotic effects by binding with the vitamin D receptor (VDR). However, the role of vitamin D assessment and its management in pancreatitis remains poorly understood. In this narrative review, we discuss the recent advances in our understanding of the molecular mechanisms involved in vitamin D/VDR signaling in pancreatic cells; the evidence from observational studies and clinical trials that demonstrate the connection among vitamin D, pancreatitis and pancreatitis-related complications; and the route of administration of vitamin D supplementation in clinical practice. Although further research is still required to establish the protective role of vitamin D and its application in disease, evaluation of vitamin D levels and its supplementation should be important strategies for pancreatitis management according to currently available evidence.

Buyang Huanwu Decoction Enhances Revascularization via Akt/GSK3ß/NRF2 Pathway in Diabetic Hindlimb Ischemia.

BACKGROUND: Peripheral arterial disease (PAD) is a typical disease of atherosclerosis, most commonly influencing the lower extremities. In patients with PAD, revascularization remains a preferred treatment strategy. Buyang Huanwu decoction (BHD) is a popular Chinese herbal prescription which has showed effects of cardiovascular protection through conducting antioxidant, antiapoptotic, and anti-inflammatory effects. Here, we intend to study the effect of BHD on promoting revascularization via the Akt/GSK3ß/NRF2 pathway in diabetic hindlimb ischemia (HLI) model of mice. MATERIALS AND METHODS: All db/db mice (n = 60) were randomly divided into 6 groups by table of random number. (1) Sham group (N = 10): 7-0 suture thread passed through the underneath of the femoral artery and vein without occlusion. The remaining 5 groups were treated differently on the basis of the HLI (the femoral artery and vein from the inguinal ligament to the knee joint were transected and the vascular stump was ligated with 7-0 silk sutures) model: (2) HLI+NS group (N = 15): 0.2 ml NS was gavaged daily for 3 days before modeling and 14 days after occlusion; (3) HLI+BHD group (N = 15): 0.2 ml BHD (20 g/kg/day) was gavaged daily for 3 days before modeling and 14 days after occlusion; (4) HLI+BHD+sh-NC group (N = 8): local injection of adenovirus vector carrying the nonsense shRNA (Ad-GFP) in the hindlimbs of mice before treatment; (5) HLI+BHD+sh-NRF2 group (N = 8): knockdown of NRF2 in the hindlimbs of mice by local intramuscular injection of adenovirus vector carrying NRF2 shRNA (Ad-NRF2-shRNA) before treatment; and (6) HLI+BHD+LY294002 group (N = 4): intravenous injection of LY294002 (1.5 mg/kg) once a day for 14 days on the basis of the HLI+BHD group. Laser Doppler examination, vascular cast, and immunofluorescence staining were applied to detect the revascularization of lower limbs in mice. Western blot analysis was used to detect the expression of vascular endothelial growth factor (VEGF), interleukin-1beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor- (TNF-) α, heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase quinone-1 (NQO-1), catalase (CAT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphorylated protein kinase B (p-AKT), and phosphorylated glycogen synthase kinase-3 beta (p-GSK3ß). HE staining was used to assess the level of muscle tissue damage and inflammation in the lower extremities. Local multipoint injection of Ad-NRF2-shRNA was used to knock down NRF2, and qPCR was applied to detect the mRNA level of NRF2. The blood glucose, triglyceride, cholesterol, MDA, and SOD levels of mice were tested using corresponding kits. The SPSS 20.0 software and GraphPad Prism 6.05 were used to do all statistics. Values of P < 0.05 were considered as statistically significant. Results and Conclusions. BHD could enhance the revascularization of lower limbs in HLI mice, while BHD has no effect on blood glucose and lipid level in db/db mice (P > 0.05). BHD could elevate the protein expression of VEGF, HO-1, NQO-1, and CAT (P < 0.05) and decrease the expression of IL-1ß, IL-6, and TNF-α (P < 0.05) in HLI mice. Meanwhile, BHD could activate NRF2 and promote the phosphorylation of AKT/GSK3ß during revascularization (P < 0.05). In contrast, knockdown of NRF2 impaired the protective effects of BHD on HLI (P < 0.05). LY294002 inhibited the upregulation of NRF2 activated by BHD through inhibiting the phosphorylation of the AKT/GSK3ß pathway (P < 0.05). The present study demonstrated that BHD could promote revascularization on db/db mice with HLI through targeting antioxidation, anti-inflammation, and angiogenesis via the AKT/GSK3ß/NRF2 pathway.

A Preclinical Systematic Review of Curcumin for Protecting the Kidney with Ischemia Reperfusion Injury.

Renal ischemia-reperfusion injury (RIRI) refers to a phenomenon associated with dysfunction of the kidney and tissue damage. Unfortunately, no specific drugs have been found that effectively prevent and treat RIRI. Curcumin (Cur), a polyphenol extracted from turmeric, possesses a variety of biological activities involving antioxidation, inhibition of apoptosis, inhibition of inflammation, and reduction of lipid peroxidation. Eight frequently used databases were searched using prespecified search strategies. The CAMARADES 10-item quality checklist was used to evaluate the risk of bias of included studies, and the RevMan 5.3 software was used to analyze the data. The risk of bias score of included studies ranged from 3 to 6 with an average score of 5.22. Compared with the control group, Cur significantly alleviated renal pathology, reduced blood urea nitrogen and serum creatinine levels, and improved inflammatory indexes, oxidant, and apoptosis in RIRI animal models. Despite the heterogeneity of the response to Cur in terms of serum creatinine, BUN, TNF-alpha, and SOD, its effectiveness for improving the injury of RIRI was remarkable. In the mouse model subgroup of serum creatinine, the effect size of the method of unilateral renal artery ligation with contralateral nephrectomy and shorter ischemic time showed a greater effect than that of the control group. No difference was seen in the methods of model establishment, mode administration, or medication times. The preclinical systematic review provided preliminary evidence that Cur partially improved RIRI in animal models, probably via anti-inflammatory, antioxidant, antiapoptosis, and antifibrosis activities and via improving microperfusion. ARRIVE guidelines are recommended; blinding and sample size calculation should be focused on in future studies. These data suggest that Cur is a potential renoprotective candidate for further clinical trials of RIRI.

Oral Administration of Quercetin or Its Derivatives Inhibit Bone Loss in Animal Model of Osteoporosis.

Objectives. Quercetin (Q) and its derivatives are the major members of the naturally occurring flavonoid family, which possess beneficial effects on disease prevention including osteoporosis. The present study is aimed at further investigating the efficacy of the Q and its derivatives on bone pathology, bone-related parameters under imageology, bone maximum load, and serum bone metabolism indexes in animal model of osteoporosis. Potential mechanisms of Q and its derivatives in the treatment of osteoporosis as well as the existing problems regarding the modeling method and limitations of researches in this area were also summarized. Eight databases were searched from their inception dates to February 2020. Nineteen eligible studies containing 21 comparisons were identified ultimately. The risk of bias and data on outcome measures were analyzed by the CAMARADES 10-item checklist and Rev-Man 5.3 software separately. The results displayed the number of criteria met varied from 3/10 to 7/10 with an average of 5.05. The present study provided the preliminary preclinical evidence that oral administration of Q or its derivatives was capable of improving bone pathology, bone-related parameters under imageology and bone maximum load, increasing serum osteocalcin, alkaline phosphatase, and estradiol, and reducing serum c-terminal cross-linked telopeptide of type I collagen (P < 0.05). No statistical difference was seen in survival rate, index of liver, or kidney function (P > 0.05). Q and its derivatives partially reverse osteopenia probably via antioxidant, anti-inflammatory, promoting osteogenesis, inhibiting osteoclasts, and its estrogen-like effect. The findings reveal the possibility of developing Q or its derivatives as a drug or an ingredient in diet for clinical treatment of osteoporosis.

Clinical and Preclinical Systematic Review of Astragalus Membranaceus for Viral Myocarditis.

Astragalus membranaceus (AM) is a traditional Chinese medicine, which possesses a variety of biological activities in the cardiovascular systems. We conducted a clinical and preclinical systematic review of 28 randomized clinical control studies with 2522 participants and 16 animal studies with 634 animals to evaluate the efficacy, safety, and possible mechanisms of AM for viral myocarditis (VM). The search strategies were performed in 7 databases from inception to January 2020. Application of the Cochrane Collaboration's tool 7-item checklist, SYRCLE's tool 10-item checklist, and Rev-Man 5.3 software to analyze the risk of bias of studies and data. The results show the score of clinical study quality ranged from 3 to 7 points with an average of 3.32, and the score of animal study quality ranged from 2 to 5 points with an average of 3. In clinical study, AM significantly reduced serum myocardial enzymes and cardiac troponin I levels and improved the clinical treatment efficiency in VM patients compared with the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions (P > 0.05). Significant increase of the survival rate and decrease of the cardiac cardiology score, cardiac enzymes, and cardiac troponin I were compared with the placebo group in animal studies (P < 0.05). The possible mechanisms of AM are largely through antivirus and antivirus receptors, anti-inflammatory, antioxidation, antiapoptotic, antifibrosis, and reducing cardiac calcium load. In conclusion, the findings suggested that AM is a cardioprotection candidate drug for VM.

Astragaloside IV Exerts Cardioprotection in Animal Models of Viral Myocarditis: A Preclinical Systematic Review and Meta-Analysis.

Astragaloside IV (AS-IV), the essential active component of astragalus, possesses diverse biological activities that have beneficial effects against cardiovascular disease. Here, we conducted a preclinical systematic review of 15 studies including 577 animals to establish the efficacy and potential mechanisms of AS-IV for animal models of viral myocarditis (VM). Six databases were searched from inception to October 2018. Application of the Cochrane Collaboration's tool 10-item checklist and Rev-Man 5.3 software to analyze risk of bias of studies and data on outcome measures revealed study quality scores ranging from 2 to 5. Compared with the control group, AS-IV induced a marked decrease in mortality (P < 0.05), inflammation of myocardium and pathological score (P< 0.05) and cardiac enzymes expression (P< 0.05), and improved the function of the heart (P< 0.05). The potential mechanisms of AS-IV action were determined as anti-remodeling of myocardium (n = 1), anti-virus (n = 2), antioxidant (n = 2), anti-inflammatory (n = 6), anti-apoptosis (n = 1) and alleviation of myocardial fibrosis (n = 2). The collective results indicate that AS-IV exerts cardioprotective effects in animals with VM via multiple signaling pathways.

Notoginsenoside R1 for Organs Ischemia/Reperfusion Injury: A Preclinical Systematic Review.

Notoginsenoside R1 (NGR1) exerts pharmacological actions for a variety of diseases such as myocardial infarction, ischemic stroke, acute renal injury, and intestinal injury. Here, we conducted a preclinical systematic review of NGR1 for ischemia reperfusion (I/R) injury. Eight databases were searched from their inception to February 23rd, 2019; Review Manager 5.3 was applied for data analysis. CAMARADES 10-item checklist and cell 10-item checklist were used to evaluate the methodological quality. Twenty-five studies with 304 animals and 124 cells were selected. Scores of the risk of bias in animal studies ranged from 3 to 8, and the cell studies ranged from 3 to 5. NGR1 had significant effects on decreasing myocardial infarct size in myocardial I/R injury, decreasing cerebral infarction volume and neurologic deficit score in cerebral I/R injury, decreasing serum creatinine in renal I/R injury, and decreasing Park/Chiu score in intestinal I/R injury compared with controls (all P < 0.05 or P < 0.01). The multiple organ protection of NGR1 after I/R injury is mainly through the mechanisms of antioxidant, anti-apoptosis, and anti-inflammatory, promoting angiogenesis and improving energy metabolism. The findings showed the organ protection effect of NGR1 after I/R injury, and NGR1 can potentially become a novel drug candidate for ischemic diseases. Further translation studies are needed.

Ginkgolide B for Myocardial Ischemia/Reperfusion Injury: A Preclinical Systematic Review and Meta-Analysis.

Ginkgolide B (GB) is an extract of dried Ginkgo biloba leaves and possesses various pharmacological activities in the cardiovascular system. Herein, we aim to assess the available preclinical evidence and possible mechanisms of GB for myocardial ischemia/reperfusion injury. The study quality score was assessed using the CAMARADES 10-item checklist. Rev-Man 5.3 software was used for data analyses. Nineteen studies with total 437 animals were included for analysis. Meta-analyses indicated that GB interventions significantly reduce myocardial infarct size and cardiac markers when compared with control (P < 0.05). The possible mechanisms via which GB exerts cardioprotective effects are mainly associated with anti-oxidation, anti-inflammation, anti-apoptosis, and improvement of energy metabolism. Our study indicates that GB might be a promising cardioprotective agent for myocardial ischemia/reperfusion injury and may contribute to future clinical trial design.

Plasma cytokines can help to identify the development of severe acute pancreatitis on admission.

Severe acute pancreatitis (AP) is associated with high morbidity and mortality. Early severity stratification remains a challenging issue to overcome to improve outcomes. We aim to find novel plasma cytokines for the early identification of severe AP according to the revised Atlanta criteria.In this prospective observational study, 30 cytokines, screened semiquantitatively with a human multicytokine array, were submitted to quantitative determination using either microparticle-based multiplex immunoassays analyzed on a Luminex 100 platform or enzyme-linked immunosorbent assay kits. The cytokine profiles of patients and the discriminative value of cytokines for severe AP were analyzed.Plasma samples of 70 patients with AP (20 mild, 30 moderately severe, and 20 severe) were selected in this study if they were admitted within 48 hours of the onset of symptoms. Plasma from healthy volunteers was collected as the healthy control. Growth differentiation factor-15 (GDF-15) and pentraxin 3 (PTX3) on admission were independent prognostic markers for the development of severe AP and had higher discriminative powers than conventional markers (GDF-15 vs hematocrit, P = .003; GDF-15 vs C-reactive protein, P = .037; GDF-15 vs creatinine, P = .048; GDF-15 vs Acute Physiology and Chronic Health Evaluation II, P = .007; PTX3 vs hematocrit, P = .006; PTX3 vs C-reactive protein, P = .047; PTX3 vs Acute Physiology and Chronic Health Evaluation II, P = .011; PTX3 vs Bedside Index for Severity in Acute Pancreatitis, P = .048).Plasma GDF-15 and PTX3 can help to identify the development of severe AP on admission. Future work should validate their accuracy in a larger, multicenter patient cohort.

Chai-Qin-Cheng-Qi Decoction and Carbachol Improve Intestinal Motility by Regulating Protein Kinase C-Mediated Ca2+ Release in Colonic Smooth Muscle Cells in Rats with Acute Necrotising Pancreatitis.

Chai-Qin-Cheng-Qi decoction (CQCQD) improves intestinal motility in acute pancreatitis (AP), but the mechanism(s) require elucidation. We investigated the effects of CQCQD and carbachol, a prokinetic agent, on colonic smooth muscle cells (SMCs) in L-arginine-induced necrotising AP model in rats. In treatment groups, intragastric CQCQD (20 g/kg, 2 hourly × 3 doses) or intraperitoneal carbachol (60 µg/kg) was given 24 hours after induction of AP. Both CQCQD and carbachol decreased the severity of pancreatic and colonic histopathology (all P < 0.05). Both CQCQD and carbachol reduced serum intestinal fatty acid binding protein, vasoactive intestinal peptide, and substance P and increased motility levels. CQCQD upregulated SMC phospholipase C-beta 1 (PLC-ß1) mRNA and PLC protein (both P < 0.05), while both treatments upregulated protein kinase C-alpha (PKC-α) mRNA and PKC protein and downregulated adenylate cyclase (AC) mRNA and protein compared with no treatment (all P < 0.05). Neither treatment significantly altered L-arginine-induced PKC-ß1 and PKC-ε mRNA reduction. Both treatments significantly increased fluorescence intensity of SMC intracellular calcium concentration [Ca2+]i (3563.5 and 3046.9 versus 1086.9, both P < 0.01). These data suggest CQCQD and carbachol improve intestinal motility in AP by increasing [Ca2+]i in colonic SMCs via upregulating PLC, PKC and downregulating AC.

Circulating microRNA 216 as a Marker for the Early Identification of Severe Acute Pancreatitis.

BACKGROUND: To study the value of circulating microRNA 216 (miR-216) as a marker for the severity of acute pancreatitis (AP) in both murine models and patients. MATERIALS AND METHODS: Mice with AP were induced by intraperitoneal injection of 50µg/kg/hour cerulean either 7 times, sacrificed at 8, 9, 10, 11 or 12 hours after the first injection, or 12 times, sacrificed at 24 hours after the first injection. Plasma samples and data from patients with AP were obtained from a prospective cohort. Quantitative reverse transcription polymerase chain reaction was used to determine the miR-216a and miR-216b level. RESULTS: The upregulation of miR-216a and miR-216b in the serum of mice was induced by cerulean injection in both the 7- and 12-injection groups (P < 0.05). The downregulation of miR-216a in pancreatic tissues of mice with AP was detected (P < 0.05), but no difference was observed in pancreatic miR-216b levels among any of the groups (all P > 0.05). The serum miR-216a level was positively correlated with pancreatic histopathology severity scores, and was negatively correlated with pancreatic miR-216a (r = -0.483, P = 0.009). The plasma miR-216a level was significantly upregulated in patients with severe AP (SAP) compared with patients with mild AP (MAP) or moderate severe AP (MSAP) (SAP versus MAP, P = 0.04; SAP versus MSAP, P = 0.00), but no difference was seen between patients with MAP and those with MSAP (P = 0.73). CONCLUSIONS: Circulating miR-216a might be a potential biomarker for the early identification of SAP.

Isolated Roux-en-Y pancreaticojejunostomy versus conventional pancreaticojejunostomy after pancreaticoduodenectomy: a systematic review and meta-analysis.

OBJECTIVE: To investigate the advantage between isolated Roux loop pancreaticojejunostomy (IPJ) and conventional pancreaticojejunostomy (CPJ) after pancreaticoduodenectomy (PD). METHODS: Comparative studies on this topic published between January 1976 and April 2015 in PubMed, EMbase, EBSCO, Science Citation Index Expanded and Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library were searched, and selected based on specific inclusion and exclusion criteria. Perioperative outcomes such as postoperative pancreatic fistula, delayed gastric emptying, operation time, intraoperative blood loss, intraoperative blood transfusion, postoperative bleeding, intra-abdominal abscess, bile leakage, wound infection, morbidity and mortality were compared. Pooled odds ratios (OR) or weighted mean differences (WMD) with 95% confidence interval (CI) were calculated using either fixed- or random-effects model. RESULTS: Six studies were included with two randomized controlled and four nonrandomized trials. A total of 712 patients (359 patients from the IPJ group and 353 patients from the CPJ group) were analyzed. The pooled results revealed that IPJ had longer operation time (WMD = 36.55, 95% CI 6.98 to 66.11, P = 0.02). However, there were no significant differences between both groups in postoperative pancreatic fistula, intraoperative blood loss, blood transfusion, delayed gastric emptying, postoperative bleeding, intra-abdominal abscess, bile leakage, wound infection, morbidity, mortality and postoperative hospital stay. CONCLUSIONS: PD with IPJ was comparable to CPJ in intraoperative outcomes and postoperative complications. However, further randomized controlled trials should be undertaken to ascertain these findings.

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 PubMed, 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 (RevMan 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.

[Hot issues on the treatment of severe acute pancreatitis by Integrated Traditional Chinese and Western Medicine].

Severe acute pancreatitis (SAP) is recognized as critical refractory disease. The case fatality rate of SAP is as high as 36%-50%. Although significant progress has been achieved on the treatment of severe acute pancreatitis (SAP) by Integrated Traditional Chinese Medicine (TCM) and Western Medicine (WM), there still exist some difficulties hindering the further improvement of therapeutic efficacy. The hot issues includes: unconfirmative curative effects and diverse treatment principles, complicated predictive scoring systems and inaccurate markers for the severity stratification, unproved new therapeutic tools and controversial methods waiting more high qualified evidence, unclarified mechanism of Integrated TCM and WM. In order to overcome the difficulties, we aim to launch the clinical pathway of Integrated TCM and WM, to strengthen the unity of multidisciplinary cooperation. We also need to keep the efforts on screening the markers for early evaluation and prediction of disease severity, improving the diagnosis and treatment, exploring the mechanism of Traditional Chinese Medicine in treating SAP with more high quality basic and clinical research. Based on these efforts, we could provide better treatments and prognosis for SAP patients.

Clinical characteristics of critical patients with pandemic influenza A (H1N1) virus infection in Chengdu, China.

OBJECTIVE: The critical illness of pandemic influenza A (H1N1) virus infection may be associated with relatively poor outcomes. The objective of this study is to describe clinical features and factors associated with the deaths of critical patients. METHODS: Medical records of 26 critical patients with H1N1 infection admitted from Sept. 1 to Dec. 31, 2009, were retrospectively reviewed. Diagnosis was established by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. RESULTS: The mean age of the patients was (40.4 ± 18.4) years and 73.1% of them were male. Clinical manifestations included fever, cough, and sputum production. The laboratory findings included leukocytosis, lymphopenia, C-reaction protein, and lactic dehydrogenase elevation. In this series, 17 subjects survived and 9 died. The parameters between the deaths and survivors were compared, which included acute physiology and chronic health evaluation II (APACHE II) scores (23.8 ± 10.1 vs. 14.3 ± 6.6, P<0.05), sequential organ failure assessment (SOFA) scores (13.3 ± 3.0 vs. 6.6 ± 3.3, P<0.05), and multiple organ dysfunction syndrome (MODS) scores (7.4 ± 2.5 vs. 3.3 ± 1.7, P<0.05). The cases of deaths had higher incidences of cardiovascular failure (100% vs. 41.2%, P<0.05), renal failure (55.6% vs. 11.7%, P<0.05), encephalopathy (44.4% vs. 5.9%, P<0.05), hepatic failure (33.3% vs. 5.9%, P<0.05), and septic shock (33.3% vs. 17.6%, P<0.05). CONCLUSIONS: The critical patients with H1N1 infection have high APACHE II, SOFA, and MODS scores, which may be associated with an increased risk of death and complex clinical courses.

Effects of Chai-Qin-Cheng-Qi Decoction on cefotaxime in rats with acute necrotizing pancreatitis.

AIM: To investigate the effect of Chai-Qin-Cheng-Qi Decoction (CQCQD) on cefotaxime (CTX) concentration in pancreas of rats with acute necrotizing pancreatitis (ANP). METHODS: Sixty healthy male Sprague-Dawley rats were divided randomly into an ANP group (ANP model + CTX, n = 20), treatment group (ANP model + CTX + CQCQD, n = 20) and control group (normal rats + CTX, n = 20). ANP models were induced by retrograde intraductal injection of 3.5% sodium taurocholate (1 mL/kg), and the control group was injected intraductally with normal saline. All rats were injected introperitoneally with 0.42 g/kg CTX (at 12-h intervals for a continuous 72 h) at 6 h after intraductal injection. Meanwhile, the treatment group received CQCQD (20 mL/kg) intragastrically at 8-h intervals, and the ANP and control group were treated intragastrically with normal saline. At 15 min after the last CTX injection, blood and pancreas samples were collected for the determination of CTX concentration using validated high-performance liquid chromatography. Pathological changes and wet-to-dry-weight (W/D) ratio of pancreatic tissue were examined. RESULTS: Serum CTX concentrations in three groups were not significantly different. Pancreatic CTX concentration and penetration ratio were lower in ANP group vs control group (4.4 +/- 0.6 microg/mL vs 18.6 +/- 1.7 microg/mL, P = 0.000; 5% vs 19%, P = 0.000), but significantly higher in treatment group vs ANP group (6.4 +/- 1.7 microg/mL vs 4.4 +/- 0.6 microg/mL, P = 0.020; 7% vs 5%, P = 0.048). The histological scores and W/D ratio were significantly decreased in treatment group vs ANP and control group. CONCLUSION: CQCQD might have a promotive effect on CTX concentration in pancreatic tissues of rats with ANP.

[Non-preventive use of antibiotics in patients with severe acute pancreatitis treated with integrated traditional Chinese and Western medicine therapy: a randomized controlled trial].

OBJECTIVE: To investigate the prognostic effects of integrated traditional Chinese and Western medicine therapy without antibiotics in treatment of patients with severe acute pancreatitis (SAP). METHODS: SAP patients were randomly divided into treatment group (26 cases included) and control group (28 cases included). In addition to the same protocol of integrated traditional Chinese and Western medicine treatment for both groups, intravenous drip infusion of 0.5 g imipenem-cilastatin was administered to the patients in the control group every eight hours for ten days. The 48-hour Ranson score, 24-hour acute physiology and chronic heath evaluation II score, and incidence rates of complications were observed. The concentrations of serum C-reactive protein (CRP) on days 1, 3, 7 and 10 were measured, and strains of infection were detected with smear and culture examination for bacteria and fungi. RESULTS: There were no statistical differences in demographic information, baseline data and incidence rates of complications between the two groups (P>0.05), but fungal infection rate in the control group was higher than that in the treatment group (P<0.05). There were no statistical differences in infection rates of G- and G+ germs between the two groups; blood and some organs including lung, pancreas, intestine, and urethra were infected with bacteria and fungi. There were also no significant differences in the serum CRP concentrations on days 1, 3, 7 and 10 between the two groups (P>0.05), but the serum CRP concentrations on days 1, 3, 7 and 10 in infected patients were higher than those in non-infected patients (P<0.05, P<0.01). CONCLUSION: The study cannot confirm that the incidence rates of secondary infection and mortality in SAP patients treated with integrated traditional Chinese and Western medicine are reduced by prophylaxis with imipenem-cilastatin.

Effect of antibiotic prophylaxis on acute necrotizing pancreatitis: results of a randomized controlled trial.

BACKGROUND AND AIMS: This study addresses whether antibiotic prophylaxis is beneficial for acute necrotizing pancreatitis. METHODS: This randomized, controlled trial enrolled 276 patients with severe acute pancreatitis. There were 56 patients with 30% or more necrosis proved by contrast-enhanced computerized tomography who were eligible for randomization: 29 in the study group and 27 in the control group, who received i.v. imipenem-cilastatin (3 x 500 mg/day) within 72 h of the onset of symptoms for 7-14 days, and no antibiotic prophylaxis, respectively. The primary end-point was the incidence of infectious complication. The secondary end-points were mortality, the incidence of necrosectomy for infected necrosis, the incidence of organ complication and hospital courses. RESULTS: Characteristics of baseline data were similar in the two groups. No significant differences were found in the incidence of infected pancreatic necrosis (37% vs 27.6%), mortality (10.3% vs 14.8%) and the incidence of operative necrosectomy (29.6% vs 34.6%) between the study group and the control group (P > 0.05). The incidence of extrapancreatic infections, organ complications and hospital courses between the groups were also not significantly different. However, a significantly increased incidence of fungal infection was observed in the study group versus the control group (36.1% vs 14.2%, P < 0.05). CONCLUSION: There was no benefit in the outcomes when antibiotic prophylaxis was routinely used in patients with acute necrotizing pancreatitis.

Infectious complications in patients with severe acute pancreatitis.

This study aims to investigate the clinical characteristics of infectious complications in severe acute pancreatitis (SAP). From September 2003 to March 2005, 140 patients with SAP were retrospectively identified. SAP was defined by the diagnostic criteria formulated for SAP at the 2002 Bangkok World Congress of Gastroenterology in Thailand. Clinical data of the infected and non-infected patients was compared and the characteristics of infection were also analyzed. There were 44 patients who developed infectious complications with a rate of 31.4% (44/140). The severity index, the incidence of complications and mortality, was significantly higher in the infected patients than in the non-infected patients (P<0.05). Of 65 episodes of infection, infected (peri) pancreatic necrosis accounted for 47.7% (31/65), pneumonia for 27.7% (18/65), bacteremia for 10.8% (7/65), urinary tract infection for 6.1% (4/65), and gastrointestinal tract infection for 7.7% (5/65). The earliest infection was observed in pneumonia (10.7±2.5 days), followed by bacteremia (13.7±1.5 days), gastrointestinal tract infection (16.8±3.9 days), infected (peri)pancreatic necrosis (17.6±2.9 days), and urinary tract infection (20.5±4.8 days). Gram-negative bacteria were preponderantly found, comprising 56.6% (64/113) of the isolated strains. Gram-positive bacteria and fungus accounted for 22.1% (25/113) and 21.2% (24/113) of the isolated strains, respectively. Infectious complications in patients with SAP occurred in those who had severe episodes, and consequently complicated the clinical courses. Infected (peri)pancreatic necrosis is the most susceptible and pneumonia is the earliest. Gram-negative bacteria were predominant in multi-microorganisms.

[Chaiqin Chengqi Decoction decreases pancreatic acinar cell calcium overload in rats with acute pancreatitis].

OBJECTIVE: To investigate the mechanism of Chaiqin Chengqi Decoction (CQCQD), a compound of traditional Chinese herbal medicine, acting on the pancreatic acinar cell calcium overload in rats with acute pancreatitis (AP). METHODS: A total of 30 SD rats were randomly divided into normal control group, untreated group and CQCQD group (n=10, respectively). AP was induced in rats by caerulein (5x50 mug/kg) intraperitoneal injection within 4 h. The pancreatic tissue SERCA1 and SERCA2 mRNA expressions were detected by fluorescent quantization polymerase chain reaction method; intracellular calcium fluorescence intensity (FI) of pancreatic acinar cells and the pancreatic pathological score were measured by laser scanning confocal microscopy and light microscopy respectively. RESULTS: There were no SERCA1 mRNA expressions in pancreatic acinar cells of rats in the normal control group and the untreated group. The expression of pancreatic SERCA2 mRNA in the untreated group was down-regulated compared with that in the normal control group (expression ratio=0.536; P=0.001); the expression of pancreatic SERCA2 mRNA in the CQCQD group was up-regulated compared with that in the untreated group (expression ratio=2.00; P=0.012). The pancreatic pathological score in the CQCQD group was lower than that in the untreated group and the FI of Ca(2+) was also lower. CONCLUSION: CQCQD can up-regulate the expression of pancreatic SERCA2 mRNA, release the calcium overload, and hence reduce the pathological changes in pancreatic tissue.