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Intra-abdominal hypertension (IAH) is an important risk factor for organ dysfunction, and it occurs in the early phase of severe acute pancreatitis (SAP). We have reported a novel step-up approach and shown the benefit of performing abdominal paracentesis drainage (APD) ahead of percutaneous catheter drainage (PCD) when treating Patients with SAP with fluid collections. This study aimed to evaluate the efficacy of APD in Patients with SAP complicated with IAH in the early phase.In the present study, 206 AP patients complicated with IAH in the early phase were enrolled in hospital between June 2017 and December 2020. The patients were divided into two groups: 109 underwent APD (APD group) and 97 were managed without APD (non-APD group). We retrospectively compared the outcomes of the APD and non-APD groups for IAH treatment. The parameters including mortality, infection, organ failure, inflammatory factors, indications for further interventions, and drainage-related complications were observed.The demographic data and severity scores of the two groups were comparable. The mortality rate was lower in the APD group (3.7%) than in the non-APD group (8.2%). Compared with the non-APD group, the intra-abdominal pressure and laboratory parameters of the APD group decreased more rapidly, and the mean number of failed organs was lower. However, there was no significant difference in incidence of infections between the two groups.Application of APD is beneficial to AP patients. It significantly attenuated inflammation injury, avoided further interventions, and reduced multiple organ failure.

BACKGROUND Severe acute pancreatitis (SAP) is a deadly inflammatory disease with complex pathogenesis and lack of effective therapeutic options. N6-methyladenosine (m6A) modification of circRNAs plays important roles in physiological and pathological processes. However, the roles of m6A circRNA in the pathological process of SAP remains unknown. AIM To identify transcriptome-wide map of m6A circRNAs and to determine their biological significance and potential mechanisms in SAP. METHODS The SAP in C57BL/6 mice was induced using 4% sodium taurocholate salt. The transcriptome-wide map of m6A circRNAs was identified by m6A-modified RNA immunoprecipitation sequencing. The biological significance of circRNAs with differentially expressed m6A peaks was evaluated through gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The underlying mechanism of m6A circRNAs in SAP was analyzed by constructing of m6A circRNA-microRNA networks. The expression of demethylases was determined by quantitative polymerase chain reaction and western blot to deduce the possible mechanism of reversible m6A process in SAP. RESULTS Fifty-seven circRNAs with differentially expressed m6A peaks were identified by m6A-modified RNA immunoprecipitation sequencing, of which 32 were upregulated and 25 downregulated. Functional analysis of these m6A circRNAs in SAP found some important pathways involved in the pathogenesis of SAP, such as regulation of autophagy and protein digestion. In m6A circRNA–miRNA networks, several important miRNAs participated in the occurrence and progression of SAP were found to bind to these m6A circRNAs, such as miR-24-3p, miR-26a, miR-92b, miR-216b, miR-324-5p and miR-762. Notably, the total m6A level of circRNAs was reduced, while the demethylase alkylation repair homolog 5 was upregulated in SAP. CONCLUSION m6A modification of circRNAs may be involved in the pathogenesis of SAP. Our findings may provide novel insights to explore the possible pathogenetic mechanism of SAP and seek new potential therapeutic targets for SAP.

BACKGROUND Our previous studies confirmed that abdominal paracentesis drainage (APD) attenuates intestinal mucosal injury in rats with severe acute pancreatitis (SAP), and improves administration of enteral nutrition in patients with acute pancreatitis (AP). However, the underlying mechanisms of the beneficial effects of APD remain poorly understood. AIM To evaluate the effect of APD on intestinal inflammation and accompanying apoptosis induced by SAP in rats, and its potential mechanisms. METHODS SAP was induced in male adult Sprague-Dawley rats by 5% sodium taurocholate. Mild AP was induced by intraperitoneal injections of cerulein (20 μg/kg body weight, six consecutive injections). Following SAP induction, a drainage tube connected to a vacuum ball was placed into the lower right abdomen of the rats to build APD. Morphological changes, serum inflammatory mediators, serum and ascites high mobility group box protein 1 (HMGB1), intestinal barrier function indices, apoptosis and associated proteins, and toll-like receptor 4 (TLR4) signaling molecules in intestinal tissue were assessed. RESULTS APD significantly alleviated intestinal mucosal injury induced by SAP, as demonstrated by decreased pathological scores, serum levels of D-lactate, diamine oxidase and endotoxin. APD reduced intestinal inflammation and accompanying apoptosis of mucosal cells, and normalized the expression of apoptosis-associated proteins in intestinal tissues. APD significantly suppressed activation of the intestinal TLR4 signaling pathway mediated by HMGB1, thus exerting protective effects against SAP-associated intestinal injury. CONCLUSION APD improved intestinal barrier function, intestinal inflammatory response and accompanying mucosal cell apoptosis in SAP rats. The beneficial effects are potentially due to inhibition of HMGB1-mediated TLR4 signaling.

To explore the effect of music therapy on children with leukemia who have peripherally inserted central catheters (PICC).In this study, we divided 107 patients undergoing PICC into music group (47 cases) and control group (60 cases). The music group received music therapy during PICC, while the control group was given no complementary treatment. The total length of catheterization, the use of sedatives and the changes of pain level and emotion level before and after PICC placement were compared between two groups.Compared with the control group, the total PICC placement time of the music group was significantly shorter (35(30-40) vs. 60(60-60); Z = -8.307;Music therapy is effective to use in PICC. It can shorten the treatment time, reduce the use of sedative medications, and improve the children's emotion and pain response significantly, which is worth clinical application.

Objective To investigate the protective effect and mechanism of placental-derived mesenchymal stem cells (P-MSCs) on lung injury in rats with severe acute pancreatitis. Methods A total of 36 healthy adult male SD rats were randomly divided into control group (n=12), SAP group (n=12) and P-MSCs group (n=12). SAP rat model was established by retrograde injection of 4% sodium taurocholate into biliopancreatic duct. P-MSCs (1×10⁶ cells/100 g) were delivered through the tail vein of the rats at 6 h after the induction of SAP. The rats were sacrificed 12 and 24 h after P-MSCs infusion. The ratio of wet to dry weight of lung tissue and the number of neutrophils, leukocytes and macrophages in bronchoalveolar lavage fluid (BALF) was calculated. The degree of pancreatic and lung injury was evaluated by HE staining. The concentration of amylase, lipase and inflammatory factors in serum was measured by ELISA. The MPO activity in pancreas and lung tissue was measured by MPO assay kit, and the mRNA expression levels of TNF-α, IL-1β in lung tissue were detected by RT-qPCR. The ratio of M1 and M2 in lung tissue was detected by immunofluorescence stain. Results Compared with SAP group, the ratio of wet to dry weight of lung tissue in P-MSCs group significantly decreased, the number of neutrophils, leukocytes and macrophages in BALF were significantly reduced (P

Objective To investigate the potential mechanism of abdominal paracentesis drainage (APD) on severe acute pancreatitis (SAP) through regulating Toll-like receptor 4 (TLR4) expression in rat intestine. Methods Male SD rats were randomized into the Sham group, SAP group, and APD group, with 15 rats in each group. Rats were treated with a retrograde injection of 5% sodium taurocholate into the pancreatic bile duct to induce SAP, followed by ADP treatment through placing a drainage tube in the right lower abdomen of rats. Rats without ADP treatment were used as controls: SAP group included rats without ADP surgical procedure; while Sham group included rats with ADP surgical procedure but without placing a drainage tube. About 24 hours after ADP treatment, pathological changes of small intestine and pancreas were observed by HE staining; serum amylase and lipase activities were detected by the automatic biochemical analyzer; serum endotoxin levels were detected by limulus amebocyte lysate method; serum DAO activity was detected by ultraviolet colorimetry; TNF-α, IL-6 and D-lactic acid levels were detected by ELISA; apoptosis of intestinal mucosal epithelial cells was detected by TUNEL assay; mRNA expression of TLR4 was detected by real-time PCR; the expression of TLR4 signaling pathway and apoptosis-related proteins were detected by immunohistochemistry and Western blotting. Results Compared with SAP rats, the pathological damage of small intestine and pancreas of APD rats was significantly reduced; the pathological score was decreased (P

Objective To investigate the effect of abdominal paracentesis drainage (APD) on pancreatic cell apoptosis in severe acute pancreatitis. Methods Male adult SD rats were randomized into the sham operation (SO) group, SAP group, and APD group, with 18 rats in each group. In the SAP group, 5% sodium sulfonate was pumped into the retrograde pancreatic bile duct to prepare the SAP model. On this basis, a gastric tube was introduced into the right lower abdomen for drainage, namely the APD group. Blood from the abdominal aorta and pancreatic tissues were collected at 6, 12, and 24 h time points in each group. The changes of serum amylase, inflammatory factor, and endotoxin were detected by ELISA. The HE staining was used to evaluate the pancreatic tissue injury. The apoptosis of pancreatic tissue was detected by TUNEL. Western blot and immunohistochemistry were used to detect the expression of apoptosis-related proteins and PI3K/AKT signaling pathway. Results Pancreatic tissue necrosis and edema were significantly lower in the APD group than in the SAP group, and the pathological score was decreased (P

Objective To observe the inflammatory response and peritoneal macrophage polarization phenotype of hypertriglyceridemic acute pancreatitis (HTG-AP) mice, and to record HTG-AP disease progression. Methods Adult male C57/BL6 mice were randomly divided into the control group, HTG group, AP group, and HTG-AP group, with 8 mice in each group. Mice in HTG and HTG-AP groups were intraperitoneally injected with Poloxamer 407 every other day for 28 days to construct the hyperlipidemia animal model. All animals anesthetized and sampled after caerulein treatment in the AP group and the HTG-AP group 12h later. Blood was collected to detect serum lipid and cytokine levels. HE staining was performed on the pancreatic tissues and pathological scores were obtained. The abdominal cavity was lavage with PBS to collect peritoneal macrophages, which were labeled by F4/80, CD11c, and CD206 and then detected by flow cytometry. Results The HTG-AP model of mice was constructed. Compared with AP group, pancreatic tissue pathology score, serum pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 levels, as well as the percentage of M1 polarization of peritoneal macrophages, were significantly increased (P

IgG4-related sclerosing cholangitis is a biliary tract manifestation of IgG4-related diseases, characterized by biliary strictures, neoplastic hyperplasia of bile duct and its surrounding tissues, an increased serum level of immunoglobulin G4 (IgG4). The pathogenesis has not been fully elucidated and histopathological features include infiltration of lympho-plasmcytes, storiform fibrosis and obliterative phlebitis. Response to corticosteroids is prompt and multi-organ involvement is common. As a result of mimicking primary sclerosing cholangitis and cholangiocarcinoma in image, misdiagnose and missed treatment are not rare. Incorporating literature involved, we will review the pathogenesis, clinical manifestations, diagnostic criteria, treatment and prognosis of IgG4-related sclerosing cholangitis. DOI: 10.11855/j.issn.0577-7402.2019.10.13

Acute pancreatitis (AP) is a systemic inflammatory disease with complex pathogenesis. Acinar cell injury is the earliest pathological change of AP. Elucidating its pathological mechanism is of great significance for the development of new therapeutic strategies for AP. Studies have shown that activation of PI3K/Akt signaling pathways plays an important role in the progression of acute pancreatitis. It can not only contribute to acinar cell necrosis by inhibiting apoptosis, but also regulate the autophagy, oxidative stress and inflammation of acinar cells. Here, we reviews the advances about the PI3K/Akt signaling pathway and its significance in modulation of acinar cells in acute pancreatitis. DOI: 10.11855/j.issn.0577-7402.2019.09.13

Objective To investigate the expression of miR-345-5p in peripheral blood of patients with hyperlipidemic acute pancreatitis (HAP) and its clinical significance. Methods From December 2017 to September 2018, 40 patients with HAP (group A) and 75 patients with non-HAP (group B) admitted to the general surgery center of the General Hospital of Western Theater Command were enrolled. 25 patiens with hyperlipidemic non-acute pancreatitis patients (group C) and 30 healthy volunteers (group D) were selected as the control group. Group A was subdivided into H-MAP group and H-SAP group. All the patients were examined for serum triacylglycerol and amylase biochemical levels, and scored on the APACHE Ⅱ. The expression level of miR-345-5p in serum was detected by real-time fluorescent quantitative PCR. The relationship between miR- 345-5p expression level and clinical indicators of HAP was analyzed and the role of miR-345-5p in predicting the severity of acute pancreatitis evaluated. Results The expression level of miR-345-5p in serum of group A (2.28±0.23) was significantly higher than that of groups B (0.35±0.21), C (0.29±0.23) and D (0.25±0.33). The difference was statistically significant (P0.05). The ROC curve analysis showed that the area under the curve of miR-345-5p detection H-SAP was 0.785(0.634~0.935). The expression of miR-345-5p in the HAP severe group (2.95±0.46) was significantly higher than that in the mild HAP group (0.69±0.23), the difference was statistically significant (P0.05). Conclusion The serum miR-345-5p is significantly up-regulated in HAP, and it increases with the severity of the disease, which may provide a new way for the clinical diagnosis and severity assessment of HAP. DOI: 10.11855/j.issn.0577-7402.2019.04.08

AIM To investigate the role of peritoneal macrophage (PM) polarization in the therapeutic effect of abdominal paracentesis drainage (APD) on severe acute pancreatitis (SAP). METHODS SAP was induced by 5% Na-taurocholate retrograde injection in Sprague-Dawley rats. APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after the induction of SAP. To verify the effect of APD on macrophages, PMs were isolated and cultured in an environment, with the peritoneal inflammatory environment simulated by the addition of peritoneal lavage in complete RPMI 1640 medium. Hematoxylin and eosin staining was performed. The levels of pancreatitis biomarkers amylase and lipase as well as the levels of inflammatory mediators in the blood and peritoneal lavage were determined. The polarization phenotypes of the PMs were identified by detecting the marker expression of M1/M2 macrophages via flow cytometry, qPCR and immunohistochemical staining. The protein expression in macrophages that had infiltrated the pancreas was determined by Western blot. RESULTS APD treatment significantly reduced the histopathological scores and levels of amylase, lipase, tumor necrosis factor-α and interleukin (IL)-1β, indicating that APD ameliorates the severity of SAP. Importantly, we found that APD treatment polarized PMs towards the M2 phenotype, as evidenced by the reduced number of M1 macrophages and the reduced levels of pro-inflammatory mediators, such as IL-1β and L-selectin, as well as the increased number of M2 macrophages and increased levels of anti-inflammatory mediators, such as IL-4 and IL-10. Furthermore, in an in vitro study wherein peritoneal lavage from the APD group was added to the cultured PMs to simulate the peritoneal inflammatory environment, PMs also exhibited a dominant M2 phenotype, resulting in a significantly lower level of inflammation. Finally, APD treatment increased the proportion of M2 macrophages and upregulated the expression of the anti-inflammatory protein Arg-1 in the pancreas of SAP model rats. CONCLUSION These findings suggest that APD treatment exerts anti-inflammatory effects by regulating the M2 polarization of PMs, providing novel insights into the mechanism underlying its therapeutic effect.

Objective To investigate the effect of early stage abdominal paracentesis drainage (APD) on phenotype transition of peritoneal macrophage in rats with severe acute pancreatitis (SAP). Methods A total of 36 adult male Sprague Dawley (SD) rats were randomized into SAP, APD, and sham-operated (Sham) groups (n=12). Pancreatitis in SAP and APD groups were induced by 5% sodium taurocholate retrograde injection. In the APD group, a drainage tube was placed in the lower right abdomen of rats with pancreatitis before closure. In the Sham group, rats didn't receive the injection procedure, and a segment of the drainage tube was placed in the abdomen. The rats were sacrificed 12 hours after model established. The histopathological injury was evaluated by HE staining and scored using a previously described scoring system. The level of amylase and lipase, pro/ anti-inflammatory mediators in serum, were determined by ELISA. The polarization of peritoneal macrophage was analyzed by flow cytometry. The mRNA expression of M1-associated protein tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), CD163 and CD206 in peritoneal cells were detected by qPCR. Results The histopathological injury and its score of the pancreas in APD group decreased as well as the serum level of amylase, lipase, TNF-α, interleukin-1β (IL-1β) compared with SAP group, however, the level of anti-inflammatory cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) in plasma increased significantly (P0.05). Conclusion APD ameliorates SAP by enhancing the M2 polarization of peritoneal macrophage and inhibiting systematic inflammation. DOI: 10.11855/j.issn.0577-7402.2018.10.05

As the firs-line treatment for acute pancreatitis (AP) related infectious walled-off necrosis (WON), percutaneous catheter drainage (PCD) are usually accomplished under CT or US guidance, either of which has certain disadvantages. It is necessary to verify the clinical effects of using US and CT images fusion as guidance of PCD.The total 94 consecutive AP patients with infected WON from January of 2013 to January of 2017 were included. Among these patients with infected WON, 48 received PCD under simple US guidance (US-PCD) and 46 under US/CT images fusion guidance (US/CT-PCD). The clinical data consisting of puncture data, drainage effectiveness indicators, intervention complications were collected.The demographic characteristics and disease related characteristics of two groups were comparable. After 48 h of PCD treatment, the US/CT-PCD group achieved a significantly higher imaging effective rate, and significantly lower inflammatory response indexes and severity score, than the US-PCD group (P 0.05). The US/CT-PCD group required fewer puncture times and drainage tubes and lower rate of advanced treatment, showing higher operational success rate than the US-PCD group (P 0.05). Moreover, the US/CT-PCD group exhibited significantly fewer puncture related complications, lower hospital stay, intubation time, and hospitalization expenses than the US-PCD group (P 0.05).PCD treatment under the US/CT images fusion guidance is a reliable intervention with definite clinical effects for AP complicated with infected WON.

Acute and chronic pancreatitis are most common gastrointestinal diseases. Recently, there are emerging evidences that immune cell play important roles in the pathogenesis of acute and chronic pancreatitis. Studies have shown that macrophages, high mobility group protein 1 (HMGB1) and interleukin-33 (IL-33) play an important role in the pathological process of pancreatitis, and are regulated by multiple levels. For example, immune cells are critical in the development and progression of pancreatitis, which not only have the ability to induce microenvironment, but also respond to danger signals derived from endogenous and exogenous molecules. Therefore, further understanding of relevant immune signaling will provide new idea and potential therapeutic targets that can prevent disease progression. Here, we review recent data from animal and human clinical studies that focus on immune responses. DOI: 10.11855/j.issn.0577-7402.2018.01.15

// Hao Luo 1, 2, * , Wei-Hui Liu 2, * , Hong-Yin Liang 2, * , Hong-Tao Yan 2, * , Ning Lin 3 , Dong-Yu Li 2 , Tao Wang 2, * and Li-Jun Tang 1, 2 1 Third Military Medical University, Chongqing 400038, China 2 General Surgery Center, Chengdu Military General Hospital, Chengdu 610083, China 3 Department of Clinical Nutrition, Chengdu Military General Hospital, Chengdu 610083, China * These authors contributed equally to this work Correspondence to: Li-Jun Tang, email: whjtlj@163.com Tao Wang, email: wangtao301020@sina.com Keywords: liver cancer stem cells; liver normal stem cells; malignant transformation; Notch inhibition; differentiation inducing therapy Received: August 23, 2017 Accepted: January 01, 2018 Epub: February 05, 2018 Published: April 10, 2018 ABSTRACT Background: Liver cancer stem cells (LCSCs) are the key factors for cancer metastasis, recurrent, and drug resistance. LCSCs are originated from either hepatocytes dedifferentiation or differentiation arresting of liver normal stem cells (LNSCs). Differentiation-inducing therapy is a novel strategy in solid tumors. Furthermore, Notch signaling pathway has been proved to play important role in the process of hepatocytes differentiation. In previous study, a malignant transformation cellular model of LNSCs has been built up, and in this study we are trying to illustrate whether inhibition of Notch can reverse this malignant tendency and drive these malignant cells back to differentiate into mature hepatocytes. Results: Inhibition of Notch signaling pathway can down-regulate the stemness-related cancer markers, lower the proliferative status, alleviate the invasive characteristic, or attenuate the metastasis tendency. What is more, it can help the malignantly transformed cells to regain the mature hepatic function of glucagon synthesis, urea metabolism, albumin production, and indocyanine-green (ICG) clearance. Materials and Methods: HOX transcript antisense RNA (HOTAIR) expression was enhanced in LNSCs via lentivirus transduction to set up the malignant transformation cellular model. Then, a Notch inhibitor was applied to induce malignantly transformed cells differentiate into mature hepatocytes, and malignant abilities of proliferation, invasiveness, tumorigenesis as well as mature hepatocyte function were observed and compared. Conclusions: The data demonstrate that the anti-tumor effects of Notch inhibition may lie not only on killing the cancer cells or LCSCs directly, it can also induce the LCSCs differentiation into mature hepatocytes via mesenchymal-epithelial transition (MET) progress or downgrade the malignancy.

The aim of this study was to investigate the role of pre-B cell colony-enhancing factor (PBEF) in the pathogenesis of bronchopulmonary dysplasia (BPD) using an established cell model of BPD. For this purpose, EA.hy926 cell cultures were divided into 4 groups as follows: the air group as the blank control, the hyperoxia group, the hyperoxia plus PBEF siRNA group and the hyperoxia plus scramble siRNA group. Cell viability and the generation of reactive oxygen species (ROS) were determined using respective kits. Moreover, the protein and mRNA expression levels of PBEF, interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) were also detected by corresponding methods. Compared with the hyperoxia group, the ROS levels in the hyperoxia plus PBEF siRNA group were significantly reduced (P

Objective To study the protective effects of human umbilical cord-derived mesenchymal stem cells (ucMSCs) against severe acute pancreatitis (SAP) in rats. Methods A total of 135 Sprague-Dawley male rats were randomly divided into Sham group, SAP group and SAP+ucMSCs group (45 each). SAP+ucMSCs group: Severe acute pancreatitis was induced by injecting 5% sodium taurocholate (0.1ml/100g) into the common biliopancreatic duct and then CM-DiI-labeled ucMSCs at 1×107cells/kg were injected via the tail vein. All the rats were sacrificed 12, 24 and 72 hours after SAP. The 72h death rate was counted. Pathological changes in the pancrease were detected by HE staining and pathological score was graded. ucMSCs colonization was observed by fluorescence microscopy. The serum levels of amylase, lipase, TNF-α, IL-1β, IL-4 and IL-10 were determined by ELISA. Results ucMSCs colonize the injured area of pancreatic tissue, the 72h death rate was reduced, and the serum amylase and lipase were also reduced significantly. Moreover, ucMSCs significantly reduced the pathological score of the pancrea and the level of proinflammatory cytokines (TNF-α and IL-1β), but the levels of anti-inflammatory cytokines were increased (IL-4 and IL-10). Conclusion Transplantation of ucMSCs can reduce the severity of pancreatic injury and inflammation in SAP rats. DOI: 10.11855/j.issn.0577-7402.2017.05.03

Background: This study aimed to investigate whether exogenous hydrogen sulfide (H2S) can protect the RAW264.7 macrophages against the inflammation induced by free fatty acids (FFA) by blunting NLRP3 inflammasome activation via a specific TLR4/NF-κB pathway. Methods: RAW264.7 macrophages were exposed to increasing concentrations of FFA for up to 3 days to induce FFA-induced inflammation. The cells were pretreated with NaHS (a donor of H2S) before exposure to FFA. Cell viability, cell apoptosis, TLR4, NF-κB, NLRP3 inflammasome, IL-1β, IL-18 and cleaved caspase-3 expression were measured by a combination of MTT assay, ELISA, and immunoblotting. Results: H2S attenuated FFA-induced cell apoptosis, and reduced the expression of NLRP3, ASC, pro-caspase-1, caspase-1, IL- 1β, IL-18 and caspase-3. In addition, H2S inhibited the FFA-induced activation of TLR4 and NF-κB. Furthermore, NLRP3 inflammasome activation was regulated by the TLR4 and NF-κB pathway. Conclusion: The present study demonstrated for the first time that H2S appears to suppress FFA-induced macrophage inflammation and apoptosis by inhibiting the TLR4/ NF-κB pathway and its downstream NLRP3 inflammasome activation. Thus H2S might possess potential in the treatment of diseases resulting from FFA overload like insulin resistance and type diabetes.

BACKGROUND Abdominal paracentesis drainage (APD) is a safe and effective strategy for severe acute pancreatitis (SAP) patients. However, the effects of APD treatment on SAP-associated cardiac injury remain unknown. AIM To investigate the protective effects of APD on SAP-associated cardiac injury and the underlying mechanisms. METHODS SAP was induced by 5% sodium taurocholate retrograde injection in Sprague-Dawley rats. APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after SAP induction. Morphological staining, serum amylase and inflammatory mediators, serum and ascites high mobility group box (HMGB) 1, cardiac-related enzymes indexes and cardiac function, oxidative stress markers and apoptosis and associated proteins were assessed in the myocardium in SAP rats. Nicotinamide adenine dinucleotide phosphate oxidase activity and mRNA and protein expression were also examined. RESULTS APD treatment improved cardiac morphological changes, inhibited cardiac dysfunction, decreased cardiac enzymes and reduced cardiomyocyte apoptosis, proapoptotic Bax and cleaved caspase-3 protein levels. APD significantly decreased serum levels of HMGB1, inhibited nicotinamide adenine dinucleotide phosphate oxidase expression and ultimately alleviated cardiac oxidative injury. Furthermore, the activation of cardiac nicotinamide adenine dinucleotide phosphate oxidase by pancreatitis-associated ascitic fluid intraperitoneal injection was effectively inhibited by adding anti-HMGB1 neutralizing antibody in rats with mild acute pancreatitis. CONCLUSION APD treatment could exert cardioprotective effects on SAP-associated cardiac injury through suppressing HMGB1-mediated oxidative stress, which may be a novel mechanism behind the effectiveness of APD on SAP.

Extracellular vesicles are membrane-bound structures released by living cells and present in body fluids. Their composition includes proteins, lipids, carbohydrates, and nucleic acids and are involved in transfers between cells. Extracellular vesicles can deliver molecules to cells and tissues even if distant. As a consequence, they have a role in information transmission and in the modulation of the biological function of recipient cells. Among other things, they are involved in antigen presentation and the induction of secretion events by immune cells. Thus, extracellular vesicles participate in the regulation of immune responses during infections. We will discuss their potential as effectors and disease biomarkers concerning only mycobacterial infections.

Helicobacter pylori (HP) is a pathogenic bacterium associated with chronic gastritis, gastric ulcer and gastric cancer. In the present study, the primary carcinogenesis process of normal gastric epithelial cells (GES‑1) infected with HP was investigated. It was determined that infected gastric mucosal epithelial GES‑1 cells secreted increased interleukin‑8 (IL‑8) and IL‑23, and exhibited enhanced expression of inducible nitric oxide synthase and cyclooxygenase‑2, inducing inflammatory reactions and resulting in apoptosis. The bacterial infection significantly increased the expression of carcinogenesis‑associated genes, including p16, c‑Myc, p53 and p21, as well as the expression of cell surface signaling molecules cluster of differentiation 44 (CD44) and CD54 in GES‑1 cells or tissues of patients with gastritis and gastric cancer in vitro or in vivo. Simultaneously, the migration and invasion abilities of normal gastric epithelial GES‑1 cells were increased following HP infection. These observations demonstrated that the inflammatory response of HP infection could cause normal gastric epithelial cells to undergo significant cancerous reactions, indicating that HP is a risk factor for gastric cancer.

NADPH oxidase (Nox) is considered a major source of reactive oxygen species (ROS) in the heart in normal and pathological conditions. However, the role of Nox in severe acute pancreatitis- (SAP-) associated cardiac injury remains unclear. Therefore, we aim to investigate the contribution of Nox to SAP-associated cardiac injury and to explore the underlying molecular mechanisms. Apocynin, a Nox inhibitor, was given at 20 mg/kg for 30 min before SAP induction by a retrograde pancreatic duct injection of 5% sodium taurocholate. Histopathological staining, Nox activity and protein expression, oxidative stress markers, apoptosis and associated proteins, cardiac-related enzyme indexes, and cardiac function were assessed in the myocardium in SAP rats. The redox-sensitive MAPK signaling molecules were also examined by western blotting. SAP rats exhibited significant cardiac impairment along with increased Nox activity and protein expression, ROS production, cell apoptosis, and proapoptotic Bax and cleaved caspase-3 protein levels. Notably, Nox inhibition with apocynin prevented SAP-associated cardiac injury evidenced by a decreased histopathologic score, cardiac-related enzymes, and cardiac function through the reduction of ROS production and cell apoptosis. This protective role was further confirmed by a simulation experiment in vitro. Moreover, we found that SAP-induced activation in MAPK signaling molecules in cardiomyocytes was significantly attenuated by Nox inhibition. Our data provide the first evidence that Nox hyperactivation acts as the main source of ROS production in the myocardium, increases oxidative stress, and promotes cell apoptosis via activating the MAPK pathway, which ultimately results in cardiac injury in SAP.

Our previous study showed that abdominal paracentesis drainage (APD) benefits patients with severe acute pancreatitis (SAP) by delaying or avoiding multiple organ failure. However, the role of APD treatment in SAP-associated lung injury (PALI) remains unclear. Therefore, we investigated the impact of APD on PALI in rats to explore the mechanisms underlying its potential treatment benefits. A drainage tube was inserted into the right lower quadrant of rats immediately after SAP induction via the retrograde infusion of 5% sodium taurocholate into the biliopancreatic duct. Mortality rates, histological scores, wet-to-dry weight (W/D) ratios, inflammatory infiltration and oxidative stress in lung tissues were then examined. Xanthine dehydrogenase (XDH) and xanthine oxidase (XOD) activities in the sera, intestines and lungs were assessed, as was P-selectin expression. APD treatment significantly decreased pathological damage scores, oxidative stress and neutrophil infiltration in lung tissues, indicating that APD has protective effects against PALI in rats. Moreover, APD decreased the levels of serum α-amylase and trypsin and resulted in a significant decrease in XDH mobilization from the intestines, which suppressed P-selectin expression in lung tissues following SAP induction. APD treatment exerts a significant protective effect against lung injury secondary to SAP by reducing the mobilization of intestinal XDH or XOD (XDH/XOD) and the expression of P-selectin in the lungs. These findings provide novel insights into the mechanisms underlying the effectiveness of APD in patients with SAP.

Objective To study the protective effect of early peritoneal drainage against injury of intestinal mucosa in rats with severe acute pancreatitis. Methods Thirty-six SD rats were randomly and equally divided into three group, i.e. control group, model (SAP) group, drainage (APD) group. Severe acute pancreatitis was induced in rats by injecting 5% sodium taurocholate (2ml/h, 0.1ml/100g) into the common biliopancreatic duct. All the rats were sacrificed 24 hours after operation. The condition of abdominal cavity was observed, and pathological changes in ileum were detected by HE staining. The serum levels of TNF-α, IL-1β, diamine oxidase (DAO) and D-lactate were determined by ELISA. Results Compared with the control group, the histopathological changes in ileum were more marked, and serum levels of TNF-α, IL-1β, DAO and D-lactate were significantly higher in SAP group and APD group (P

Macrophages are major pathogen-killing cells. Mycobacteria can represent a serious threat to human health, in particular Mycobacterium tuberculosis and, less so, the opportunistic Mycobacterium avium. They can cause disseminated infections because of their capacity to survive and proliferate within macrophage phagolysosomes. Accumulating evidence indicates that the regulation of miRNA expression is implicated in the mechanisms of defense of macrophages against mycobacterial infections. Nevertheless, the precise contribution of miRNAs is largely unknown. The present study analyzes the expression profile of miRNAs during M. avium infection of macrophages by means of microarrays. We detected that the levels of 23 miRNAs were significantly changed ≥2.5-fold 24 h after M. avium infection. In particular, MiR-125a-5p was found to be highly expressed as part of the known immunological response of macrophages to bacterial or viral infections. MiR-125a-5p overexpression inhibited the expression of target signal transducers and activators of transcription 3 (STAT3) in THP-1 cells. Conversely, inhibitors of miR-125a-5p had the opposite effect. Silencing of STAT3 significantly enhanced the level of autophagy in both uninfected and M. avium-infected cells. Overexpression of miR-125a-5p significantly increased autophagy and decreased M. avium survival within THP-1 cells. Instead, co-transfection with miR-125a-5p mimic and a human STAT3 expressing construct reversed the effects: autophagy decreased and intracellular bactericidal survival was improved. Taken together, our findings indicate that miR-125a-5p participates in the regulation of innate host defenses by targeting STAT3 and enhancing autophagy levels. The results reported here contribute to a better understanding of host defense mechanisms against mycobacterial infections and offer some clues about their control.

OBJECTIVE: To investigate the effects of different doses of Yinzhihuang oral liquid and different concentrations of Lonicera japonica extract on hemolysis and hyperbilirubinemia in rats with glucose-6-phosphate dehydrogenase (G6PD) deficiency. METHODS: Male Wistar rats were randomly divided into 10 groups (n=10 each):normal control group (untreated), negative control group (saline-treated), positive control group (primaquine-treated), low-, medium-and high-dose Yinzhihuang oral liquid groups (13.4, 26.8, and 53.6 mL/kg, respectively), and low-, medium-, high-, and very-high-concentration Lonicera japonica groups (6.7 mL/kg administered, containing 8, 40, 80, and 160 mg/mL Lonicera japonica extract, respectively). A rat model of acetylphenylhydrazine-induced G6PD deficiency was established in all groups except the normal control group, as confirmed by the morphological changes in erythrocytes observed using Wright's stain. After treatment, routine blood and biochemical tests were conducted to measure hemolytic indices, as well as changes in total and indirect bilirubin levels. RESULTS: Rats with G6PD deficiency demonstrated irregular erythrocytes with a lighter-staining center. In the positive control group, the red blood cell count decreased, while the free hemoglobin count and the reticulocyte percentage increased, as compared with before treatment (P < 0.05); in all the Yinzhihuang oral liquid groups and Lonicera japonica extract groups, all the above indices except reticulocyte percentage returned to the levels before treatment (P < 0.05). Compared with the positive control group, all the Yinzhihuang oral liquid groups had significantly reduced total and indirect bilirubin levels (P < 0.05), and all the Lonicera japonica group had significantly reduced indirect bilirubin levels (P < 0.05). However, the total bilirubin level was significantly higher in the Lonicera japonica groups than in the Yinzhihuang oral liquid groups (P < 0.05). The low-dose Yinzhihuang oral liquid group demonstrated a significantly greater decrease in total bilirubin level than the medium-and high-dose Yinzhihuang oral liquid group (P < 0.05). CONCLUSIONS: Administration of high-dose Yinzhihuang oral liquid and different concentrations of Lonicera Japonica extract do not cause hemolysis in rats with G6PD deficiency. Yinzhihuang oral liquid is more effective in treating hyperbilirubinemia than Lonicera Japonica extract. However, the efficacy of Yinzhihuang oral liquid may not be dose-dependent.