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Macrophages are typically identified as classically activated (M1) macrophages and alternatively activated (M2) macrophages, which respectively exhibit pro- and anti-inflammatory phenotypes, and the balance between these two subtypes plays a critical role in the regulation of tissue inflammation, injury, and repair processes. Recent studies indicate that tissue cells and macrophages interact via the release of small extracellular vesicles (EVs) in processes where EVs released by stressed tissue cells can promote the activation and polarization of adjacent macrophages which can in turn release EVs and factors that can promote cell stress and tissue inflammation and injury, and vice versa. This review discusses the roles of such EVs in regulating such interactions to influence tissue inflammation and injury in a number of acute and chronic inflammatory disease conditions, and the potential applications, advantage and concerns for using EV-based therapeutic approaches to treat such conditions, including their potential role of drug carriers for the treatment of infectious diseases., Graphical abstract Macrophages and tissue cells can communicate via extracellular vehicles (EVs) to regulate tissue injury and tissue repair. Targeting these EV interactions mechanisms may lead to new therapeutic strategies for acute and chronic inflammatory conditions.Image 1

Background: Emodin, one of the most dominant components of the traditional Chinese medicine rhubarb, has been utilized to treat acute pancreatitis (AP). Acute lung injury (ALI) is one of the most common complications of acute pancreatitis, leading to a serious mortality rate. However, the specific mechanism of emodin in the treatment of AP-associated lung injury remains unclear. Therefore, we investigated the protective roles of emodin in AP-ALI and its underlying mechanisms in two clinically relevant experimental AP models.Methods: NaT-AP model in rats was constructed using 3.5% sodium taurocholate, and CER+LPS-AP model in mice was constructed using caerulein combined with Lipopolysaccharide. Animals were divided randomly into sham, AP, Ac‐YVAD‐CMK (caspase-1 specific inhibitor, AYC), and emodin groups. AP-associated lung injury was assessed through H&E staining, inflammatory cytokine levels, and myeloperoxidase activity. Alveolar macrophages (AMs) pyroptosis was evaluated by flow cytometry. In bronchoalveolar lavage fluid, the levels of lactate dehydrogenase and inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Pyroptosis-related protein expressions were detected by Western Blot. Results: Emodin, similar to the positive control AYC, significantly alleviated pancreatic and lung damage in rats and mice. Additionally, emodin decreased the pyroptotic rates of AMs, inflammatory cytokines, and the lactate dehydrogenase level. More importantly, the protein expressions of NLRP3, ASC, Caspase1 p10, GSDMD, and GSDMD-NT in AMs were significantly downregulated after emodin intervention. Conclusion: Emodin has a therapeutic effect on AP-associated lung injury, which is at least partially due to the inhibition of NLRP3/Caspase1/GSDMD-mediated AMs pyroptosis signaling ways.

Cytokine storms, defined by the dysregulated and excessive production of multiple pro-inflammatory cytokines, are closely associated with the pathology and mortality of several infectious diseases, including coronavirus disease 2019 (COVID-19). Effective therapies are urgently needed to block the development of cytokine storms to improve patient outcomes, but approaches that target individual cytokines may have limited effect due to the number of cytokines involved in this process. Dysfunctional macrophages appear to play an essential role in cytokine storm development, and therapeutic interventions that target these cells may be a more feasible approach than targeting specific cytokines. Nanomedicine-based therapeutics that target macrophages have recently been shown to reduce cytokine production in animal models of diseases that are associated with excessive proinflammatory responses. In this mini-review, we summarize important studies and discuss how macrophage-targeted nanomedicines can be employed to attenuate cytokine storms and their associated pathological effects to improve outcomes in patients with severe infections or other conditions associated with excessive pro-inflammatory responses. We also discuss engineering approaches that can improve nanocarriers targeting efficiency to macrophages, and key issues should be considered before initiating such studies.

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 (β-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.

Exosomes are abundantly secreted extracellular vesicles that accumulate in the circulation and are of great interest for disease diagnosis and evaluation since their contents reflects the phenotype of their cell of origin. Tumor‐derived exosomes (TDEs) are of particular interest for cancer diagnosis and therapy, since most tumor demonstrate highly elevated exosome secretion rates and provide specific information about the genotype of a tumor and its response to treatment. TDEs also contain regulatory factors that can alter the phenotypes of local and distant tissue sites and alter immune cell functions to promote tumor progression. The abundance, information content, regulatory potential, in vivo half‐life, and physical durability of exosomes suggest that TDEs may represent a superior source of diagnostic biomarkers and treatment targets than other materials currently under investigation. This review will summarize current information on mechanisms that may differentially regulate TDE biogenesis, TDE effects on the immune system that promote tumor survival, growth, and metastasis, and new approaches understudy to counteract or utilize TDE properties in cancer therapies.

Severe acute pancreatitis-associated acute lung injury (SAP-ALI) is a serious disease associated with high mortality. Emodin has been applied to alleviate SAP-ALI; however, the mechanism remains unclear. We report that the therapeutic role of emodin in attenuating SAP-ALI is partly dependent on an exosomal mechanism. SAP rats had increased levels of plasma exosomes with altered protein contents compared to the sham rats. These infused plasma exosomes tended to accumulate in the lungs and promoted the hyper-activation of alveolar macrophages and inflammatory damage. Conversely, emodin treatment decreased the plasma/pancreatic exosome levels in the SAP rats. Emodin-primed exosomes showed less pro-inflammatory effects in alveolar macrophages and lung tissues than SAP exosomes. In detail, emodin-primed exosomes suppressed the NF-κB pathway to reduce the activation of alveolar macrophage and ameliorate lung inflammation by regulating PPARγ pathway, while these effects were amplified/abolished by PPARγ agonist/antagonist. Blockage of pancreatic acinar cell exosome biogenesis also exhibited suppression of alveolar macrophage activation and reduction of lung inflammation. This study suggests a vital role of exosomes in participating inflammation-associated organ-injury, and indicates emodin can attenuate SAP-ALI by reducing the pancreatic exosome-mediated alveolar macrophage activation.

BACKGROUND AND AIMS Alcoholic hepatitis (AH) is diagnosed by clinical criteria, although several objective scores facilitate risk stratification. Extracellular vesicles (EVs) have emerged as biomarkers for many diseases and are also implicated in the pathogenesis of AH. Therefore, we investigated whether plasma EV concentration and sphingolipid cargo could serve as diagnostic biomarkers for AH and inform prognosis to permit dynamic risk profiling of AH subjects. APPROACH AND RESULTS EVs were isolated and quantified from plasma samples from healthy controls, heavy drinkers, and subjects with end-stage liver disease (ESLD) attributed to cholestatic liver diseases and nonalcoholic steatohepatitis, decompensated alcohol-associated cirrhosis (AC), and AH. Sphingolipids were quantified by tandem mass spectroscopy. The median plasma EV concentration was significantly higher in AH subjects (5.38 × 1011 /mL) compared to healthy controls (4.38 × 1010 /mL; P

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.

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.

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.

Background and Aims. Nonalcoholic fatty liver disease (NAFLD) is an alarming public health problem that directly contributes to increased prevalence of liver cirrhosis and hepatic cell cancer, but without any specific pharmacological option. Sheng-jiang powder (SJP), an empirical Chinese medicine formula to treat NAFLD, showed great efficacy but the specific mechanisms have never been reported. Therefore, we performed this study to explore the effect of SJP on NAFLD and the potential mechanism.Methods. NAFLD was induced by high fat diet (HFD) feeding. Rats were treated with SJP/normal saline daily for 10 weeks and all rats were euthanized after 12 weeks’ feeding. Liver tissue samples were obtained for biochemistry test and pathological evaluation. Additionally, oleic acid induced LO2 cells were employed to simulate a cell model of NAFLD. Cells were subjected to western blotting for Akt, mTOR, S6, SREBP1-c, and FASN detection after coincubated with SJP, LY294002 (a selective PI3K inhibitor), or the combination for 24h.Results. HFD significantly induced hepatic steatosis. Plenty of lipid droplets were observed under transmission electron microscope. The ultrastructure of liver cells showed distinct changes with obvious endoplasmic reticulum expansion, mitochondrial contraction, and cell matrix solidification. Although no difference was detected in serum hepatic enzymes and tissue proinflammatory cytokines, the tissue level of SOD and GSH-px was much lower and the pathologic injuries were much severe in HFD feeding rats. However, SJP treatment significantly attenuated the ultrastructure changes and protected rat liver against inflammatory injury. Abundant of lipid droplets and high expression of pAkt, pmTOR, pS6, and FASN were observed in oleic acid treated LO2 cells, while these changes were restored by SJP treatment.Conclusions. SJP is efficient in attenuating HFD induced NAFLD in rats and this effect might be partly related to the inhibition of Akt/mTOR/S6 pathway.

AIM To investigate the mechanisms by which Sheng-jiang powder (SJP) ameliorates obesity-induced pancreatic inflammatory injury. METHODS Sprague-Dawley rats were randomized into three groups: normal group (NG), obese group (HLG), or SJP treatment group (HSG). Obesity was induced by feeding a high-fat diet in the HLG and HSG, while the NG received standard chow. Rats were euthanized after 12 wk, and blood and pancreatic tissues were collected for histopathological analyses. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transforming growth factor beta (TGF-β) expression, serum triglyceride and adiponectin levels, and apoptosis in pancreatic acinar cells were assessed. A high-fat AR42J acinar cell injury model was established using very low-density lipoprotein (VLDL). AR42J acinar cell culture supernatant, treated with different interventions, was applied to seven groups of pancreatic stellate cells (PSCs). The proliferation of PSCs and the expression of fibronectin and type I collagenase were assessed. RESULTS Compared with the NG, we found higher pathological scores for pancreatic tissues, lower serum adiponectin levels, higher expression levels of NF-κB in pancreatic tissues and TGF-β in pancreatic inflammatory cells, and increased apoptosis among pancreatic acinar cells for the HLG (P < 0.05). Compared with the HLG, we found reduced body weight, Lee’s index scores, serum triglyceride levels, and pathological scores for pancreatic tissues; higher serum adiponectin levels; and lower expression levels of NF-κB, in pancreatic tissue and TGF-β in pancreatic inflammatory cells for the HSG (P < 0.05). The in vitro studies showed enhanced PSC activation and increased expression levels of fibronectin and type I collagenase after SJP treatment. An adenosine 5‘-monophosphate-activated protein kinase (AMPK) inhibitor inhibited PSC activation. CONCLUSION SJP may ameliorate obesity-induced pancreatic inflammatory injury in rats by regulating key molecules of the adiponectin-AMPK signalling pathway.

Background The traditional Chinese formula Da-Cheng-Qi-decoction (DCQD) has been used to treat acute pancreatitis for decades. DCQD could ameliorate the disease severity and the complications of organ injuries, including those of the liver and lungs. However, the pharmacological effects in the kidney, a target organ, are still unclear. This study aimed to investigate the herbal tissue pharmacology of DCQD for acute kidney injury (AKI) in rats with severe acute pancreatitis (SAP). Methods Rats were randomly divided into the sham-operation group (SG), the model group (MG) and the low-, medium- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Sodium taurocholate (3.5%) was retrogradely perfused into the biliopancreatic duct to establish the model of SAP in rats. Different doses of DCQD were administered to the treatment groups 2 h after the induction of SAP. The major components of DCQD in kidney tissues were detected by HPLC–MS/MS. Inflammatory mediators in the kidney tissues, as well as serum creatinine (Scr), blood urea nitrogen (BUN) and pathologic scores, were also evaluated. Results Ten components of DCQD were detected in the kidneys of the treatment groups, and their concentrations increased dose-dependently. Compared with the SG, the levels of inflammatory mediators, Scr, BUN and pathological scores in the MG were obviously increased (p

AIM To identify the optimal oral dosing time of Da-Cheng-Qi decoction (DCQD) in rats with acute pancreatitis (AP) based on the pharmacokinetic and pharmacodynamic parameters. METHODS First, 24 male Sprague-Dawley rats were divided into a sham-operated group [NG(a)] and three model groups [4hG(a), 12hG(a) and 24hG(a)]. The NG(a) and model groups were administered DCQD (10 g/kg.BW) intragastrically at 4 h, 4 h, 12 h and 24 h, respectively, after AP models induced by 3% sodium taurocholate. Plasma samples were collected from the tails at 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, 8 h, 12 h and 24 h after a single dosing with DCQD. Plasma and pancreatic tissue concentrations of the major components of DCQD were determined by high-performance liquid chromatography tandem mass spectroscopy. The pharmacokinetic parameters and serum amylase were detected and compared. Second, rats were divided into a sham-operated group [NG(b)] and three treatment groups [4hG(b), 12hG(b) and 24hG(b)] with three corresponding control groups [MG(b)s]. Blood and pancreatic tissues were collected 24 h after a single dosing with DCQD. Serum amylase, inflammatory cytokines and pathological scores of pancreatic tissues were detected and compared. RESULTS The concentrations of emodin, naringin, honokiol, naringenin, aloe-emodin, chrysophanol and rheochrysidin in the 12hG(a) group were higher than those in the 4hG(a) group in the pancreatic tissues (P < 0.05). The area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration values (AUC0→t) for rhein, chrysophanol, magnolol and naringin in the 12hG(a) group were larger than those in the 4hG(a) or 24hG(a) groups. The 12hG(a) group had a higher Cmax than the other two model groups. The IL-10 levels in the 12hG(b) and 24hG(b) groups were higher than in the MG(b)s (96.55 ± 7.84 vs 77.46 ± 7.42, 251.22 ± 16.15 vs 99.72 ± 4.7 respectively, P < 0.05), while in the 24hG(b) group, the IL-10 level was higher than in the other two treatment groups (251.22 ± 16.15 vs 154.41 ± 12.09/96.55 ± 7.84, P < 0.05). The IL-6 levels displayed a decrease in the 4hG(b) and 12hG(b) groups compared to the MG(b)s (89.99 ± 4.61 vs 147.91 ± 4.36, 90.82 ± 5.34 vs 171.44 ± 13.43, P < 0.05). CONCLUSION Late-time dosing may have higher concentrations of the most major components of DCQD, with better pharmacokinetics and pharmacodynamics of anti-inflammation than early-time dosing, which showed the late time to be the optimal dosing time of DCQD for AP.

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.

Background Serum C-peptide concentrations reflect insulin secretion and beta cell function and can be used to diagnose and distinguish type-1 and type-2 diabetes. C-peptide is a more accurate indicator of insulin status than direct insulin measurement for monitoring patients with diabetes. However, the current methods available for C-peptide quantification exhibit poor reproducibility, are costly, and require highly trained laboratory personnel. Here, we have developed and evaluated a matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based assay to standardize C-peptide measurements, providing highly accurate and comparable results across testing systems and laboratories. Methods C-peptide from human serum was enriched using antibody-conjugated magnetic beads. The eluted isolates were further modified with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) to enhance the ionization of naturally acidic C-peptide. After desalting with ZipTips, the samples were subjected to MALDI-TOF MS analysis. Recombinant human C-peptide was used to develop the assay, and a heavy isotope labeled human C-peptide was used as an internal standard for quantification. Results The MALDI-TOF MS method was validated in accordance with the restrictions of the device, with a limit of quantitation of 25 pmol/L. A correlation between the MAL-DI-TOF MS assay and a reference method was conducted using patient samples. The resulting regression revealed good agreement. Conclusions A simple, high-throughput, cost effective and quantitative MALDI-TOF MS C-peptide assay has been successfully developed and validated in clinical serum samples.

Infected or malignant cells frequently secrete more exosomes, leading to elevated levels of disease-associated exosomes in the circulation. These exosomes have the potential to serve as biomarkers for disease diagnosis and to monitor disease progression and treatment response. However, most exosome analysis procedures require exosome isolation and purification steps, which are usually time-consuming and labor-intensive, and thus of limited utility in clinical settings. This report describes a rapid procedure to analyze specific biomarkers on the outer membrane of exosomes without requiring separate isolation and purification steps. In this method, exosomes are captured on the surface of a slide by exosome-specific antibodies and then hybridized with nanoparticle-conjugated antibody probes specific to a disease. After hybridization, the abundance of the target exosome population is determined by analyzing low-magnification dark-field microscope (LMDFM) images of the bound nanoparticles. This approach can be easily adopted for research and clinical use to analyze membrane-associated exosome biomarkers linked to disease.

Extracellular vesicles (EVs) can represent a novel source of disease biomarkers, and are under intensive study for their clinical potential. Most EV-based cancer diagnostic studies have focused on establishing EV assays that detect increased expression of a single cancer-associated marker or marker signatures based on multiplex detection of these biomarkers. EV biomarker readouts can be obscured by high background signal leading to false positives, and may markedly differ between analyses due to variation in sample purity during EV isolation. This can obstruct the comparisons among studies and lead to conflicting conclusions. This work reports that the nucleic acid to protein UV absorption ratio of an EV is a cell-specific EV characteristic. This EV collective attribute can be measured at low-cost to discriminate EVs derived from malignant and non-malignant cells rather than employing single markers that may be cancer- or subtype-specific. Our work also highlighted the application for accessing purity in EV preparations irrelevant to EV yield. It can be employed to distinguish from patients with and without malignant disease upon analysis of EVs isolated from their serum samples.

Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas frequently associated with metabolic causes, contributing factors, or consequences, including hypertriglyceridemia, obesity, and disorders of intermediary metabolism, respectively. To date, there is no specific therapy for this disease. Future optimal therapy should correct both inflammatory and metabolic components of the disease. Peroxisome proliferator-activated receptors (PPARs) are lipid-sensing nuclear receptors that control inflammatory and metabolic pathways via ligand-dependent and ligand-independent mechanisms. There are 3 known subtypes, PPAR-α, PPAR-β/δ, and PPAR-γ, which are differentially expressed in various tissues. The PPARs interact closely with other transcription factors such as nuclear factor κB and signal tranducers and activators of transcription that have pivotal roles in the pathobiology of AP. In this comprehensive review, we summarize the role of PPARs in AP, highlighting important in vitro and in vivo experimental findings. Finally, we propose future research directions as well as potential translational use of PPAR agonists in the treatment of AP.

To explore the effect of acute pancreatitis (AP) on the pharmacokinetics of herbal ointment micron Liuhe Pill (微米六合丹, MLHP) components in anesthetized rats. Rats were randomly divided into a AP model group (n=6) and a normal group as a control (n=6). The rat model of AP was induced by intraperitoneal injection of L-arginine in rats (15 mg/kg, twice, interval 1 h). Chinese herbal ointment MLHP was used externally on the belly after the 2nd injection for 48 h in both groups. Emodin, rhein, aloe emodin, physcion, chrysophanol from MLHP were detected and quantified in rat serum and pancreas (at 48 h) by high performance liquid chromatography-tandem mass spectrometry. Among the five components, only emodin, aloe emodin and physcion from MLHP were detected in all rat serum and most of the rats' pancreas. Rhein and chrysophanol were not detected in both serum and pancreas. T1/2α of emodin and physcion in MLHP were obviously shorter in the AP model group than those in the normal group (P 0.05). Physcion could be detected in pancreas of most rats in the AP model while only two rats in the normal group. AP could significantly affect the pharmacokinetics of absorbed components of Chinese herbal MLHP ointment in rats.

Objectives To examine the effects of electroacupuncture (EA) on inflammatory responses in patients with acute pancreatitis (AP). Methods Eighty patients with mild or severe AP were randomly allocated to a control group or an EA group. All patients were managed conservatively. In addition, the EA group received acupuncture for 30 min per day for 7 days at bilateral points ST36, LI4, TE6, ST37 and LR3. Interleukin (IL)-6, IL-10 and C-reactive protein (CRP) levels were measured on admission and on day 7. The time to re-feeding and length of stay in hospital were also recorded. Results A total of 58 patients provided complete data. The characteristics of the patients in the EA and control groups were similar. After 7 days the serum concentrations of IL-10 were higher in the EA group than in the control group (mild AP: 6.2±1.2 vs 5.2±0.9 pg/mL, pConclusions EA may reduce the severity of AP by inducing anti-inflammatory effects and reducing the time to re-feeding; however, it did not reduce the length of hospital stay. Trial Registration Number ChiCTR-TRC-13003572.

Background and Aims. Obesity has become the main public health issue nowadays with poor control and has been associated with increased risk of multiorgan disease, but the specific mechanism and effective medication are still to be addressed. Sheng-jiang powder (SJP) showed great potential in preventing obesity in Chinese researches but has no trace in English reports. This study was designed to investigate the effect of SJP on obesity and obesity-mediated multiorgan injuries. Methods. Rats were randomized into normal group (NG), obese group (OG), and SJP treatment group (SG). Obesity was induced by high-fat diet feeding. Rats were gavaged with SJP/normal saline daily from the third week and all rats were sacrificed after 12 weeks’ feeding. Tissues were obtained for cytokines tests. Results. Firstly, high-fat diet feeding led to significant obesity. Compared to NG, the level of SOD in the liver, spleen, lung, and kidney was much lower in OG (p<0.05), while the pathological scores of pancreas, liver, spleen, lung, and kidney were much higher. SJP significantly increased SOD level in the liver, spleen, and lung and reduced the pathological scores of pancreas, liver, spleen, lung, and kidney correspondingly (p<0.05). Conclusions. SJP ameliorates inflammatory response and mitigates obesity-induced multiple organ injuries.

Extracellular vesicles (EVs), or exosomes, are nanovesicles of endocytic origin that carry host and pathogen-derived protein, nucleic acid, and lipid cargos. They are secreted by most cell types and play important roles in normal cell-to-cell communications but can also spread pathogen- and host-derived molecules during infections to alter immune responses and pathophysiological processes. New research is beginning to decipher how EVs influence viral and bacterial pathogenesis. In this review, we will describe how EVs influence viral and bacterial pathogenesis by spreading pathogen-derived factors and how they can promote and inhibit the immune response to these pathogens. We will also discuss the emerging potential of EVs as diagnostic and therapeutic tools.

Severe acute pancreatitis (SAP) is a critical abdominal disease associated with high death rates. A systemic inflammatory response promotes disease progression, resulting in multiple organ dysfunction. The functions of neutrophils in the pathology of SAP have been presumed traditionally to be activation of chemokine and cytokine cascades accompanying the inflammatory process. Recently, since their discovery, a new type of antimicrobial mechanism, neutrophil extracellular traps (NETs), and their role in SAP, has attracted widespread attention from the scientific community. Significantly different from phagocytosis and degranulation, NETs kill extracellular microorganisms by releasing DNA fibers decorated with granular proteins. In addition to their strong antimicrobial functions, NETs participate in the pathophysiological process of many noninfectious diseases. In SAP, NETs injure normal tissues under inflammatory stress, which is associated with the activation of inflammatory cells, to cause an inflammatory cascade, and SAP products also trigger NET formation. Thus, due to the interaction between NET generation and SAP, a treatment targeting NETs might become a key point in SAP therapy. In this review, we summarize the mechanism of NETs in protecting the host from pathogen invasion, the stimulus that triggers NET formation, organ injury associated with SAP involving NETs, methods to interrupt the harmful effects of NETs, and different therapeutic strategies to preserve the organ function of patients with SAP by targeting NETs.

Objective. Gastrointestinal disfunction and acute lung injury (ALI) were common in acute pancreatitis (AP). The effect of electro-acupuncture (EA) on gastrointestinal motility and ALI in rats with AP was investigated to verify the theory of “lung and large intestine are interior exteriorly related” in traditional Chinese medicine.Methods. Male Sprague-Dawley rats were randomly divided into the normal group, model group, and EA group. AP model was established by three injections of 20% L-arginine at 1 h intervals. EA were applied to bilateral ST-25 and ST-36 for 30 minutes twice a day after modeling for 3 days. Arterial blood, pancreas, lung, and intestinal tissues were collected for detecting the inflammatory factors and histopathology. Intestinal propulsion rate (IPR) was also measured at 72 h.Results. EA treatment improved IPR and increased CCK-8 level compared with model group (P< 0.05). It lowered the serum levels of TNF-αand IL-6 and increased the level of IL-4 with no effect on IL-10. EA treatment reduced serum vasoactive intestinal peptide (VIP) and myeloperoxidase (MPO) level in the lung and the pathologic scores of pancreas, lung and intestine were decreased (P< 0.05).Conclusion. EA treatment could promote gastrointestinal motility through inhibiting VIP, and promoting CCK expression and regulate pro- and anti-inflammatory mediators to ameliorate ALI in AP.

Objectives. The Chinese herbal medicine Da-Cheng-Qi decoction can regulate a necrosis-apoptosis switch in injured pancreatic acinar cells. This study investigated the effects of rhein, a component of this medicine, on a necrosis-apoptosis switch in pancreatic rat AR42J cells.Methods. Cerulein-treated AR42J cells were used. After pretreatment with 479, 119.8, or 29.9 μg/L rhein, cells were cocultured with rhein and cerulein (10−8 M) for 4, 8, or 16 h. Apoptosis and necrosis were examined using annexin V and propidium iodide costaining. Mitochondria-dependent apoptosis-associated proteins were examined using enzyme-linked immunosorbent assays and western blotting.Results. Few cells died in untreated samples. The number was significantly higher in 16-h-cerulein-treated samples and treatment with 479 μg/L rhein most effectively increased the apoptotic-to-necrotic cell ratio (P<0.05). In cerulein-treated cells, rhein increased the concentrations of p53, cytochrome C, and caspase-3, and increased the Bax/Bcl-2 ratio in a time- and dose-dependent manner, with the maximum effect in cells treated with 479 μg/L rhein for 16 h (P<0.05).Conclusions. Rhein induces the necrosis-apoptosis switch in injured pancreatic acinar cells in a time- and dose-dependent manner. Mitochondria-dependent apoptosis signaling pathways might play an important role in this effect.

Aim. To compare the pharmacokinetics and pharmacodynamics of herbal ointment Liu-He-Dan (LHD) and micron LHD (MLHD) in rats with acute pancreatitis (AP).Methods. Twenty rats were allocated into normal, AP, LHD, and MLHD groups. LHD or MLHD was applied on rats’ abdomens. Plasma levels of emodin, rhein, aloe emodin, physcion, and chrysophanol were determined by high performance liquid chromatography—mass spectrometry—mass spectrometry (HPLC-MS-MS) at different time points, and the pharmacokinetic parameters were calculated. Serum amylase, TNF-α, IL-6, and IL-10 levels, and the pancreatic pathological scores were determined at 48 h after LHD or MLHD treatment.Results.T1/2αand area under the curve (AUC) of emodin in the MLHD group were lower than those in the LHD group, whileT1/2αand AUC of aloe emodin in the MLHD group were higher than those in the LHD group(P<0.05).T1/2αandTmaxof physcion in the MLHD group were significantly shorter than those in the LHD group(P<0.05). Compared with the AP group, the amylase, malondialdehyde (MDA), TNF-α, and IL-6 levels decreased significantly after three days of treatment in LHD and MLHD groups, while the levels of superoxide dismutase (SOD), TNF-α, and the pancreatic pathological score, were similar. The pharmacodynamic parameters between the LHD and MLHD groups were similar.Conclusion. MLHD had better pharmacokinetics than, and similar pharmacodynamics to, LHD in the management of rats with AP, which indicated that MLHD might be substituted for LHD in the treatment of AP and thus reduce the amount of medicinal herbs used.

To evaluate the safety and efficacy of early oral refeeding (EORF) in patients with mild acute pancreatitis (AP) and to investigate the optimal duration to commence EORF.A prospective, randomized, controlled trial was conducted in patients with mild AP. Patients with EORF (started oral feeding once they subjectively felt hungry) were compared with patients receiving routine oral refeeding (RORF) for time interval between disease onset and initiation of oral refeeding, total length of hospitalization (LOH), postrefeeding LOH, and adverse gastrointestinal events.There were 75 and 74 patients in the EORF group and the RORF group, respectively, with comparable baseline characteristics. Patients in the EORF group started refeeding significantly earlier than those in the RORF group (4.56 ± 1.53 vs 6.75 ± 2.29 days; P0.05). Moreover, patients in the EORF group had significantly shorter total (6.8 ± 2.1 vs 10.4 ± 4.1 days; P0.01) and post refeeding LOH (2.24 ± 0.52 vs 3.27 ± 0.61 days; P0.01). There was no significant difference in adverse gastrointestinal events between the 2 groups.In patients with mild AP, EORF, with the subjective feeling of hunger, is safe, feasible, and reduces LOH.

To investigate the changing trends of clinical management for severe acute pancreatitis (SAP) with integrative medicine. Clinical data of 1 561 patients with SAP from 1980 to 2005 was retrospectively analyzed. The mortality and morbidity of complications were compared. Of the 1 561 patients, 400 patients accepted surgical operation, while the rest were treated conservatively with integrative medicine. There was a change toward conservative management together with Chinese purgative herbal medication use after 1990 (22.4% from 1980–1990 compared with 45.5% from 1991–1993) because of high postoperative mortality. From 1994–2005, the treatment integrating Western medicine with Chinese herbal medications came to be preferred over the classic Western operation-based method. This change was associated with decreased morbidity (35.4% in 1980–1990 compared with 24.7% in 1991–1993 and 11.0% in 1994–2005, P

To investigate the effect of dexamethasone (Dx) combined with modified Dachengqi Decoction (DCQD), a Chinese herbal decoction for purgation, on patients with severe acute on patients with severe acute, a Chinese herbal decoction for purgation, on patients with severe acute pancreatitis (SAP) accompanied with systematic inflammatory response syndrome (SIRS).A total of 81 patients diagnosed as SAP were randomly assigned to a control group or treatment group according to a random number table generated from an SPSS software. The patients in the control group (38 cases) received standard treatment and Chinese herbal decoction for purgation; those in the treatment group (43 cases) received additional 1 mg/(kg·d) dexamethasone (Dx) treatment for three days based on the above treatment. The mortality rate, acute respiratory distress syndrome (ARDS), renal failure, hemorrhage, sepsis, pancreatic pseudocyst, pancreatic abscess, operability, and days of hospitalization were compared between the two groups.Three patients in the control group and eight patients in the treatment group dropped out from the study with a drop-out rate of 7.8% and 18.6%, respectively, and no statistics difference was shown between the two groups (P0.05). Dx treatment significantly reduced ARDS rate and shortened the length of hospitalization compared to those in the control group (7/35, 20.0% versus 15/35, 42.9%, P=0.0394; 32.5±13.2 days versus 40.2±17.5 days, P=0.0344). Other parameters including the mortality rate were not significant different between the two groups.Dx combined with DCQD could decrease the risk of developing ARDS in SAP patients with SIRS and shorten their length of hospitalization.

To explore the effect of Tanreqing Injection (痰热清注射液, TRQI) on the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with Chinese medicine syndrome of retention of phlegm and heat in Fei (痰热阻肺证, RPHF). In a prospective randomized controlled clinical trial, 90 patients with AECOPD of RPHF syndrome were randomly assigned to 3 groups, TRQI and controls A and B, each with 30 cases. The TRQI group was administered with the intravenous injections of 20 mL TRQI once a day and conventional Western medicine treatment. Control group A was administered with the intravenous injection of 15 mg ambroxol hydrochloride twice a day and conventional Western medicine treatment, and control group B was administered with conventional Western medicine treatment only. The treatments were administered for 10 days. Chinese medical symptoms and signs were scored, and plasma concentrations of interleukin (IL)-8 and neutrophil elastase (NE) were recorded. (1) The Chinese medical symptoms (cough, sputum amount, expectoration, dyspnea and fever) and signs (tongue and pulse) improved significantly in the TRQI group (P 0.05). The sign of tongue was also improved significantly in the TRQI group (P 0.05). There was no significant difference in the total effective rate among the three groups (P>0.05). (3) After treatment, the plasma concentrations of IL-8 and NE decreased in the TRQI group and control group A (P 0.05). TRQI could improved the Chinese medical signs and symptoms in the patients with AECOPD, possibly because of the decreasing plasma levels of IL-8 and NE which could improve response to airway inflammation and mucus hypersecretion.

To study the association of binge drinking and the outcomes of severe acute pancreatitis (SAP).This retrospective study included 347 patients with first-attack SAP from January 2001 to February 2004. On the basis of the history of binge drinking or not, the patients were divided into the alcohol (n = 77) and the control groups (n = 270). Clinical data of the 2 groups were compared.Patient age and comorbidity were similar between the 2 groups. There were more men (64, 83.1%) than women (13, 16.9%; P0.05) in the alcohol and the control groups (111, 41.1%; P0.05). The 2 groups had significant differences in admission serum triglyceride levels (5.0 +/- 5.0 vs 3.0 +/- 3.5, P0.05), Balthazar computed tomographic score (6.3 +/- 5.4 vs 4.2 +/- 4.5, P0.05), and Acute Physiology and Chronic Heath Evaluation II score (19.1 +/- 5.1 vs 16.2 +/- 6.0, P0.05). Total mortality and the incidences of complications were higher in the alcohol group than in the control group (P0.05).Binge drinking might be a contributor to the aggravation of first-attack SAP.

To investigate the prognostic effects of integrated traditional Chinese and Western medicine therapy without antibiotics in treatment of patients with severe acute pancreatitis (SAP).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.There were no statistical differences in demographic information, baseline data and incidence rates of complications between the two groups (P0.05), but fungal infection rate in the control group was higher than that in the treatment group (P0.05). 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 (P0.05), but the serum CRP concentrations on days 1, 3, 7 and 10 in infected patients were higher than those in non-infected patients (P0.05, P0.01).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.

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.

Da Cheng Qi decoction (DCQD) is composed of Dahuang, Houpu, Zhishi and Mangxiao. It is a formula created under the theory of Chinese medicine to purge the ‘evil heat’ in the gastrointestitinal tract, which arises from the ileus and acute pancreatitis. The present study was conducted to evaluate the herb–drug interaction between DCQD and ranitidine, which are often co-administered in clinical practice. Ranitidine was administered orally alone or together with DCQD to rats, and plasma ranitidine concentrations were measured by HPLC. Following oral administration, ranitidine plasma levels revealed curves characterized by peaks at 1.8 and 4.2 h corresponding to ranitidine alone and ranitidine with DCQD at mean concentrations of 16.315 and 1.455 µg/mL, respectively. After ranitidine was orally dosed alone or with DCQD, the half-lives were 1.787 and 3.758 h, while the area under the concentration–time curve (0–12 h) was 28.083 and 9.826 µg/L h, respectively, suggesting that DCQD might significantly affect the pharmacokinetics of ranitidine in rats. When physicians or pharmacists administer DCQD and ranitidine, they must make a careful effort to adjust the dosage of the drug and Chinese decoction, or avoid the herb–drug co-administration. Copyright © 2008 John Wiley & Sons, Ltd.

Da-Cheng-Qi decoction (DCQD) is composed of dahuang, houpu, zhishi and mangxiao, while Xiao-Cheng-Qi decoction (XCQD) just contains dahuang, houpu, and zhishi. A validated high-performance liquid chromatographic (HPLC) method was developed for the determination and pharmacokinetic comparison of rhein in rats. It was performed on a reversed-phase C(18) column (150 x 4.6 mm) with a mobile phase of methanol and 0.2% acetic acid (89:11, v/v) and ultraviolet detection at 254 nm. The assay was linear over the range 30-3000 ng/mL (r(2) = 0.9991), with mean percentage recovery of 101.4%. The RSD of intra- and inter-day precision were less than 3.0%, with accuracy in the range 96.8-102.5% for each of the concentrations tested. Following oral administration, rhein plasma levels revealed curves characterized by peaks at 20.5 and 30.1 min corresponding to dosages of 15 mg/kg (XCQD) and 20 mg/kg (DCQD) at mean concentrations of 1184.67 and 1814.27 ng/mL, respectively. The half-lives of rhein from XCQD and DCQD were 45.3 and 139.6 min, respectively. AUC(0-12h) of rhein after oral dosage with XCQD and DCQD were 3435.68 and 5382.25 microg/L h, respectively. The pharmacokinetic parameters may be used to guide the clinical prescription compatibility of traditional Chinese prescriptions related to dahuang and mangxiao.

Objectives: Noninvasive positive-pressure ventilation (NPPV) in acute respiratory distress syndrome (ARDS) is controversial. We aimed to assess the efficacy of NPPV on ARDS in acute pancreatitis (AP). Methods: In this retrospective, single-center cohort study, demographic data, clinical and biochemical parameters of AP and developed ARDS on admission as well as before and after use of NPPV, and clinical outcomes were retrieved from the medical record database. Degrees of ARDS at presentation were retrospectively classified using the Berlin Definition. Results: Of 379 patients identified, 127 were eligible for inclusion and had NPPV for more than 24 hours. There were 44 mild, 64 moderate, and 19 severe patients with ARDS at presentation; endotracheal intubation rates were 0% (0/44), 23.4% (15/64), and 47.4% (9/19); and the mortality rates were 0% (0/44), 9.4% (6/64), and 15.8% (3/19), respectively. After NPPV treatment, systolic pressure, heart rate, respiratory rate, and fraction of inspired oxygen decreased, whereas oxygen saturation increased significantly in the NPPV success group compared with the failed group. Similar findings were also observed between survivors and nonsurvivors. Conclusions: Noninvasive positive-pressure ventilation may be an effective option for the initial treatment of ARDS patients in AP, but the use of NPPV should be applied prudently in the most severe cases.

Background Qing-Yi Decoction (QYD) has been used for severe acute pancreatitis (SAP) patients in China for many years. There were two kinds of QYD: Num 1. QYD (QYD1) which is used in the acute response stage of SAP and Num 2. QYD (QYD2) which is used in the second stage of SAP. This study aims to evaluate the therapeutic efficacy of QYD in participants with SAP. Methods In this prospective, randomized, double-blind, placebo-controlled trial, participants aged 18–70 years within the first 7 days after acute onset of typical abdominal pain (the definition of SAP was according to the 2007 Guidelines for Management of Severe Acute Pancreatitis in China) were selected. The disease severity was determined by the Ranson, Acute Physiology and Chronic Health Evaluation II, and Balthazar CT scores. The test group received Western medicine and Chinese medicine (Num.1 QYD and Num.2 QYD), while the control group received Western medicine and placebo. The primary end-points were length of hospital stay, total hospitalization expenses, operation rate, and mortality. The secondary end-points were organ complications (i.e., heart failure, respiratory failure, acute renal failure, and hepatic failure), duration of paralytic ileus, infection, intensive care unit stay, and respirator use. Results From March 2008 to July 2010, a total of 300 participants with severe acute pancreatitis were assessed for eligibility in West China Hospital, and 100 were eligible for randomized allocation. Eighty-five participants (46 in the test group; 39 in the control group) were included in the statistical analyses. The two groups were similar in their baseline clinical characteristics (age, sex, and etiology) and disease severity. After the interventions, there were no differences between the two groups for length of hospital stay (P = 0.323), total hospitalization expenses (P = 0.252), operation rate (P = 0.231), mortality (P = 0.462), organ complications (P > 0.05), intensive care unit stay (P = 0.209), and respirator use (P > 0.05). However, the duration [median (interquartile range)] of paralytic ileus, i.e., 4 (2–6) days vs. 6 (4–8) days (P = 0.014) and rate of infection, i.e., (13.0 % vs. 35.9 %) (P = 0.013) differed significantly. Conclusions QYD could restore gastrointestinal motility to normal and reduce the infection rates in the SAP patients who completed a full course of QYD treatment according to per protocol analysis. Electronic supplementary material The online version of this article (doi:10.1186/s13020-015-0039-8) contains supplementary material, which is available to authorized users.

OBJECTIVE To evaluate the immuno-modulatory effect of short course administration of somatostatin (stilamin) continuously at early stage in patients with severe acute pancreatitis (SAP). METHODS Thirty-nine patients with SAP (22 men, 17 women; the middle age was 49 years)were randomly allocated into control group (20 patients treated with non-surgical integrated traditional Chinese and Western medicine) and treatment group (19 patients treated with somatostatin administered intravenously at a dosage of 250 mug/h for consecutive 72 hours as well as the treatment for the control group). Laboratory parameters, including the expressions of CD(3), CD(4) and CD(8) in lymphocytes (tested by flow cytometry) and C reactive protein (CRP), and indexes of therapeutic effect, including the occurrence of organic dysfunction, local complication and mortality between the two groups were compared. Another group of 30 healthy volunteers (19 men, 11 women; the middle age was 47 years) were recruited for testing the normal levels of CD(3), CD(4) and CD(8). RESULTS (1) The levels of CD(3), CD(4) and CD(4)/CD(8) in lymphocytes before treatment in both groups were significantly lower than those in the healthy subjects (P

Objectives. The Chinese herbal medicine Da-Cheng-Qi Decoction (DCQD) can ameliorate the severity of acute pancreatitis (AP). However, the potential pharmacological mechanism remains unclear. This study explored the potential effective components and the pharmacokinetic characteristics of DCQD in target tissue in experimental acute pancreatitis in rats.Methods. Acute pancreatitis-like symptoms were first induced in rats and then they were given different doses of DCQD (6 g/kg, 12 g/kg, and 24 g/kg body weight) orally. Tissue drug concentration, tissue pathological score, and inflammatory mediators in pancreas, intestine, and lung tissues of rats were examined after 24 hours, respectively.Results. Major components of DCQD could be found in target tissues and their concentrations increased in conjunction with the intake dose of DCQD. The high-dose compounds showed maximal effect on altering levels of anti-inflammatory (interleukin-4 and interleukin-10) and proinflammatory markers (tumor necrosis factorαand interleukin-6) and ameliorating the pathological damage in target tissuesP<0.05.Conclusions. DCQD could alleviate pancreatic, intestinal, and lung injury by altering levels of inflammatory cytokines in AP rats with tissue distribution of its components.

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.

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).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.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.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.

s / Pancreatology 16 (2016) S1eS63 S35 Introduction: Pancreatic ductal adenocarcinoma (PDAC) is still one of the poorest prognoses cancers, lacking understanding. In PDAC, abnormal activity of Hedgehog (HH) pathway, inflammation(Nuclear factor-kappa B, NF-kB) and K-ras mutation were all involved in. Exploring the interaction of the three elements of PDAC is quite critical to uncover the mechanism of PDAC. Methods: K-ras gene-type, protein expression of Shh and nuclear protein expression of Gli1 and NF-kB of 32 PDAC tissues were detected, the correlation of the three factors were also analyzed. SW1990 were transfected with Gli1 cDNA;SW1990, Panc-1and BxPC-3 were treated with Shh, using untreated group as control, then we examined expression of Shh, Gli1 and NF-kB, cell proliferation and apoptosis changes; K-ras downstream p-/t-ERK1/2 and p-/t-AKT1 expression, as well as Ras activity were tested to estimate K-ras activation. And, the correlation between HH pathway and NF-kB in different K-ras gene-type cells were analyzed separately. Then K-ras expression was knocked-down by si-Kras, experiments above were done again. At last, mutant K-ras cDNA was transfected into K-ras wild-type cells, Shh, Gli1 and NF-kB mRNA expression changes were detected after Shh stimulation. Results: Positive correlation of HH pathway and NF-kB was significant in K-ras mutant PDAC tissues. In K-ras mutant PDAC cells, HH activation could promote NF-kB activation, accelerate cell proliferation, and inhibit apoptosis, up-regulate p-ERK1/2 and p-AKT1, and increase active-Ras expression. When K-ras expression was down-regulated by si-Kras, all the effects above were all weakened. But in wild-type K-ras cells, little significant change happened under such circumstances. But when they transfectedwithmutant K-ras cDNA, themRNA expression of Shh, Gli1 and NF-kB were all increased significantly by Shh stimulation. Conclusions: HH pathway induced NF-kB activation was based on mutant K-ras gene-type in PDAC, and K-ras activity change is the critical molecular mechanism behind them.