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.

Recognition of food images based on transfer learning and ensemble learning.

The recognition of food images is of great significance for nutrition monitoring, food retrieval and food recommendation. However, the accuracy of recognition had not been high enough due to the complex background of food images and the characteristics of small inter-class differences and large intra-class differences. To solve these problems, this paper proposed a food image recognition method based on transfer learning and ensemble learning. Firstly, generic image features were extracted by using the convolutional neural network models (VGG19, ResNet50, MobileNet V2, AlexNet) pre-trained on the ImageNet dataset. Secondly, the 4 pre-trained models were transferred to the food image dataset for model fine-tuning. Finally, different basic learner combination strategies were adopted to establish the ensemble model and classify feature information. In this paper, several kinds of experiments were performed to compare the results of food image recognition between single models and ensemble models on food-11 dataset. The experimental results demonstrated that the accuracy of the ensemble model was the highest, reaching 96.88%, which was superior to any base learner. Therefore, the convolutional neural network model based on transfer learning and ensemble learning has strong learning ability and generalization ability, and it is feasible and practical to apply the method to food image recognition.

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.

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.

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.

Trends in medication use and treatment patterns in Chinese patients with inflammatory bowel disease.

BACKGROUND: Medications for inflammatory bowel disease (IBD) have changed dramatically over time. However, no study on long-term medication profiles has been conducted in the Chinese population. AIM: To evaluate temporal changes in medication use and treatment patterns for Chinese patients with IBD. METHODS: A multicenter retrospective cohort study was conducted among Chinese patients newly diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) between January 1999 and December 2019. Baseline characteristics and drug prescriptions were collected. Trends in medication use and therapeutic patterns were analyzed. RESULTS: In total, 3610 patients were analyzed. During follow-up, 5-aminosalicylates (5-ASA) and corticosteroids (CS) prescriptions gradually decreased, accompanied by a notable increase in immunosuppressants (IMS) and infliximab (IFX) prescriptions in patients with CD. Prescription rates of 5-ASA and CS were stable, whereas IMS and IFX slightly increased since 2007 in patients with UC. Subgroup (n = 957) analyses showed a switch from conventional medications to IFX in patients with CD, while 5-ASA and CS were still steadily prescribed in patients with UC. Logistic regression analyses revealed that surgical history, disease behavior, and disease location were associated with initial therapeutic strategies in patients with CD. However, medications before diagnosis, disease location, and diagnostic year might affect initial strategies in patients with UC. CONCLUSION: Long-term treatment strategies analyses has provided unique insight into the switch from conventional drugs to IFX in Chinese patients with CD.

High-Sensitive CRP Correlates With the Severity of Liver Steatosis and Fibrosis in Obese Patients With Metabolic Dysfunction Associated Fatty Liver Disease.

Background: Metabolic dysfunction associated fatty liver disease (MAFLD) is the most common hepatopathy worldwide due to the obesity epidemic and is associated with chronic low-grade inflammation. High-sensitive C-reactive protein (hsCRP) as an inflammatory marker has been used in diagnosing MAFLD. However, the association between hsCRP and the severity of liver steatosis and fibrosis among obese patients with MAFLD remains to be elucidated. Objective: To explore the correlation of hsCRP with the severity of liver steatosis and fibrosis among Chinese obese patients with MAFLD. Methods: A total of 393 obese patients with mean BMI 34.8 ± 6.6 kg/m2 were selected and categorized as MAFLD and non-MAFLD groups. Anthropometric data, biochemical indices, and hsCRP were measured. The severity of hepatic steatosis and fibrosis was assessed using FibroScan. Multivariate logistic regression analysis was performed to determine the relationship between hsCRP and the risk of MAFLD and its disease severity. Results: Patients with MAFLD showed significantly elevated hsCRP levels and were more likely to have severe steatosis and fibrosis compared to those without MAFLD. The proportions of MAFLD, severe steatosis, and severe fibrosis were significantly increased across the hsCRP quartiles (P-trend = 0.004, 0.021, and 0.006, respectively). After multivariable adjustments, the adjusted ORs (AORs) and 95%CI for MAFLD were 1.00 (reference), 1.298 (0.587-2.872), 2.407 (1.002-5.781), and 2.637(1.073-6.482) (Q1-Q4, P-trend = 0.014). Likewise, the AORs (95%CI) for severe steatosis and severe fibrosis were remarkably increased with the increment of serum hsCRP quartiles (P-trend < 0.001, P-trend = 0.021, respectively). Conclusions: Elevated serum hsCRP levels were associated with increased risk of MAFLD among Chinese obese patients and correlated positively with the severity of liver steatosis and fibrosis, suggesting that hsCRP can be used as a potential biomarker to monitor and predict disease severity among Chinese obese population with MAFLD.

Bone morphogenetic protein 4 alleviates nonalcoholic steatohepatitis by inhibiting hepatic ferroptosis.

Nonalcoholic steatohepatitis (NASH) is a state of simple steatosis that progresses to inflammation and liver injury accompanied by ferroptosis. Bone morphogenetic protein 4 (BMP4) plays an important role in adipogenesis and differentiation, as well as in hepatic steatosis and iron regulation. However, the direct impact of BMP4 on NASH remains unclear. In this study, our aim was to investigate the effect of BMP4 on NASH and its underlying mechanism. We first explored BMP4 expression in vivo in mice and patients and in vitro in HepG2 and LO2 cell lines, and then, determined whether ferroptosis occurs in NASH. Further overexpression or inhibition of BMP4 was induced to observe the effect of BMP4 on liver ferroptosis in NASH. BMP4 expression was upregulated in patients and mice with nonalcoholic fatty liver disease, and free fatty acid (FFA)-induced HepG2 and LO2 cell lines. We observed ferroptosis in high-fat diet and high-fructose diet-fed mice and FFA-induced HepG2 and LO2 cell lines. BMP4 overexpressing plasmid was constructed and the HepG2 and LO2 cells were transfected with lentivirus (oe-BMP4), or treated with exogenously added recombinant human BMP4 or BMP antagonist noggin. BMP4 suppressed the markers of hepatic steatosis, liver inflammation, and liver injury. Upregulated BMP4 expression in HepG2 and LO2 cells reduced reactive oxygen species and malondialdehyde content and relieved ferroptosis. Mechanistically, BMP4 overexpression in hepatocytes upregulated the mRNA and protein levels of glutathione peroxidase 4 (GPX4), a central regulator of ferroptosis, while exogenous inhibition of BMP4 by noggin decreased their levels. Immunoprecipitation assays demonstrated a physical interaction between BMP4 and GPX4 in HepG2 and LO2 cells, and confocal imaging confirmed colocalization of BMP4 and GPX4. Consistently, BMP4 overexpression plays an important role in NASH by increasing GPX4 expression, therefore decreasing hepatic ferroptosis. This study proposes BMP4 as a therapeutic target for preventing steatohepatitis.

J-Shaped Relationship Between Serum Prolactin and Metabolic-Associated Fatty Liver Disease in Female Patients With Type 2 Diabetes.

Background: Metabolic-associated fatty liver disease (MAFLD) has become a worldwide epidemic. Prolactin (PRL), a pituitary hormone, has been linked to MAFLD. As a result, we set out to look into the relationship between serum PRL and the risk of MAFLD in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 724 adults with T2DM were enrolled and categorized as MAFLD and non-MAFLD groups. Anthropometric data, biochemical parameters, and serum PRL levels were collected. Liver steatosis and fibrosis were assessed using FibroScan. Patients were stratified into normal PRL (NP) and high PRL (HP) groups and divided into four groups based on serum PRL quartiles. Multivariate logistic regression analysis was performed to evaluate the association between serum PRL and MAFLD risk. Results: Female but not male patients with MAFLD, liver steatosis, and fibrosis had significantly lower PRL levels in the NP group but higher PRL levels in the HP group than their counterparts. The proportions of MAFLD, liver steatosis, and fibrosis were significantly decreased in the NP group but increased in the HP group across the PRL quartiles in females but not in males. After multivariate adjustment, the adjusted ORs (AORs) and 95% CI for MAFLD among females were 18.165 (3.425-96.336), 1.784 (0.658-5.002), 1.744 (0.608-4.832), and 1.00 (reference) in the NP group (Q1-Q4, P-trend < 0.001) and 1.00 (reference), 11.098 (1.819-110.356), 15.225 (1.996-116.112), and 18.211 (2.579-128.568) in the HP group (Q1-Q4, P-trend = 0.020). Such associations were also found between serum PRL and liver fibrosis in females but not in males. Conclusion: We observed a J-shaped association between serum PRL and the risk of MAFLD and liver fibrosis in females but not in males with T2DM, indicating that PRL may be relevant to MAFLD and its progression in a gender-specific manner. Clinical Trial Registration: Chinese Clinical Trial Registry, number ChiCTR-OCS-12002381.

Development of a New Index Based on Preoperative Serum Lipocalin 2 to Predict Post-LSG Weight Reduction.

BACKGROUND: Bariatric surgery is the most effective therapy for obesity, but targeted weight reduction is not always achieved. Serum lipocalin-2 (LCN2) is closely associated with obesity, but its impact on weight loss after surgery is unknown. We aimed to access the reliability of LCN2 levels and other parameters as effective predictors of excellent weight loss (≥ 75% excess weight loss (EWL)) 1 year after bariatric surgery. METHODS: This retrospective study evaluated 450 patients (aged 18-65 years) with obesity at 3 months and 1 year after laparoscopic sleeve gastrectomy (LSG) surgery. Seventy-four patients who underwent LSG surgery and met the inclusion and exclusion criteria were included in this study. Serum LCN2, thyroid function, and metabolic and anthropometric parameters were assessed. Weight reduction was expressed as %EWL and percent total weight loss (%TWL) at 3 months and 1 year post surgery. Multivariable logistic regression analysis and receiver operating characteristic (ROC) curve analysis were used to evaluate predictors of ≥ 75%EWL. RESULTS: In our cohort, %EWL and %TWL were both strongly associated with preoperative serum LCN2 levels. The binary logistic regression analysis showed that preoperative LCN2, waist circumference, and glycated hemoglobin were independent predictors of excellent weight loss. CONCLUSIONS: Based on these results, we determined a new P index with better predictive value for excellent weight reduction (≥ 75%EWL) 1 year after LSG surgery.

The relationship between Lipocalin-2 level and hepatic steatosis in obese patients with NAFLD after bariatric surgery.

BACKGROUND: Lipocalin-2 (LCN2) has a critical effect on obesity as well as its associated comorbidities. The present study focused on analyzing serum LCN2 levels of obese patients with nonalcoholic fatty liver disease (NAFLD) and on determining relationship of hepatic steatosis improvement with LCN2 levels after laparoscopic sleeve gastrectomy (LSG). METHODS: This work enrolled ninety patients with obesity and NAFLD. Twenty-three of them underwent LSG. Anthropometric and biochemical parameters and serum LCN2 levels were determined at baseline and those at 6-month post-LSG. Controlled attenuation parameter (CAP) measured by FibroScan was adopted for evaluating hepatic steatosis. RESULTS: Among severe obesity patients, serum LCN2 levels were significantly increased (111.59 ± 51.16 ng/mL vs. 92.68 ± 32.68 ng/mL, P = 0.035). The CAP value was higher indicating higher liver fat content (360.51 ± 45.14 dB/m vs. 340.78 ± 45.02 dB/m, P = 0.044). With regard to surgical patients, liver function, glucose, and lipid levels were significantly improved after surgery. Serum LCN2 levels significantly decreased (119.74 ± 36.15 ng/mL vs. 87.38 ± 51.65 ng/mL, P = 0.001). Decreased CAP indicated a significant decrease in liver fat content (358.48 ± 46.13 dB/m vs. 260.83 ± 69.64 dB/m, P < 0.001). The decrease in LCN2 levels was significantly related to the reduced hepatic fat content and improvement in steatosis grade after adjusting for gender, age, and BMI decrease. CONCLUSIONS: Serum LCN2 levels are related to obesity and NAFLD. The decreased serum LCN2 levels could be an indicator of hepatic steatosis improvement.

Obesity-associated up-regulation of lipocalin 2 protects gastric mucosa cells from apoptotic cell death by reducing endoplasmic reticulum stress.

Gastric mucosal injury is a less well known complication of obesity. Its mechanism remains to be further elucidated. Here, we explored the protective role of lipocalin 2 (LCN2) against endoplasmic reticulum stress and cell apoptosis in gastric mucosa in patients and mice with obesity. Through molecular and genetic analyses in clinical species, LCN2 secreted by parietal cells expression is elevated in obese. Immunofluorescence, TUNEL, and colorimetry results show that a more significant upregulation of pro-inflammatory factors and increased amount of apoptotic cells in gastric tissue sections in obese groups. Loss- and gain-of-function experiments in gastric epithelial cells demonstrate that increased LCN2 protected against obesity associated gastric injury by inhibiting apoptosis and improving inflammatory state. In addition, this protective effect was mediated by repressing ER stress. Our findings identify LCN2 as a gastric hormone could be a compensatory protective factor against gastric injury in obese.

The Increased Risk of Thyroid Cancer-Specific Mortality With Tumor Size in Stage IVB Patients.

Purpose: To investigate the risk-stratifying utility of tumor size and a threshold for further stratification on cancer-specific mortality of thyroid cancer (TC) patients in stage IVB. Methods: One thousand three hundred and forty-five patients (620 males and 725 females) with initial distant metastasis over 55 years between 2004 and 2016 from Surveillance, Epidemiology, and End Results databases were investigated, with a median follow-up time of 23 months [interquartile range (IQR), 5-56 months] and a median age of 70 years (IQR, 63-77 years). TC-specific mortality rates were calculated under different classifications. Cox regressions were used to calculate hazard ratios (HRs) and Kaplan-Meier Analyses were conducted to investigate TC-specific survivals. Results: In the whole cohort, patients with tumors >4 cm had the highest TC-specific mortality (67.9%, 330/486), followed by tumor size >1 cm but ≤ 4 cm (43.08%, 190/441), and tumor size ≤ 1 cm (32.69%, 34/104). Kaplan-Meier curves showed the increased tumor size was associated with a statistically significant decrease in TC-specific survival (P < 0.001). Papillary thyroid cancer (PTC) patients with tumors >4 cm had significantly higher hazard ratios (HRs) of 2.84 (1.72-4.70) and 3.11 (1.84-5.26) after adjusting age, gender, race, and radiation treatment, compared with patients with tumors ≤ 1 cm (P < 0.001). The TC-specific mortalities and survivals were further investigated among more detailed subgroups divided by different tumor size, and a threshold of 3 cm could be observed (P < 0.005) for risk stratification. Conclusions: Mortality risk increased with tumor size in PTC patients in stage IVB. Our findings demonstrated the possibility of further stratification in IVB stage in current TNM staging system. Patients with tumor size over 3 cm had an excessively high risk of PTC-specific mortality, which may justify the necessity of more aggressive treatment for them.

miR-383 ameliorates high glucose-induced ß-cells apoptosis and hyperglycemia in high-fat induced diabetic mice.

Islet beta-cell dysfunction is an important condition leading to the development of diabetes. Numerous studies have found that miRNA regulates islet ß-cell function. In our previous research, the aberrant expression of miR-383 was revealed in type 2 diabetes mellitus (T2DM) serum. Herein, we aimed to assess the function and underlying mechanism of miR-383 in ß-cells through in vitro and in vivo experiments. Using high glucose media, the ß-cell injury was induced and transfected miR-383 overexpression vector to detect cell function in MIN6. Moreover, miR-383 overexpression lentivirus was administrated into high-fat induced diabetes mice to assess the in vivo effect. Results showed that overexpressing miR-383 reversed the cell apoptosis and oxidative stress, induced by high glucose which targets Toll-like receptors (TLR4) and Apolipoprotein C3 (ApoC3) genes. Furthermore, mechanistic studies demonstrated that miR-383 targeted the TLR4 and ApoC3 3' UTR consequently inhibiting TLR4 and ApoC3 expression in MIN6 cells. Besides, overexpression of miR-383 ameliorated hyperglycemia and pancreatic apoptosis in high-fat induced diabetic mice. Conclusively, miR-383 potentially alleviate pancreatic ß-cell injury induced by high glucose and ameliorates high-fat induced diabetes by suppressing TLR4 and ApoC3 expression.

J-shaped association between fasting blood glucose levels and COVID-19 severity in patients without diabetes.

AIMS: Coronavirus disease 2019 (COVID-19) has become a recognized worldwide pandemic. Researchers now know that mortality from COVID-19 can be reduced through early prevention measures. This retrospective, multi-centered study of 293 COVID-19 patients without diabetes explores the association between fasting blood glucose (FBG) levels and the risk of COVID-19 disease progression, with the goal of providing clinical evidence for glycemic targets in patients. METHODS: The multivariate stepwise binary logistic regression analysis was used to test the dose-response effects of FBG levels on the risk of severe and critical condition in COVID-19 patients. RESULTS: FBG levels were plotted in quintiles with set at <4.74, 4.74-5.21, 5.21-5.78, 5.78-7.05, and ≧7.05 mmol/L. The constituent ratio of severe or critical cases in each FBG quintile was 20.7%, 1.7%, 13.8%, 27.1%, and 67.2%, respectively (P < 0.0001). When the second quintile was used as the reference, the adjusted odds ratios (AORs) (95%CI) for the risk of severe/critical condition in COVID-19 was 25.33 (2.77, 231.64), 1.00 (Reference), 3.13 (0.33, 29.67), 10.59 (1.23, 91.24), 38.93 (4.36, 347.48) per FBG quintile respectively (P < 0.001). CONCLUSIONS: We provide evidence of J-shaped associations between FBG and risk of severe and critical condition in non-diabetes patients with COVID-19, with nadir at 4.74-5.78 mmol/L.