Evidence for a causal relationship between psoriasis and cutaneous melanoma: a bidirectional two-sample Mendelian randomized study.

Background and objective: Existing cross-sectional and retrospective studies were unable to establish a causal relationship between psoriasis and cutaneous melanoma (CM). We sought to evaluate the causal role between psoriasis and CM. Methods: We performed a bidirectional two-sample Mendelian randomization analysis using summary statistics from genome-wide association studies of psoriasis and CM among individuals of predominantly European ancestry. Mendelian randomization-Egger regression, inverse variance weighting, Mendelian Randomization Pleiotropy RESidual Sum and Outlier, weighted mode, and weighted median were used to examine the causal effect between psoriasis and CM. Results: Genetically predicted psoriasis was a significant risk factor for CM (odds ratio, 1.69; 95% confidence interval, 1.15-2.48; P = 0.025). In contrast, no association was observed between genetically predicted CM and psoriasis. Conclusion: Our findings corroborated the existence of genetically predicted psoriasis increases risk of CM. Enhanced early screening of cutaneous melanoma in patients with psoriasis may improve clinical burden. However, we did not find evidence for a causal link from CM to psoriasis, so further studies are required to elucidate the effect of CM activity on psoriasis.

Gut Microbiota Signature of Obese Adults Across Different Classifications.

Purpose: Obesity is currently a major global public health issue. It has been shown by many that gut microbiota and microbial factors regulate the pathogenesis of obesity and metabolic abnormalities, but little is known about their roles in the different degrees of obesity. Here, we sought to investigate the microbial signatures of obesity of various severities. Patients and Methods: We did this by characterizing the intestinal microbiome signature in a Chinese cohort of obese patients and healthy controls using 16S rRNA gene sequencing. To this end, obesity was sub-divided into four subgroups, including "Overweight", Class I, Class II, and Class III obesity, based on body mass index (BMI). Results: Microbial diversity decreased in obese subjects, and the reduction trend was correlated with the severity of obesity. We detected an expansion of Escherichia shigella in obese patients compared to healthy controls. The family Eubacterium coprostanoligenes and Tannerellaceae, the genera Eubacterium coprostanoligenes, Lachnospiraceae NK4A136, Parabacteroides, and Akkermansia, and the species Prevotella copri were microbial biomarkers of healthy people. Gammaproteobacteria and Enterobacterales were biomarkers of being "Overweight". Erysipelatoclostridiaceae was a biomarker of Class I obesity. The class Bacilli and the order Lactobacillales were both biomarkers of Class II obesity. Negativicutes was a biomarker of Class III obesity. We further established relationships between this microbiome data and other biochemical data, including albumin, low-density lipoprotein (LDL), high-density lipoprotein (HDL), vitamin folic acid (FA) and vitamin B12 (VB12), and Interleukin-6 (IL-6) levels. Function prediction results showed a marked energy metabolism dysbiosis in obesity, especially in patients with Class III obesity. Conclusion: These results suggested that people with different levels of obesity had distinct gut microbial signatures. Decreased microbial diversity, depletion of some specific taxa, and deviation in potential functions mirrored the severity of obesity in this cohort.

Etiology of serum vitamin B12 elevation 1 month after bariatric surgery: A case-control study based on China population.

ABSTRACT: Few studies have reported an increase in vitamin B12 (VitB12) levels after bariatric surgery. This study reports the phenomenon and adverse reactions of serum VitB12 elevation 1 month after surgery and explores the possible etiologies.Retrospective analysis was performed on VitB12 data for 112 patients from January 2018 to October 2019. Then, 87 patients were included between November 2019 and August 2020. They were divided into 2 groups according to the level of VitB12 after surgery, and the demographic and clinical data were analyzed. Then, LASSO regression model analysis and multiple logistic regression analysis were performed to explore the risk factors for VitB12 elevation after surgery.Retrospective data showed that the VitB12 level was significantly increased 1 month after surgery. Comparison of data between the 2 groups found that more patients also had diabetes in the nonelevated group. The postoperative folic acid and VitB12 levels of the elevated group were significantly higher than those of the nonelevated group. More patients had concurrent constipation in the elevated group than in the nonelevated group. Two meaningful variables in LASSO regression analysis were incorporated into the multivariate logistic regression analysis, and constipation was found to be an independent risk factor for the increase in VitB12 after surgery. Of the 199 patients in this study, 111 patients had elevated VitB12 levels after surgery. Among them, 7 patients had peripheral nerve symptoms.Constipation is an independent risk factor for increased VitB12 levels after surgery. High levels of VitB12 may cause some peripheral nerve symptoms. Therefore, it is necessary to pay attention to patients with postoperative constipation, monitor their VitB12 level as soon as possible, and take measures to improve constipation to avoid some adverse reactions caused by elevated VitB12 levels.

Clinical significance and prognostic role of an immune-related gene signature in gastric adenocarcinoma.

Limited progress has been made in the treatment of gastric adenocarcinoma (GAC) in recent years, but the potential of immunotherapy in GAC is worthy of consideration. The purpose of this study was to develop a reliable, personalized signature based on immune genes to predict the prognosis of GAC. Here, we identified two groups of patients with significantly different prognoses by performing unsupervised clustering analysis of The Cancer Genome Atlas (TCGA) database based on 881 immune genes. The immune signature was constructed with a training set composed of 350 GAC samples from the TCGA and subsequently validated with 431 samples from GSE84437, 432 samples from GSE26253, and 145 GAC samples from real-time quantitative reverse transcription polymerase chain reaction data. This classification system can also be used to predict prognosis in different clinical subgroups. Further analysis suggested that high-risk patients were characterized by low immune scores, distinctive immune cell proportions, different immune checkpoint profiles, and a low tumor mutational burden. Ultimately, the signature was identified as an independent prognostic factor. In general, the signature can accurately predict recurrence and overall survival in patients with GAC and may serve as a powerful prognostic tool to further optimize cancer immunotherapy.

High expression of CD52 in adipocytes: a potential therapeutic target for obesity with type 2 diabetes.

The aim of the present study was to evaluate the involvement of CD52 in adipocytes as well as to explore its effect on type 2 diabetes mellitus (T2DM), and to improve our understanding of the potential molecular events of obesity with type 2 diabetes. Global changes in the CD52 expression patterns were detected in adipocytes and preadipocytes derived from obese and lean individuals. In particular, CD52 was identified as significantly differentially upregulated and was analyzed, both in vitro and in vivo, using various approaches. In vitro experiments, CD52 was a significantly up-regulated mRNA in mature adipocytes and preadipocytes. In addition, CD52 gradually increased with the differentiation of preadipocytes. In vivo experiments, the expression of CD52 in high-fat diet (HFD) -fed mice tended to be higher than that in regular diet (RD) -fed mice. Further analysis showed that CD52 expression was positively correlated with Smad3 and TGF-ß in mice, and the downregulation of CD52 was accompanied by increased glucose tolerance and insulin sensitivity. Moreover, a comparison of CD4+CD52high T cells and CD4+CD52low T cells showed that many T2DM-related genes were aberrantly expressed. Overall, CD52 may functioned as an important potential target for obesity with T2DM via TGF-ß/Smad3 axis.

Improvement of left ventricular systolic function in morbidly obese patients after bariatric surgery: Case report.

INTRODUCTION: Morbid obesity (body mass index > 40 kg/m2) is a risk factor for the development of left ventricular systolic dysfunction (LVSD) and can complicate the management of LVSD. Bariatric surgery is increasingly recognized as a safe and effective way to achieve marked weight loss, but studies on improving LVSD populations are limited. We retrospectively analyzed the first case of the Asia-Pacific region with morbid obesity and left ventricular ejection fraction (LVEF) < 50% who underwent bariatric surgery at our medical center. PATIENT CONCERNS: The patient was admitted to the hospital due to progressive weight gain for more than 10 years. The patient used to be in good health. One year before admission, the patient was hospitalized in another hospital due to shortness of breath. After the relevant examination, the patient was diagnosed with dilated cardiomyopathy. DIAGNOSIS: The body mass index of the patient was 45.9 kg/m2, and the patient was diagnosed with morbid obesity. He was diagnosed with dilated cardiomyopathy and cardiac function class IV in another hospital. After completing a preoperative examination, the patient was diagnosed with hyperuricemia, hyperlipidemia, fatty liver disease and severe sleep apnea. INTERVENTIONS: The patient successfully underwent laparoscopic sleeve gastrectomy plus jejunal bypass. OUTCOMES: Six months after the surgery, patient weight lost was 33.6 kg, and the LVEF increased from 31% to 55%. The cardiac function of the patient recovered from class IV to class I, and the patient's hyperuricemia, hyperlipidemia and sleep apnea were significantly improved. CONCLUSION: Bariatric surgery may be a safe and effective intervention for morbidly obese patients with LVSD. Bariatric surgery was associated with an improvement in LVEF. However, the specific mechanism still needs further study.

Nomograms for Predicting Non-remission in Patients Who Underwent Bariatric Surgery: A Multicenter Retrospective Study in China.

BACKGROUND: As a reflection of the increasing global incidence of obesity, there is a corresponding increase in the proportion of obese patients undergoing bariatric surgery. This study reviewed the factors and outcomes of patients who underwent bariatric surgical procedures and determined the relationships and developed a nomogram to calculate individualized patient risk. METHODS: The nomogram was based on a retrospective study on 259 patients who underwent bariatric surgery at the Chengdu Third People's Hospital from June 2017 to June 2019. The predictive accuracy and discriminative ability of the nomogram were determined by the ROC curve and C-index, respectively. The results were validated using bootstrap resampling and a retrospective study on 121 patients operated on from May 2015 to May 2019 at the Tenth People's Hospital of Shanghai. RESULTS: The predictors contained in the prediction nomogram included age, sex, surgical approach, hyperlipidemia, blood pressure (BP), hyperuricemia, body mass index (BMI), and waist circumference (WC). The 6-month model displayed good discrimination with a C-index of 0.765 (95% CI: 0.756 to 0.774) and good calibration. The 1-year model reached a C-index of 0.768 (95% CI, 0.759 to 0.777) in the training cohort. CONCLUSIONS: The proposed nomogram resulted in more accurate non-remission prediction for patients with obesity after bariatric surgery and may provide a reference for the preoperative choice of surgical methods.

The lncRNA RP11-142A22.4 promotes adipogenesis by sponging miR-587 to modulate Wnt5ß expression.

Emerging evidence suggests that long noncoding RNAs (lncRNAs) play essential roles in the regulation of gene expression. However, the functional contributions of lncRNAs to adipogenesis remain largely unexplored. In this study, we investigated global changes in the expression patterns of lncRNAs in visceral adipose tissue and identified RP11-142A22.4 as a significantly upregulated lncRNA. In isolated preadipocytes, knockdown of RP11-142A22.4 inhibited differentiation and reduced C/EBP-α and PPAR-γ expression. Investigations of the underlying mechanisms revealed that RP11-142A22.4 contains a functional miR-587 binding site. Mutation of the binding sites for RP11-142A22.4 in miR-587 abolished the interaction, as indicated by a luciferase reporter assay. Furthermore, RP11-142A22.4 affected the expression of miR-587 and its target gene Wnt5ß. Overexpression of miR-587 blocked the inhibitory effect of RP11-142A22.4 on preadipocyte differentiation. Moreover, the downregulation of miR-587 restored preadipocyte differentiation upon inhibition by RP11-142A22.4 silencing. Our results suggest that RP11-142A22.4 can control adipocyte differentiation via the miR-587/Wnt5ß signaling pathway and serve as a potential target for obesity treatments.

Circular RNA SAMD4A controls adipogenesis in obesity through the miR-138-5p/EZH2 axis.

A growing body of evidence has suggested that circular RNAs (circRNAs) are crucial for the regulation of gene expression and their dysregulation is implicated in several diseases. However, the function of circRNAs in obesity remains largely unexplored. Methods: Global changes in the circRNA expression patterns were detected in adipose tissues derived from obese and lean individuals. In particular, circSAMD4A was identified as significantly differentially upregulated and was functionally analyzed, both in vitro and in vivo, using various approaches. Results: CircSAMD4A overexpression was correlated with a poor prognosis in obese patients. By contrast, circSAMD4A knockdown inhibited differentiation in isolated preadipocytes. In high-fat diet (HFD) -induced obese mice, circSAMD4A knockdown reversed the associated weight gain, reduced food intake, lower body fat, and increased energy expenditure. These mice also exhibited increased insulin sensitivity and glucose tolerance. Furthermore, in vitro experiments indicated that circSAMD4A affected differentiation by binding to miR-138-5p and regulating EZH2 expression. Conclusions: CircSAMD4A regulated preadipocyte differentiation by acting as a miR-138-5p sponge, and thus increasing EZH2 expression. These results suggested that circSAMD4A can serve as a potential target for obesity treatments and/or as a potential prognostic marker for obese patients following bariatric surgery.