Metabolomic profiles illuminate the efficacy of Chinese herbal Da-Cheng-Qi decoction on acute pancreatitis in rats.

BACKGROUND AND OBJECTIVES: Chinese herbal drug Da-Cheng-Qi decoction (DCQD) has been widely used for decades to treat acute pancreatitis (AP). Previous trials are mostly designed to state the potential mechanisms of the therapeutic effects rather than to detect its whole effect on metabolism. This study aimed to investigate the efficacy of DCQD on metabolism in AP. METHODS: Twenty-two male adult Sprague-Dawley rats were randomized into three groups. AP was induced by retrograde ductal infusion of 3.5% sodium taurocholate solution in DCQD and AP group, while 0.9% saline solution was used in sham operation (SO) group. Blood samples were obtained 12 h after drug administration and a 600 MHz superconducting Nuclear Magnetic Resonance (NMR) spectrometer was used to detected plasma metabolites. Principal Components Analysis (PCA) and Partial Least Squares-Discriminant Analysis after Orthogonal Signal Correction (OSC-PLS-DA) were applied to analyze the Longitudinal Eddy-delay (LED) and Carr-Purcell-Meiboom-Gill (CPMG) spectra. RESULTS: Differences in concentrations of metabolites among the three groups were detected by OSC-PLS-DA of 1HNMR spectra (both LED and CPMG). Compared with SO group, DCQD group had higher levels of plasma glycerol, glutamic acid, low density lipoprotein (LDL), saturated fatty acid (FA) and lower levels of alanine and glutamine, while the metabolic changes were reversed in the AP group. CONCLUSIONS: Our results demonstrated that DCQD was capable of altering the changed concentrations of metabolites in rats with AP and 1HNMR-based metabolomic approach provided a new methodological cue for systematically investigating the efficacies and mechanisms of DCQD in treating AP.

1HNMR-based metabolomic profile of rats with experimental acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a common inflammatory disease of the pancreas accompanied by serious metabolic disturbances. Nevertheless, the specific metabolic process of this disease is still unclear. Characterization of the metabolome may help identify biomarkers for AP. To identify potential biomarkers, this study therefore investigated the 1H-nuclear magnetic resonance (NMR)-based metabolomic profile of AP. METHODS: Fourteen male adult Sprague-Dawley rats were randomized into two groups: the AP group, in which AP was induced by retrograde ductal infusion of 3.5% sodium taurocholate; and the sham operation group (SO), in which rats were infused with 0.9% saline. Blood samples were obtained 12 hours later and a 600 MHz superconducting NMR spectrometer was used to detect plasma metabolites. Principal components analysis (PCA) and partial least squares-discriminant analysis after orthogonal signal correction (OSC-PLS-DA) were used to analyze both longitudinal Eddy-delay (LED) and Carr-Purcell-Meiboom-Gill (CPMG) spectra. RESULTS: Differences in plasma metabolites between the two groups were detected by PCA and PLS-DA of 1HNMR spectra. Compared with the SO group, plasma levels of lactate (δ 1.3, 1.34, 4.1), valine (δ 0.98, 1.02), succinic acid (δ 2.38), 3-hydroxybutyric acid (3-HB, δ 1.18), high density lipoprotein (HDL, δ 0.8), and unsaturated fatty acid (UFA, δ 2.78, 5.3) were elevated in the AP group, while levels of glycerol (δ 3.58, 3.66), choline (δ 3.22), trimethylamine oxide (TMAO, δ 3.26), glucose (δ 3-4), glycine (δ 3.54), very low density lipoprotein (VLDL, δ 1.34) and phosphatidylcholine (Ptd, δ 2.78) were decreased. CONCLUSIONS: AP has a characteristic metabolic profile. Lactate, valine, succinic acid, 3-HB, HDL, UFA, glycerol, choline, TMAO, glucose, glycine, VLDL, and Ptd may be potential biomarkers of early stage AP.

[Pharmacological study on free anthraquinones compounds in rhubarb in rats with experimental acute pancreatitis].

OBJECTIVE: To verify the pharmacological hypothesis of prescriptions by studying the targeted distribution of major components in stewed rhubarb in the rat model with acute pancreatitis (AP). METHOD: Normal SD rats (control group, n = 5) and the AP model induced with intraperitoneal cerulein (model group, n = 5) were taken as the experimental objects. Rats of the two groups were orally administered with stewed rhubarb granules (20 g x kg(-1)). Their heart, liver, spleen, lung, kidney and pancreas were collected two hours after the administration. Such constituents as emodin, chrysophanol, physcion, rhein and aloe-emodin and their concentrations in each tissue homogenate were detected by high performance liquid chromatography-mass-mass. RESULT: Aloe-emodin and physcion in stewed rhubarb whose concentrations in liver and kidney of normal rats were higher than that in pancreatic tissues, while the distribution spectrums and concentrations of the remaining components in pancreatic tissues had no significant difference with that of other organs. The concentrations of emodin, aloe-emodin, rhein and chrysophanol in stewed rhubarb in pancreatic tissues of the AP model group were higher than that in other tissues and organs, while their concentrations in pancreatic, renal and splenic tissues were notably higher than that in the normal group. CONCLUSION: In the conditions of AP, effective components in stewed rhubarb show a targeted distribution feature in pancreas, which provides experimental basis for the pharmacological hypothesis of prescriptions.

Pancreatic injuries in earthquake victims: what have we learnt?

OBJECTIVE: To analyze the clinical characteristic and management of patients with pancreatic injuries from the Wen-Chuan and Lu-Shan earthquakes. METHODS: We retrospectively reviewed 39,784 patients from the Wen-Chuan earthquake and 1489 from the Lu-Shan earthquake. The demographics, clinical data, treatment strategies, and outcomes of patients with pancreatic injuries were recorded and compared between survivors of the two earthquakes. RESULTS: Pancreatic injury occurred only in a small proportion (0.2%) in patients with trauma on admission, and most (61%) patients had Grades I-II pancreatic injuries. Blunt trauma was the leading cause of pancreatic trauma. Most patients (95%) suffered multiple injuries, of which chest injuries (61%) were the most common. Elevated serum amylase levels were observed in 50 (86%) of 58 patients, and computed tomography (CT) identified pancreatic injuries in 32 (80%) of 40 patients. A significantly higher rate (p = 0.043) of pancreatic complication was present in patients with Grade III and IV injuries (38%) than in those with Grade I and II injuries (18%). Forty patients were initially treated by conservative management with 6 (15%) requiring delayed operations. Four (67%) pancreatic complications and 2 (33%) deaths occurred in patients with delayed operations. CONCLUSIONS: Repeated serum amylase analysis, CT, and laparoscopic exploration were reliable diagnostic modalities to diagnose pancreatic injury. Conservative management was safe in patients with Grade I and II injuries. Delayed operation, especially for Grade III patients, resulted in increased morbidity and mortality.

[Effects of electro-acupuncture at Zusanli point on gastric and intestinal blood flow in rats with acute necrotizing pancreatitis].

OBJECTIVE: To investigate the effects of electro-acupuncture (EA) at Zusanli point on gastric and intestinal blood flow and serum endothelin-1(ET-1), nitricoxide(NO), thromboxaneB2 (TXB2), 6-keto-prostaglandin F1alpha (6-K-PGF1alpha) in rats with acute necrotizing pancreatitis (ANP). METHODS: Thirty-six male Sprague Dawley (SD) rats were randomly divided into sham operation (sham), ANP and EA groups (n = 12). ANP model was induced by retrograde injection of 5% sodium taurocholate into pancreaticobiliary. EA was applied to Zusanli for 30 min at 2 h and 6 h after the operation in EA group. Gastric and intestinal mucosal blood flow was measured by laser doppler flowmetry (LDF) at 12 h and 24 h after operation, while the levels of serum ET-1, NO, TXB2 and 6-K-PGF1alpha were detected. RESULTS: The gastric and intestinal blood flow in ANP rats were significantly lower than those in the sham group (P < 0.05), but those of EA groups were higher than those in ANP groups (P < 0.05). The serum ET-1, NO and ET-1/NO levels in ANP group were increased when compared with SO group (P < 0.05). After the electro-acupuncture treatment at Zusanli point, the levels of ET-1, NO and ET-1/N were decreased, and there were significant differences of ET-1 (at 12 h, 24 h), NO (at 12 h) and ET-1/NO (at 24 h) between EA and ANP group (P < 0.05). The levels of serum TXB2, 6-K-PGF1alpha and TXB2/6-K-PGF1alpha in ANP group were also increased (P < 0.05), but those in EA group were decreased, and there were significant differences of TXB2 (at 12 h, 24 h), 6-K-PGF1alpha (at 12 h) and TXB2/6-K-PGF1alpha (at 24 h) compared with ANP groups (P < 0.05). CONCLUSION: Electro-acupuncture at Zusanli point can significantly improve the gastric and intestinal mucosa blood flow in ANP rats, which may be related to the regulation of serum ET-1, NO, TXB2, 6-K-PGF1alpha.

[Health economic evaluation of clinical pathway of traditional Chinese medicine in the treatment of mild acute pancreatitis].

OBJECTIVE: To evaluate the health economic value clinical pathway (CP) of traditional Chinese medicine in the treatment of mild acute pancreatitis (MAP). METHODS: Ninty one patients with MAP were enrolled prospectively in TCM clinical pathway group from June 2012 to February 2013, while the data of 80 MAP patients who were treated without TCM clinical pathway from June 2011 to May 2012, were analyzed retrospectively as control group. The health economic evaluation data used for the two groups comparison included: average length of stay, hospitalization expenses (total hospitalization expenses, total treatment cost, TCM treatment cost, herbal fees, medicine fees, and nursing care cost), as well as the usage of antibiotics/somatostatin, the release time of abdominal pain, the time of re-feeding, and patient satisfaction. RESULTS: There were no significant statistical differences in demographics, etiology, Ranson and Balthazar CT scores between the two groups (P > 0.05). Compared with non-CP group, the usage of antibiotics and somatostatin, the release time of abdominal pain, the time of re-feeding and patient satisfaction were all improved significantly in CP group (P < 0.05). The average length of stay in CP group was shorter than that of non-CP group (P < 0.05). Total hospitalization expenses [yen (11,089.89 +/- 4,318.29) vs. yen (8,960.34 +/- 4,328.91)], medicine fees [yen (6,563.80 +/- 2,743.87) vs. yen (3,988.28 +/- 2,128.10)] and nursing care cost [yen (110.51 +/- 37.24) vs. yen (93.32 +/- 35.20)] were all reduced in CP group, while TCM treatment cost [yen (609.59 +/- 624.42) vs. (968.29 +/- 769.68)] and herbal fees [yen (162.72 +/- 135.13) vs. yen (303.49 +/- 149.90)] were increased (P < 0.05). There was no significant statistical difference in total treatment cost between the two groups (P > 0.05). CONCLUSION: TCM clinical pathway of MAP can not only ensure the therapeutic effects, but also shorten the average length of stay, reduce medical cost and increase patient satisfaction.

Zengye Decoction Attenuated Severe Acute Pancreatitis Complicated with Acute Kidney Injury by Modulating the Gut Microbiome and Serum Amino Acid Metabolome.

Objective: To explore the effect and underlying mechanism of Zengye decoction (ZYD), a traditional formula from China, on the severe acute pancreatitis (SAP) rat model with acute kidney injury (AKI). Methods: The SAP-AKI model was induced by 3.5% sodium taurocholate. Rats were treated with normal saline or ZYD twice and sacrificed at 36 h after modeling. Amylase, lipase, creatinine, blood urea nitrogen, kidney injury molecule 1(KIM-1), and multiple organs' pathological examinations were used to assess the protective effect of ZYD. Gut microbiome detected by 16S rRNA sequencing analysis and serum amino acid metabolome analyzed by liquid chromatography-mass spectrometry explained the underlying mechanism. The Spearman correlation analysis presented the relationship between microflora and metabolites. Results: ZYD significantly decreased KIM-1(P < 0.05) and the pathological score of the pancreas (P < 0.05), colon (P < 0.05), and kidney (P < 0.05). Meanwhile, ZYD shifted the overall gut microbial structure (ß-diversity, ANOSIM R = 0.14, P=0.025) and altered the microbial compositions. Notably, ZYD reduced the potentially pathogenic bacteria-Bacteroidetes, Clostridiales vadin BB60 group, and uncultured_Clostridiales_bacterium, but promoted the short-chain fatty acid (SCFA) producers-Erysipelotrichaceae, Bifidobacterium, Lactobacillus, and Moryella (all P < 0.05). Moreover, principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and hierarchical clustering analysis (HCA) presented a remarkable change in amino acid metabolome after SAP-AKI induction and an apparent regulation by ZYD treatment (R2Y 0.878, P=0.01; Q2 0.531, P=0.01). Spearman's correlation analysis suggested that gut bacteria likely influenced serum metabolites levels (absolute r > 0.4 and FDR P < 0.02). Conclusions: ZYD attenuated SAP-AKI by modulating the gut microbiome and serum amino acid metabolome, which may be a promising adjuvant treatment.

Extracellular vesicles in the pathogenesis and treatment of acute lung injury.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common life-threatening lung diseases associated with acute and severe inflammation. Both have high mortality rates, and despite decades of research on clinical ALI/ARDS, there are no effective therapeutic strategies. Disruption of alveolar-capillary barrier integrity or activation of inflammatory responses leads to lung inflammation and injury. Recently, studies on the role of extracellular vesicles (EVs) in regulating normal and pathophysiologic cell activities, including inflammation and injury responses, have attracted attention. Injured and dysfunctional cells often secrete EVs into serum or bronchoalveolar lavage fluid with altered cargoes, which can be used to diagnose and predict the development of ALI/ARDS. EVs secreted by mesenchymal stem cells can also attenuate inflammatory reactions associated with cell dysfunction and injury to preserve or restore cell function, and thereby promote cell proliferation and tissue regeneration. This review focuses on the roles of EVs in the pathogenesis of pulmonary inflammation, particularly ALI/ARDS.

[The influnence of dachengqi tang on acute lung injury and intra abdominal hypertension in rats with acute pancreatitis].

OBJECTIVE: To test the hypothesis "lung and large intestine are interior exteriorly related" through investgating into the effect of Dacheng qi tang (DCQT) on intra abdominal hypertension (IAH) and acute lung injury (ALI) in rats with acute pancreatitis. METHODS: Male SD rats were randomly divided into three groups with ten rats for each group: rats with sham-operations (SO); rats with acute necrosis pancreatitis (ANP); rats with ANP plus DCQT treatment. ANP was induced by retrograde infusion of 5% taurocholic acid into pancreatic duct. Two hours after operations, 10 mL/kg of normal saline was orally adminstered to the rats in both SO and ANP groups, whereas 10 mL/kg DCQT was adminstered to the rats in the treatment group. Aterial blood, pancreas and lung tissues were collected for biomarkers and histopathology 24 hours after operations. Intra-abdominal pressure and intestinal propulsion rate were also measured. RESULTS; DCQT treatment reduced intra-abdominal pressure and improved intestinal propulsion rate compared with those treated with saline (P < 0.05). The ANP rats treated with DCQT had lower wet to dry weight ratio, and milder myeloperoxidase activity and histopathology changes in pancreas and lung than those treated with saline (P < 0.05). Higher pressure of oxygen (PO2) was found in the rats treated with DCQT, while no difference in PCO2 was found between the DCQT and ANP groups (P > 0.05). Only two rats in the ANP group died. CONCLUSION: DCQT can effectively relieve IAH and cure ALI at the same time in rats with acute pancreatitis. The result provides evidence to support the hypothesis "lung and large intestine are interior exteriorly related".

Effect of Sheng-Jiang Powder on Gut Microbiota in High-Fat Diet-Induced NAFLD.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is an alarming global health problem that is predicted to be the major cause of cirrhosis, hepatocellular carcinoma, and liver transplantation by next decade. Gut microbiota have been revealed playing an important role in the pathogenesis of NAFLD. Sheng-Jiang Powder (SJP), an empirical Chinese medicine formula to treat NAFLD, showed great hepatoprotective properties, but the impact on gut microbiota has never been identified. Therefore, we performed this study to investigate the effect of SJP on gut microbiota in NAFLD mice. METHODS: NAFLD was induced by 12 weeks' high-fat diet (HFD) feeding. Mice were treated with SJP/normal saline daily for 6 weeks. Blood samples were obtained for serum biochemical indices and inflammatory cytokines measurement. Liver tissues were obtained for pathological evaluation and oil red O staining. The expression of lipid metabolism-related genes was quantified by RT-PCR and Western blotting. Changes in gut microbiota composition were analyzed by the 16s rDNA sequencing technique. RESULTS: HFD feeding induced significant increase in bodyweight and serum levels of TG, TC, ALT, and AST. The pathological examination revealed obvious hepatic steatosis in HFD feeding mice. Coadministration of SJP effectively protected against bodyweight increase and lipid accumulation in blood and liver. Increased expression of PPARγ mRNA was observed in HFD feeding mice, but a steady elevation of PPARγ protein level was only found in SJP-treated mice. Meanwhile, the expression of FASN was much higher in HFD feeding mice. Microbiome analysis revealed obvious changes in gut microbiota composition among diverse groups. SJP treatment modulated the relative abundance of short-chain fatty acids (SCFAs) producing bacteria, including norank-f-Erysipelotrichaceae and Roseburia. CONCLUSIONS: SJP is efficient in attenuating HFD-induced NAFLD, and it might be partly attributed to the regulation of gut microbiota.

Effects of Yue-Bi-Tang on water metabolism in severe acute pancreatitis rats with acute lung-kidney injury.

BACKGROUND: The complications acute lung injury and acute kidney injury caused by severe inflammation are the main reasons of high mortality of severe acute pancreatitis (SAP). These two complications can both lead to water metabolism and acid-base balance disorders, which could act as additional critical factors affecting the disease trend. Aquaporins (AQPs), which can regulate the transmembrane water transport, have been proved to participate in the pathophysiological process of SAP and the associated complications, such as acute lung injury and acute kidney injury. Thus, exploring herbs that can effectively regulate the expression of AQP in SAP could benefit the prognosis of this disease. AIM: To determine whether Yue-Bi-Tang (YBT) can regulate the water metabolism in rats with severe acute pancreatitis via regulating the expression of aquaporins. METHODS: Sprague-Dawley rats were randomly divided into three groups, sham operation group (SOG), model group (MG), and treatment group (TG). SAP was induced with 3.5% sodium taurocholate in the MG and TG. Rats in the TG were administered with YBT while SOG and MG rats were given the same volume of saline. Blood and tissue samples were harvested to detect serum inflammatory cytokines, histopathological changes, malondialdehyde and superoxide dismutase in the lung, and protein and mRNA expression of kidney injury molecule-1, α-smooth muscle actin, and vimentin in the kidney, and AQP1 and 4 in the lung, pancreas, and kidney. RESULTS: The serum interleukin-10, tumor necrosis factor α, and creatinine levels were higher in the MG than in the SOG. Tumor necrosis factor α level in the TG was lower than that in the MG. Malondialdehyde level in lung tissues was higher than in the SOG. The pathological scores and edema scores of the pancreas, lung, and kidney tissues in the MG were all higher than those in the SOG and TG. The protein expression of AQP4 in lung tissues and AQP1 in kidney tissues in the MG were higher than those in the SOG and TG. The expression of vimentin was significantly higher in the MG than in the SOG. The expression of AQP1 mRNA in the lung and kidney, and AQP4 mRNA in the kidney was up-regulated in the MG compared to the SOG. CONCLUSION: YBT might regulate water metabolism to reduce lung and kidney edema of SAP rats via decreasing AQP expression, and alleviate the tissue inflammatory injury.

Optimal dosing time of Dachengqi decoction for protection of extrapancreatic organs in rats with experimental acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a pancreatic inflammatory disorder that is commonly complicated by extrapancreatic organ dysfunction. Dachengqi decoction (DCQD) has a potential role in protecting the extrapancreatic organs, but the optimal oral administration time remains unclear. AIM: To screen the appropriate oral administration time of DCQD for the protection of extrapancreatic organs based on the pharmacokinetics and pharmacodynamics of AP rats. METHODS: This study consisted of two parts. In the first part, 24 rats were divided into a sham-operated group and three model groups. The four groups were intragastrically administered with DCQD (10 g/kg) at 4 h, 4 h, 12 h, and 24 h postoperatively, respectively. Tail vein blood was taken at nine time points after administration, and then the rats were euthanized and the extrapancreatic organ tissues were immediately collected. Finally, the concentrations of the major DCQD components in all samples were detected. In the second part, 84 rats were divided into a sham-operated group, as well as 4 h, 12 h, and 24 h treatment groups and corresponding control groups (4 h, 12 h, and 24 h control groups). Rats in the treatment groups were intragastrically administered with DCQD (10 g/kg) at 4 h, 12 h, and 24 h postoperatively, respectively, and rats in the control groups were administered with normal saline at the same time points. Then, six rats from each group were euthanized at 4 h and 24 h after administration. Serum amylase and inflammatory mediators, and pathological scores of extrapancreatic organ tissues were evaluated. RESULTS: For part one, the pharmacokinetic parameters (C max, T max, T 1/2, and AUC 0 → t) of the major DCQD components and the tissue distribution of most DCQD components were better when administering DCQD at the later (12 h and 24 h) time points. For part two, delayed administration of DCQD resulted in lower IL-6 and amylase levels and relatively higher IL-10 levels, and pathological injury of extrapancreatic organ tissues was slightly less at 4 h after administration, while the results were similar between the treatment and corresponding control groups at 24 h after administration. CONCLUSION: Delayed administration of DCQD might reduce pancreatic exocrine secretions and ameliorate pathological injury in the extrapancreatic organs of AP rats, demonstrating that the late time is the optimal dosing time.

Effect of Different-Volume Fluid Resuscitation on Organ Functions in Severe Acute Pancreatitis and Therapeutic Effect of Poria cocos.

OBJECTIVE: To explore the effect of different-volume fluid resuscitation (FR) on organ functions in severe acute pancreatitis (SAP) and to elucidate the therapeutic effect and mechanism of Poria cocos on organ injuries caused by high-volume FR. METHODS: 1. Clinical study: retrospective analysis of thirty-one patients about the effect of titrated fluid resuscitation protocol (TFR) on the occurrence of acute kidney injury (AKI) secondary to SAP. 2. Experimental study: rats (N = 30) were randomly divided into five groups: sham, model, low-volume FR (1.5 ml/kg/h), high-volume FR (10 ml/kg/h), and Poria cocos combined with high-volume FR (10 ml/kg/h + intraintestinal administration Poria cocos 5 g/kg); serum or plasma indicators and histopathologic scores were compared to explore the effect and mechanism of different fluid volumes and Poria cocos on organ function in SAP. RESULTS: The occurrence of AKI, fluid volume, and fluid velocity in TFR group was lower than that in the control group. Logistic regression analysis showed that increased Marshall scores and fluid velocity were risk factors for predicting occurrence of AKI in SAP. Low-volume FR decreased the levels of blood urea nitrogen (BUN), serum creatinine (Cr), matrix metalloproteinase (MMP), and pathologic scores of the pancreas and kidney. High-volume FR increased ascites, MMPs, and kidney pathologic scores. Poria cocos decreased the levels of BUN, Cr, MMPs, and pathologic scores of the pancreas and kidney and increased the arterial oxygen saturation. CONCLUSION: TFR-associated lower fluid volume and velocity reduced the occurrence of AKI secondary to SAP. High volume might aggravate AKI via increased MMP release leading to endothelial glycocalyx damage and vascular endothelial dysfunction. Poria cocos reduced MMP release, relieved glycocalyx damage, and alleviated the pancreas and kidney injury aggravated by high fluid volume in SAP. Therefore, endothelial glycocalyx protection might be a new strategy in the treatment of SAP.

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.

[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.

[Dachengqi Decoction induces pancreatic acinar cell apoptosis in experimental acute pancreatitis in rats].

OBJECTIVE: To explore the effects of Dachengqi Decoction (DCQD), a compound traditional Chinese herbal medicine, on pancreatic acinar cell apoptosis in a rat model of experimental acute pancreatitis. METHODS: A total of 36 Sprague-Dawley rats were randomly divided into sham-operated group, untreated group and DCQD-treated group (12 rats in each group). Acute pancreatitis was induced in 24 rats by retrograde injection of 3.5% sodium taurocholate into pancreatic bile duct. The other 12 rats were allocated as sham-operated group. After the operation, the spray-dried DCQD (2 g/mL of crude drugs) or normal saline at 10 mL/kg body weight of rats were orally administered. The rats were sacrificed by decapitation 12 h and 24 h after the administration, and samples were collected. Amylase activity in serum, nitric oxide (NO) content and inducible NO synthetase (iNOS) activity in pancreatic tissue were measured respectively. Pancreatic acinar cell apoptosis was identified by terminal deoxy-nucleotidyl transferase mediated dUTP nick end-labeling, and pathological scores of pancreatic tissues were determined under a light microscope. RESULTS: At the two time points after treatment, the activities of serum amylase in the treated group were significantly lower than those in the untreated group (P<0.05), while the contents of pancreatic NO and activities of iNOS were higher than those in the untreated group (P<0.05), respectively. The pancreatic acinar cell apoptosis rates in the treatment group at 12 h and 24 h were higher than those in the untreated group, and the mean pancreatic pathomorphologic scores decreased correspondingly (P<0.05). CONCLUSION: DCQD can induce pancreatic acinar cell apoptosis by increasing NO content and iNOS activity in the pancreas of experimental acute pancreatitis, which helps attenuate the pancreatic pathomorphology.

Effect of Sheng-jiang powder on multiple-organ inflammatory injury in acute pancreatitis in rats fed a high-fat diet.

BACKGROUND: Obesity worsens inflammatory organ injury in acute pancreatitis (AP), but there is no effective preventive strategy. Sheng-jiang powder (SJP) has been shown to alleviate multiple-organ inflammatory injury in rats with high-fat diet-induced obesity. Hence, SJP is supposed to have an effect on multiple-organ inflammatory injury in AP in rats fed a high-fat diet. AIM: To explore how obesity may contribute to aggravating inflammatory organ injury in AP in rats and observe the effect of SJP on multiple-organ inflammatory injury in AP in rats fed a high-fat diet. METHODS: Rats were randomly assigned to a control group (CG), an obese group (OG), and an SJP treatment group (SG), with eight rats per group. The rats in the OG and SG were fed a high-fat diet. From the third week, the rats in the SG were given oral doses of SJP (5 g/kg of body weight). After 12 wk, AP was induced in the three groups. Serum amylase level, body weight, Lee's index, serum biochemistry parameters, and serum inflammatory cytokine and tissue cytokine levels were assessed, and the tissue histopathological scores were evaluated and compared. RESULTS: Compared with the CG, serum triglyceride, total cholesterol, interleukin-6, and interleukin-10 levels were significantly higher in the OG, and serum high-density lipoprotein cholesterol level was significantly lower in the OG. Moreover, enhanced oxidative damage was observed in the pancreas, heart, spleen, lung, intestine, liver, and kidney. Evidence of an imbalanced antioxidant defense system, especially in the pancreas, spleen, and intestine, was observed in the obese AP rats. Compared with the OG, serum high-density lipoprotein cholesterol, interleukin-10, and superoxide dismutase expression levels in the pancreas, spleen, and intestine were increased in the SG. Additionally, SJP intervention led to a decrease in the following parameters: body weight; Lee's index; serum triglyceride levels; serum total cholesterol levels; malondialdehyde expression levels in the pancreas, heart, spleen, lung, and liver; myeloperoxidase expression levels in the lung; and pathological scores in the liver. CONCLUSION: Obesity may aggravate the inflammatory reaction and pathological multiple-organ injury in AP rats, and SJP may alleviate multiple-organ inflammatory injury in AP in rats fed a high-fat diet.

Effect of admission hypertriglyceridemia on the episodes of severe acute pancreatitis.

AIM: To investigate the effect of admission hypertriglyceridemia (HTG) on the episodes of severe acute pancreatitis (SAP). METHODS: One hundred and seventy-six patients with SAP were divided into HTG group (n = 45) and control group (n = 131) according to admission triglyceride (TG) > or = 5.65 mmol/L and < 5.65 mmol/L, respectively. Demographics, etiology, underlying diseases, biochemical parameters, Ranson' s score, acute physiology and chronic heath evaluation II (APACHE II) score, Balthazar's computed tomography (CT) score, complications and mortality were compared. Correlation between admission TG and 24-h APACHE II score was analyzed. RESULTS: SAP patients with HTG were younger (40.8 +/- 9.3 years vs 52.6 +/- 13.4 years, P < 0.05) with higher etiology rate of overeating, high-fat diet (40.0% vs 14.5%, P < 0.05) and alcohol abuse (46.7% vs 23.7%, P < 0.01), incidence rate of hypocalcemia (86.7% vs 63.4%, P < 0.01) and hypoalbuminemia (84.4% vs 60.3%, P < 0.01), 24-h APACHE II score (13.6 +/- 5.7 vs 10.7 +/- 4.6, P < 0.01) and admission serum glucose (17.7 +/- 7.7 vs 13.4 +/- 6.1, P < 0.01), complication rate of renal failure (51.1% vs 16.8%, P < 0.01), shock (37.9% vs 14.5%, P < 0.01) and infection (37.4% vs 18.3%, P < 0.01) and mortality (13.1% vs 9.1%, P < 0.01). Logistic regression analysis showed a positive correlation between admission TG and 24-h APACHE II score (r = 0 .509, P = 0.004). CONCLUSION: The clinical features of SAP patients with HTG are largely consistent with previous studies. HTG aggravates the episodes of SAP.

Effect of Chaiqinchengqi decoction on sarco/endoplasmic reticulum Ca2+-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 x 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 microg/kg.h x 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.