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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

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

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

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

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

Objective To study the characteristics of phospholipase A2 (PLA2) activity and expression of PLA2 subtypes in rat serum and pancreas tissue with an established simple pancreatic trauma model in rats. Methods One hundred and twenty Wistar rats were divided into two groups in a one-to-two ratio: control group and impact group. The two groups were subsequently divided into four subgroups at 6h, 24h, 72h, 7d time point. For the animals in the impact groups, the pancreas was injured by a BIM-Ⅲ biotical impact machine, and the animals in control group were sham injured. The total catalytic activity of PLA2 in serum and pancreatic tissue, the expressions of mRNA and protein and immunohistochemical localization of secretory PLA2 (sPLA2), cytosolic PLA2 (cPLA2) and calcium independent PLA2 (iPLA2) in pancreatic tissue were determined after the corresponding pretreatments in each group. Results The total catalytic activity of PLA2 in serum and pancreatic tissue of impact groups increased at 6h after injury, and the PLA2 activity reached peak value at 24h in pancreatic tissue and at 72h in serum after trauma, and at 7d in serum and pancreatic tissue were still higher than that in control group at the same time (P

Objective To observe the renal protection effect of gastric bypass, and explore its possible mechanism in type 2 diabetes mellitus (T2DM) rats. Methods Forty SD rats were randomly divided into normal control group (n=8) and diabetes model group (n=32). Rats in diabetes model group were injected STZ (35 mg/kg). After the diabetes model was reproduced successfully, they were randomly divided into diabetes control group (n=8), diabetes sham-operation group (n=8) and diabetes operation group (n=14). Roux-en-Y gastric bypass was performed in rats of diabetes operation group. The fasting blood glucose (FBG), renal hypertrophy index (kidney weight/body weight), blood urea nitrogen (BUN), serum creatinine (Cr), activity of total superoxide dismutase (TSOD) and glutathione peroxidase (GSH-PX), content of malondialdehyde (MDA), activity of aldose reductase (AR) and AR mRNA expression in the kidney were determined 8 weeks after operation. The renal tissue was examined with light microscopy. Results Compared with normal control group, the renal hypertrophy index, FBG, BUN, Cr, content of MDA, activity of AR and AR mRNA expression in the kidney significantly increased in diabetes control group and diabetes sham-operation group, while the activity of TSOD and GSH-PX decreased (P

Objective To observe the changes in oxidative stress in type 2 diabetic(T2DM) patients after gastric bypass,and investigate the mechanism of gastric bypass treatment for T2DM.Methods Thirty T2DM patients who underwent gastric bypass(T2DM group) and thirty healthy subjects(control group) were included in present study from Aug.2009 to Apr.2010.Values of fasting plasma glucose(FPG),2-hour postprandial plasma glucose(2hPG),glycosylated hemoglobin(HbA1c),fasting plasma insulin(FIns),superoxide dismutase(SOD),malondialdehyde(MDA) and glutathione peroxidase(GSH-PX) were determined in T2DM group before surgery and 1,3,6 months after surgery.All the parameters were determined once in control group.Results Compared with control group,MDA was significantly higher(3.6±1.3 vs 2.2±0.7μmol/L,P < 0.01),and SOD and GSH-PX were significantly lower(45.2±18.8 vs 87.6±20.4kU/L,P < 0.01;53.6±16.8 vs 78.9±15.6mmol/L,P < 0.01) in T2DM group.Compared with the preoperative values,the MDA decreased significantly(P < 0.05),and SOD and GSH-PX increased significantly(P < 0.01) in T2DM group 3 months after operation.Compared with preoperative values,FPG,2hPG and HbA1c decreased significantly(P < 0.01) in T2DM group one month after operation.Compared with the values one month after operation,2hPG and HbA1c decreased significantly(P < 0.01,P < 0.05) 3 months after operation.Values of HOMA-IR decreased significantly from one month to six months after surgery(P < 0.01).Conclusions Oxidative stress can be improved markedly after gastric bypass in T2DM patients.It may be one of the mechanisms of suceessful treatment of T2DM with gastric bypass.