Th1 bias of liver mucosal-associated invariant T cells promotes hepatic gluconeogenesis in type 2 diabetes mellitus.

AIMS: It is acknowledged that aberrant liver immunity contributes to the development of type 2 diabetes mellitus (T2DM). Mucosal-associated invariant T (MAIT) cells, an innate-like T-cell subset, are enriched in the human liver. Nevertheless, the characterisation and potential role of hepatic MAIT cells in T2DM remain unclear. MATERIALS AND METHODS: Fourteen newly diagnosed T2DM subjects and 15 controls received liver biopsy. The frequency and cytokine production of MAIT cells were analysed by flow cytometry. The expression of genes involved in glucose metabolism was determined in HepG2 cells co-cultured with hepatic MAIT cells. RESULTS: Compared with controls, hepatic MAIT cell frequency was significantly increased in T2DM patients (24.66% vs. 14.61%, p = 0.001). There were more MAIT cells producing interferon-γ (IFN-γ, 60.49% vs. 33.33%, p = 0.021) and tumour necrosis factor-α (TNF-α, 46.84% vs. 5.91%, p = 0.021) in T2DM than in controls, whereas their production of interleukin 17 (IL-17) was comparable (15.25% vs. 4.55%, p = 0.054). Notably, an IFN-γ+ TNF-α+ IL-17+/- producing MAIT cell subset was focussed, which showed an elevated proportion in T2DM (42.66% vs. 5.85%, p = 0.021) and positively correlated with plasma glucose levels. A co-culture experiment further indicated that hepatic MAIT cells from T2DM upregulated the gene expression of pyruvate carboxylase, a key molecule involved in gluconeogenesis, in HepG2 cells, and this response was blocked with neutralising antibodies against IFN-γ and TNF-α. CONCLUSIONS: Our data implicate an increased Th1-like MAIT cell subset in the liver of newly diagnosed T2DM subjects, which induces hyperglycaemia by promoting hepatic gluconeogenesis. It provides novel insights into the immune regulation of metabolic homoeostasis. CLINICAL TRIAL REGISTRATION NUMBER: NCT03296605 (registered at www. CLINICALTRIALS: gov on 12 October 2018).

Dorsal approach with Glissonian approach for laparoscopic right anatomic liver resections.

BACKGROUND: Laparoscopic anatomic hepatectomy (LAH) has gradually become a routine surgical procedure. However, how to expose the whole hepatic vein and avoid the hepatic vein laceration is still a challenge because of the caudate lobe, particularly in right hepatectomy. We adopted a dorsal approach combined with Glissionian appraoch to perform laparoscopic right anatomic hepatectomy (LRAH). METHODS: Twenty patients who underwent LRAH from January 2017 to November 2018 were retrospectively analysed. Of these patients, seven patients underwent laparoscopic right hemihepatectomy (LRH group), seven patients who underwent laparoscopic right posterior hepatectomy (LRPH group), and six patients who underwent laparoscopic hepatectomy for segment 7 (LS7 group). The paracaval portion of caudate lobe could be transected firstly through dorsal approach and the corresponding major hepatic vein could be exposed from its root to the peripheral branches safely. Due to exposure along the major hepatic vein trunk, the remaining liver parenchyma could be quickly transected from dorsal to cranial side. RESULTS: The mean age of the patients was 53.8 years and the male: female ratio was 8:12. The median operation time was 306.0 ± 58.2 min and the mean estimated volume of blood loss was 412.5 ± 255.4 mL. The mean duration of postoperative hospital stay was 10.2 days. The mean Pringle maneuver time was 64.8 ± 27.7 min. Five patients received transfusion of 2-4 U of red blood cells. Two patients suffered from transient hepatic dysfunction and one suffered from pleural effusion. None of the patients underwent conversion to an open procedure. The operative duration, volume of the blood loss, Pringle maneuver time, and postoperative hospital stay duration did not differ significantly among the LRH, LRPH, and LS7 groups (P > 0.05). CONCLUSIONS: Dorsal approach combined with Glissonian approach for right lobe is feasible and effective in laparoscopic right anatomic liver resections.

Body Adiposity Index Is Predictive of Weight Loss after Roux-en-Y Gastric Bypass.

BACKGROUND/AIMS: Roux-en-Y gastric bypass (RYGB) is one of the most effective therapies for morbid obesity, yet some patients who have taken the surgery still undergo insufficient weight loss. Visceral adiposity index (VAI), lipid accumulation product (LAP), body adiposity index (BAI), and cardiometabolic index (CMI) have been regarded as clinical indicators of adiposity phenotypes that associated closely with obesity-related metabolic diseases. However, no studies have evaluated the relationship between these indexes and weight loss after bariatric surgery. In this prospective study, we aimed to evaluate whether VAI, LAP, BAI, and CMI would predict postoperative weight loss outcomes after RYGB. METHODS: This study included 38 men and 67 women who have undergone RYGB between January 2017 and May 2018 and recorded their %TWL (percent of total weight loss), %EBMIL (percent of excess body mass index loss), %EWL (percent of excess weight loss), anthropometric indices, and biochemical parameters before and 12 months after the surgery. In addition, VAI, LAP, BAI, and CMI were measured with anthropometric measures or lipid profiles using related equations and analyzed with metabolic characteristics. RESULTS: Subjects with lower BAI (<32.54 in men and 37.39 in women) displayed higher %EBMIL and %EWL 12 months after surgery. BAI was independently associated with %EWL 12 months after surgery in both men and women (both p < 0.05). The area under the receiver operating characteristic curve for BAI was significantly higher (0.773 in men and 0.818 in women) than VAI, LAP, and CMI. CONCLUSIONS: BAI serves as a reliable surrogate marker of the weight loss outcome after RYGB. The predictivity of adiposity indexes in beneficial outcomes after weight loss therapies is of important referential value for the implementation and optimization of individualized and refined weight loss treatments for obese patients.

Laennec's approach for laparoscopic anatomical hemihepatectomy.

BACKGROUND: Laennec's capsule has been found for about 200 years. However, laparoscopic anatomical right and left hemihepatectomy (LARH and LALH) using Laennec's approach are rarely reported. METHODS: We retrospectively analyzed the technical details and the surgical outcomes of 15 patients who underwent LAH via Laennec's approach between May 2017 and July 2020. The operation time, intraoperative blood loss, postoperative complications, and hospital stay were recorded and analyzed. RESULTS: Four of 15 patients were diagnosed with hepatic hemangioma, 2 had hepatolithiasis, and 9 patients had primary liver cancer. During the surgery, Laennec's approach was used for LAH without conversion to open surgery. Four patients were treated with LARH, and 11 patients were cured with LALH. The mean age of the patients was 62.1 ± 6.5 years, and four were male. The mean operative time, blood loss, and length of the postoperative hospital stay were 193 ± 49 min, 247 ± 120 mL, and 8.7 ± 2.0 days, respectively. There was no incidence of postoperative bile leakage and bleeding. No mortality occurred. We also demonstrated that Laennec's capsule does exist around the peripheral hepatic veins with histological confirmation. CONCLUSIONS: Laennec's approach is safe and feasible for LAH. Precise isolation of Laennec's approach based on Laennec's capsule helps to standardize the surgical techniques for laparoscopic anatomical hepatectomy.

Laparoscopic hepatectomy is superior to open procedures for hepatic hemangioma.

BACKGROUND: Laparoscopic hepatectomy (LH) has become increasingly popular for liver neoplasms, but its safety and effectiveness remain controversial. Hepatic hemangiomas are the most common benign liver neoplasm; the main approaches to hepatic hemangiomas include open hepatectomy (OH) and LH. In this study, we compared early outcomes between patients undergoing OH and those with LH. METHODS: Patients underwent OH or LH in our hospital for hepatic hemangiomas between December 2013 and December 2017 were enrolled. All patients underwent comprehensive preoperative evaluations. The clinicopathological index and risk factors of hemangioma resection were assessed. RESULTS: In total, 41 patients underwent OH while 53 underwent LH. There was no significant difference in any preoperative clinical variables, including liver function, prothrombin time, or platelet count. Hepatic portal occlusion time and operative time were 39.74 vs. 38.35 minutes (P = 0.717) and 197.20 vs. 203.68 minutes (P = 0.652) in the OH and LH groups, respectively. No mortality nor significant perioperative complications were observed between the two groups. In LH group, two cases were converted to OH, one for an oversized tumor and the other for hemorrhage. Compared with OH patients, those with LH had less blood loss (361.69 vs. 437.81 mL, P = 0.024), shorter postoperative hospital stay (7.98 vs. 11.07 days, P = 0.001), and lower postoperative C-reactive protein (43.63 vs. 58.21 mg/L, P = 0.026). CONCLUSIONS: LH is superior to OH in terms of postoperative recovery and blood loss for selected patients with hepatic hemangioma.

Correction to: A newly noninvasive model for prediction of non-alcoholic fatty liver disease: utility of serum prolactin levels.

Following publication of the original article [1], we have been notified that the given name of one of the authors was spelled incorrectly.

Metabolic effects and safety of Roux-en-Y gastric bypass surgery vs. conventional medication in obese Chinese patients with type 2 diabetes.

AIM: To assess metabolic effects and safety of Roux-en-Y gastric bypass (RYGB) versus conventional medication (CM) in obese Chinese patients with type 2 diabetes (T2DM). METHODS: This retrospective cohort study included 40 patients who underwent RYGB (mean age 44.1 years, body mass index [BMI] 33.3 kg/m2 ) and 36 patients administered CM (mean age 49.4 years, BMI 32.1 kg/m2 ). The primary endpoint was achievement of the triple endpoint (haemoglobin A1C [HbA1c] < 7.0%, low-density lipoprotein cholesterol < 2.6 mmol/L, and systolic blood pressure < 130 mmHg). Changes in weight, BMI, medication usage, complications, and adverse events were assessed. RESULTS: After 1-year follow-up, 35% of RYGB patients and 8% of CM patients achieved the triple endpoint (P = 0.005). More patients in the RYGB group achieved complete (48% vs 3%, P < 0.001) and partial (23% vs 0%, P = 0.007) remission of diabetes, and complete remission of hypertension (58% vs 24%, P = 0.019). Patients in the RYGB group had greater weight loss and decrease in BMI, waist circumference, fasting and postprandial of blood glucose and insulin levels, HbA1c, blood pressure, triglycerides, and increased high-density cholesterol (P < 0.001- < 0.05). A lower proportion of the RYGB group received antidiabetics, antihypertensives, or antilipemic treatments, and had non-alcoholic fatty liver disease (NAFLD) than the CM group during follow-up. More patients had nutrient deficiency-related diseases in the RYGB group over 1-year follow-up. CONCLUSIONS: For obese Chinese patients with T2DM, RYGB resulted in better metabolic control, greater weight loss, and lower medication usage and NAFLD, but more frequently resulted in diseases related to nutrient deficiency.

Laennec's approach for laparoscopic anatomic hepatectomy based on Laennec's capsule.

BACKGROUND: Although isolating Glissonean pedicles and hepatic veins are critical procedures during anatomical hepatectomy, there is no standardized approach. We propose the novel Laennec's approach for laparoscopic anatomic hepatectomy (LAH) based on Laennec's capsule, which serves as the anatomic landmark for LAH. The aim of this study was to elucidate that the natural gap between Laennec's capsule and the adjacent tissues contributes to standardization of the surgical technique for LAH. METHODS: Eighty-four cases were enrolled in this observable clinical trial. They underwent LAH for liver diseases. Laennec's approach was proposed for LAH based on Laennec's capsule. The liver tissues close to Glissonean pedicle, hepatic veins, naked area, and inferior vena cava were collected for hematoxylin and eosin, resorcinol-fuchsin staining, and immunohistochemistry. RESULTS: The staining revealed capsule packaging of the whole liver independent of the adjacent tissues and intrahepatic vessels. A natural gap was found between Laennec's capsule and the adjacent tissues at different sites. Laennec's capsule served as the landmark for isolating Glissonean pedicle and hepatic veins, mobilizing the liver, and performing Hanging maneuver. Eighty-four cases underwent LAH for liver diseases using this strategy. The operation time was 277.23 min. The mean of hospital days was 9.8. CONCLUSIONS: Laennec's approach based on Laennec's capsule contributes to standardization of the surgical technique for LAH, and brings innovations that facilitates safe and effective liver resection under laparoscopy.

A newly noninvasive model for prediction of non-alcoholic fatty liver disease: utility of serum prolactin levels.

BACKGROUNDS: To investigate the value of prolactin (PRL) in diagnosing non-alcoholic fatty liver disease (NAFLD). METHODS: Metabolic parameters and serum PRL levels were measured in 452 males and 421 females, who were randomized to the estimation or the validation group as a 1:1 ratio. Hepatic steatosis was diagnosed via abdominal ultrasound. Variables that significantly associated with NAFLD in univariate analysis were included in multiple logistic regression. We used the receiver operator characteristic (ROC) curves to test the model performance. Besides, 147 patients underwent metabolic and liver biopsy were analyzed to validate the diagnostic value of this model. RESULTS: Body mass index, alanine aminotransferase, prolactin, high density lipoprotein cholesterol and HbA1c were included into models. In males, the area under ROC curve (AUC) was 0.86 (95%CI: 0.82-0.91) for the validation group. With two cut-off points (- 0.79 and 1.71), the sensitivity and specificity for predicting NALFD was 95.2 and 91.1% in the validation group, respectively. In females, the AUC was 0.82 (95%CI: 0.76-0.88) for the validation group. With two cut-off points (- 0.68 and 2.16), the sensitivity and specificity for predicting NALFD was 97.1 and 91.4% in the validation group, respectively. In subjects with liver pathology, the AUC was higher than that of fatty liver index. A positive correlation between the scores of the model and the severities of NAFLD was observed. Importantly, we demonstrated a potential value of this model in predicting nonalcoholic steatohepatitis. CONCLUSION: We established a mathematic model that can conveniently and effectively diagnose the existence and severities of NAFLD.

Geranylgeranyl diphosphate synthase (GGPPS) regulates non-alcoholic fatty liver disease (NAFLD)-fibrosis progression by determining hepatic glucose/fatty acid preference under high-fat diet conditions.

Patients with obesity have a high prevalence of non-alcoholic fatty liver disease (NAFLD) and, in parallel, increased susceptibility to fibrosis/cirrhosis/hepatocellular carcinoma (HCC). Herein, we report that a high-fat diet (HFD) can augment glycolysis and then accelerate NAFLD-fibrosis progression by downregulating the expression of geranylgeranyl diphosphate synthase (GGPPS), which is a critical enzyme in the mevalonate pathway. Long-term HFD overloading decreases GGPPS expression in mice, which shifts the fuel preference from fatty acids towards glucose. Liver-specific Ggpps deficiency drives the Warburg effect by impairing mitochondrial function, and then induces hepatic inflammation, thus exacerbating fibrosis. Ggpps deficiency also enhances the hyperfarnesylation of liver kinase B1, and promotes metabolic reprogramming by regulating 5'-AMP-activated protein kinase activity. Clinical data further imply that GGPPS expression can predict the stage of NAFLD and recurrence of NAFLD-associated HCC. We conclude that the level of GGPPS is a susceptibility factor for NAFLD-fibrosis progression, and requires more stringent surveillance to ensure early prediction and precision of treatment of NAFLD-related HCC. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Prolactin improves hepatic steatosis via CD36 pathway.

BACKGROUND & AIMS: Prolactin (PRL) is a multifunctional polypeptide with effects on metabolism, however, little is known about its effect on hepatic steatosis and lipid metabolism. Herein, we aimed to assess the role of PRL in the development of non-alcoholic fatty liver disease (NAFLD). METHODS: The serum PRL levels of 456 patients with NAFLD, 403 controls without NAFLD diagnosed by ultrasound, and 85 individuals with liver histology obtained during metabolic surgery (44 female and 30 male patients with NAFLD and 11 age-matched non-NAFLD female individuals) were evaluated. The expression of the gene encoding the prolactin receptor (PRLR) and signalling molecules involved in hepatic lipid metabolism were evaluated in human liver and HepG2 cells. The effects of overexpression of PRLR or fatty acid translocase (FAT)/CD36 or knockdown of PRLR on hepatic lipid metabolism were tested in free fatty acid (FFA)-treated HepG2 cells. RESULTS: Circulating PRL levels were lower in individuals with ultrasound-diagnosed NAFLD (men: 7.9 [range, 5.9-10.3] µg/L; women: 8.7 [range, 6.1-12.4] µg/L) than those with non-NAFLD (men: 9.1 [range, 6.8-13.0] µg/L, p = 0.002; women: 11.6 [range, 8.2-16.1] µg/L, p <0.001). PRL levels in patients with biopsy-proven severe hepatic steatosis were lower compared with those with mild-to-moderate hepatic steatosis in both men (8.3 [range, 5.4-9.5] µg/L vs. 9.7 [range, 7.1-12.3] µg/L, p = 0.031) and women (8.5 [range, 4.2-10.6] µg/L vs. 9.8 [range, 8.2-15.7] µg/L, p = 0.027). Furthermore, hepatic PRLR gene expression was significantly reduced in patients with NAFLD and negatively correlated with CD36 gene expression. In FFA-induced HepG2 cells, PRL treatment or PRLR overexpression significantly reduced the expression of CD36 and lipid content, effects that were abrogated after silencing of PRLR. Furthermore, overexpression of CD36 significantly reduced the PRL-mediated improvement in lipid content. CONCLUSIONS: Our results reveal a novel association between the central nervous system and the liver, whereby PRL/PRLR improved hepatic lipid accumulation via the CD36 pathway. LAY SUMMARY: Our clinical study suggests a negative association between prolactin (PRL)/prolactin receptor (PRLR) and the presence of non-alcoholic fatty liver disease (NAFLD). Using cell experiments, we found that PRL ameliorates hepatic steatosis via the hepatic PRLR and fatty acid translocase (FAT)/CD36, a key transporter of free fatty acid uptake in liver. Our findings suggest a novel approach to improving NAFLD using PRL and PRLR. Clinical trial number: NCT03296605.

Hepatic expression of Yin Yang 1 (YY1) is associated with the non-alcoholic fatty liver disease (NAFLD) progression in patients undergoing bariatric surgery.

BACKGROUND: This study is to investigate the association between the hepatic expression of Yin Yang 1 (YY1) and the progression of non-alcoholic fatty liver disease (NAFLD) in patients undergoing bariatric surgery. METHODS: Obese patients undergoing bariatric surgery were included. Liver tissues were subjected to the quantitative real-time PCR, Western blot analysis, and immunohistochemical assay, to determine the expression levels of YY1. RESULTS: Totally 88 patients were included. According to the NAFLD activity score (NAS), these patients were divided into the control (n = 12), steatosis (n = 20), non-defining NASH (n = 38), and NASH (n = 18) groups. Significant differences in the serum glucose, insulin, ALT, AST, and HOMA-IR levels were observed among these different NAFLD groups. Hepatic YY1 expression had correlation with serum glucose, insulin, HOMA-IR, ALT, AST, triglycerides, HDL, and GGT. Immunohistochemical analysis showed that, compared with the control group, the expression levels of YY1 were significantly higher in the non-defining NASH and NASH groups. In addition, multivariate regression model showed that the serum ALT and YY1 levels were strongly associated with the NAFLD activity. CONCLUSIONS: Several factors are associated with NAFLD progression, including the expression of YY1. Our findings contribute to understanding of the pathogenesis of NAFLD. TRIAL REGISTRATION: NCT03296605 , registered on September 28, 2017.

Glissonian approach combined with major hepatic vein first for laparoscopic anatomic hepatectomy.

BACKGROUND: Laparoscopic anatomic hepatectomy remains challenging because of the complex interior structures of the liver. Our novel strategy includes the Glissonian approach and the major hepatic vein first, which serves to define the external and internal landmarks for laparoscopic anatomic hepatectomy. METHODS: Eleven cases underwent laparoscopic anatomic hepatectomy, including three right hepatectomies, three left hepatectomies, three right posterior hepatectomies, and two mesohepatectomies. The Glissonian approach was used to transect the hepatic pedicles as external demarcation. The major hepatic vein near the hepatic portal was exposed and served as the internal landmark for parenchymal transection. The liver parenchyma below and above the major hepatic vein was transected along the major hepatic vein. Fifty-nine subjects were used to compare the distance between the major hepatic vein and secondary Glisson pedicles among different liver diseases. RESULTS: The average operative time was 327 min with an estimated blood loss of 554.55 mL. Only two patients received three units of packed red blood cells. The others recovered normally and were discharged on postoperative day 7. The distance between right posterior Glissonian pedicle and right hepatic vein was shorter in the patients with cirrhosis than that without cirrhosis, and this distance was even shorter in patients with hepatocellular carcinoma. CONCLUSION: The Glissonian approach with the major hepatic vein first is easy and feasible for laparoscopic anatomic hepatectomy, especially in patients with hepatocellular carcinoma and cirrhosis.

[Development of Magnetic Anastomosis Device for Colostomy].

Introduction of a new magnetic anastomosis device for colostomy including its design and operaging principal. The anastomosis device is composed of magnetic base and anastomosis ring. It is convenient for colon and abdominal subcutaneous tissue going together through the magnetic attraction. The colostomy completes with magnetic compression anastomosis. The device has the advantage of making operation easer, reducing the operation steps and can better solve the colostomy ischemic necrosis, colostomy retraction, colostomy joint complications of skin mucous membrane and the skin diease around the colostomy. Patients can real y benefit from this device.

Bile duct stone formation around a Prolene suture after cholangioenterostomy.

The iatrogenic cause of bile duct stone formation is mainly due to suture materials, especially silk sutures. In recent years, Prolene and Vicryl sutures have been widely used in biliary surgery, and bile duct stone formation related to sutures are seemingly becoming rare, as there has only been one report of bile duct stone formation caused by Prolene sutures in the literature. In the last few years we have had two cases of Prolene suture-related bile duct stone formation within our unit. We therefore suggest that Vicryl sutures should be used as the first choice in biliary surgery, in order to prevent the formation of iatrogenic bile duct stones.

Repair of extrahepatic bile duct defect using a collagen patch in a Swine model.

Extrahepatic bile duct (EBD) injury can happen during surgery. To repair a defect of the EBD and prevent postoperative biliary complications, a collagen membrane was designed. The collagen material was porous, biocompatible, and degradable and could maintain its shape in bile soaking for about 4 weeks. The goal was to induce rapid bile duct tissue regeneration. Twenty Chinese experimental hybrid pigs were used in this study and divided into a patch group and a control group. A spindle-shaped defect (20 mm × 6 mm) was made in the anterior wall of the lower EBD in the swine model, and then the defect was reconstructed using a collagen patch with a drainage tube and wrapped with greater omentum. Ultrasound was performed at 2, 4, 8, and 12 weeks postoperatively. Liver function tests and white blood cell count (WBC) were measured. Hematoxylin-eosin staining, cytokeratin 7 immunohistochemical staining, and Van Gieson's staining of EBD were used. The diameter and thickness of the EBD at the graft site were measured. There was no significant difference in liver function tests or WBC in the patch group compared with the control group. No evidence of leakage or stricture was observed, but some pigs developed biliary sludge or stone at 4 and 8 weeks. The drainage tube was lost within 12 weeks. The neo-EBD could withstand normal biliary pressure 2 weeks after surgery. Histological study showed the accessory glands and epithelial cells gradually regenerated at graft sites from 4 weeks, with increasing vessel infiltration and decreasing inflammation. The collagen fibers became regular with full coverage of epithelial cells. The statistical analysis of diameter and thickness showed no stricture formation at the graft site, but the EBD wall was slightly thicker than in the normal bile duct due to collagen fiber deposition. The structure of the neo-EBD was similar to that of the normal EBD. The collagen membrane patch associated with a drainage tube and wrapped with greater omentum effectively induced the regeneration of the EBD defect within 12 weeks.

Machine learning analysis of lab tests to predict bariatric readmissions.

The purpose of this study was to develop a machine learning model for predicting 30-day readmission after bariatric surgery based on laboratory tests. Data were collected from patients who underwent bariatric surgery between 2018 and 2023. Laboratory test indicators from the preoperative stage, one day postoperatively, and three days postoperatively were analyzed. Least absolute shrinkage and selection operator regression was used to select the most relevant features. Models constructed included support vector machine (SVM), generalized linear model, multi-layer perceptron, random forest, and extreme gradient boosting. Model performance was evaluated and compared using the area under the receiver operating characteristic curve (AUROC). A total of 1262 patients were included, of which 7.69% of cases were readmitted. The SVM model achieved the highest AUROC (0.784; 95% CI 0.696-0.872), outperforming other models. This suggests that machine learning models based on laboratory test data can effectively identify patients at high risk of readmission after bariatric surgery.

Genetically predicted metabolites mediate the causal associations between autoimmune thyroiditis and immune cells.

Introduction: We aimed to comprehensively investigate the causal relationship between 731 immune cell traits and autoimmune thyroiditis (AIT) and to identify and quantify the role of 1400 metabolic traits as potential mediators in between. Methods: Using summary-level data from genome-wide association studies (GWAS) we performed a two-sample bidirectional Mendelian randomization (MR) analysis of genetically predicted AIT and 731 immune cell traits. Furthermore, we used a two-step MR analysis to quantify the proportion of the total effects (that the immune cells exerted on the risk of AIT) mediated by potential metabolites. Results: We identified 24 immune cell traits (with odds ratio (OR) ranging from 1.3166 6 to 0.6323) and 10 metabolic traits (with OR ranging from 1.7954 to 0.6158) to be causally associated with AIT, respectively. Five immune cell traits (including CD38 on IgD+ CD24-, CD28 on CD28+ CD45RA+ CD8br, HLA DR+ CD4+ AC, TD CD4+ %CD4+, and CD8 on EM CD8br) were found to be associated with the risk of AIT, which were partially mediated by metabolites (including glycolithocholate sulfate, 5alpha-androstan-3alpha,17beta-diol disulfate, arachidonoylcholine, X-15486, and kynurenine). The proportion of genetically predicted AIT mediated by the identified metabolites could range from 5.58% to 17.7%. Discussion: Our study identified causal associations between AIT and immune cells which were partially mediated by metabolites, thus providing guidance for future clinical and basic research.

Metabolic surgery results in greater metabolic benefits in patients who achieve healthy weight.

BACKGROUND: A percentage of total weight loss (%TWL) >20% as the expected weight loss target after metabolic surgery might be insufficient to produce adequate metabolic benefits. OBJECTIVES: This study identified the optimal weight loss target to achieve substantial benefits from metabolic surgery. SETTING: University-affiliated tertiary care center. METHODS: In this retrospective study, participants were categorized into healthy weight (18.5 kg/m2 ≤ body mass index [BMI] < 24 kg/m2), overweight (24 kg/m2 ≤ BMI < 28 kg/m2), and obesity groups (BMI ≥28 kg/m2) according to their BMI 1 year after metabolic surgery. The weight loss and remission of obesity-related comorbidities were evaluated. Ordinal logistic regression analysis was used to identify predictors for achieving healthy weight 1 year postoperatively. RESULTS: Overall, 125 patients (112 sleeve gastrectomies, 13 Roux-en-Y gastric bypasses) were recruited in this study. Forty-two participants achieved healthy weight, 38 were overweight, and 45 had obesity. Type 2 diabetes mellitus and obstructive sleep apnea were relieved in all groups. Individuals who achieved healthy weight showed more improvements in nonalcoholic fatty liver disease, hypertension, and hyperuricemia than those who did not. Preoperative BMI was an independent predictor for the BMI achieved postoperatively, and the optimal cut-off point for achieving healthy weight was 34.9 kg/m2. CONCLUSIONS: Healthy weight was a more stringent target for patients who underwent metabolic surgery than the %TWL. Populations with a preoperative BMI of <34.9 kg/m2 were prone to realize the goal. Additional weight loss interventions could be considered for those with higher preoperative BMIs and enforced within 1 year postoperatively.