Sex differences in the association between chest computed tomography-defined sarcopenia and cardiovascular risk factors among inpatients.

Background: While sarcopenia has been found to be associated with increased risks of cardiovascular diseases (CVDs), evidence exploring sex-related differences remains insufficient. This study aimed to investigate the differences in how often sarcopenia occurs in each sex, as determined by skeletal muscle area (SMA) in chest CT images, and its association with CVD common risk factors. Methods: This cross-sectional study involved 1,340 inpatients from the Department of Geriatrics of Renji Hospital, affiliated to Shanghai Jiaotong University School of Medicine. Data on age, sex, body mass index (BMI), smoking status, disease history, and clinical parameters were collected. Sarcopenia was defined using chest CT images with a cut-off value of T12-SMA/height2 <25.75 cm2/m2 in male patients and <20.16 cm2/m2 in female patients. Cardiovascular risk was assessed using the Framingham risk score (FRS). The association between T12-SMA/height2-defined sarcopenia and CVD risk factors by sex was evaluated using a multivariate logistic regression analysis. Results: The overall prevalence of T12-SMA/height2-defined sarcopenia (<25.75 cm2/m2 for male patients, <20.16 cm2/m2 for female patients) was 54.03%, with 48.09% in male patients and 63.19% in female patients. The proportion of male patients with high CVD risk was greater than that of female patients. The multivariate analysis revealed that T12-SMA/height2-defined sarcopenia was independently associated with age (in male patients only), systolic blood pressure (SBP), cholesterol, and high-density lipoprotein cholesterol (HDL-C) among the six FRS cardiovascular risk indices. Conclusion: Our results suggest that T12-SMA/height2-defined sarcopenia was more prevalent in male patients than in female patients. Sarcopenia was associated with higher levels of SBP and HDL-C and lower levels of cholesterol. Increasing age had a more significant effect on CVD risk in male patients.

A Study of the Relationship Between the Triglyceride-Glucose Index and Skeletal Muscle Mass in a General Chinese Population.

Objective: There is no study on the relationship between triglyceride-glucose index (TyG index) and skeletal muscle mass in middle-aged and elderly C population. Therefore, the aim of the study is to investigate the relationship between the TyG index and weight-adjusted relative skeletal muscle index (RSMI) in middle-aged and elderly C population. Methods: We retrospectively studied 947 aged ⩾40 years subjects who got a routine medical examination in the Department of Geriatrics of R Hospital from May 2021 to March 2023. The RSMI was designed to evaluate skeletal muscle mass and calculated based on lean mass of the limbs(kg)/body weight(kg) × 100%. Skeletal muscle mass reduction was defined as a RSMI of 1-2 standard deviations (SD) below of healthy adults aged 30-49 years old. Considering the quartile groups of the TyG index, the subjects were assigned to 4 groups: Q1 (less than or equal to 8.171), Q2 (from 8.172 to 8.569), Q3 (from 8.570 to 8.992), and Q4 (greater than or equal to 8.993). Results: With TyG index increased, RSMI levels significantly reduced(P < .001). Spearman's correlation analysis showed that the TyG index was negatively correlated with RSMI in males (r = -0.320) and females (r = -0.240). The TyG index was positively correlated with body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) (P < .05). Besides, binary logistic regression analysis showed that the risk of developing reduced skeletal muscle mass in the group Q4 was 2.131 (95%CI:1.118-4.064) in males; and was 2.472 (95%CI:1.581-3.867) in females compared to the Q1 group. Conclusion: TyG index was negatively correlated with relative skeletal muscle index, and a higher TyG index was associated with the development of reduced skeletal muscle mass independently of other influencing factors. Therefore, the TyG index promises to be a predictor of skeletal muscle mass loss.

Mito-Tempo alleviates ox-LDL-provoked foam cell formation by regulating Nrf2/NLRP3 signaling.

Our previous studies have demonstrated that Mito-Tempol (also known as 4-hydroxy-Tempo), a mitochondrial reactive oxygen species scavenger, alleviates oxidized low-density lipoprotein (ox-LDL)-triggered foam cell formation. Given the effect of oxidative stress on activating the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome, which promotes foam cell formation, we aimed to explore whether Mito-Tempo inhibits ox-LDL-triggered foam cell formation by regulating NLRP3 inflammasome. The results revealed that Mito-Tempo re-activated Nrf2 and alleviated macrophage foam cell formation induced by ox-LDL, whereas the effects were reversed by ML385 (a specific Nrf2 inhibitor). Mito-Tempo restored the expression and nuclear translocation of Nrf2 by decreasing ox-LDL-induced ubiquitination. Furthermore, Mito-Tempo suppressed ox-LDL-triggered NLRP3 inflammasome activation and subsequent pyroptosis, whereas the changes were blocked by ML385. Mito-Tempo decreased lipoprotein uptake by inhibiting CD36 expression and suppressed foam cell formation by regulating the NLRP3 inflammasome. Taken together, Mito-Tempo exhibits potent anti-atherosclerotic effects by regulating Nrf2/NLRP3 signaling.

Akkermansia muciniphila might improve anti-PD-1 therapy against HCC by changing host bile acid metabolism.

PD-1 monoclonal antibodies (mAb) have demonstrated remarkable efficacy in a variety of cancers, including Hepatocellular carcinoma (HCC). However, the patient response rates remain suboptimal, and a significant proportion of initial responders may develop resistance to this therapeutic approach. Akkermansia muciniphila (AKK), a microorganism implicated in multiple human diseases, has been reported to be more abundant in patients who exhibit favorable responses to PD-1mAb. However, the underlying mechanism has yet to be elucidated. In our study, we found that AKK could enhance the efficacy of PD-1mAb against HCC in a tumor-bearing mouse model. It promotes HCC tumor cells apoptosis and raise the CD8+ T proportion in the tumor microenvironment. Additionally, AKK downregulates PD-L1 expression in tumor cells. Furthermore, the analysis of metabonomics demonstrates that AKK induces alterations in the host's bile acid metabolism, leading to a significant increase in serum TUDCA levels. Considering the immunosuppresive roles of TUDCA in HCC development, it is plausible to speculate that AKK may reinforce the immunotherapy of PD-1mAb against HCC through its impact on bile acid metabolism.

Gut microbiota as a promising therapeutic target for age-related sarcopenia.

Sarcopenia is characterized by a progressive loss of skeletal muscle mass and function with aging. Recently, sarcopenia has been shown to be closely related with gut microbiota. Strategies such as probiotics and fecal microbiota transplantation have shown potential to ameliorate the muscle loss. This review will focus on the age-related sarcopenia, in particular on the relationship between gut microbiota and age-related sarcopenia, how gut microbiota is engaged in sarcopenia, and the potential role of gut microbiota in the treatment of age-related sarcopenia.

Correlation Between Bioelectrical Impedance Analysis and Chest CT-Measured Erector Spinae Muscle Area: A Cross-Sectional Study.

Background: Skeletal muscle mass (SMM) plays an important part in diverse health and disease states. Bioelectrical impedance analysis (BIA) and computed tomography (CT) are available for its assessment. However, muscle mass assessed by BIA may be influenced by multiple factors. The erector spinae muscle area (ESA) on chest CT is recently presumed to be representative of SMM. This study aimed to derive BIA from the ESA and evaluate the magnitude of association (between ESA measured from chest CT) and BIA. Methods: Subjects hospitalized for health checkups between December 2020 and December 2021, having undergone both BIA (50 kHz, 0.8 mA) and chest CT, were included. ESA was quantified at the level of the 12th thoracic vertebra (T12-ESA) by a standardized semi-automated segmentation algorithm. Low SMM was defined using the Asian Working Group for Sarcopenia criteria. The association between T12-ESA and BIA was then evaluated. Stratified analyses by sex and BMI were also performed. Results: Among 606 included subjects (59.7 ± 16.6 years, 63.5% male), 110 (18.2%) had low SMM. BMI in low and normal SMM groups was 20.1 and 24.7 kg/m2, respectively. Current smoking, drinking, chronic obstructive pulmonary disease, and chronic renal dysfunction were more frequently seen in the low SMM group than in the normal SMM group. The final regression model included T12-ESA, weight, BMI, and age, and had an adjusted R2 of 0.806 with BIA. In the validation group, the correlation between T12-ESA-derived BIA and BIA remained high (Pearson correlation = 0.899). Stratified analysis disclosed a stronger correlation between T12-ESA and BIA in male subjects than in female subjects (adjusted R2 = 0.790 vs. adjusted R2 = 0.711, p < 0.05), and a better correlation was observed in obese (BMI ≥ 30 kg/m2) compared with underweight (BMI < 18.5 kg/m2) subjects (adjusted R2 = 0.852 vs. adjusted R2 = 0.723, p < 0.05). Additional analysis revealed a significant correlation between T12-ESA and skeletal muscle cross-sectional area at the 3rd lumbar vertebra (L3-CSA) (adjusted R2 = 0.935, p < 0.001). Conclusions: CT-based assessment of ESA at the T12 level is feasible and correlated well with BIA, especially in male subjects and obese subjects.

Muscle Fat Content Is Strongly Associated With Hyperuricemia: A Cross-Sectional Study in Chinese Adults.

Studies have indicated that the skeletal muscle mass and strength was related to serum uric acid (UA), but there is a lack of research on the association of skeletal muscle fat content with UA. The purpose of this cross-sectional study is to investigate the correlation of skeletal muscle fat index (SMFI) and hyperuricemia (HUA) in Chinese adults. 500 subjects (306 men and 194 women) were included in the study. The participants were divided into four groups according to SMFI quartiles. Pearson's correlations between SMFI and metabolic variables were calculated. Logistic regression analysis was used to estimate the association between the quartiles of SMFI and risk of hyperuricemia. UA showed a positive association with SMFI after adjusted for BMI, age and gender. A significant association between the SMFI and risk of HUA was found, the OR for HUA was 2.79 (95% CI 1.18-6.59, p<0.05) in Q2, 2.41(95% CI 1.00-5.81, p<0.05) in Q3, and 2.63 (95% CI 1.03-6.72, p<0.05) in Q4, after adjusted for BMI. In conclusion, the SMFI was significantly associated with the level of serum UA, and the higher SMFI may indicate a higher risk of HUA, independent of BMI.

Sprouting Angiogenesis in Human Pituitary Adenomas.

Introduction: Angiogenesis in pituitary tumors is not fully understood, and a better understanding could help inform new pharmacologic therapies, particularly for aggressive pituitary tumors. Materials and Methods: 219 human pituitary tumors and 12 normal pituitary glands were studied. Angiogenic genes were quantified by an angiogenesis qPCR array and a TaqMan probe-based absolute qPCR. Angiogenesis inhibition in pituitary tumors was evaluated in vitro with the endothelial tube formation assay and in vivo in RbΔ19 mice. Results: 71 angiogenic genes, 40 of which are known to be involved in sprouting angiogenesis, were differentially expressed in pituitary tumors. Expression of endothelial markers CD31, CD34, and ENG was significantly higher in pituitary tumors, by 5.6, 22.3, and 8.2-fold, respectively, compared to in normal pituitary tissue. There was no significant difference in levels of the lymphatic endothelial marker LYVE1 in pituitary tumors compared with normal pituitary gland tissue. Pituitary tumors also expressed significantly higher levels of angiogenesis growth factors, including VEGFA (4.2-fold), VEGFB (2.2), VEGFC (19.3), PGF (13.4), ANGPT2 (9.2), PDGFA (2.7), PDGFB (10.5) and TGFB1 (3.8) compared to normal pituitary tissue. Expression of VEGFC and PGF was highly correlated with the expression of endothelial markers in tumor samples, including CD31, CD34, and ENG (endoglin, a co-receptor for TGFß). Furthermore, VEGFR inhibitors inhibited angiogenesis induced by human pituitary tumors and prolonged survival of RbΔ19 mice. Conclusion: Human pituitary tumors are characterized by more active angiogenesis than normal pituitary gland tissue in a manner consistent with sprouting angiogenesis. Angiogenesis in pituitary tumors is regulated mainly by PGF and VEGFC, not VEGFA and VEGFB. Angiogenesis inhibitors, such as the VEGFR2 inhibitor cabozantinib, may merit further investigation as therapies for aggressive human pituitary tumors.

Tumor Microenvironment-Mediated Immune Profiles Characterized by Distinct Survival Outcome and Immunotherapeutic Efficacy in Breast Cancer.

Background: Numerous reports have highlighted that the tumor microenvironment (TME) is closely linked to survival outcome and therapeutic efficacy. However, a comprehensive investigation of the TME feature in breast cancer (BC) has not been performed. Methods: Here, we performed consensus clustering analysis based on TME cell expression profiles to construct TME pattern clusters and TME-related gene signature in BC. GSVA combined with CIBERSORT and ssGSEA algorithms were applied to evaluate the differences in biological pathway and immune cell infiltration level, respectively. The PCA method was employed to construct TME-score to quantify the TME-mediated pattern level in individual BC patients. Results: We determined two distinct TME gene clusters among 3,738 BC samples, which exhibited distinct survival outcome and enriched biological processes. The TME features demonstrated that these two clusters corresponded to the established immune profiles: hot and cold tumor phenotypes, respectively. Based on TME-related signature genes, we constructed the TME-score and stratified BC patients into low and high TME-score groups. Patients with high TME-score exhibited favorable outcome and increased infiltration of immune cells. Further investigation revealed that high TME-score was also related with high expression of immunosuppressive molecules, decreased tumor mutation burden (TMB), and high rate of mutation in significantly mutated genes (SMGs) (e.g., PIK3CA and CDH1). Conclusion: Assessing the TME-mediated pattern level of individual BC patients will assist us in better understanding the responses of BC patients to immunotherapies and directing more effective immunotherapeutic approaches.

Sarcopenic Obesity with Normal Body Size May Have Higher Insulin Resistance in Elderly Patients with Type 2 Diabetes Mellitus.

Objective: Data are limited regarding how body composition is linked to insulin resistance in elderly patients with type 2 diabetes mellitus (T2DM). We examined the association between body composition and insulin resistance in elderly T2DM patients. Methods: The cross-sectional study included 488 Chinese elderly patients wth T2DM. Subjects were classified into four groups based on body composition: normal body composition (NBC), low muscle mass alone (LMM), high body fat alone (HBF), both low muscle mass and high body fat (LMMHBF). Results: The percentage of subjects with LMMHBF was 14.5% (11.9% in men and 17.7% in women). Homeostasis model assessment of insulin resistance (HOMA2-IR) was higher in the LMMHBF group than in the HBF group (p = 0.045), and was also significantly higher in the LMMHBF or HBF group than in the NBC or LMM group. The HBF group showed the highest body mass index (BMI) of the four groups of different body compositions, and the LMMHBF group showed lower BMI than the HBF group; however, there was no significant difference in BMI or waist to hip ratio (WHR) between the LMMHBF group and the NBC group. The LMMHBF and HBF groups were significantly associated with increased risk of insulin resistance compared to the NBC group, with odds ratios (ORs) of 4.47 [95% confidence interval (CI) 2.06-9.68, p < 0.001] and 1.76 (95% CI 1.02-3.02, p = 0.041) respectively, even after the adjustment for covariates. Conclusion: In China, though elderly T2DM patients with the body composition of sarcopenic obesity (as defined by coexistence of low muscle mass and high body fat) seemed to have normal body size, they exhibited the most severe degree and the highest risk of insulin resistance.

Pyroptosis-Mediated Molecular Subtypes are Characterized by Distinct Tumor Microenvironment Infiltration Characteristics in Breast Cancer.

BACKGROUND: Numerous reports have highlighted that pyroptosis is closely linked to tumorigenesis and drug resistance of tumors. However, the potential role of pyroptosis in regulating immune cell infiltration in tumor microenvironment (TME) remains unclear. METHODS: Here, we performed consensus clustering analysis based on the expression of 10 typical pyroptosis-related regulators (PRRs) to construct pyroptosis-mediated tumor pattern clusters and pyroptosis-related gene signature in breast cancer (BC). GSVA combined with ssGSEA methods were applied to evaluate the differences in biological pathway and immune cell infiltration level, respectively. The PCA method was employed to construct the pyro-score to quantify the pyroptosis pattern level of individual BC patient. RESULTS: We determined three distinct pyro-clusters among 1852 BC samples, which exhibited different survival outcomes and enriched biological processes. The TME features demonstrated that these three clusters corresponded to three established immune profiles: immune-desert, immune-excluded and immune-inflamed phenotype, respectively. Based on pyroptosis-related signature genes, we constructed the pyro-score and stratified BC patients into high and low pyro-score group. Patients with high pyro-score exhibited favorable outcome and increased infiltration of immune cells. Further investigation revealed that high pyro-score was also related to high expression of immunosuppressive molecules, decreased tumor mutation burden (TMB) and high rate of mutation in significantly mutated genes (SMGs) (eg, PIK3CA and CDH1). CONCLUSION: This research emphasizes the indispensable role of pyroptosis in TME complexity and diversity. Assessing the pyroptosis pattern level of individual BC patient will assist us in better understanding TME features and directing more effective immunotherapeutic approaches.

Irisin alleviates FFA induced ß-cell insulin resistance and inflammatory response through activating PI3K/AKT/FOXO1 signaling pathway.

PURPOSE: Type 2 diabetes mellitus is characterized by insulin resistance and ß-cell dysfunction. Elevated free fatty acids-induced lipotoxicity may play a vital role in the pathogenesis of ß-cell insulin resistance. Exercise-stimulated myokine irisin has been reported to be closely related to T2DM. However, its function on ß-cell insulin signaling and the underlying mechanisms are only partially elucidated as yet. METHODS: High-fat diet-fed C57BL/6J mice and palmitic acid-treated MIN6 cell models were utilized as lipotoxic models. Factors associated with ß-cell insulin signaling transduction and inflammatory responses were assessed in these models. Furthermore, the role of irisin in ß-cells and the underlying mechanisms were also explored. RESULTS: Irisin effectively decreased lipid levels in HFD mice, enhanced glucose-stimulated insulin secretion and nullified the expressions of inflammatory cytokines in vivo and in vitro experiments. Moreover, irisin improved PI3K/AKT insulin signaling pathway and inhibited TLR4/NF-κB inflammatory signaling pathway in both islets of HFD mice and PA-treated MIN6 cells. Mechanistic analysis indicated that FOXO1 might serve as a bridge between the two pathways. CONCLUSION: Irisin alleviates lipotoxicity-induced ß-cell insulin resistance and inflammatory response through the activation of PI3K/AKT/FOXO1 signaling pathways and the inhibition of TLR4/NF-κB signaling pathways. Irisin might provide a novel therapeutic strategy for T2DM.

A Giant Pituitary Adenoma Can Coexist with an Incidental Aneurysm: Look Beyond the Pituitary Adenoma and Don't Miss the Diagnosis.

An intracranial aneurysm in a pituitary adenoma (PA) is not uncommon; however, preoperative angiography is not clinically used as a routine screening test for PA patients. Therefore an intracranial aneurysm is often missed while diagnosing PA patients. When an aneurysm is missed in patients with pituitary tumors, the supporting power by the tumor to the blood vessels or aneurysm will disappear when the tumor is removed and patients may suffer intraoperative or postoperative aneurysm rupture, which may lead to fatal, catastrophic hemorrhage. Herein, we report a case of a PA patient with the signal shadow of vessel flow void, observed vaguely in the right internal carotid artery cavernous segment on magnetic resonance imaging, and a small aneurysm was found via digital subtraction angiography. In order to ensure the safety of surgery, we first performed embolization of the aneurysm and then resected the tumor.

A novel compound heterozygous mutation of SLC12A3 gene in a pedigree with Gitelman syndrome and literature review.

BACKGROUND: Gitelman syndrome (GS) is a tubulopathy characterized by hypokalemia, hypomagnesemia, hypocalciuria and metabolic alkalosis, which is caused by mutations in SLC12A3 gene. OBJECTIVE: The objective of this study was to investigate the mutation of SLC12A3 gene in a pedigree with GS and analyzed the clinical manifestations. METHODS: Next-generation sequencing and Sanger sequencing were performed to explore the mutations of SLC12A3 gene in a GS pedigree that included a 59-year-old male GS patient and a total of 11 family members within three generations. RESULTS: A novel compound heterozygous mutation of SLC12A3 gene (c.1712T > C in exon14 and c.2986_2987ins GCT in exon26) was identified by genetic testing in the proband. Moreover, we demonstrated that two brothers shared the same heterozygous mutation with the proband, but only one brother had the GS related symptoms. His nephew was the carrier of one mutation (c.1712T > C), and one of his brother, his sister and niece were carriers of the other (c.2986_2987ins GCT). CONCLUSIONS: This is the first study to report the novel pathogenic compound heterozygous mutation of SLC12A3 gene in GS. Our result further supports the lack of phenotype-genotype correlations in GS. Further functional studies are required to investigate pathophysiologic mechanisms of GS.

Role of Asparagine Endopeptidase in Mediating Wild-Type p53 Inactivation of Glioblastoma.

BACKGROUND: Isocitrate dehydrogenase wild-type (WT) glioblastoma (GBM) accounts for 90% of all GBMs, yet only 27% of isocitrate dehydrogenase WT-GBMs have p53 mutations. However, the tumor surveillance function of WT-p53 in GBM is subverted by mechanisms that are not fully understood. METHODS: We investigated the proteolytic inactivation of WT-p53 by asparaginyl endopeptidase (AEP) and its effects on GBM progression in cancer cells, murine models, and patients' specimens using biochemical and functional assays. The sera of healthy donors (n = 48) and GBM patients (n = 20) were examined by enzyme-linked immunosorbent assay. Furthermore, effects of AEP inhibitors on GBM progression were evaluated in murine models (n = 6-8 per group). The statistical significance between groups was determined using two-tailed Student t tests. RESULTS: We demonstrate that AEP binds to and directly cleaves WT-p53, resulting in the inhibition of WT-p53-mediated tumor suppressor function in both tumor cells and stromal cells via extracellular vesicle communication. High expression of uncleavable p53-N311A-mutant rescue AEP-induced tumorigenesis, proliferation, and anti-apoptotic abilities. Knock down or pharmacological inhibition of AEP reduced tumorigenesis and prolonged survival in murine models. However, overexpression of AEP promoted tumorigenesis and shortened the survival time. Moreover, high AEP levels in GBM tissues were associated with a poor prognosis of GBM patients (n = 83; hazard ratio = 3.94, 95% confidence interval = 1.87 to 8.28; P < .001). A correlation was found between high plasma AEP levels and a larger tumor size in GBM patients (r = 0.6, P = .03), which decreased dramatically after surgery. CONCLUSIONS: Our results indicate that AEP promotes GBM progression via inactivation of WT-p53 and may serve as a prognostic and therapeutic target for GBM.

Appraisal of Non-Cardiovascular Safety for Sodium-Glucose Co-Transporter 2 Inhibitors: A Systematic Review and Meta-Analysis of Placebo-Controlled Randomized Clinical Trials.

Background: Whereas the cardiovascular safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors has been well reported, there is limited data from controlled clinical trials regarding the non-cardiovascular safety. This was the focus of our study. Methods and Findings: We systematically searched MEDLINE, EMBASE, and Cochrane Library (5th Sep 2018) for randomized controlled trials (RCTs) that reported safety data for SGLT2 inhibitors and placebo. Relative risks (RRs) and their 95% confidence intervals (CIs) were pooled using random-effects models. Seventy RCTs (83 studies enrolling 36,958 patients in 78 publications) were identified. SGLT2 inhibitors were associated with a lower risk of serious adverse events (RR 0.90, 95% CI 0.86 to 0.94, P < 0.001), death (RR 0.78, 95% CI 0.64 to 0.94, P < 0.05), gastroenteritis (RR 0.38, 95% CI 0.20 to 0.72, P < 0.05), arthralgia (RR 0.72, 95% CI 0.54 to 0.96, P < 0.05), hypertension (RR 0.61, 95% CI 0.50 to 0.75, P < 0.001), and edema/peripheral edema (RR 0.49, 95% CI 0.33 to 0.72, P < 0.001) compared to placebo. SGLT2 inhibitors were associated with higher risk of infections compared to placebo (RR 1.27, 95% CI 1.17 to 1.37, P < 0.001), especially for genital mycotic infection (GMI) (RR 3.71, 95% CI 3.19 to 4.32, P < 0.001). Other significant effects were observed for osmotic diuresis-related AEs (RR 2.73, 95% CI 2.20 to 3.40, P < 0.001), volume-related AEs (RR 1.26, 95% CI 1.08 to 1.46, P < 0.05), renal-related AEs (RR 1.36, 95% CI 1.02 to 1.80, P < 0.05), hypoglycemia (RR 1.18, 95% CI 1.10 to 1.26, P < 0.001), and increased blood ketone bodies (RR 2.00, 95% CI 1.01 to 3.97, P < 0.05). Subgroup and sensitivity analyses strengthened the robustness of primary results. Conclusion: Results from RCTs confirmed lower risk of death, serious adverse events, hypertension, and edema associated with type 2 diabetes mellitus (T2DM) patients treated with SGLT2 inhibitors when compared with placebo. The use of SGLT2 inhibitors were associated with higher risk of infection, osmotic diuresis, volume depletion effects, renal related AEs, and higher blood ketone bodies when compared with placebo.

Rare Intrasellar Arachnoid Cyst Distinguishing From Other Benign Cystic Lesions and its Surgical Strategies.

The study reported a case of an intrasellar arachnoid cyst with visual disturbances as the main symptom. Arachnoid cyst is a common intracranial benign space-occupying lesion, but rarely seen in intrasellar region with less than 100 cases reported available in English language literature. Therefore, it is still controversial about the diagnosis and treatment of such patients. This article reviewed previous literature and discussed the differential diagnosis and surgical strategies of intrasellar arachnoid cyst in combination with our own case.

TRB3 stimulates SIRT1 degradation and induces insulin resistance by lipotoxicity via COP1.

Fatty acid-induced lipotoxicity plays an important role in the pathogenesis of diabetes mellitus. Our previous studies have documented that lipotoxicity contributes to the onset and development of diabetes via insulin resistance and/or compromised function of the pancreatic ß-cells. However, the underlying molecular mechanisms associating lipotoxicity with insulin resistance remain to be fully elucidated. In this study, we explored the role of TRB3-COP1-SIRT1 in lipotoxicity leading to insulin resistance in hepatocytes. High fat diet (HFD)-fed mice and hepG2 cells stimulated with palmitate were utilized as models of lipid metabolism disorders. We analyzed the interactions of SIRT1 and COP1 with each other and with TRB3 using co-immunoprecipitation, western blotting. SIRT1 ubiquitination was also explored. Animal and cell experiments showed that lipotoxicity induced SIRT1 down-regulation at the protein level without altering the mRNA level, whereas, lipotoxicity led to up-regulation of TRB3 and COP1 at both the gene and protein levels. Mechanistic analysis indicated that COP1 functioned as an E3 Ub-ligase of SIRT1, responsible for its proteasomal degradation under lipotoxic conditions. TRB3 recruited COP1 to SIRT1 to promote its ubiquitination. Our data indicated for the first time that TRB3-COP1-SIRT1 pathway played an important role in lipotoxicity leading to insulin resistance in hepatocytes, and suggested that COP1 could be a potential therapeutic choice for the treatment of diabetes mellitus, with lipotoxicity being the important pathomechanism.

High Thyroid Stimulating Hormone Level Is Associated With Hyperandrogenism in Euthyroid Polycystic Ovary Syndrome (PCOS) Women, Independent of Age, BMI, and Thyroid Autoimmunity: A Cross-Sectional Analysis.

Background: Infertility and dyslipidemia are frequently present in both women with polycystic ovary syndrome (PCOS) and subjects with thyroid dysfunction. Limited study regarding the association between thyroid stimulating hormone (TSH) level and phenotypes in euthyroid PCOS women. We aimed to determine whether the variation of TSH level associates with phenotypes in euthyroid PCOS patients. Methods: Cross-sectional study including 600 PCOS and 200 age, body mass index (BMI), and thyroid autoimmunity-matched Chinese women from Renji hospital, Shanghai Jiaotong university during January 2010 and August 2018. The anthropometric and serum biochemical parameters related to TSH, thyroid autoimmunity, lipid profiles, and sex steroids were detected. Results: The TSH level is higher in (2.29 ± 1.24 vs. 1.86 ± 0.90 mu/L, p < 0.001) in PCOS than controls. In euthyroid PCOS patients, TSH, TG, TC, LDL-c, and apoB level increased from non-hyperandrogenism (nonHA) to HA group (all p < 0.05). TSH level is positively associated with TG, apoB, free T, FAI, and negatively associated with apoA (all p < 0.05). The percentage of HA increased from TSH level (57.93% in TSH < = 2.5 group vs. 69.46% in TSH > 2.5 mU/L group, p = 0.006). HA phenotype is increased with TSH level independently of age, BMI, WC, LDL-C. Besides, in multivariate logistic regression analysis TSH and TG significantly associated with HA phenotype. Conclusions: Higher TSH level is associated with increased prevalence of HA phenotype independent of age, BMI and thyroid autoimmunity in euthyroid PCOS.

Palliative Interventional Embolization for Finding of Ectopic Noradrenaline-Secreting Pheochromocytoma in the Nasal Cavity.

A 52-year-old male who had chronic hypertension for several years presented with abrupt epistaxis. The CT scan revealed a 40 mm × 40 mm mass in the nasal cavity intended to the maxillary sinus and the base of skull. Nasal endoscope biopsy and serum/urinary catecholamine detection conformed an ectopic noradrenaline-secreting pheochromocytoma. The present research was to discuss the clinical characteristics of the rare pheochromocytoma and the palliative interventional embolization for it.