Composition of gut microbiota and non-alcoholic fatty liver disease: A systematic review and meta-analysis.

The present systematic review and meta-analysis aimed to summarize the associations between gut microbiota composition and non-alcoholic fatty liver disease. To compare the differences between individuals with or without NAFLD, the standardized mean difference and 95% confidence interval were computed for each α-diversity index and relative abundance of gut microbes. The ß-diversity indices were summarized in a qualitative manner. A total of 54 studies with 8894 participants were included. Overall, patients with NAFLD had moderate reduction in α-diversity indices including Shannon (SMD = -0.36, 95% CI = [-0.53, -0.19], p < 0.001) and Chao 1 (SMD = -0.42, 95% CI = [-0.68, -0.17], p = 0.001), but no significant differences were found for Simpson, observed species, phylogenetic diversity, richness, abundance-based coverage estimator, and evenness (p ranged from 0.081 to 0.953). Over 75% of the included studies reported significant differences in ß-diversity. Although there was substantial interstudy heterogeneity, especially for analyses at the phylum, class, and family levels, the majority of the included studies showed alterations in the depletion of anti-inflammatory microbes (i.e., Ruminococcaceae and Coprococcus) and the enrichment of proinflammatory microbes (i.e., Fusobacterium and Escherichia) in patients with NAFLD. Perturbations in gut microbiota were associated with NAFLD, commonly reflected by a reduction in beneficial species and an increase in the pathogenic species.

Ketogenic Diet and Multiple Health Outcomes: An Umbrella Review of Meta-Analysis.

Numerous studies have examined the effects of ketogenic diets (KD) on health-related outcomes through meta-analyses. However, the presence of biases may compromise the reliability of conclusions. Therefore, we conducted an umbrella review to collate and appraise the strength of evidence on the efficacy of KD interventions. We conducted a comprehensive search on PubMed, EMBASE, and the Cochrane Database until April 2023 to identify meta-analyses that investigated the treatment effects of KD for multiple health conditions, which yielded 23 meta-analyses for quantitative analyses. The evidence suggests that KD could increase the levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), the respiratory exchange rate (RER), and could decrease total testosterone and testosterone levels (all p-random effects: <0.05). The combination of KD and physical activity can significantly reduce body weight and increase the levels of LDL-C and cortisol. In addition, KD was associated with seizure reduction in children, which can be explained by the ketosis state as induced by the diet. Furthermore, KD demonstrated a better alleviation effect in refractory childhood epilepsy, in terms of median effective rates for seizure reduction of ≥50%, ≥90%, and seizure freedom. However, the strength of evidence supporting the aforementioned associations was generally weak, thereby challenging their credibility. Consequently, future studies should prioritize stringent research protocols to ascertain whether KD interventions with longer intervention periods hold promise as a viable treatment option for various diseases.

Successful totally laparoscopic right trihepatectomy following conversion therapy for hepatocellular carcinoma: A case report.

BACKGROUND: About 20%-30% of newly diagnosed hepatocellular carcinoma (HCC) patients are surgically feasible due to a variety of reasons. Active conversion therapy may provide opportunities of surgery for these patients. Nevertheless, the choice of surgical procedure is controversial after successful conversion therapy. We report a patient with HCC who underwent successful laparoscopic right trisectionectomy after conversion therapy with portal vein embolization and transarterial chemoembolization. CASE SUMMARY: A 67-year-old male patient presented to our hospital with epigastric distention/ discomfort and nausea/vomiting for more than 1 mo. Contrast-enhanced computed tomography scan of the abdomen demonstrated multiple tumors (the largest was ≥ 10 cm in diameter) located in the right liver and left medial lobe, and the left lateral lobe was normal. The future remnant liver (FRL) of the left lateral lobe accounted for only 18% of total liver volume after virtual resection on the three-dimensional liver model. Conversion therapy was adopted after orally administered entecavir for antiviral treatment. First, the right portal vein was embolized. Then tumor embolization was performed via the variant hepatic arteries. After 3 wk, the FRL of the left lateral lobe accounted for nearly 30% of the total liver volume. Totally laparoscopic right trisectionectomy was performed under combined epidural and general anesthesia. The in situ resection was performed via an anterior approach. The operating time was 240 min. No clamping was required during the surgery, and the intraoperative blood loss was 300 mL. There were no postoperative complications such as bile leakage, and the incision healed well. The patient was discharged on the 8th postoperative day. During the 3-mo follow-up, there was no recurrence and obvious hyperplasia of residual liver was observed. Alpha-fetoprotein decreased significantly and tended to be normal. CONCLUSION: Due to the different biological characteristics of the liver cancer and the pathophysiological features of the liver from other organs, the conversion treatment should take into account both the feasibility of tumor downstaging and the volume and function of the remnant liver. Our case provides a reference for clinicians in terms of both conversion therapy and laparoscopic right trisectionectomy.

Establishment of a Canine Training Model for Digestive Tract Reconstruction after Pancreaticoduodenectomy.

PURPOSE: Practical training models can be a viable and effective educational tool that allows surgeons to acquire specific surgical techniques or skills. However, a suitable animal training model for reconstruction after a pancreaticoduodenectomy (PD) has not yet been reported. Therefore, we explored the feasibility and safety of establishing an animal training model for digestive tract reconstruction after a simulated PD using mongrel dogs. METHODS: We used the anatomical similarity between the canine and human digestive tract to simulate the digestive tract reconstruction after pancreatoduodenectomy. A hepatobiliary surgeon performed simulated PD digestive reconstructions on 6 mongrel canines. Pancreaticojejunostomy (PJ), biliary-enteric anastomosis (BEA), and jejuno-jejunal anastomosis (JJ) were performed sequentially. The survival rate, surgical operation time, complications, body weight changes, gross specimen, and pathological examination of the anastomotic region were observed 30 days after surgery. RESULTS: The survival rate 30 days after surgery was 100%. Total mean operative time was 230.5 ± 39.7 min. The operative time for PJ, BEA, and JJ was calculated as 21.5 ± 7 min, 21.7 ± 8.7 min, and 13.2 ± 1.8 min, respectively. An incision infection occurred in 1 case (16.7%); there was 1 case of ascites (16.7%), and 1 case of vomiting (16.7%). The total protein and total bilirubin indicators of the 6 dogs and the serum amylase index of 5 dogs 30 days postoperatively were within the normal range. The 6th dog's serum amylase was approximately double the normal value, possibly due to pancreatitis. Observing the gross specimen, the mucosa of the anastomosis was intact and smooth. Masson staining showed that the bile duct and jejunum anastomosis, the pancreas, and jejunum of the 6 canines were all integrated with rich collagen. CONCLUSION: Establishing an animal model for digestive tract reconstruction after a simulated PD in canines is feasible and safe.

Effects of sleeve gastrectomy on lipid and energy metabolism in ZDF rats via PI3K/AKT pathway.

Sleeve Gastrectomy (SG), as the most effective bariatric surgery, has been using to chronically lose weight and control glucose metabolism in Type 2 diabetes mellitus patients. However, the underlining mechanism is still unclear. In this study, we performed SG on Zucker diabetes fatty (ZDF) rat and investigated visceral lipid metabolism and energy metabolism. After performance of SG, weight, food intake, fasting plasma glucose (FPG) and oral glucose tolerance teat (OGTT) of rats were measured. Furthermore, whole-body metabolic parameters were obtained through TSE LabMaster. Blood lipid and renal function were analyzed by serum from rats' tail vein. Furthermore, the renal genes expression was either detected by real-time PCR, while western blotting was employed to detect the AKT/PI3K proteins level in rats' kidney. Compared to control groups, body weight of ZDF rats treated with SG were significantly reduced, simultaneously with glucose homeostasis and energy metabolism improved including RER (P<0.05), energy expenditure (P<0.05) at night and activity of animal. Meanwhile, serum lipid of ZDF rats after SG was decreased, and renal function recovered. Histology analysis confirmed that the size of perirenal adipose from SD treated ZDF rats obviously decreased (P<0.001), effectively stimulating up-regulation of lipogenesis genes (P<0.05), while adipogenesis genes (P<0.05) in kidney was down-regulated. In addition, phosphorylation of PI3K (p-PI3K) and AKT (p-AKT) in rats kidney were significantly decreased in SG group (P<0.05). Weight loss, food intake, fasting plasma glucose and glucose tolerance in SG surgery rats were improved, which were coincident with energy metabolism changes. In conclusion, SG improves lipid and energy metabolism in ZDF rats model due to activating PI3K/Akt signaling pathway, which was contributed to the mechanism of bariatric surgery toward kidney.

Tanshinone IIA Exerts an Antinociceptive Effect in Rats with Cancer-induced Bone Pain.

BACKGROUND: Cancer-induced bone pain (CIBP) is a common chronic pain characterized by 2 components, ongoing pain and breakthrough pain. Tanshinone IIA (TSN IIA) is a bioactive constituent of the traditional Chinese medicine Danshen, which has been reported to have an antinociceptive effect on neuropathic and inflammatory pain through downregulation of the late proinflammatory cytokine high-mobility group protein B1 (HMGB1). OBJECTIVE: To assess the antinociceptive effect of TSN IIA on CIBP. STUDY DESIGN: A randomized, double-blind, controlled animal trial was performed. SETTING: University lab in China. METHODS: A rat CIBP model was established by injecting Walker 256 mammary gland carcinoma cells into the intramedullary cavity of the tibia. Both ongoing pain, e.g., flinching and guarding, and breakthrough pain, e.g., limb use and von Frey threshold, were evaluated. The effects of intraperitoneally administered TSN IIA on pain behavior and the expression levels of spinal HMGB1, interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6 were determined. The effect of TSN IIA on the electrically evoked response of spinal wide-dynamic range (WDR) neurons was performed in vivo. RESULTS: TSN IIA dose-dependently inhibited cancer-induced ongoing pain and breakthrough pain. The expression levels of spinal HMGB1 and other inflammatory factors (IL-1beta, TNF-alpha, and IL-6) were increased in the rat model, but they were suppressed by TSN IIA in a dose-dependent manner. Moreover, TSN IIA significantly inhibited the neuronal responses of WDR neurons in spinal deep layers. LIMITATIONS: Further studies are warranted to ascertain how TSN IIA attenuates cancer-induced ongoing pain. CONCLUSIONS: Our results indicate that TSN IIA attenuates cancer-induced ongoing pain and breakthrough pain, possibly via suppression of central sensitization in CIBP rats. Therefore, we have provided strong evidence supporting TSN IIA as a potential and effective therapy for relieving CIBP. KEY WORDS: Cancer-induced bone pain, high-mobility group protein B1, Tanshinone IIA, ongoing pain, breakthrough pain.

Studied microRNA gene expression in human hepatocellular carcinoma by microRNA microarray techniques.

AIM: To achieve a better understanding of the molecular mechanisms of microRNA expression changes involved in hepatocellular carcinoma. METHODS: In this research process, patients were not treated with antivirals, immunosuppressants or immunomodulators for at least 6 mo before collecting serum. The study population was composed of 35 outpatient hepatitis B virus (HBV) cases and 12 healthy control cases from the Affiliated Hospital of Inner Mongolia Medical University (Inner Mongolia, China) from July 2013 to April 2014. The 35 HBV cases were divided into two groups: a hepatocirrhosis group with 20 cases and a liver cancer group with 15 cases. All 35 cases carried HBsAg. The diagnostic criteria followed the European Association for the Study of the Liver 2012 (EASL2012) standards. MicroRNA (miRNA) was extracted from a control group of patients, a group with hepatocirrhosis and a group with liver cancer and its quality was analyzed using the human V2 microRNA expression beadchip. Cluster analysis and a radar chart were then applied to the miRNA changes. RESULTS: The miRNA-qualified rate of human serum samples was 93%. The concentration of a single sample was > 200 ng/µL and the volume was > 5 µL. All miRNA serum samples were uncontaminated by the genome. The Mann-Whitney test showed significant differences in miRNA between each group, with a detection P-value of < 0.05. Illumina software was set up with Diff Score set to ± 13, meaning that P = 0.001.There were significant changes in miRNA expression between the three groups. miRNA-183 was the most up-regulated, followed by miRNA-373. miRNA-129 and miRNA-188 were both strongly down-regulated and miRNA-378 was down-regulated a small amount. The liver cancer group had greater changes, which indicated that changes in miRNA expression levels were caused by hepatocirrhosis. The liver cancer disease course then further increased these changes. In the pentagon created by these five miRNAs, three groups showed significant deviation. The liver cancer group had a bigger deviation trend. The chart indicated that miRNA expression changes occurred in the hepatocirrhosis group, which increased in the liver cancer disease course and were irreversible. CONCLUSION: There was a significant relationship between the irreversible up-regulation of miRNA-183/373 and down-regulation of miRNA-129/188/378 and incidences of hepatocirrhosis and liver cancer.

Correlation between miR-23a and onset of hepatocellular carcinoma.

BACKGROUND AND AIMS: To clarify the role of miR-23a in the onset and development of hepatocarcinoma on the cellular, genetic and molecular levels. PATIENTS AND METHODS: Seventy-eight patients were included after hepatectomy. Relationships between the clinical pathological factors of tumor and paracancerous tissues were analyzed. Risk factors of overall and recurrence-free survival rates were subject to multi-variable analysis. Tissues were sequenced by digital miRNA expression profiling, and new miRNA was subject to target gene prediction. RESULTS: miR-23a expression was correlated with the stage of the TNM Classification of Malignant Tumours most significantly, followed by tumor size (P=0.041 and 0.047). High miR-23a, vascular invasion, tumor size≥7cm, tumor capsule and late pathological stage were the risk factors of overall survival rate, and those of recurrence-free survival rate also included alpha-fetoprotein level≥200µg/L and multiple tumors. Compared with normal hepatic cell line L-02, the miR-23a expression levels in tumor cell lines SMMC-7721 and HepG2 were up-regulated and down-regulated respectively. Transfecting miR-23a inhibitor suppressed cell growth. Apoptotic rates of the control and those transfected with inhibitor-NC and miR-23a inhibitor for 48h were similar. CONCLUSION: High miR-23a expression is the independent prognostic factor of overall and recurrence-free survival rates, and miR-23a may be involved in the onset of hepatocarcinoma as an oncogene.

Prophylactic antibiotics used in patients of hepatobiliary surgery.

OBJECTIVE: To clarify the use of antibiotics in our hospital and to guide the prophylactic use in future hepatobiliary surgical procedures. METHODOLOGY: A retrospective review of patients who underwent hepatobiliary surgery from January 2011 to June 2011 was included. Data were collected, and surgical site infection (SSI) was defined by the criteria of Center for Disease Control and Prevention. Patients were prescribed antibiotics for the clinical diagnosis of hepatobiliary system diseases. RESULTS: 1564 patients were identified, in which 784 patients (50.13%) did not receive preoperative antibiotic prophylaxis. Of these 355 patients with 784 surgical sites received either preoperative or both preoperative and postoperative antibiotic prophylaxis. The SSI rate of the patients who received prophylaxis alone (2.56%, 20 of 780 sites) was not statistically higher than that of the patients who have not received prophylaxis (2.68%, 21 of 784 sites), and the two groups were not statistically correlated (P=0.77). CONCLUSION: The number of the patients who developed SSI was relatively low, and no reduction in the SSI rate was observed among the patients who have received antibiotic prophylaxis.

Association between the GSTP1 codon 105 polymorphism and gastric cancer risk: an updated meta-analysis.

OBJECTIVE: The current meta-analysis was performed to address a more accurate estimation of the association between glutathione S-transferase P1 (GSTP1) codon 105 polymorphism and risk of gastric cancer (GC), which has been widely reported with conflicting results. METHODS: A comprehensive literature search was conducted to identify all the relevant studies. Fixed or random effect models were selected based on the heterogeneity test. Publication bias was estimated using Begg's funnel plots and Egger's regression test. RESULTS: A total of 20 studies containing 2,821 GC cases and 6,240 controls were finally included in the analyses. Overall, no significant association between GSTP1 polymorphism and GC risk was observed in worldwide populations. However, subgroup analysis stratified by ethnicity showed that GSTP1 polymorphism was significantly associated with increased risk of GC in Asians (G vs. A, OR = 1.273, 95%CI=1.011-1.605; GG vs. AA, OR=2.103, 95%CI=1.197- 3.387; GG vs. AA+AG, OR =2.103, 95%CI=1.186-3.414). In contrast, no significant association was found in Caucasians in any genetic models, except for with AG vs. AA (OR=0.791, 95%CI=0.669-0.936). Furthermore, the GSTP1 polymorphism was found to be significantly associated with GC in patients with H. pylori infection and in those with a cardiac GC. Subgroup analysis stratified by Lauren's classification and smoking status showed no significant association with any genetic model. No studies were found to significantly influence the pooled effects in each genetic mode, and no potential publication bias was detected. CONCLUSIONS: This meta-analysis suggested that the GSTP1 polymorphism might be associated with increased risk of GC in Asians, while GSTP1 heterozygote genotype seemed to be associated with reduced risk of GC. Since potential confounders could not be ruled out completely, further studies are needed to confirm these results.

Development of a new auxiliary heterotopic partial liver transplantation technique using a liver cirrhosis model in minipigs: Preliminary report of eight transplants.

This study aimed to develop a new auxiliary heterotopic partial liver transplantation (AHPLT) technique in minipigs using a model of liver cirrhosis. Based on our previous study, 14 minipigs were induced to cirrhosis by administration of carbon tetrachloride (CCl(4)) through intraperitoneal injection. All of the cirrhotic animals were utilized as recipients. The donor's liver was placed on the recipient's splenic bed, and the anastomosis was performed as follows: end-to-end anastomosis between the donor's portal vein and the recipient's splenic vein, end-to-side anastomosis between the donor's suprahepatic vena cava and the recipient's suprahepatic vena cava, and end-to-end anastomosis between the donor's hepatic artery and the recipient's splenic artery. The common bile duct of the donor was intubated and bile was collected with an extracorporeal bag. Vital signs, portal vein pressure (PVP), hepatic venous pressure (HVP) and portal vein pressure gradient (PVPG) were monitored throughout the transplantation. All 8 minipigs that developed liver cirrhosis were utilized to establish the new AHPLT; 7 cases survived. Following the surgical intervention, the PVP and PVPG of the recipients were lower than those prior to the operation (P<0.05), whereas the PVP and PVPG of the donors increased significantly compared to those of the normal animals (P<0.05). A new operative technique for AHPLT has been successfully described herein using a model of liver cirrhosis.