AGR2: The Covert Driver and New Dawn of Hepatobiliary and Pancreatic Cancer Treatment.

The anterior gradient protein 2 (AGR2) plays a crucial role in facilitating the formation of protein disulfide bonds within the endoplasmic reticulum (ER). Research suggests that AGR2 can function as an oncogene, with its heightened expression linked to the advancement of hepatobiliary and pancreatic cancers through invasion and metastasis. Notably, AGR2 not only serves as a pro-oncogenic agent but also as a downstream targeting protein, indirectly fostering cancer progression. This comprehensive review delves into the established functions and expression patterns of AGR2, emphasizing its pivotal role in cancer progression, particularly in hepatobiliary and pancreatic malignancies. Furthermore, AGR2 emerges as a potential cancer prognostic marker and a promising target for immunotherapy, offering novel avenues for the treatment of hepatobiliary and pancreatic cancers and enhancing patient outcomes.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Posterior capsular radial sign: a novel method to confirm anterior vitreous cortex resection in phacovitrectomy.

BACKGROUND: The main purpose of this paper is to introduce a method that can accurately locate the posterior capsule of the lens to facilitate a relatively complete resection of the anterior vitreous body. METHODS: A total of 51 patients in the experimental group and control group were enrolled in this study. Phacoemulsification combined with vitrectomy was performed in all cases. After the cataract procedure was completed in the control group, the surgeon performed a conventional anterior vitrectomy with the operative eye. In the experimental group, anterior vitrectomy was performed according to the threadiness corrugation of the posterior capsule of the lens. During the operation, with the help of triamcinolone, two surgeons confirmed the resection of the anterior vitreous cortex; the best corrected visual acuity and intraocular pressure of all patients were recorded at 1 week, 1 month and 3 months after surgery. RESULTS: Fifty patients underwent phacoemulsification combined with vitrectomy, except one patient in the experimental group who was lost to follow-up. After surgery, no significant complications were observed in all patients except two patients in the control group with temporary increases in intraocular pressure. There was no significant difference in preoperative visual acuity between the two groups (t = 0.83, P = 0.25). Both groups had varying degrees of improvement in best corrected visual acuity at 1 week, 1 month and 3 months after surgery. Moreover, there was no significant difference in BCVA between the two groups at the three follow-up time points (t=-1.15, -1.65, -1.09, P = 0.53, 0.21, 0.23). After surgery, no significant complications were observed in all patients except two patients in the control group with temporary increases in intraocular pressure. Incomplete resection of the anterior vitreous cortex was observed in 2 patients in each group, but there was no significant difference (χ2 = 7.81, P > 0.05). CONCLUSION: In the process of cataract surgery combined with vitrectomy, thready corrugation appears in the posterior capsule of the lens and is an important sign of its localization. Anterior vitrectomy can be accomplished safely and effectively with the help of thread-like corrugation, and the surgical effect is almost the same as that of traditional surgery. Especially suitable for beginners in vitreous surgery.

Bariatric Surgery and Its Metabolic Echo Effect on Serum Uric Acid Levels.

Bariatric surgery (BS) has been a significant means of reducing weight in obese individuals. The metabolic changes after bariatric surgery are crucial as they extend its advantages beyond weight loss. As its name implies, "metabolic surgery" also addresses obesity-related metabolic concerns. Bariatric surgery has always been associated with lessened serum uric acid (SUA) levels. In this review, we examined current studies to understand how surgical therapies impact serum uric acid levels. Strongly minded on the extent and timing of changes in the level of serum uric acid after bariatric surgeries. We conducted a comprehensive search for relevant current studies in PubMed, Google Scholar, JAMA, and the Cochrane Library until February 1, 2024. We aimed to analyze the metabolic advantages of bariatric surgery, focusing on its function in treating hyperuricemia and lowering the risk of associated disorders. Our review elaborates on factors contributing to decreased serum uric acid levels after bariatric surgery, such as alterations in renal function, insulin sensitivity, and inflammatory markers.

Correlation Between Impaired Sensitivity to Thyroid Hormones and Serum Uric Acid in Female Patients With Obesity and After Laparoscopic Sleeve Gastrectomy.

OBJECTIVE: An alterable risk factor for hyperuricemia is obesity. Additionally, obese people may have a moderate form of acquired resistance to thyroid hormones. Thyrotropin, thyroid hormones, and obesity all interact subtly. However, the connection between thyroid hormone sensitivity and hyperuricemia in obese patients both before and after laparoscopic sleeve gastrectomy (LSG) has not yet been clarified. The objective of our study was to investigate the connection between impaired thyroid hormone sensitivity and elevated uric acid (UA) levels before and after LSG. METHODS: In total, 1054 euthyroid patients with obesity (481 males, 573 females), 248 (143 female patients) of whom underwent subsequent LSG, were enrolled in this retrospective study. Anthropometric measurements and thyroid hormone and UA levels were taken before and 3 months after LSG. RESULTS: Female patients with obesity with impaired sensitivity to thyroid hormones had higher UA levels (P for trend <.01). The odds ratio of the fourth vs first quartile of thyroid feedback quantile index, thyrotropin index, and thyrotropin-thyroxine resistance index were 4.285 (confidence interval: 1.360-13.507), 3.700 (confidence interval: 1.276-10.729), and 2.839 (confidence interval: 1.014-7.948), respectively, with robust relationships with female hyperuricemia (all P < .05). However, there was only a positive correlation between the decline in UA levels and thyroid feedback quantile index, thyrotropin, and thyrotropin-thyroxine resistance index in female patients following LSG. CONCLUSION: Female hyperuricemia is correlated with higher thyroid hormone resistance index scores. Resistance to thyroid hormones was greatly improved by LSG. The decrease in UA levels after surgery is correlated with the improvement of thyroid hormone resistance after LSG.

Sex-dependent impact of obesity on aggressiveness of papillary thyroid cancer.

PURPOSE: To investigate the impact of body mass index (BMI) on the aggressiveness of papillary thyroid cancer (PTC). METHODS: A total of 1720 PTC patients with total thyroidectomy or lobectomy, from January 2017 to April 2020, were retrospectively evaluated. Based on BMI, they were divided into two groups, as follows: control (CON, < 24 kg/m2) and overweight and obesity (OB, ≥ 24 kg/m2), each sex being analyzed separately. RESULTS: In the whole cohort, the OB group had significantly higher rates of extrathyroidal extension (21.5 vs. 16.8%, p = 0.013), multifocality (43.2 vs. 37.7%, p = 0.018), and BRAF-V600E mutation (82.9 vs. 79.3%, p = 0.015) than the CON group. In males, the OB group had increased rates of tumor size over 1cm (54.4 vs. 42.7%, p = 0.008), extrathyroidal extension (24.9 vs. 12.4%, p = 0.001), and multifocality (42.7 vs. 33.5%, p = 0.038). The OB group had significantly higher adjusted odds ratios (ORs) of 1.63 (1.14-2.33, p = 0.008), 2.12 (1.26-3.57, p = 0.005), and 1.56 (1.07-2.29, p = 0.022) for tumor size over 1cm, extrathyroidal extension, and multifocality compared with CON. Additionally, overweight and obesity were analyzed alone and the rates of extrathyroidal extension (30/100, 30.0%, p = 0.001) and tumor size over 1cm (65/100, 65.0%, p = 0.001) were significantly higher in the obesity group than in the overweight and CON groups. The obesity group had robust higher adjusted ORs of 2.51(1.50-4.20, p < 0.001), 2.93 (1.50-5.73, p = 0.002) and 1.89 (1.11-3.22, p = 0.020) for tumor size over 1cm, extrathyroidal extension, and multifocality compared with CON. CONCLUSIONS: Overweight and obesity were predominant independent risk factors for PTC aggressiveness in males. These data indicated that the therapeutic treatment should be based on risk stratification by BMI in males.

The relationship between serum superoxide dismutase and thyroid function in obese patients after Laparoscopic sleeve gastrectomy.

To investigate the cross-sectional and longitudinal correlation between serum superoxide dismutase (SOD) levels and thyroid function with obesity before and after laparoscopic sleeve gastrectomy (LSG). Patients with morbid obesity (n = 219, 112 males and 107 females) who underwent LSG were selected and they were subdivided into normal levels of SOD (NSOD, n = 112) and high levels of SOD (HSOD, n = 107) according to the median value of SOD levels (183 U/mL). SOD and thyroid hormones were measured and compared at baseline, 3, 6, and 12 months after LSG. The HSOD group had lower body mass index (BMI), total thyroxine (TT4), and thyroid-stimulating hormone (TSH) than the NSOD group (p < 0.001, p = 0.031, p < 0.001, respectively). However, they had higher free triiodothyronine (FT3) and free thyroxine (FT4) (p = 0.019 and p = 0.017, respectively). SOD was significantly negatively associated with TSH and positively associated with FT4. Of all the patients, 22.31% (NSOD: 66.67%; HSOD: 33.33%) had subclinical hypothyroidism (SH), and there were lower SOD levels in the SH group. Preoperative SOD was a protective factor for SH. After LSG, SOD and FT4 levels were increased at 12 months after LSG, however, TSH, FT3, total triiodothyronine (TT3) and TT4 levels decreased compared to the preoperative levels at 3, 6, and 12 months in the SH group. Postoperative changes in FT4 and TT4 levels correlated with changes in SOD levels. SOD, which is correlated with thyroid hormones, protects against SH in patients with obesity. The improvement in thyroid function with SH after LSG may be related to increased SOD levels.

Derlin-1 ameliorates nonalcoholic hepatic steatosis by promoting ubiquitylation and degradation of FABP1.

BACKGROUND AND AIMS: The functions of liver fatty acid binding protein 1 (FABP1) in the regulation of nonalcoholic fatty liver disease (NAFLD) have been previously established. However, how FABP1 expression is dynamically regulated in metabolic disorders is unclear. Previous studies have reported that ubiquitin proteasome-mediated degradation of FABP1 is involved, but the mechanism remains unknown. METHODS: Dysregulated expression of hepatic FABP1 and Derlin-1 was observed in NAFLD patients. We performed mice hepatic tissue coimmunoprecipitation based mass spectrum assays. Interaction between Derlin-1 and FABP1, and its impact on FABP1 ubiquitination status was evaluated by coimmunoprecipitation. The role of Derlin-1 in lipid deposition was tested using adenovirus-mediated overexpression in C57BL/6 mice, as well as by Derlin-1 overexpression or knockdown in HepG2 cells. RESULTS: As a subunit of the endoplasmic reticulum-associated degradation complex, Derlin-1 was negatively associated with NAFLD patients, interacted with and ubiquitinated FABP1. Derlin-1 suppressed FABP1 levels and inhibited lipid deposition through a FABP1-dependent pathway. Additionally, Trim25, an E3 ubiquitin ligase present in the endoplasmic reticulum, was recruited to promote Derlin-1-related polyubiquitylation of FABP1, thereby creating a ubiquitin-associated network for FABP1 regulation. Derlin-1 overexpression ameliorated hepatic steatosis in both C57BL/6 mice and HepG2 cells, and contributed to attenuated weight gain, lower liver weight, and visceral fat mass. CONCLUSIONS: FABP1 was degraded by Derlin-1 through ubiquitin modification. Negative regulation of FABP1 by Derlin-1 overexpression, suppressed lipid metabolism and alleviated lipid deposition in vivo and in vitro. Hence, Derlin-1 activation in hepatocytes may represent a potential therapeutic strategy for NAFLD.

Weight loss and metabolic benefits of bariatric surgery in China: A multicenter study.

BACKGROUND: This retrospective multicenter study evaluated the efficacy and safety of bariatric surgery in Chinese patients with obesity. METHODS: Patients with obesity who underwent laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass and completed a 12-month follow-up between February 2011 and November 2019 were enrolled. Weight loss, glycemic and metabolic control, insulin resistance, cardiovascular risk, and surgery-related complications at 12 months were analyzed. RESULTS: We enrolled 356 patients aged 34.3 ± 0.6 years with a mean body mass index of 39.4 ± 0.4 kg/m2 . Successful weight loss occurred in 54.6%, 86.8%, and 92.7% of patients at 3, 6, and 12 months, respectively, with no difference in percent excess weight loss between the laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass surgery groups. The average percentage of total weight loss was 29.5% ± 0.6% at 12 months; 99.4%, 86.8%, and 43.5% of patients achieved at least 10%, 20%, and 30% weight loss, respectively, at 12 months. Significant improvements in metabolic indices, insulin resistance, and inflammation biomarkers were observed at 12 months. CONCLUSIONS: Bariatric surgery resulted in successful weight loss and improved metabolic control, insulin resistance, and cardiovascular risk in Chinese patients with obesity. Both laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass are suitable approaches for such patients.

Predictive Factors of Menstrual Recovery After Laparoscopic Sleeve Gastrectomy in Polycystic Ovary Syndrome Women with Obesity.

Objective: To explore the predictors of menstrual recovery in polycystic ovary syndrome (PCOS) women with obesity following laparoscopic sleeve gastrectomy (LSG). Methods: A total of 88 PCOS patients with obesity and 76 control patients with obesity aged 18-45 years were enrolled between May 2013 and December 2020. PCOS was diagnosed using the Rotterdam diagnostic criteria (2003). Anthropometric measurements, biochemical parameters, sex hormones, and circulating fibrinogen-like protein 1 (FGL-1) levels were collected before and six-month after LSG. The data on postoperative menstrual status, body weight, and fertility were obtained through telephone follow-ups for all individuals with PCOS. Results: Patients with PCOS were followed up for at least six months after surgery, and the mean follow-up time was 3.23 years. At 6 months after LSG, circulating total testosterone (TT), calculated free testosterone (cFT), and FGL-1 levels declined significantly. The mean percent excess weight loss (%EWL) and percent total weight loss (%TWL) in PCOS patients at the final follow-up was 97.52% ± 33.90% and 31.65% ± 10.31%, respectively. The proportion of regular menstruation in PCOS patients significantly increased within six months (75.86% vs 0.03% at baseline). In the logistic regression analysis, time from PCOS diagnosis (P=0.007), body mass index (BMI) (P=0.007), TT (P=0.038) at baseline were demonstrated to be independent predictive factors for the regular menstruation in women with PCOS and obesity within 6 months after LSG. Conclusion: In PCOS patients with obesity, time from PCOS diagnosis, BMI, and TT levels at baseline were independently and negatively associated with menstrual recovery within 6 months after LSG, which could be applied in preoperative evaluation.

Symptom clusters after chemoradiotherapy in discharged nasopharyngeal carcinoma patients.

Objective: To investigate the incidence of complications and types of chemoradiotherepy induces symptom clusters in patients with nasopharyngeal carcinoma (NPC) who were first diagnosed after treatment and discharged from hospital. Methods: After their discharge home, 130 NPC patients who had been treated with chemoradiotherapy were asked to complete a modified Chinese version of the Quality of Life Questionnaire-Head and Neck Module developed by the European Organization for the Research and Treatment of Cancer in the Head and Neck. Symptom clusters in patients were identified through exploratory factor analysis. Results: The most serious symptoms for discharged NPC patients who had received chemoradiotherapy were dental problems, a sense of obstruction while swallowing, embarrassment in physical contact with family members and friends, difficulty in speaking with others, and embarrassment in public. The six symptom clusters identified through exploratory factor analysis were (1) painful eating, (2) social difficulties, (3) psychological disorders, (4) symptomatic shame, (5) teeth/throat injuries, and (6) sensory abnormalities. The total contribution rate of variance was 65.73%. Conclusion: NPC patients who are treated with chemoradiotherapy can experience adverse symptom clusters that continue after discharge. Nurses should evaluate the patients' symptoms before discharge and provide targeted health education services which would reduce the patients' complications and improve the quality of life at home. Besides, medical staff should evaluate the complications in a timely and comprehensive manner and provide individualized health education for the affected patients to help them manage chemoradiotherapy side effects.

Effects of a Dulaglutide plus Calorie-Restricted Diet versus a Calorie-Restricted Diet on Visceral Fat and Metabolic Profiles in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial.

The effects of dulaglutide and a calorie-restricted diet (CRD) on visceral adipose tissue (VAT) and metabolic profiles in polycystic ovary syndrome (PCOS) have not been extensively investigated. In this study, we investigated whether dulaglutide combined with CRD could further reduce VAT and promote clinical benefits as compared with a CRD regimen alone in overweight or obese PCOS-affected women. Between May 2021 and May 2022, this single-center, randomized, controlled, open-label clinical trial was conducted. Overall, 243 participants with PCOS were screened, of which 68 overweight or obese individuals were randomly randomized to undergo dulaglutide combined with CRD treatment (n = 35) or CRD treatment alone (n = 33). The duration of intervention was set as the time taken to achieve a 7% weight loss goal from baseline body weight, which was restricted to 6 months. The primary endpoint was the difference in the change in VAT area reduction between the groups. The secondary endpoints contained changes in menstrual frequency, metabolic profiles, hormonal parameters, liver fat, and body composition. As compared with the CRD group, the dulaglutide + CRD group had a considerably shorter median time to achieve 7% weight loss. There was no significant between-group difference in area change of VAT reduction (-0.97 cm2, 95% confidence interval from -14.36 to 12.42, p = 0.884). As compared with CRD alone, dulaglutide + CRD had significant advantages in reducing glycated hemoglobin A1c and postprandial plasma glucose levels. The results of the analyses showed different changes in menstruation frequency, additional metabolic profiles, hormonal markers, liver fat, and body composition between the two groups did not differ significantly. Nausea, vomiting, constipation, and loss of appetite were the main adverse events of dulaglutide. These results emphasize the value of dietary intervention as the first line of treatment for PCOS-affected women, while glucagon-like peptide 1 receptor agonist therapy provides an efficient and typically well tolerated adjuvant therapy to aid in reaching weight targets based on dietary therapy in the population of overweight/obese PCOS-affected women.

The Association of Serum Irisin with Impaired Glucose Before and After Laparoscopic Sleeve Gastrectomy in Obesity.

BACKGROUND: To demonstrate the association of irisin levels with impaired glucose before and after laparoscopic sleeve gastrectomy (LSG) in patients with obesity. METHODS: Thirty-six patients with obesity undergoing LSG were included. We tested the irisin levels before and after LSG and conducted an evaluation of baseline irisin levels with elevated glucose as well as irisin changes with weight loss and its association with glucose control after LSG. RESULTS: Anthropometric measurements, body fat index, and metabolic parameters were significantly improved in 3 months following LSG (all p < 0.05). Baseline irisin levels were significantly higher in obesity with elevated fasting glucose than that with normal glucose (2.98 [2.37, 3.63] vs. 3.72 [3.06, 5.32], p = 0.031). After adjustment for sex, gender, and body mass index (BMI), obesity with higher irisin levels was prone to have impaired fasting glucose (OR = 2.499, 95% CI = 1.047-5.964). According to receiver operating characteristic curve analysis, the diagnostic accuracy and sensitivity of baseline irisin levels on impaired fasting glucose were 75% and 77.8%. Irisin levels decreased from 3.29 (2.67, 4.43) to 2.82 (2.41, 3.25) ng/mL (p = 0.009) after LSG. The decreases of weight, BMI, and FFA were more in irisin changes group (△irisin ≥ 0.5) than in no irisin changes group (△irisin < 0.5). And △irisin was negatively associated with postprandial glucose (PG) at 3 months after LSG (0.5 h-PG, r = - 0.478, p = 0.029; 2 h-PG, r = - 0.406, p = 0.017). CONCLUSIONS: Elevated baseline irisin levels indicated the impaired glucose in obesity. The decrease of irisin with weight loss provided more evidence for the contribution of serum irisin secretion by fat mass in obesity.

Hydrogeochemical evolution induced by long-term mining activities in a multi-aquifer system in the mining area.

The hydrogeochemical evolution of groundwater is related to and affected by long-term mining activities, which may deteriorate the quality of groundwater. The Fengfeng mine in Handan, North China has a 30-y history of coal mining with long-term mining activities and complex geological conditions, resulting in a complex hydrogeochemical environment in the mining region. In this study, the hydrogeochemical evolution mechanism of groundwater in a multi-aquifer system in the Fengfeng Mining Area was investigated using machine learning (self-organizing maps combined with K-means clustering) and sulfur and oxygen isotopes (δ34SSO4 and δ18OSO4). The hydrogeochemical characteristics of different aquifers in the mining area changed to different degrees after mining compared with the characteristics before mining. The spatiotemporal variations in groundwater components were found to be controlled by pyrite oxidation, gypsum dissolution, and carbonate dissolution, which are affected by mining activities. Pyrite oxidation primarily occurred in the Carboniferous thin-layer limestone aquifer (CLA) and Permian sandstone aquifer (PSA). The hydrogeochemical evolution in the Ordovician limestone aquifer (OLA), the main aquifer in the study area, was affected by leakage recharge from CLA and PSA caused by mining activities. The results showed that owing to the effects of long-term mining, the altered groundwater flow system affected the evolution of groundwater components in each aquifer, particularly the sulfate concentration. This study reveals a distinct hydrogeochemical evolution induced by mining activities, which can provide a basis for groundwater resource management in mining areas.

High Diagnostic Accuracy of Epigenetic Imprinting Biomarkers in Thyroid Nodules.

PURPOSE: To explore the novel diagnostic value of epigenetic imprinting biomarkers in thyroid nodules. PATIENTS AND METHODS: A total of 550 patients with fine-needle aspiration (FNA)-evaluated and histopathologically confirmed thyroid nodules were consecutively recruited from eight medical centers. Quantitative chromogenic imprinted gene in situ hybridization (QCIGISH) was used to assess the allelic expression of imprinted genes SNRPN and HM13, on the basis of which a diagnostic grading model for thyroid nodules was developed. The model was retrospectively trained on 124 postsurgical thyroid samples, optimized on 32 presurgical FNA samples, and prospectively validated on 394 presurgical FNA samples. Blinded central review-based cytopathologic and histopathologic diagnoses were used as the reference standard. RESULTS: For thyroid malignancy, the QCIGISH test achieved an overall diagnostic sensitivity of 100% (277/277), a specificity of 91.5% (107/117; 95% CI, 86.4 to 96.5), a positive predictive value (PPV) of 96.5% (95% CI, 94.4 to 98.6), and a negative predictive value (NPV) of 100% in the prospective validation, with a diagnostic accuracy of 97.5% (384/394; 95% CI, 95.9 to 99.0). QCIGISH demonstrated a PPV of 97.8% (95% CI, 94.7 to 100) and NPV of 100%, with a diagnostic accuracy of 98.2% (111/113; 95% CI, 95.8 to 100), for indeterminate Bethesda III-V thyroid nodules. QCIGISH demonstrated a PPV of 96.6% (95% CI, 91.9 to 100) and a NPV of 100%, with a diagnostic accuracy of 97.5% (79/81; 95% CI, 94.2 to 100), for Bethesda III-IV. For Bethesda VI, QCIGISH showed a 100% (184/184) accuracy. CONCLUSION: This imprinting biomarker-based test can effectively distinguish malignant from benign thyroid nodules. The high PPV and NPV make the test both an excellent rule-in and rule-out diagnostic tool. With such a diagnostic performance and its technical simplicity, this novel thyroid molecular test is clinically widely applicable.

A New Index Based on Serum Creatinine and Cystatin C Can Predict the Risks of Sarcopenia, Falls and Fractures in Old Patients with Low Bone Mineral Density.

As new screening tools for sarcopenia, the serum sarcopenia index (SI) and creatinine/cystatin C ratio (CCR) had not been confirmd in a population with a high fragility fracture risk. This study aimed to evaluate whether SI and CCR indicators are useful for diagnosing sarcopenia and to determine their prediction values for future falls and fractures. A total of 404 hospitalized older adults were enrolled in this longitudinal follow-up study (mean age = 66.43 ± 6.80 years). The receiver operating curve (ROC) was used to assess the diagnostic accuracy of SI and CCR. Backward-selection binary logistic regression was applied to develop the optimal models for the diagnosis of new falls and fractures. SI had a significantly higher area under the curve (AUC) than CCR for predicting sarcopenia. The optimal models had acceptable discriminative powers for predicting new falls and fractures. Lower SI and CCR are the independent risks for sarcopenia, new falls, and fractures in the low-BMD population. SI and CCR, as easily accessible biochemical markers, may be useful in the detection of sarcopenia and in predicting the occurrence of new falls and fractures in patients with low BMD who have not previously experienced falls or fractures. However, further external validations are required.

A multi-center study on glucometabolic response to bariatric surgery for different subtypes of obesity.

Objectives: To assess the benefit of a bariatric surgery in four artificial intelligence-identified metabolic (AIM) subtypes of obesity with respect to the improvement of glucometabolism and the remission of diabetes and hyperinsulinemia. Methods: This multicenter retrospective study prospectively collected data from five hospitals in China from 2010 to 2021. At baseline 1008 patients who underwent a bariatric surgery were enrolled (median age 31 years; median BMI 38.1kg/m2; 57.40% women) and grouped into the four AIM subtypes. Baseline and follow-up data (506 and 359 patients at 3- and 12-month post-surgery) were collected for longitudinal effect analysis. Results: Out of the four AIM subgroups, hypometabolic obesity (LMO) group was characterized by decompensated insulin secretion and high incidence of diabetes (99.2%) pre-surgery. After surgery, 62.1% of LMO patients with diabetes achieved remission, lower than the other three subgroups. Still, the bariatric surgery significantly reduced their blood glucose (median HbA1c decreased by 27.2%). The hypermetabolic obesity-hyperinsulinemia (HMO-I) group was characterized by severe insulin resistance and high incidence of hyperinsulinemia (87.8%) pre-surgery, which had been greatly alleviated post-surgery. For both metabolic healthy obesity (MHO) and hypermetabolic obesity-hyperuricemia (HMO-U) groups who showed a relatively healthy glucometabolism pre-surgery, rate of glucometabolic comorbidities improved moderately post-surgery. Conclusion: In terms of glucometabolism, the four AIM subtypes of patients benefited differently from a bariatric surgery, which significantly relieved hyperglycemia and hyperinsulinemia for the LMO and HMO-I patients, respectively. The AIM-based subtypes may help better inform clinical decisions on bariatric surgery and patient counseling pertaining to post-surgery outcomes.

Identification of MRAP protein family as broad-spectrum GPCR modulators.

BACKGROUND: The melanocortin receptor accessory proteins (MRAP1 and MRAP2) are well-known endocrine regulators for the trafficking and signalling of all five melanocortin receptors (MC1R-MC5R). The observation of MRAP2 on regulating several non-melanocortin G protein-coupled receptors (GPCRs) has been sporadically reported, whereas other endogenous GPCR partners of the MRAP protein family are largely unknown. METHODS: Here, we performed single-cell transcriptome analysis and drew a fine GPCR blueprint and MRAPs-associated network of two major endocrine organs, the hypothalamus and adrenal gland at single-cell resolution. We also integrated multiple bulk RNA-seq profiles and single-cell datasets of human and mouse tissues, and narrowed down a list of 48 GPCRs with strong endogenous co-expression correlation with MRAPs. RESULTS: 36 and 46 metabolic-related GPCRs were consequently identified as novel interacting partners of MRAP1 or MRAP2, respectively. MRAPs exhibited protein-protein interactions and varying pharmacological properties on the surface translocation, constitutive activities and ligand-stimulated downstream signalling of these GPCRs. Knockdown of MRAP2 expression by hypothalamic administration of adeno-associated virus (AAV) packed shRNA stimulated body weight gain in mouse model. Co-injection of corticotropinreleasing factor (CRF), the agonist of corticotropin releasing hormone receptor 1 (CRHR1), suppressed feeding behaviour in a MRAP2-dependent manner. CONCLUSIONS: Collectively, our study has comprehensively elucidated the complex GPCR networks in two major endocrine organs and redefined the MRAP protein family as broad-spectrum GPCR modulators. MRAP proteins not only serve as a vital endocrine pivot on the regulation of global GPCR activities in vivo that could explain the composite physiological phenotypes of the MRAP2 null murine model but also provide us with new insights of the phenotyping investigation of GPCR-MRAP functional complexes.

Association between liver-type fatty acid-binding protein and hyperuricemia before and after laparoscopic sleeve gastrectomy.

Background: Liver-type fatty acid-binding protein (FABP1) contributes to metabolic disorders. However, the relationship between FABP1 and hyperuricemia remains unknown. We aimed to evaluate the correlation between serum FABP1 and hyperuricemia in patients with obesity before and after laparoscopic sleeve gastrectomy (LSG). Methods: We enrolled 105 patients (47 men and 58 women) with obesity who underwent LSG. They were divided into two groups: normal levels of uric acid (UA) (NUA, n = 44) and high levels of UA (HUA, n = 61) with matching sexes. FABP1 levels and other biochemical parameters were measured at baseline and 3, 6, and 12 months after LSG. Results: Serum FABP1 levels were significantly higher in the HUA group than in the NUA group (34.76 ± 22.69 ng/mL vs. 25.21 ± 21.68 ng/mL, P=0.024). FABP1 was positively correlated with UA (r=0.390, P=0.002) in the HUA group. The correlation still existed after adjusting for confounding factors. Preoperative FABP1 levels were risk factors for hyperuricemia at baseline. UA and FABP1 levels decreased at 3, 6, and 12 months postoperatively. FABP1 showed a more significant decrease in the HUA group than in the NUA group at 12 months (27.06 ± 10.98 ng/mL vs. 9.54 ± 6.52 ng/mL, P=0.003). Additionally, the change in FABP1 levels positively correlated with changes in UA levels in the HUA group 12 months postoperatively (r=0.512, P=0.011). Conclusions: FABP1 was positively associated with UA and may be a risk factor for hyperuricemia in obesity. FABP1 levels were higher but decreased more after LSG in obese patients with hyperuricemia than in those without hyperuricemia.