Generation of a human induced pluripotent stem cell line harboring heteroplasmic m.3243A > G mutation in MT-TL1 gene.

Mitochondrial diseases are disorders caused primarily by mutations in mitochondrial DNA, with the mitochondrial 3243A > G (m.3243A > G) mutation being one of the most common pathogenic mutations. Here, a pluripotent stem cell line with high m.3243A > G mutation load was generated by reprogramming the skin fibroblasts from a patient with mitochondrial disease. This cell line exhibited pluripotency, multilineage differentiation potential and normal karyotype, representing a valuable cell resource for studying the pathogenesis of mitochondrial diseases and screening drugs.

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.

Salvianolic Acid B Alleviates High Glucose-Induced Vascular Smooth Muscle Cell Inflammation by Upregulating the miR-486a-5p Expression.

The macrovascular complications of diabetes cause high mortality and disability in patients with type 2 diabetes mellitus (T2DM). The inflammatory response of vascular smooth muscle cell (VSMC) runs through its pathophysiological process. Salvianolic acid B (Sal B) exhibits beneficial effects on the cardiovascular system. However, its role and mechanism in diabetic vascular inflammatory response remain unclear. In this study, we found that Sal B reduced vascular inflammation in diabetic mice and high glucose- (HG-) induced VSMC inflammation. Subsequently, we found that Sal B reduced HG-induced VSMC inflammation by downregulating FOXO1. Furthermore, miR-486a-5p expression was obviously reduced in HG-treated VSMC. Sal B attenuated HG-induced VSMC inflammation by upregulating miR-486a-5p. Loss- and gain-of-function experiments had proven that the transfection of the miR-486a-5p mimic inhibited HG-induced VSMC inflammation whereas that of the miR-486a-5p inhibitor promoted HG-induced VSMC inflammation, thereby leading to the amelioration of vascular inflammation in the diabetic mice. Furthermore, studies had shown that miR-486a-5p inhibited FOXO1 expression by directly targeting its 3'-UTR. In conclusion, Sal B alleviates the inflammatory response of VSMC by upregulating miR-486a-5p and aggravating its inhibition of FOXO1 expression. Sal B exerts a significant anti-inflammatory effect in HG-induced VSMC inflammation by modulating the miR-486a-5p/FOXO1 axis.

Exceptional points enhance sensing in silicon micromechanical resonators.

Exceptional points (EPs) have recently emerged as a new method for engineering the response of open physical systems, that is, systems that interact with the environment. The systems at the EPs exhibit a strong response to a small perturbation. Here, we show a method by which the sensitivity of silicon resonant sensors can be enhanced when operated at EPs. In our experiments, we use a pair of mechanically coupled silicon micromechanical resonators constituting a parity-time (PT)-symmetric dimer. Small perturbations introduced on the mechanically coupled spring cause the frequency to split from the EPs into the PT-symmetric regime without broadening the two spectrum linewidths, and this frequency splitting scales with the square root of the perturbation strength. The overall signal-to-noise ratio is still greatly enhanced, although the measured noise spectral density of the EP sensing scheme has a slight increase comparable to the traditional counterpart. Our results pave the way for resonant sensors with ultrahigh sensitivity.

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.

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.

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.

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.

Dehydroepiandrosterone inhibits vascular proliferation and inflammation by modulating the miR-486a-3p/NLRP3 axis.

OBJECTIVES: In vascular remodeling diseases, proliferation and inflammation of vascular smooth muscle cells (VSMCs) constitute the basic pathologic processes. Dehydroepiandrosterone (DHEA) exerts a protective effect on the cardiovascular system, but the molecular mechanism is unclear. METHODS: The plasma DHEA was measured using enzyme-linked immunosorbent assay (ELISA) kits. The neointima hyperplasia was assessed by hematoxylin/eosin staining. MiRNA microarray analysis was used to compare the influence of Ang II and DHEA on miRNA expression profiles in VSMCs. Cell counting and MTS assay were used to evaluate the effect of Ang II, DHEA and miR-486a-3p on VSMCs proliferation. qRT-PCR was performed to detect the expression of miR-486a-3p, PCNA, IL-1ß and NLRP3. Western blot analysis was performed to detect the expressions of PCNA, IL-1ß and NLRP3 after miR-486a-3p was knocked down or overexpressed in VSMCs. RESULTS: DHEA suppressed neointimal and VSMCs proliferation and inflammation. Using miRNA microarray analysis, we found that DHEA upregulated the expression of miR-486a-3p in VSMCs. Further experiments indicated that DHEA promoted miR-486a-3p expression in VSMCs and in the vascular intima. Gain- and loss-of-function experiments revealed that transfection of miR-486a-3p mimic inhibited proliferation and inflammation of VSMCs, which improved intimal hyperplasia. On the contrary, deletion of miR-486a-3p promoted VSMCs proliferation and inflammation. Furthermore, DHEA suppressed NOD-like receptor family pyrin domain containing 3 (NLRP3) expression and reduced VSMCs proliferation and inflammation. Importantly, DHEA inhibited NLRP3 expression via miR-486a-3p in VSMCs. CONCLUSIONS: DHEA inhibited VSMCs and vascular intimal proliferation and inflammation by regulating the miR-486a-3p/NLRP3 axis. Therefore, DHEA might be a candidate cardiovascular protective agent in the future.

17ß-estradiol reduces NF-κB expression induced by increased crosstalk between KLF5 and ERα in murine vascular smooth muscle cells.

Pathological vascular remodeling and cell proliferation play vital roles in many proliferative vascular diseases. Estrogen can protect the cardiovascular system, but its exact molecular mechanism is unknown. Here we report that 17ß-estradiol (E2) suppressed vascular smooth muscle cells (VSMCs) proliferation and inflammation. qRT-PCR and Western blot demonstrated that E2 decreased NF-κB p50 expression and reduced VSMCs proliferation and inflammation. Mechanistically, a dual luciferase reporter assay and chromatin immunoprecipitation suggested that KLF5 promoted NF-κB p50 expression by binding to the NF-κB p50 promoter, whereas E2 reduced the effect of KLF5 binding to the NF-κB p50 promoter and inhibited NF-κB p50 expression. Furthermore, a coimmunoprecipitation assay and immunofluorescence staining showed that the interaction between KLF5 and ERα increased in VSMCs treated with E2, which in turn decreased NF-κB p50 expression levels. Altogether, we reveal that E2 inhibits VSMCs proliferation and inflammation by reducing NF-κB expression induced by an increased interaction between KLF5 and ERα. These data provide further insights into how E2 inhibits vascular proliferation and inflammation.

Serum Fibrinogen-Like Protein 1 Levels in Obese Patients Before and After Laparoscopic Sleeve Gastrectomy: A Six-Month Longitudinal Study.

Purpose: Fibrinogen-like protein (FGL)-1 is an original hepatokine with a critical role in developing hepatic steatosis. This study intends to examine the pre- and postoperative serum FGL-1 levels in bariatric patients and identify its relationship with other clinical indicators. Patients and Methods: Ninety-two individuals (60 bariatric patients and 32 people with normal weight) were enrolled in this research between July 2018 and April 2021. All bariatric patients finished follow-up visits 6 months after laparoscopic sleeve gastrectomy (LSG). Clinical data, anthropometric parameters, biochemical variables, FibroScan, and serum FGL-1 levels were collected at baseline and 6 months after LSG. Results: FGL-1 levels in patients with obesity (44.66±20.03 ng/mL) were higher than in individuals with normal weight (20.73±9.73 ng/mL, p < 0.001). After LSG, FGL-1 levels were significantly decreased (27.53±11.45 ng/mL, p < 0.001). Besides, body mass index (BMI), liver enzyme levels, glucose metabolism, lipid metabolism, uric acid (UA), controlled attenuation parameter (CAP), and liver stiffness measurement (LSM) were significantly improved. After adjusting possible confounders, FGL-1 levels at baseline were negatively associated with changes in LSM levels; changes in FGL-1 levels showed positive correlations with changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and UA levels at 6 months after surgery. Conclusion: Serum FGL-1 levels were significantly decreased following LSG in patients with obesity. The preoperative serum FGL-1 levels could be a predictor of postoperative liver fibrosis improvement. Furthermore, the decreased FGL-1 levels were associated with improved liver enzymes and UA but not with bodyweight or glucolipid metabolism.

Prevalence of anaemia and the associated factors among hospitalised people living with HIV receiving antiretroviral therapy in Southwest China: a cross-sectional study.

OBJECTIVES: To estimate anaemia prevalence and the associated factors among hospitalised people living with HIV (PLHIV) receiving antiretroviral therapy (ART). DESIGN: A cross-sectional study. SETTING: PLHIV receiving ART and hospitalised in a specialised hospital for infectious disease in Guizhou Province, Southwest China, between 1 January 2018 and 31 March 2021. PARTICIPANTS: A total of 6959 hospitalised PLHIV aged ≥18 years and receiving ART were included in this study. PRIMARY AND SECONDARY OUTCOME MEASURES: Anaemia was diagnosed as a haemoglobin concentration <120 g/L for non-pregnant females and <130 g/L for males. Mild, moderate and severe anaemia were diagnosed as below the gender-specific lower limit of normal but ≥110 g/L, 80-110 g/L and <80 g/L, respectively. RESULTS: The prevalence of anaemia was 27.5%, and that of mild, moderate and severe anaemia was 9.2%, 12.2% and 6.1%, respectively. Results from multivariate logistic regression showed that females had increased odds of anaemia (adjusted OR (aOR)=1.60, 95% CI: 1.42 to 1.81) compared with males. Widowed or divorced inpatients (anaemia: aOR=1.26, 95% CI: 1.08 to 1.47; severe anaemia: aOR=1.52, 95% CI: 1.16 to 1.97) and thrombocytopenia inpatients (anaemia: aOR=4.25, 95% CI: 3.54 to 5.10; severe anaemia: aOR=4.16, 95% CI: 3.24 to 5.35) had increased odds of anaemia and severe anaemia compared with their counterparts. Hepatitis C was associated with increased odds of severe anaemia (aOR=1.80, 95% CI: 1.11 to 2.92). CONCLUSIONS: Anaemia was prevalent among hospitalised PLHIV. Female sex, those widowed or divorced, and thrombocytopenia were associated with increased odds of anaemia, and those widowed or divorced, thrombocytopenia and hepatitis C were associated with increased odds of severe anaemia. Determination of anaemia predictors, early detection and timely management of anaemia are crucial to prevent anaemia progression.

Fermentation characteristics of Pixian broad bean paste in closed system of gradient steady-state temperature field.

A closed system of gradient steady-state temperature field (GSTF) was constructed to ferment Pixian broad bean paste (PBP). The contents of physicochemical factors and organic acids in the fermentation under GSTF (FG) were closer to those in the traditional fermentation (TF). The taste intensities of 8 free amino acids in the FG were higher than those in the constant temperature fermentation (CTF), but 14 in the TF showed the highest among the processes of FG, CTF and TF. The FG product had the most volatiles with 87, and its flavor properties were more stable. The FG produced great effects on the microbe evolutions especially improved the fungal diversity. Bacillus were identified as the core microbes in the FG while the roles of Staphylococcus, Lactobacillus and Pantoea were strengthened. The results indicated that the fermentation characteristics in the FG had been further improved compared with the CTF.

Decreased Monocyte Count Is Associated With Gestational Diabetes Mellitus Development, Macrosomia, and Inflammation.

CONTEXT: The immune system plays a central role in the pathophysiology of gestational diabetes mellitus (GDM). Monocytes, the main innate immune cells, are especially important in the maintenance of a normal pregnancy. OBJECTIVE: Here, we investigated the potential effect of monocytes in GDM. METHODS: Monocyte count was monitored throughout pregnancy in 214 women with GDM and 926 women without in a case-control and cohort study. Circulating levels of inflammatory cytokines, placenta-derived macrophages, and their products were measured. RESULTS: Throughout pregnancy, monocyte count was significantly decreased in women with GDM, and was closely associated with glucose level, insulin resistance, and newborn weight. First-trimester monocyte count outperformed that of the second and third trimester as a risk factor and diagnostic predictor of GDM and macrosomia both in the case-control and cohort study. In addition, our cohort study showed that as first-trimester monocyte count decreased, GDM and macrosomia incidence, glucose level, and newborn weight increased in a stepwise manner. Risk of GDM started to decrease rapidly when first-trimester monocyte count exceeded 0.48 × 109/L. Notably, CD206 and interleukin 10 (IL-10) were significantly lower, whereas CD80, CD86, tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) were higher both in GDM placental tissue and peripheral blood. First-trimester monocyte count was positively related to IL-10 and CD206, but negatively related to CD80, CD86, TNF-α, and IL-6. CONCLUSION: Decreased monocyte count throughout pregnancy was closely associated with the development of GDM, macrosomia, and the chronic inflammatory state of GDM. First-trimester monocyte count has great potential as an early diagnostic marker of GDM.

Efficacy of canagliflozin versus metformin in women with polycystic ovary syndrome: A randomized, open-label, noninferiority trial.

OBJECTIVES: To determine the safety and efficacy of canagliflozin in comparison to metformin in polycystic ovary syndrome (PCOS) patients with insulin resistance (IR). METHODS: A single-centre, prospective, randomized open-label (ratio 1:1) noninferiority trial was conducted at the Department of Endocrinology, Shanghai Tenth People's Hospital, between July 2019 and April 2021. Women aged 18 to 45 years with PCOS and IR were enrolled and randomly assigned to either 100 mg (n = 33) canagliflozin daily or 1500 to 2000 mg metformin daily (n = 35) for 12 weeks. The primary outcome was changes in homeostatic model assessment (HOMA)-IR after 12 weeks of treatment. The secondary outcomes included changes in anthropometric measurements, menstrual frequency, sex hormone levels, metabolic variables and body fat distribution. RESULTS: For lowering of HOMA-IR after 12 weeks of treatment, canagliflozin was found to be noninferior to metformin (least-squares mean difference -0.81% [95% confidence interval -2.13 to 0.51]). Both canagliflozin and metformin significantly improved menstrual pattern, reduced body weight and total fat mass, and decreased triglyceride levels. Compared with metformin, canagliflozin had significant advantages in reducing uric acid and dehydroepiandrosterone sulphate levels. Pruritus vulvae (9.09%) and gastrointestinal reaction (55.55%) were the main adverse events in the metformin group and canagliflozin group, respectively. CONCLUSION: This study demonstrates that canagliflozin was not inferior to metformin in PCOS patients with IR, which suggests that sodium-glucose cotransporter-2 inhibitors should be considered as effective drugs in the treatment of PCOS patients with IR.

Correlation Between Sex Hormones and Non-alcoholic Fatty Liver Disease Before and After Laparoscopic Sleeve Gastrectomy.

OBJECTIVES: To investigate the cross-sectional and longitudinal correlation between sex hormones and non-alcoholic fatty liver disease (NAFLD) in patients with obesity before and after laparoscopic sleeve gastrectomy (LSG). METHODS: A total of 360 patients with obesity aged 16-48 years (170 men and 190 women) were enrolled between May 2017 and March 2021. Among them, 132 patients (55 men and 77 women) who underwent LSG had follow-up data. Anthropometric parameters, metabolic variables, and sex hormones were measured. NAFLD was assessed by FibroScan with controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). RESULTS: In the preoperative cohort, levels of CAP and LSM were significantly higher in men than women. Lower total testosterone (TT) was associated with higher CAP and LSM in men, whereas higher TT was associated with higher CAP in women. In the postoperative cohort, TT levels and NAFLD were significantly modified after LSG in both genders. Changes in TT levels at 3 months after surgery were negatively correlated with changes in CAP levels in men, and changes in TT levels at 6 months after surgery were positively correlated with changes in CAP levels in women. After adjusting possible confounders, the changes in TT levels were independently correlated with CAP variation in both genders. CONCLUSIONS: LSG significantly modified TT levels and NAFLD in both genders. The correlation between TT levels and NAFLD at baseline as well as the changes after surgery suggested TT levels play an important role in the development and regression of NAFLD in both genders.

17ß-Estradiol Attenuates LPS-Induced Macrophage Inflammation In Vitro and Sepsis-Induced Vascular Inflammation In Vivo by Upregulating miR-29a-5p Expression.

Excessive release of cytokines such as IL-1ß and other inflammatory mediators synthesized and secreted by macrophages is the fundamental link of uncontrolled inflammatory response in sepsis. 17ß-Estradiol (E2) plays anti-inflammatory and vascular protective effects by regulating leukocyte infiltration and the expression of chemokines or cytokines induced by injury. However, the role of E2 in the inflammatory response of macrophages in sepsis and its mechanism are still not fully understood. In the present study, we show that E2 alleviates vascular inflammation in sepsis mice induced by cecal ligation puncture (CLP). E2 significantly decreases RAW 264.7 cell inflammation response by downregulating the expression of NLRP3. Furthermore, we found that miR-29a-5p was significantly downregulated in LPS-treated macrophages. Treating RAW 264.7 cells with E2 markedly upregulated the miR-29a-5p expression level. More importantly, we demonstrated that miR-29a-5p repressed NLRP3 expression by directly targeting its 3'-UTR. Loss- and gain-of-function experiments revealed that transfection of the miR-29a-5p mimic abrogates LPS-induced macrophage inflammation. Moreover, depletion of miR-29a-5p by its inhibitor largely promotes LPS-induced macrophage inflammation. In summary, miR-29a-5p upregulation induced by E2 alleviated RAW 264.7 cell inflammation response by aggravating miR-29a-5p repression of NLRP3 expression. E2 exerts significant anti-inflammatory efficacy in macrophages by regulating the miR-29a-5p/NLRP3 axis. Targeting miR-29a-5p may be a novel therapeutic strategy to suppress sepsis-induced vascular inflammation.

Incidence and Risk Factors of Hypogonadism in Male Patients With Latent Autoimmune Diabetes and Classic Type 2 Diabetes.

Objectives: This study aimed to compare the prevalence of hypogonadism between male patients with latent autoimmune diabetes (LADA) and type 2 diabetes (T2DM) and investigate the risk factors for hypogonadism in these patients. Methods: This cross-sectional study evaluated 367 male patients with LADA (n=73) and T2DM (n=294) who visited the endocrinology department of Shanghai Tenth People's Hospital between January 2016 and October 2019 for diabetes management. Sex hormones, lipid profiles, sex hormone-binding globulin (SHBG), glycosylated hemoglobin A1c, beta-cell function, uric acid, and osteocalcin were determined in serum samples. Hypogonadism was defined as calculated free testosterone (cFT) less than 220 pmol/L along with the presence of symptoms (positive ADAM score). Results: The rate of hypogonadism in the LADA and T2DM group were 8.2, and 21.7%, respectively (p=0.017). After adjusting possible confounders, the rate of hypogonadism in the LADA group was comparable to those of the T2DM group. Univariate logistic regressions demonstrated that age, BMI, fasting C-peptide, triglycerides, total cholesterol and uric acid were associated with hypogonadism in men with diabetes, BMI, triglycerides and estradiol were independent risk for hypogonadism in men with diabetes. Conclusion: This is the first evidence to explore the rate of hypogonadism in male patients with latent autoimmune diabetes (LADA). In the population requiring admission to a large urban hospital in China, the rate of hypogonadism was comparable to those of the T2DM group after adjusting for possible confounders. BMI, triglycerides and estradiol were independently associated with the presence of HH in male diabetic patients.

The Changes in Body Composition in Obese Patients with Polycystic Ovary Syndrome after Laparoscopic Sleeve Gastrectomy:a 12-Month Follow-up.

OBJECTIVES: To investigate the changes in body fat distribution and predicting factors of these changes in polycystic ovary syndrome (PCOS) patients with obesity, after laparoscopic sleeve gastrectomy (LSG). METHODS: This study consecutively enrolled 153 patients with obesity aged 18-45 years (83 with PCOS and 70 control patients) who underwent LSG from May 2013 to September 2020 at the Department of Endocrinology, Shanghai Tenth People's Hospital, with a 12-month follow-up. Dual-energy X-ray absorptiometry (DEXA) was used to assess body fat distribution. RESULTS: The percentage of fat mass loss in the visceral adipose tissue (VAT) region (55.08%) was more than that in any other body regions at 12 months post-surgery in the PCOS group yet insignificant. Homeostatic model assessment of insulin resistance (HOMA-IR) at baseline and Δ HOMA-IR were only negatively correlated with the variations in VAT mass and volume at 3 months post-surgery in the PCOS group. Logistic regression analysis showed that HOMA-IR <6.65 was an independent predictive factor for the changes in VAT mass and volume at 3 months post-surgery in the PCOS group. CONCLUSIONS: In this study, the percentage loss of fat mass was greater in the VAT region than in any other body regions in all patients. The rate of VAT decrease in the PCOS group was higher than that in the control group yet insignificant. Compared with control patients, HOMA-IR at baseline was an independent risk factor for the changes in VAT mass and volume at 3 months post-surgery in patients with PCOS. KEY POINTS: • The percentage loss of fat mass was greater in the VAT region than in any other body regions in all patients. • The rate of VAT decrease in the PCOS group was higher than that in the control group yet insignificant. • HOMA-IR at baseline was an independent risk factor for the changes of VAT mass in patients with PCOS.

Low serum alkaline phosphatase levels in patients with chronic liver diseases: Possible contributions to disease pathogenesis.

OBJECTIVES: A low serum alkaline phosphatase (ALP) level is an uncommon finding in patients with chronic liver disease (CLD). The prevalence of this finding and whether low ALP expression influences CLD remain to be determined. The objectives of this study were: (1) to document the prevalence of low serum ALP levels in adult CLD patients and (2) compare features of CLD in patients with low versus normal or elevated serum ALP levels. METHODS: An adult, outpatient liver disease database was searched for patients with low serum ALP levels (<40 IU/L). Hepatic inflammation, function, fibrosis and disease severity were determined by serum aminotransferases, albumin, bilirubin and INR levels, Fib-4 calculations and MELD scores respectively. RESULTS: Of 19,037 patients entered into the database, 47 (0.25%) had consistently low serum ALP levels, 51 (0.27%) low levels on the majority and 469 (2.44%) on the minority of determinations. Patients with consistently low levels were matched (1:2) by age, gender and nature of the underlying liver disease to patients with normal or elevated serum ALP levels. Matched patients with consistently low ALP levels had significantly lower serum aminotransferase and bilirubin levels at their initial visit and throughout the follow-up period (p < 0.05 respectively) while Fib-4 levels and MELD scores were similar at the initial and last follow-up visit. CONCLUSIONS: These results establish the prevalence of low serum ALP levels in adult CLD patients and describe a hitherto unreported association between low serum ALP levels and less biochemical evidence of active disease.