Plasma exosomal miR-122 regulates the efficacy of metformin via AMPK in type 2 diabetes and hepatocellular carcinoma.

Metformin is a drug that has been applied in clinical use for many years for the treatment of type 2 diabetes mellitus (T2DM). It achieves its function through multiple targets and modulation of multiple signaling pathways. To date, the mechanism of the action of metformin is still not fully understood. Along with glycemic control, metformin has shown good inhibitory effects on the development of many tumors. Here, we elucidated that plasma exosomal microRNA-122-5p (miR-122) is closely related to the mechanism of metformin. MiR-122 regulates glycogen-glucose metabolism in hepatocytes or hepatocellular carcinoma cells (HCC) by inhibiting the phosphorylation of AMPK. Since miR-122 and metformin regulate glucose metabolism homeostasis through similar mechanisms, miR-122 can antagonize the effects of metformin. MiR-122 expression increases the sensitivity of hepatocytes or HCC to metformin. Conversely, decreased expression of miR-122 results in hepatocyte insensitivity to metformin. Therefore, significantly elevated levels of miR-122 in plasma exosomes of hepatocellular carcinoma patients could enhance their sensitivity to metformin. The results of the present study revealed a key regulatory role of plasma exosomal miR-122 on the molecular mechanism of metformin. The regulation of key molecules of related signaling pathways by miR-122 may lead to similar glycemic lowering and tumor suppression therapeutic effects as metformin. This provides new ideas for the development of new therapeutic strategies for hepatocellular carcinoma based on the mechanism of miR-122 and metformin.

Clinical observation and risk assessment after splenectomy in hepatolenticular degeneration patients associated with hypersplenism.

Background: Both hepatolenticular degeneration (HLD) and viral hepatitis B (HBV) can cause hypersplenism, but whether splenectomy is needed or can be performed in HLD patients associated with hypersplenism is still controversial. At present, HLD combined with hypersplenism has not been listed as the indication of splenectomy. Objective: This study aimed to investigate the efficacy, risks, and postoperative complications of splenectomy in HLD patients associated with hypersplenism. Methods: We retrospectively analyzed the clinical data of 180 HLD patients with hypersplenism who underwent splenectomy in the Department of General Surgery, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, from January 2001 to December 2015. To evaluate the efficacy of splenectomy, the hemogram of white blood cells (WBC), red blood cells (RBC), platelets (PLT), and the liver function indexes including alanine aminotransferase, aspartate aminotransferase, and total bilirubin were recorded before surgery and 1, 3, 5, 7, and 14 days after surgery. In addition, the clinical data of 142 HBV patients with hypersplenism who underwent splenectomy over the same period were also recorded and compared with that of HLD patients. In particular, aiming to assess the risks of splenectomy in HLD, we also compared postoperative complications and 36-month mortality between the two groups. Result: The level of WBC, RBC, and PLT were all elevated after splenectomy in both the HLD group and the HBV group. However, there was no significant difference in the variation of hemogram after splenectomy between the two groups (P > 0.05). Similarly, the variation of liver function indexes showed no statistical difference between the two groups. In terms of the incidence of postoperative complications including abdominal bleeding, pancreatic leakage, portal vein thrombosis treatment, incision infection, lung infection, and 36-month mortality, there were no significant differences between the two groups. Conclusion: After splenectomy, the hemogram as well as liver function in the HLD group improved a lot and showed a consistent tendency with that in the HBV group. Meanwhile, compared to the HBV group, there was no significant difference in the incidence of postoperative complications in the HLD group. All these results indicate that splenectomy in HLD patients combined with hypersplenism is completely feasible and effective.

Calycosin Improves Intestinal Mucosal Barrier Function after Gastrectomy in Rats through Alleviating Bacterial Translocation, Inflammation, and Oxidative Stress.

Objective: Calycosin is the main bioactive extract of Astragali Radix with anti-inflammation, antioxidant, and anticancer properties. Here, our study evaluated the protective effects and mechanisms of calycosin on intestinal mucosal barrier under gastrectomy. Methods: After receiving gastrectomy, the rats were administrated with 20 mg/kg, 40 mg/kg, or 80 mg/kg calycosin. Endotoxin, bacterial translocation, and intestinal bacterial flora were assayed. Intestinal injury was detected via hematoxylin and eosin staining. Tight junction indicators (occludin, claudin, and ZO-1) and apoptotic proteins (Bax, Bcl-2, and cleaved caspase 3) were examined in intestinal tissues. Inflammatory indicators (IL-1ß, IL-6, and TNF-α) were examined in serum or intestinal specimens via ELISA. Apoptosis was assessed via TUNEL staining. IgA + B cells in intestinal tissues and sIgA in intestinal lumen were examined through immunohistochemistry and ELISA, respectively. Oxidative stress indicators (TSH, SOD, CAT, GSH-Px, and MDA) were also detected via ELISA. Results: Our results showed that calycosin administration decreased endotoxin levels in peripheral blood, intestine, and portal vein blood; lowered the bacterial translocation ratio; and regained the balance among intestinal bacterial flora (comprising bifidobacterium, lactic acid bacillus, enterobacter, enterococcus, aerobic bacteria, and anaerobic bacteria) in the rats with gastrectomy. After calycosin treatment, intestinal mucosal damage of the rats with gastrectomy was ameliorated, with the increase in expression of tight junction proteins. Additionally, calycosin reduced intestinal inflammation, apoptosis, secretion of sIgA, and oxidative stress in the rats with gastrectomy. Conclusion: Altogether, our findings demonstrate that calycosin may improve intestinal mucosal barrier function under gastrectomy via reducing bacterial translocation, inflammation, and oxidative stress.

Research on Portal Venous Hemodynamics and Influencing Factors of Portal Vein System Thrombosis for Wilson's Disease after Splenectomy.

Objective: Splenectomy is one crucial solution for hypersplenism with portal hypertension. However, portal vein system thrombosis (PVST) caused by hemodynamic changes affects the prognosis of patients. We analyze the changes in portal vein hemodynamics following splenectomy for Wilson's disease combined with portal hypertension and the influencing factors that lead to PVST. Methods: A retrospective cohort study was conducted, in which 237 Wilson's disease patients with hypersplenism underwent splenectomy. The hemodynamic indices of the portal vein were monitored before surgery and on the 1st, 7th, and 14th days around surgery. The patients were divided into PVST and non-PVST groups. The clinical factors were identified by univariate and multivariate logistic regression. The Logit P was calculated according to the logistic regression prediction model, and the ROC curve for each independent factor was plotted. Results: The portal vein velocity, flow, and inner diameter showed a downward trend around surgery, with statistically significant differences between each time point (P < 0.01). The PVST incidence rate was 55.7%. Univariate analysis revealed that the platelet (PLT) levels on the postoperative 3rd and 7th days (P = 0.001; P < 0.001), D-dimer (D-D) on the postoperative 7th and 14th days (P = 0.002; P < 0.001), preoperative portal vein velocity, flow, diameter (P < 0.001), and splenic vein diameter (P < 0.001) were all statistically and significantly different between the two groups. Multivariate logistic regression revealed a significant increase in PLT on the postoperative 7th day (OR = 1.043, 95% CI, 1.027-1.060, P < 0.001) and D-D on the postoperative 14th day (OR = 1.846, 95% CI, 1.400-2.435, P < 0.001). Preoperative portal and splenic vein diameters (OR = 1.565, 95% CI, 1.213-2.019, P = 0.001; OR = 1.671, 95% CI, 1.305-2.140, P < 0.001) were the risk factors for PVST. However, preoperative portal vein velocity and flow (OR = 0.578, 95% CI, 0.409-0.818, P = 0.002; OR = 0.987, 95% CI, 0.975-0.990, P = 0.046) were protective factors for PVST. Logit P was calculated using a logistic regression prediction model with a cut-off value of -0.32 and an area under receiver operating characteristic curve of 0.952 with 88.61% accuracy. Conclusions: Splenectomy relieves portal hypertension by reducing the hemodynamics index. PVST is linked to multiple factors, including preoperative portal vein diameter, velocity, flow, and splenic vein diameter, especially PLT on the postoperative 7th day and D-D on the postoperative 14th day. The predictive model is accurate in predicting PVST.

Effects of Pressurized Aeration on the Biodegradation of Short-Chain Chlorinated Paraffins by Escherichia coli Strain 2.

Short-chain chlorinated paraffins (SCCPs) were defined as persistent organic pollutants in 2017, and they can migrate and transform in the environment, accumulate in organisms, and amplify through the food chain. Although they pose a serious threat to environmental safety and human health, there are few papers on their removal. The current SCCP removal methods are expensive, require severe operating conditions, involve time-consuming biological treatment, and have poor removal specificities. Therefore, it is important to seek efficient methods to remove SCCPs. In this paper, a pressurized reactor was introduced, and the removal performance of SCCPs by Escherichia coli strain 2 was investigated. The results indicated that moderate pure oxygen pressurization promoted bacterial growth, but when it exceeded 0.15 MPa, the bacterial growth was severely inhibited. When the concentration of SCCPs was 20 mg/L, the removal rate of SCCPs was 85.61% under 0.15 MPa pure oxygen pressurization for 7 days, which was 25% higher than at atmospheric pressure (68.83%). In contrast, the removal rate was only 69.28% under 0.15 MPa air pressure. As the pressure continued to increase, the removal rate of SCCPs decreased significantly. The total amount of extracellular polymeric substances (EPS) increased significantly upon increasing the pressure, and the amount of tightly bound EPS (TB-EPS) was higher than that of loosely bound EPS (LB-EPS). The pressure mainly promoted the secretion of proteins in LB-EPS. Furthermore, an appropriate pure oxygen pressure of 0.15 MPa improved the dehydrogenase activity. The gas chromatography-mass spectrometry (GC-MS) results indicated that the degradation pathway possibly involved the cleavage of the C-Cl bond in SCCPs, which produced Cl-, followed by C-C bond breaking. This process degraded long-chain alkanes into short-chain alkanes. Moreover, the main degradation products detected were 2,4-dimethylheptane (C9H20), 2,5-dimethylheptane (C9H20), and 3,3-dimethylhexane (C8H18).

Significance of Amylase Monitoring in Peritoneal Drainage Fluid after Splenectomy: A Clinical Analysis of Splenectomy in 167 Patients with Hepatolenticular Degeneration.

Different kinds of complications after splenectomy in hepatolenticular degeneration patients with hypersplenism have been reported in the past decades, but studies on pancreatic fistula and the corresponding targeted prevention and treatment after splenectomy still remain much unexplored. The present work investigated the pathogenic factors of pancreatic fistula after splenectomy and the variation tendency of amylase in drainage fluid, aiming to verify the significance of monitoring amylase in the abdominal drainage fluid in the early diagnosis of pancreatic fistula after splenectomy. One hundred sixty-seven patients with hepatolenticular degeneration and hypersplenism who underwent splenectomy in the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from January 2016 to August 2018 were selected and analyzed. The amylase in the abdominal drainage fluid was monitored routinely after splenectomy. We also conducted the statistics on the incidence of different types of pancreatic fistula and analyzed the influence factors of pancreatic fistula formation. After splenectomy, biochemical fistula occurred in 11 patients (6.6%), grade B fistula in six patients (3.6%), grade C fistula in one patient (0.6%), and the incidence of pancreatic fistula was 4.2 per cent (biochemical fistula excluded). The amylase in the peritoneal drainage fluid was closely concerned with the incidence of pancreatic fistula according to our statistics. Furthermore, by analyzing the different influence factors of pancreatic fistula, Child-Pugh grading of liver function (P = 0.041), pancreatic texture (P = 0.029), degree of splenomegaly (P = 0.003), and operative method (P = 0.001) were supposed to be closely related to the formation of pancreatic fistula. Monitoring of amylase in peritoneal drainage fluid is regarded as an important physiological parameter in the early diagnosis of pancreatic fistula after splenectomy, which provides effective clinical reference and plays a significant role in preventing the occurrence and development of pancreatic fistula.

Effect of Qihuang Decoction Combined with Enteral Nutrition on Postoperative Gastric Cancer of Nutrition and Immune Function.

OBJECTIVE: Early nutritional support in patients with gastric cancer can improve their nutritional status, but the impact on immune function has not been confirmed. This study aimed to analyze the effects of Qihuang decoction combined with enteral nutrition on nutrition and the immune function of postoperative gastric cancer. METHODS: 120 patients with postoperative gastric cancer in the study group and 117 in the control group were selected as the study subjects from our hospital at random. Indications of nutrition and immune and the rates of complications were compared the day before surgery and 1, 3, 7, and 14 days after surgery. RESULTS: Indications of nutrition except hemoglobin (HB) in the study group were significantly higher than those before operation and the albumin (ALB) and prealbumin (TP) were significantly increased 7 and 14 days after surgery (P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 and P < 0.001 versus P < 0.001 and P < 0.001) and the protein (PA) 3, 7, and 14 days after surgery (P=0.011, P=0.002, and P=0.022) in the study group compared to those in the control group. Cellular and humoral immunity indications in the study group are significantly higher than those before operation compared to those in the control group, and the CD3+, CD4+, and CD4+/CD8+ were significantly increased 7 and 14 days after surgery (P=0.027 and P < 0.001 versus P=0.008 and P < 0.001 versus P=0.010 and P < 0.001) and IgA, IgG, and IgM 3, 7, and 14 days after surgery in the study group (P < 0.001, P < 0.001, and P < 0.001 versus P < 0.001, P < 0.002, and P < 0.001 versus P < 0.001, P < 0.001, and P < 0.001). The complications such as abdominal, lung, wound, and urinary infection were also significantly decreased (P χ 2 =0.017; P < 0.001 and P < 0.001 versus P < 0.001 and P < 0.001) and the protein (PA) 3, 7, and 14 days after surgery (P=0.011, P=0.002, and P=0.022) in the study group compared to those in the control group. Cellular and humoral immunity indications in the study group are significantly higher than those before operation compared to those in the control group, and the CD3+, CD4+, and CD4+/CD8+ were significantly increased 7 and 14 days after surgery (P=0.027 and P < 0.001 versus P=0.008 and P < 0.001 versus P=0.010 and P < 0.001) and IgA, IgG, and IgM 3, 7, and 14 days after surgery in the study group (P < 0.001, P < 0.001, and P < 0.001 versus P < 0.001, P < 0.002, and P < 0.001 versus P < 0.001, P < 0.001, and P < 0.001). The complications such as abdominal, lung, wound, and urinary infection were also significantly decreased (P χ 2 =0.017; P < 0.001 and P < 0.001 versus P < 0.001 and P < 0.001) and the protein (PA) 3, 7, and 14 days after surgery (P=0.011, P=0.002, and P=0.022) in the study group compared to those in the control group. Cellular and humoral immunity indications in the study group are significantly higher than those before operation compared to those in the control group, and the CD3+, CD4+, and CD4+/CD8+ were significantly increased 7 and 14 days after surgery (P=0.027 and P < 0.001 versus P=0.008 and P < 0.001 versus P=0.010 and P < 0.001) and IgA, IgG, and IgM 3, 7, and 14 days after surgery in the study group (P < 0.001, P < 0.001, and P < 0.001 versus P < 0.001, P < 0.002, and P < 0.001 versus P < 0.001, P < 0.001, and P < 0.001). The complications such as abdominal, lung, wound, and urinary infection were also significantly decreased (P χ 2 =0.017; P < 0.001 and P < 0.001 versus P < 0.001 and P < 0.001) and the protein (PA) 3, 7, and 14 days after surgery (P=0.011, P=0.002, and P=0.022) in the study group compared to those in the control group. Cellular and humoral immunity indications in the study group are significantly higher than those before operation compared to those in the control group, and the CD3+, CD4+, and CD4+/CD8+ were significantly increased 7 and 14 days after surgery (P=0.027 and P < 0.001 versus P=0.008 and P < 0.001 versus P=0.010 and P < 0.001) and IgA, IgG, and IgM 3, 7, and 14 days after surgery in the study group (P < 0.001, P < 0.001, and P < 0.001 versus P < 0.001, P < 0.002, and P < 0.001 versus P < 0.001, P < 0.001, and P < 0.001). The complications such as abdominal, lung, wound, and urinary infection were also significantly decreased (P χ 2 =0.017; P χ 2 =0.036; P χ 2 =0.041; P χ 2 =0.004). CONCLUSIONS: Qihuang decoction combined with enteral nutrition can promote the absorption of enteral nutrition with improving the immune and reducing complications of infection.

Qihuang decoction promotes the recovery of intestinal immune barrier dysfunction after gastrectomy in rats.

OBJECTIVE: This study aims to observe the effect of Qihuang decoction on small intestinal mucosal barrier after gastrectomy in rats. MATERIALS AND METHODS: A total of 80 Wistar rats were randomly divided into normal group, sham operation group, enteral nutrition group (EN) and Qihuang decoction group (EN+QH), there were 20 rats in each group. Both the EN group and the EN+QH group underwent gastrectomy. Instillation of enteral nutrition in the small intestine was performed after operation in the EN group. Instillation of enteral nutrition and Qihuang decoction in the small intestine was performed after operation in the EN+QH group. Only the abdominal incision and closing was performed in the sham operation group without drug and nutritional intervention. The expression levels of tight junction proteins in intestinal epithelial cells were determined by western blotting method. The sIgA content in different anatomic sites of intestinal mucosa was determined by double antibody-PEG radioimmunoassay technique. The number of IgA+B cells in different anatomic sites of intestinal mucosa was determined by immunohistochemical method. RESULTS: The sIgA content in the sham operated group was significantly lower than that of normal group (P<0.05). The sIgA content and the number of IgA+B cells in Peyer's patches and lamina propria lym-phocytes in the EN+QH group were significantly higher than that of EN group (P<0.01, P<0.05). The expression levels of RhoA, Rac1 and Cdc42 increased in the EN group, and the phosphorylation levels of occludin, claudin-1, claudin-5, ZO-1 and ZO-2 also increased in the EN group, while the expression levels of non-phosphorylated occluding, claudin-1, claudin-5, ZO-1 and ZO-2 proteins decreased in the EN group (P<0.01, P<0.05). After treatment of Qihuang decoction for 7 days, compared with EN group, the expression levels of RhoA, Rac1 and Cdc42, and the phosphorylation levels of occludin, claudin-1, claudin-5, ZO-1 and ZO-2 significantly decreased in the EN+QH group, while the expression levels of non-phosphorylated occluding, claudin-1, claudin-5, ZO-1 and ZO-2 proteins significantly increased in the EN+QH group (P<0.01, P<0.05). CONCLUSIONS: Qihuang decoction can promote the proliferation and differentiation of IgA+B lymphocytes and increase the sIgA content in intestinal mucosal immune barrier after gastrectomy in rats, it also can promote the expression of tight junction proteins to improve the permeability of intestinal mucosa and promote the recovery of intestinal immune barrier dysfunction in rats after gastrectomy by inhibiting the tight junction associated proteins' phosphorylation induced by Rho/ROCK signaling pathway.