Hepatic IL22RA1 deficiency promotes hepatic steatosis by modulating oxysterol in the liver.

BACKGROUND AIMS: Imbalance in lipid metabolism is the main cause of nonalcoholic fatty liver disease (NAFLD). While the pathogenesis of lipid accumulation mediated by extrahepatic regulators has been extensively studied, the intrahepatic regulators modulating lipid homeostasis remain unclear. Previous studies have shown that systemic administration of interleukin-22 (IL-22) protects against NAFLD; however, the role of IL-22/IL22RA1 signaling in modulating hepatic lipid metabolism remains uncertain. APPROACH RESULTS: This study shows hepatic IL22RA1 is vital in hepatic lipid regulation. IL22RA1 is downregulated in palmitic acid-treated mouse primary hepatocytes, as well as in the livers of NAFLD model mice and patients. Hepatocyte-specific Il22ra1 knockout (HKO) mice display diet-induced hepatic steatosis, insulin resistance, impaired glucose tolerance, increased inflammation, and fibrosis compared with flox/flox mice. This is attributed to increased lipogenesis mediated by the accumulation of hepatic oxysterols, particularly, 3 beta-hydroxy-5-cholestenoic acid (3ß HCA). Mechanistically, hepatic IL22RA1 deficiency facilitates 3ß HCA deposition via the activating transcription factor 3 (ATF3)/oxysterol 7 alpha-hydroxylase (CYP7B1) axis. Notably, 3ß HCA facilitates lipogenesis in MPHs and human liver organoids (HLOs) by activating LXR-alpha signaling, but IL-22 treatment attenuates this effect. Additionally, restoring CYP7B1 or silencing hepatic ATF3 reduces both hepatic 3ß HCA and lipid contents in HKO mice. CONCLUSIONS: These findings indicate that IL22RA1 plays a crucial role in maintaining hepatic lipid homeostasis in an ATF3/CYP7B1-dependent manner, and establish a link between 3ß HCA and hepatic lipid homeostasis.

Analysis Using Various Models on the Effect of Metabolic Surgery on Cardiovascular Disease Risk in the Chinese Population with Obesity.

Background: Some research have indicated that Bariatric and metabolic surgery (BMS) can reduce the risk of cardiovascular disease (CVD) among individuals with obesity. However, there are few reports available that focuses on assessing effect of BMS on the risk of CVD in Chinese population using multiple models. Objective: This research aims to assess the function of BMS on the risk of CVD in Chinese patients with obesity using multiple CVD risk models. Methods: We performed a retrospective analysis of the basic data and glycolipid metabolism data preoperatively and postoperatively from patients with obesity at our hospital. Subgroup analysis was carried out according to different surgical procedures. Then, the function of BMS on the risk of CVD in the Chinese population was assessed using four models, including: China-PAR risk model, Framingham risk score (FRS), World Health Organization (WHO) risk model, and Globorisk model. Results: We enrolled 64 patients, 24 (37.5%) of whom underwent laparoscopic sleeve gastrectomy (LSG) while 40 (62.5%) underwent Roux-en-Y gastric bypass (RYGB). The 10-year CVD risk for patients calculated using the China-PAR risk model decreased from 6.3% preoperatively to 2.0% at 1 year postoperatively and was statistically significantly different. Similarly, the 10-year CVD risk of patients calculated using the FRS, WHO, Global risk model decreased significantly at 1 year postoperatively compared to preoperatively. When the FRS risk model was used to calculate the patients' 30-year postoperative CVD risk, there was a significant decrease at 1 year after surgery compared to the preoperative period. When employing various models to evaluate the 10-year CVD risk for LSG and RYGB, no statistically significant difference was found in the 1-year postoperative RRR between the procedures. Conclusion: The CVD risk after BMS was significantly reduced compared to preoperatively. In terms of improving cardiovascular risk, SG and RYGB appear to be equally effective.

Prevalence, Risk Factors, and Metabolic Characteristics of Metabolically Healthy Obesity in Patients Seeking Bariatric Surgery: A Cohort Study.

BACKGROUND: Bariatric surgery is an effective treatment for morbid obesity. However, a subset of individuals seeking bariatric surgery may exhibit a metabolically healthy obesity (MHO) phenotype, suggesting that they may not experience metabolic complications despite being overweight. OBJECTIVE: This study aimed to determine the prevalence and metabolic features of MHO in a population undergoing bariatric surgery. METHODS: A representative sample of 665 participants aged 14 or older who underwent bariatric surgery at our center from January 1, 2010 to January 1, 2020 was included in this cohort study. MHO was defined based on specific criteria, including blood pressure, waist-to-hip ratio, and absence of diabetes. RESULTS: Among the 665 participants, 80 individuals (12.0%) met the criteria for MHO. Female gender (P = .021) and younger age (P < .001) were associated with a higher likelihood of MHO. Smaller weight and BMI were observed in individuals with MHO. However, a considerable proportion of those with MHO exhibited other metabolic abnormalities, such as fatty liver (68.6%), hyperuricemia (55.3%), elevated lipid levels (58.7%), and abnormal lipoprotein levels (88%). CONCLUSION: Approximately 1 in 8 individuals referred for bariatric surgery displayed the phenotype of MHO. Despite being metabolically healthy based on certain criteria, a significant proportion of individuals with MHO still exhibited metabolic abnormalities, such as fatty liver, hyperuricemia, elevated lipid levels, and abnormal lipoprotein levels, highlighting the importance of thorough metabolic evaluation in this population.

Giant lipoma in the Retzius space resected under laparoscopy: A case report.

Lipoma is a common type of benign soft tissue tumor that can occur in the shoulders, neck and back, in addition to other body parts. The Retzius space is a small anatomical space between the pubic symphysis and the bladder located extraperitoneally and filled with loose fatty connective tissue. Giant lipomas are rare in the Retzius space. A 61-year-old Chinese male arrived at Beijing Yanhua Hospital (Beijing, China) due to frequent urination, and CT scan images of the lower abdomen observed a large pelvic mass and left inguinal hernia. Preoperative clinical manifestations and auxiliary examination suggested that the tumor originated from the urinary bladder wall. The maximum tumor diameter was ~25 cm and abdominal pressure was increased. Therefore, laparoscopic pelvic tumor resection combined with inguinal hernia repair was attempted. Intraoperatively, the tumor was found to originate from the Retzius space and the postoperative pathological diagnosis was lipoma. The present case report may serve as a reference for minimally invasive treatment of this type of rare disease in future.

Comparison of various prediction models in the effect of laparoscopic sleeve gastrectomy on type 2 diabetes mellitus in the Chinese population 5 years after surgery.

BACKGROUND: The effect of bariatric surgery on type 2 diabetes mellitus (T2DM) control can be assessed based on predictive models of T2DM remission. Various models have been externally verified internationally. However, long-term validated results after laparoscopic sleeve gastrectomy (LSG) surgery are lacking. The best model for the Chinese population is also unknown. METHODS: We retrospectively analyzed Chinese population data 5 years after LSG at Beijing Shijitan Hospital in China between March 2009 and December 2016. The independent t -test, Mann-Whitney U test, and chi-squared test were used to compare characteristics between T2DM remission and non-remission groups. We evaluated the predictive efficacy of each model for long-term T2DM remission after LSG by calculating the area under the curve (AUC), sensitivity, specificity, Youden index, positive predictive value (PPV), negative predictive value (NPV), and predicted-to-observed ratio, and performed calibration using Hosmer-Lemeshow test for 11 prediction models. RESULTS: We enrolled 108 patients, including 44 (40.7%) men, with a mean age of 35.5 years. The mean body mass index was 40.3 ± 9.1 kg/m 2 , the percentage of excess weight loss (%EWL) was (75.9 ± 30.4)%, and the percentage of total weight loss (%TWL) was (29.1± 10.6)%. The mean glycated hemoglobin A1c (HbA1c) level was (7.3 ± 1.8)% preoperatively and decreased to (5.9 ± 1.0)% 5 years after LSG. The 5-year postoperative complete and partial remission rates of T2DM were 50.9% [55/108] and 27.8% [30/108], respectively. Six models, i.e., "ABCD", individualized metabolic surgery (IMS), advanced-DiaRem, DiaBetter, Dixon et al' s regression model, and Panunzi et al 's regression model, showed a good discrimination ability (all AUC >0.8). The "ABCD" (sensitivity, 74%; specificity, 80%; AUC, 0.82 [95% confidence interval [CI]: 0.74-0.89]), IMS (sensitivity, 78%; specificity, 84%; AUC, 0.82 [95% CI: 0.73-0.89]), and Panunzi et al' s regression models (sensitivity, 78%; specificity, 91%; AUC, 0.86 [95% CI: 0.78-0.92]) showed good discernibility. In the Hosmer-Lemeshow goodness-of-fit test, except for DiaRem ( P <0.01), DiaBetter ( P <0.01), Hayes et al ( P = 0.03), Park et al ( P = 0.02), and Ramos-Levi et al' s ( P <0.01) models, all models had a satifactory fit results ( P >0.05). The P values of calibration results of the "ABCD" and IMS were 0.07 and 0.14, respectively. The predicted-to-observed ratios of the "ABCD" and IMS were 0.87 and 0.89, respectively. CONCLUSION: The prediction model IMS was recommended for clinical use because of excellent predictive performance, good statistical test results, and simple and practical design features.

Nutritional status and its correlation to prognosis of nasopharyngeal carcinoma patients in different ages in China: a multicenter cohort study.

Nasopharyngeal carcinoma (NPC) patients usually presented malnutrition under chemoradiotherapy (CRT)/radiotherapy (RT). Few studies stratified by age to investigate the association of nutritional status with overall survival (OS) in NPC patients. This study aimed to explore the nutritional parameters related prognosis of NPC patients in different age. The total 1365 NPC patients were classified into young (18~45), middle-aged (46~60), and old groups (> 60). PG-SGA scores, NRS-2002 scores, Karnofsky performance status scores, anthropometric, and blood indicators (albumin, prealbumin, transferrin, C-reactive protein, hemoglobin, and total lymphocyte) were assessed. Cox regression analysis was performed to evaluate the association between risk factors of nutritional status and the overall survival in different age group of NPC patients. Kaplan-Meier (KM) survival analysis was used to estimate the effect of nutritional indexes on prognosis. The abnormal rate of albumin, prealbumin, hemoglobin, hand grip strength, and calf circumference increased with age. The malnutrition occurred in all age group and low calf circumference (HR, 4.427, 1.167-16.791) was an independent death risk in young adults. Distant metastasis (HR, 4.754, 2.737-8.260), low albumin (HR, 3.530, 1.708-7.296), hand grip strength (HR, 1.901, 1.160-3.115), and the nutritional intervention requirement (NRS-2002 ≥ 3) (HR, 2.802, 1.211-6.483) was significantly correlated with poor OS in NPC patients with middled age adults. Distant metastasis (HR, 2.546, 1.497-4.330), low albumin (HR, 1.824, 0.949-3.507), low hemoglobin (HR, 1.757, 1.015-3.044), low hand grip strength (HR, 1.771, 1.112-2.818), and low calf circumference (HR, 1.951, 1.074-3.545) were associated with increased risk of death in the elderly. KM analysis indicated that over 60 years, distant metastasis, low albumin, low hand grip strength, low calf circumference, and malnutritional risk (NRS-2002 ≥ 3) were correlated to prognosis of NPC patients. Low calf circumference could be a prognosis not only in elderly but also in young adults of NPC patients, whereas low albumin and distant metastasis were the prognostic factors in middle-aged and elderly patients. Patients aged over 60 years exhibited poorer OS compared with young and middle-aged adults.

An Assessment of the Effect of Bariatric Surgery on Cardiovascular Disease Risk in the Chinese Population Using Multiple Cardiovascular Risk Models.

Background: Many studies have reported that bariatric surgery may reduce postoperative cardiovascular risk in patient with obesity, but few have addressed this risk in the Chinese population. Objective: To assess the impact of bariatric surgery on cardiovascular disease (CVD) risk in the Chinese population using the World Health Organization (WHO) risk model, the Global risk model, and the Framingham Risk Score. Methods: We retrospectively analyzed data collected on patient with obesity who underwent bariatric surgery at our institution between March 2009 and January 2021. Their demographic characteristics, anthropometric variables, and glucolipid metabolic parameters were assessed preoperatively and at their 1-year postoperative follow-up. Subgroup analysis compared body mass index (BMI) < 35 kg/m2 and BMI ≥ 35 kg/m2, as well as gender. We used the 3 models to calculate their CVD risk. Results: We evaluated 61 patients, of whom 26 (42.62%) had undergone sleeve gastrectomy (SG) surgery and 35 (57.38%) Roux-en-Y gastric bypass (RYGB) surgery. Of the patients with BMI ≥ 35 kg/m2, 66.67% underwent SG, while 72.97% with BMI < 35 kg/m2 underwent RYGB. HDL levels were significantly higher at 12 months postoperatively relative to baseline. When the models were applied to calculate CVD risk in Chinese patients with obesity, the 1-year CVD risk after surgery were reduced lot compared with the preoperative period. Conclusion: Patient with obesity had significantly lower CVD risks after bariatric surgery. This study also demonstrates that the models are reliable clinical tools for assessing the impact of bariatric surgery on CVD risk in the Chinese population.

Long-term weight loss outcome of laparoscopic Roux-en-Y gastric bypass predicted by weight loss at 6 months in Chinese patients with BMI ≥ 32.5 kg/m2.

Laparoscopic Roux-en-Y gastric bypass (LRYGB) is classic bariatric procedure with long-term safety and efficacy. However, no studies have focused on predicting long-term weight loss after LRYGB in Chinese patients with body mass index (BMI) ≥ 32.5 kg/m2. To explore the relationship between initial and long-term weight loss after LRYGB in patients with BMI ≥ 32.5 kg/m2. All patients were followed-up to evaluate BMI, percentage of excess weight loss (%EWL), and comorbidities. Linear and logistic regression were performed to assess the relationship between initial and long-term weight loss. Receiver operating characteristic curve was used to determine optimal cutoff value. We enrolled 104 patients. The median preoperative BMI was 41.44 (37.92-47.53) kg/m2. %EWL ≥ 50% at 5 years was considered as successful weight loss, and 75.00% of the patients successfully lost weight. The cure rates of hypertension, hyperlipidemia, and type 2 diabetes mellitus at 1 year were 84.38%, 33.93%, and 60.82%, respectively. %EWL at 6 months and 5 years were positively correlated and its relationship could be described by following linear equation: %EWL5 years = 43.934 + 0.356 × %EWL6 months (P < .001; r2 = 0.166). The best cutoff %EWL at 6 months after LRYGB to predict 5-year successful weight loss was 63.93% (sensitivity, 53.85%; specificity, 84.62%; area under the curve (AUC) = 0.671). In Chinese patients with BMI ≥ 32.5 kg/m2, %EWL at 6 months and 5 years were positively correlated and %EWL at 5 years could be calculated by following linear equation: %EWL5 years = 43.934 + 0.356 × %EWL6 months.

Combination of Single-Nucleotide Polymorphisms and Preoperative Body Mass Index to Predict Weight Loss After Laproscopic Sleeve Gastrectomy in Chinese Patients with Body Mass Index ≥ 32.5 kg/m2.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) associated with obesity predict laparoscopic Roux-en-Y gastric bypass (LRYGB) and biliopancreatic diversion with duodenal switch (BPD/DS) for weight loss with good efficiency. However, prediction of weight loss after laparoscopic sleeve gastrectomy using SNPs has not been well investigated. OBJECTIVES: To predict weight loss after laparoscopic sleeve gastrectomy using obesity-related SNPs and clinical variants in Chinese patients with body mass index (BMI) ≥ 32.5 kg/m2. METHODS: We detected 29 SNPs. Binary logistic regression was used to screen SNPs and clinical variables with predictive value. Receiver operating characteristic (ROC) curves were plotted for clinical variables, SNPs, and their combination, and areas under the ROC curve (AUC) were compared. Internal and external validation tests were performed. RESULTS: rs12535708, rs651821, and rs5082 were constructed as the genetic risk score (GRS). Preoperative BMI was constructed as the clinical risk score (CRS). Preoperative BMI and SNPs were constructed as the cumulative genetic risk score (CGRS). ROC curves of GRS, CRS, and CGRS showed that the optimal cutoffs were 0.831 (AUC = 0.840; sensitivity, 92.96%; specificity, 64.29%), 43.46 kg/m2 (AUC = 0.830; sensitivity, 76.06%; specificity, 85.71%), and 0.921 (AUC = 0.931; sensitivity, 77.46%; specificity, 92.86%), respectively. The AUC of CGRS was significantly greater than that of CRS (P < 0.05) and greater than GRS without statistical significance. CONCLUSION: In Chinese patients with BMI ≥ 32.5 kg/m2, GRS and CRS could predict weight loss success. However, CGRS was superior to GRS or CRS alone.

APEX1 promotes the oncogenicity of hepatocellular carcinoma via regulation of MAP2K6.

OBJECTIVE: Apurinic/apyrimidinic endonuclease 1 (APEX1), a key enzyme responsible for DNA base excision repair, has been linked to development and progression of cancers. In this work, we aimed to explore the role of APEX1 in hepatocellular carcinoma (HCC) and elucidate its molecular mechanism. METHODS: The expression of APEX1 in HCC tissues and matched adjacent normal tissues (n = 80 cases) was evaluated by immunohistochemistry. Web-based tools UALCAN and the Kaplan-Meier plotter were used to analyze the Cancer Genome Atlas database to compare expression of APEX1 mRNA to 5-year overall survival. APEX1 was stably silenced in two HCC cell lines, Hep 3B and Bel-7402, with shRNA technology. An in vivo tumorigenesis model was established by subcutaneously injecting sh-APEX1-transfected Bel-7402 cells into mice, and tumor growth was determined. We performed high-throughput transcriptome sequencing in sh-APEX1-treated HCC cells to identify the key KEGG signaling pathways induced by silencing of APEX1. RESULTS: APEX1 was significantly upregulated and predicted poor clinical overall survival in HCC patients. Silencing APEX1 inhibited the proliferation of HCC cells in vivo and in vitro, and it repressed invasion and migration and increased apoptosis and the percentage of cells in G1. Differentially expressed genes upon APEX1 silencing included genes involved in TNF signaling. A positive correlation between the expression of APEX1 and MAP2K6 was noted, and overexpressing MAP2K6 overcame cancer-related phenotypes associated with APEX1 silencing. CONCLUSION: APEX1 enhances the malignant properties of HCC via MAP2K6. APEX1 may represent a valuable prognostic biomarker and therapeutic target in HCC.

Enteric VIP-producing neurons maintain gut microbiota homeostasis through regulating epithelium fucosylation.

Interactions between the enteric nervous system (ENS) and intestinal epithelium are thought to play a vital role in intestinal homeostasis. How the ENS monitors the frontier with commensal and pathogenic microbes while maintaining epithelial function remains unclear. Here, by combining subdiaphragmatic vagotomy with transcriptomics, chemogenetic strategy, and coculture of enteric neuron-intestinal organoid, we show that enteric neurons expressing VIP shape the α1,2-fucosylation of intestinal epithelial cells (IECs). Mechanistically, neuropeptide VIP activates fut2 expression via the Erk1/2-c-Fos pathway through the VIPR1 receptor on IECs. We further demonstrate that perturbation of enteric neurons leads to gut dysbiosis through α1,2-fucosylation in the steady state and results in increased susceptibility to alcohol-associated liver disease (ALD). This was attributed to an imbalance between beneficial Bifidobacterium and opportunistic pathogenic Enterococcus faecalis in ALD. In addition, Bifidobacterium α1,2-fucosidase may promote Bifidobacterium adhesion to the mucosal surface, which restricts Enterococcus faecalis overgrowth and prevents ALD progression.

Long-Term Weight Loss Outcome of Laparoscopic Sleeve Gastrectomy Predicted by the Percentage of Excess Weight Loss at 6 Months in Chinese Patients with Body Mass Index ≥ 32.5 Kg/m2.

Purpose: To evaluate the predictive effect of the initial weight loss on the long-term weight loss in Chinese patients with a body mass index (BMI) ≥ 32.5 kg/m2 who underwent LSG. Patients and Methods: The follow-up was completed via phone or WeChat for outpatients and at the hospital for inpatients. We evaluated the BMI, percentage of excess weight loss (%EWL), and type 2 diabetes mellitus, hypertension, and hyperlipidemia statuses. Linear and logistic regression analyses were performed on the relationship between the initial and long-term weight loss. The optimal cut-off value was determined by receiver operating characteristic (ROC) curve analysis. Results: We enrolled 307 patients, with a median preoperative BMI of 39.68 (35.68, 45.47) kg/m2. %EWL ≥ 50% was regarded as successful weight loss, and 76.55% of the patients lost their weight successfully. (Reviewer #1, comment #4) %EWL at 6 months and 5 years were positively correlated (P < 0.001). Further, the following linear equation could express the relationship: (%EWL5 years = 29.193 + 0.526 × %EWL6 months). %EWL ≥ 58.57% at 6 months was the best predictor of successful weight loss at 5 years after LSG (Reviewer #1, comment #5) (sensitivity, 73.62%; specificity, 73.61%; AUC value, 0.780). Internal verification of the prediction model revealed satisfactory results in terms of discrimination and calibration. Conclusion: In Chinese patients with BMI ≥ 32.5 kg/m2 who underwent LSG, %EWL at 6 months and 5 years were correlated. %EWL ≥ 58.57% at 6 months was a predictor of successful long-term weight loss.

Neutral ceramidase-dependent regulation of macrophage metabolism directs intestinal immune homeostasis and controls enteric infection.

It is not clear how the complex interactions between diet and intestinal immune cells protect the gut from infection. Neutral ceramidase (NcDase) plays a critical role in digesting dietary sphingolipids. We find that NcDase is an essential factor that controls intestinal immune cell dynamics. Mice lacking NcDase have reduced cluster of differentiation (CD) 8αß+ T cells and interferon (IFN)-γ+ T cells and increased macrophages in the intestine and fail to clear bacteria after Citrobacter rodentium infection. Mechanistically, cellular NcDase or extracellular vesicle (EV)-related NcDase generates sphingosine, which promotes macrophage-driven Th1 immunity. Loss of NcDase influences sphingosine-controlled glycolytic metabolism in macrophages, which regulates the bactericidal activity of macrophages. Importantly, administration of dietary sphingomyelin and genetic deletion or pharmacological inhibition of SphK1 can protect against C. rodentium infection. Our findings demonstrate that sphingosine profoundly alters macrophage glycolytic metabolism, leading to intestinal macrophage activation and T cell polarization, which prevent pathogen colonization of the gut.

K-Wire Retractor, a Trocar-Free Liver Retraction Technique in Bariatric Surgery.

BACKGROUND: Liver retractor helps in the provision of an adequate operative field in bariatric surgery. Though several retractors have been introduced, an optimal retraction method is yet to be desired. We have developed a K-wire retractor, a simple trocar-free liver retractor used in our bariatric surgery. The efficacy and safety of the K-wire retractor were examined. METHODS: A retrospective review was performed on patients undergoing laparoscopic bariatric surgery from January 2016 to April 2019. Based on the application of liver retractors during surgery, patients were divided into the K-wire retractor group and the suture-based retractor group for comparative analyses. Patients with severe liver injury or missing data, or treated with other types of retractors were excluded. RESULTS: A total of 317 patients were included in our study and there was no conversion to open surgery. There were no significant differences in patient demographics (age, gender, BMI) and types of bariatric surgery between the two groups. The time taken for placement of retractor was significantly shorter in the K-wire retractor group, in addition to higher operative view score and lesser ALT/AST elevation compared with the suture-based retractor group. Although the K-wire retractor group was less inclined to require additional retraction techniques, patients with BMI ≥ 50 Kg/m2 were associated with higher risk (OR:3.8; 95% CI: 1.2, 12.8) of requiring additional retractors. There were no severe K-wire retractor-related complications observed. CONCLUSION: The trocar-free K-wire liver retractor is safe, simple, and effective as a standard liver retraction method in bariatric surgery.

Recent advances in the mechanisms underlying the beneficial effects of bariatric and metabolic surgery.

Bariatric and metabolic surgery (BMS) is the most effective treatment for obesity, type 2 diabetes and co-morbidities, including nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. The beneficial effects of BMS are beyond the primary goal of gastric restriction and nutrients malabsorption. Roux-en-Y gastric bypass and vertical sleeve gastrectomy are the 2 most commonly performed procedures of BMS. Both surgeries lead to physiologic changes in gastrointestinal tract; subsequently alter bile acids pool and composition, gut microbial activities, gut hormones, and circulating exosomes; and ultimately contribute to the improved glycemic control, insulin sensitivity, lipid metabolism, energy expenditure, and weight loss. The mechanisms underlying the benefits of BMS likely involve the bile acid-signaling pathway mediated mainly by nuclear farnesoid X receptor and the membrane Takeda G protein-coupled receptor, bile acids-gut microbiota interaction, and exosomes. In this review, we focus on recent advances in potential mechanisms and aim to learn novel insights into the molecular mechanisms underlying metabolic disorders.

CD146, from a melanoma cell adhesion molecule to a signaling receptor.

CD146 was originally identified as a melanoma cell adhesion molecule (MCAM) and highly expressed in many tumors and endothelial cells. However, the evidence that CD146 acts as an adhesion molecule to mediate a homophilic adhesion through the direct interactions between CD146 and itself is still lacking. Recent evidence revealed that CD146 is not merely an adhesion molecule, but also a cellular surface receptor of miscellaneous ligands, including some growth factors and extracellular matrixes. Through the bidirectional interactions with its ligands, CD146 is actively involved in numerous physiological and pathological processes of cells. Overexpression of CD146 can be observed in most of malignancies and is implicated in nearly every step of the development and progression of cancers, especially vascular and lymphatic metastasis. Thus, immunotherapy against CD146 would provide a promising strategy to inhibit metastasis, which accounts for the majority of cancer-associated deaths. Therefore, to deepen the understanding of CD146, we review the reports describing the newly identified ligands of CD146 and discuss the implications of these findings in establishing novel strategies for cancer therapy.

High-resolution manometry in the upright position could improve the manometric evaluation of morbidly obese patients with esophagogastric junction outflow obstruction.

BACKGROUND: Esophagogastric junction outflow obstruction (EGJOO) detected by manometry in the supine position is prevalent in patients with morbid obesity, but not all EGJOOs are clinically significant. We investigated whether including upright swallows during high-resolution manometry (HRM) could help identify non-clinically significant EGJOO in patients with morbid obesity. METHODS: We performed a retrospective study of consecutive morbidly obese patients diagnosed with EGJOO by HRM from July 2012 through July 2018. The HRM protocol included 10 supine and five upright 5-mL water swallows. Endoscopy, esophagram, and computed tomography were performed to identify whether the patients should be diagnosed as having clinically significant EGJOO. KEY RESULTS: A total of 230 patients with morbid obesity underwent HRM in the supine position during the study period. Fifty (21.7%) patients were diagnosed with EGJOO, among which 32 completed HRM both in the supine and upright positions. Only 8/32 patients were diagnosed with EGJOO in an upright position. Fewer artifacts were displayed in esophageal pressure topography in the upright position. None of the 32 patients could be diagnosed as clinically significant EGJOO based on all the examinations. Median esophageal gastric junction pressure, integrated relaxation pressure, and distal contractile integral were higher, and median distal latency was longer in the supine position compared with the upright position (all P < .05). CONCLUSIONS AND INFERENCES: Esophagus manometry in the upright position could reduce EGJOO overdiagnosis in patients with morbid obesity. Prolongation of the HRM study with some swallows in the upright position could be recommended in obese patients.

Abdominal infectious complications associated with the dislocation of intraperitoneal part of drainage tube and poor drainage after major surgeries.

Abdominal drainage, serving as a diagnostic and therapeutic tool, has been widely applied to prevent complications after major abdominal surgical procedures. However, dislocation of intraperitoneal portion of drainage tube and poor drainage after major surgery has never been detailed. In this retrospective study, we determined whether postoperative abdominal infectious complications are attributed to dislocation of intraperitoneal portion of drainage tube. Patients were recruited from the Department of General Surgery at Beijing Shijitan Hospital, Capital Medical University, between June 2015 and June 2018. All of the enrolled patients had undergone different major abdominal surgical procedures with abdominal drainage. According to different fixation methods of the drainage tube, the patients were categorised as follows: group 1 as conventional extra-abdominal fixation where the tubes were fixed on abdominal wall; group 2 as double fixation where the tubes were fixed by both extra-abdominal and intra-abdominal fixation. Among 60 patients (40 in group 1 and 20 in group 2) with suspected postoperative abdominal infection, abdominal computed tomography (CT) was performed to determine the presence of abnormality. Dislocation of drainage tubes, morbidity, treatment, and prognosis were compared between the two groups. None of the patients showed slip knot or drainage tube slipping from the abdomen based on physical examination and CT imaging. Drainage tube was fixed firmly on the abdominal wall. In group 1, 18 (45%) patients developed postoperative complications resulting from abdominal infection where severe dislocation of intraperitoneal portion of drainage tubes was confirmed by CT. Drainage tubes of six cases were significantly dislocated to the anterior abdominal wall from the target area; 7 upper abdominal drainage tubes dislocated to the lower abdomen; and 5 lower abdominal drainage tubes dislocated to the upper abdomen. Common complications included localised peritonitis (n = 4), abdominal abscess (n = 8), and anastomotic leakage (n = 6). Among them, 8 patients were cured by abdominal puncture catheter drainage; 5 underwent secondary operation and 5 were cured by conservative treatment. In group 2, no tube dislocation was identified by CT. Five patients (25%) developed complications, including localised peritonitis (n = 1), abdominal abscess (n = 1), and anastomotic leakage (n = 3). All the five patients were cured by conservative treatment. Postoperative abdominal infection complications can stem from dislocation of intraperitoneal portion of drainage tube and poor drainage after major abdominal surgery. Maintaining the intraperitoneal portion of drainage tube at the proper location, for example, by applying intraabdominal fixation, is paramount to decrease the incidence and severity of postoperative complications.

Technical details of and prognosis for the "China stitch", a novel technique for totally laparoscopic hand-sewn esophagojejunostomy.

The current study describes the technical details of and the clinical prognosis for the "China stitch", a novel technique for hand-sewn esophagojejunostomy in totally laparoscopic total gastrectomy. This study also explores the feasibility and safety of the technique. Clinical data of 20 patients with esophagogastric junction cancer in Beijing Shijitan Hospital, Capital Medical University from January 2017 to April 2018 were retrospectively analyzed. All 20 patients underwent esophagojejunostomy via a novel hand-sewn technique that uses traction to turn the left or right wall of the esophagus into an anterior wall. This avoids the difficulty of suturing the posterior wall. All patients were followed until June 2019. All 20 patients successfully underwent the procedure. The mean operating time was 216.5 ± 24.9 (176-254) min, the mean hand-sewn reconstruction time was 44.4 ± 9.4 (26-61) min, intraoperative bleeding was 141.2 ± 24.9 (130-160) mL, and the number of resected lymph nodes was 23 ± 8 (14-33). After surgery, there was one case of anastomotic leakage and one case of anastomotic stenosis, but both were alleviated with conservative treatment. The mean duration of follow-up was 15 (4-33) months. There was no significant difference in postoperative complications of and short-term oncologic prognosis for the 20 patients who underwent hand-sewn esophagojejunostomy and the 21 patients who underwent mechanical esophagojejunostomy during the same period. In conclusion, the "China stitch", a novel hand-sewn technique, is a cost-effective, safe, and reliable method for esophagojejunostomy in totally laparoscopic total gastrectomy.

Laparoscopic treatment of median arcuate ligament syndrome.

Median arcuate ligament syndrome (MALS) refers to a clinical syndrome caused by compression of the median arcuate ligament due to the fibers of this ligament that connect the diaphragmatic crura on the two sides of the aortic foramina, forming the anterior edge of the aortic foramina. If MALS is suspected, invasive digital subtraction angiography and computed tomography angiography or magnetic resonance angiography (MRA) can be used to verify the location of the celiac trunk. A disrupted or increased blood flow in the proximal end of the celiac trunk can be detected with doppler ultrasound, indicating stenosis. Treatment needs to alleviate celiac trunk compression. A common procedure involves separation of the ligament fibers and other surrounding tissues around the beginning of the celiac trunk. This can be achieved by either laparotomy or laparoscopic surgery. Patient prognosis is good, with a cure rate of about 80%.