High Vasohibin-2 expression correlated with autophagy in proliferative diabetic retinopathy.

Vasohibin-2 (VASH2) is confirmed to be associated with angiogenesis. To investigate the vitreous levels of VASH2 and how VASH2 induces angiogenesis in proliferative diabetic retinopathy (PDR), a total of 120 eyes were enrolled in this prospective and randomized controlled study and the vitreous level of VASH2 was quantified by Luminex liquid suspension chip. Vector systems were applied in human retinal microvascular endothelial cells (HRMECs) for VASH2 gene overexpression, along with interfering lentiviral vectors (VASH2-shRNA) for VASH2 gene silencing. Cell migration, autophagic flux, as well as the expression of α-tubulin, detyrosinated ⍺-tubulin, LC3 II/LC3 I, P62 were detected under normal, VASH2 overexpression, or interference conditions. The level of VASH2 in PDR patients was significantly higher (218.61 ± 30.14 pg/ml) than that in ERM/MH patients (80.78 ± 2.05 pg/ml) (P = 0.001). The migration ability of HRMECs was significantly increased in VASH2 overexpression group, while in the interfering group, the migration ability decreased. VASH2 increased the detyrosination of ⍺-tubulin. The high fluorescence intensity of autophagic flux showed an activation of autophagy in VASH2 overexpression group, which was also confirmed by the increase of LC3 II/LC3 I ratio and the decrease of P62. Collectively, the present study shows in PDR, vitreous level of VASH2 is higher. VASH2 promotes neovascularization by inducing autophagy, suggesting VASH2 could be a new anti-angiogenic drug target for PDR.

Long-term exercise preserves pancreatic islet structure and ß-cell mass through attenuation of islet inflammation and fibrosis.

Islet fibrosis is associated with the disruption of islet structure and contributes to ß-cell dysfunction, playing an essential role in the pathogenesis of type 2 diabetes. Physical exercise has been shown to attenuate fibrosis in various organs; however, the effect of exercise on islet fibrosis has not been defined. Male Sprague-Dawley rats were divided into four groups: normal diet sedentary [N-Sed], normal diet + exercise [N-Ex], high-fat diet sedentary [H-Sed], and high-fat diet + exercise [H-Ex]. After 60 weeks of exercise, 4452 islets from Masson-stained slides were analyzed. Exercise led to a 68% and 45% reduction in islet fibrosis in the normal and high-fat diet groups and was correlated with a lower serum blood glucose. Fibrotic islets were characterized by irregular shapes and substantial loss of ß-cell mass, which were significantly reduced in the exercise groups. Remarkably, the islets from exercised rats at week 60 were morphologically comparable to those of sedentary rats at 26 weeks. In addition, the protein and RNA levels of collagen and fibronectin, and the protein levels of hydroxyproline in the islets were also attenuated by exercise. This was accompanied by a significant reduction in inflammatory markers in the circulation Interleukin-1 beta (IL-1ß)] and pancreas [IL-1ß, Tumor Necrosis Factor-alpha, Transforming Growth Factor-ß, and Phosphorylated Nuclear Factor Kappa-B p65 subunit], lower macrophage infiltration, and stellate cell activation in the islets of exercised rats. In conclusion, we have demonstrated that long-term exercise preserves pancreatic islet structure and ß-cell mass through anti-inflammatory and anti-fibrotic actions, suggesting additional rationales for the success of exercise training in the prevention and treatment of type 2 diabetes that should be further explored.

KLF10 promotes nonalcoholic steatohepatitis progression through transcriptional activation of zDHHC7.

Nonalcoholic steatohepatitis (NASH), characterized by hepatic steatosis, inflammation, and liver injury, has become a leading cause of end-stage liver diseases and liver transplantation. Krüppel-like factors 10 (KLF10) is a Cys2/His2 zinc finger transcription factor that regulates cell growth, apoptosis, and differentiation. However, whether it plays a role in the development and progression of NASH remains poorly understood. In the present study, we found that KLF10 expression was selectively upregulated in the mouse models and human patients with NASH, compared with simple steatosis (NAFL). Gain- and loss-of function studies demonstrated that hepatocyte-specific overexpression of KLF10 aggravated, whereas its depletion alleviated diet-induced NASH pathogenesis in mice. Mechanistically, transcriptomic analysis and subsequent functional experiments showed that KLF10 promotes hepatic lipid accumulation and inflammation through the palmitoylation and plasma membrane localization of fatty acid translocase CD36 via transcriptionally activation of zDHHC7. Indeed, both expression of zDHHC7 and palmitoylation of CD36 are required for the pathogenic roles of KLF10 in NASH development. Thus, our results identify an important role for KLF10 in NAFL-to-NASH progression through zDHHC7-mediated CD36 palmitoylation.

Screening for frailty and its association with activities of daily living, cognitive impairment, and falls among community-dwelling older adults in China.

OBJECTIVES: Frailty is a prevalent geriatric condition that significantly impacts the health of older adults. This study aimed to examine the prevalence of frailty among older Chinese adults aged ≥ 65 years and to assess its association with adverse geriatric outcomes. METHOD: This study included 20,724 older adults aged ≥ 65 years in Jiangsu Province, China, utilizing a random, stratified, multistage cluster sampling approach. Frailty was assessed using the 5-item FRAIL scale. Geriatric outcomes, such as independence in activities of daily living (ADL), cognitive impairment, and frequent fall events (occurring four or more times in the preceding year), were evaluated. Logistic regression models were employed to evaluate the association between frailty and geriatric outcomes, with results presented as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The mean age of the participants was 73.4 ± 6.4 years. The standardized prevalence of prefrailty and frailty was 35.2% and 10.3%, respectively. Individuals identified as prefrail or frail tended to live in rural areas, have lower educational levels, be widowed, have lower incomes, and engage in less physical activity. Prefrailty and frailty were associated with an increased risk of limitations in BADL (OR: 9.62, 95% CI: 7.43-12.46; and OR: 29.25, 95% CI: 22.42-38.17, respectively) and IADL (OR: 2.54, 95% CI 2.35-2.74; and OR: 5.19, 95% CI 4.66-5.78, respectively), positive cognitive impairment screening (OR: 1.23, 95% CI: 1.16-1.31; and OR: 1.72, 95% CI: 1.56-1.91, respectively), and frequent falls (occurring four or more times in the preceding year) (OR: 3.38, 95% CI: 2.50-4.56; and OR: 8.37, 95% CI: 6.01-11.65). The association between frailty and both limitations in BADL and falls was notably more pronounced among the younger age groups (p for interaction < 0.001). CONCLUSIONS: According to the 5-item FRAIL scale, frailty was associated with limitations in BADLs and IADLs, positive cognitive impairment screening, and recent falls among older adults living in the community. Screening for frailty in younger age groups has the potential to prevent declines in physical function and falls.

The clinical evaluation of the triglyceride-glucose index as a risk factor for coronary artery disease and severity of coronary artery stenosis in patients with chronic kidney disease.

INTRODUCTION: Insulin resistance (IR) plays an important role in the occurrence and development of cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). The triglyceride-glucose (TyG) index is a simple and effective tool to evaluate IR. This study aimed to evaluate the association of the TyG index with coronary artery disease (CAD) and the severity of coronary artery stenosis (CAS) in nondialysis patients with stages 3-5 CKD. METHODS: Nondialysis patients with stages 3-5 CKD who underwent the first coronary angiography at Zhongda Hospital affiliated with Southeast University from August 2015 to January 2017 were retrospectively analyzed. CAS was measured by coronary angiography, and the CAS score was calculated as the Gensini score. Logistic regression analysis was used to determine the related factors of CAD and severe CAS. RESULTS: A total of 943 patients were enrolled in this cross-sectional study and 720 (76.4%) of these patients were diagnosed with CAD. The TyG index in the CAD group (7.29 ± 0.63) was significantly higher than that in the non-CAD group (7.11 ± 0.61) (p < 0.001). Multivariate logistic regression analysis showed that a higher TyG index was an independent risk factor for CAD in CKD patients after adjusting for related confounding factors (OR = 2.865, 95% CI 1.681-4.885, p < 0.001). Patients in the CAD group were divided into three groups according to the Gensini integral quantile level. Multivariate logistic regression analysis showed that the TyG index was an independent related factor for severe CAS after adjusting for relevant confounding factors (p < 0.001). CONCLUSIONS: The TyG index is associated with CAD and the severity of CAS in patients with nondialysis stages 3-5 CKD. A higher TyG index is an independent factor for CAD and severe CAS.

Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Vaccination for Negative Conversion Time of Nucleic Acid in Nonsevere COVID-19 Patients Infected by SARS-CoV-2 Omicron Variant.

SARS-CoV-2 Omicron variant is significantly different from all the previous variants and has rapidly replaced other variants as the dominant variant across the globe. An easily obtained, inexpensive, and rapid marker is needed to predict the negative conversion time (NCT) of nucleic acid in nonsevere COVID-19 patients infected by the Omicron variant. This retrospective study enrolled 226 patients infected by the Omicron variant between April 23, 2022, and May 16, 2022. The median age of the patients was 61 (interquartile range (IQR), 48-70) years, and 56.2% were male. 84 patients (37.2%) had at least one comorbidity, and 49 patients (21.7%) were classified into the moderate illness group. 145 patients (64.2%) received at least one dose of vaccine, in which 67 patients (29.6%) received a booster dose of vaccine. The median duration of NCT was 8 (IQR, 7-11) days. Univariate Cox analyses found that high NLR (>2.22), aged ≥65 years, vaccination, and moderate illness were significantly related to the NCT of nucleic acid. Multivariate Cox regression analysis showed that high NLR (NLR > 2.22, hazard ratio (HR):0.718, 95% CI: 0.534-0.964, p = 0.028) and vaccination (vaccinated ≥1 dose, HR: 1.536, 95% CI: 1.147-2.058, p = 0.004) were independently associated with NCT of nucleic acid. NLR is a rapid, simple, and useful prognostic factor for predicting NCT of nucleic acid in nonsevere COVID-19 patients with the Omicron variant. In addition, vaccination may also play a valuable role in predicting the NCT of nucleic acid.

MicroRNA-193b impairs muscle growth in mouse models of type 2 diabetes by targeting the PDK1/Akt signalling pathway.

AIMS/HYPOTHESIS: Type 2 diabetes is associated with a reduction in skeletal muscle mass; however, how the progression of sarcopenia is induced and regulated remains largely unknown. We aimed to find out whether a specific microRNA (miR) may contribute to skeletal muscle atrophy in type 2 diabetes. METHODS: Adeno-associated virus (AAV)-mediated skeletal muscle miR-193b overexpression in C57BLKS/J mice, and skeletal muscle miR-193b deficiency in db/db mice were used to explore the function of miR-193b in muscle loss. In C57BL/6 J mice, tibialis anterior-specific deletion of 3-phosphoinositide-dependent protein kinase-1 (PDK1), mediated by in situ AAV injection, was used to confirm whether miR-193b regulates muscle growth through PDK1. Serum miR-193b levels were also analysed in healthy individuals (n = 20) and those with type 2 diabetes (n = 20), and correlations of miR-193b levels with HbA1c, fasting blood glucose (FBG), body composition, triacylglycerols and C-peptide were assessed. RESULTS: In this study, we found that serum miR-193b levels increased in individuals with type 2 diabetes and negatively correlated with muscle mass in these participants. Functional studies further showed that AAV-mediated overexpression of miR-193b induced muscle loss and dysfunction in healthy mice. In contrast, suppression of miR-193b attenuated muscle loss and dysfunction in db/db mice. Mechanistic analysis revealed that miR-193b could target Pdk1 expression to inactivate the Akt/mammalian target of rapamycin (mTOR)/p70S6 kinase (S6K) pathway, thereby inhibiting protein synthesis. Therefore, knockdown of PDK1 in healthy mice blocked miR-193b-induced inactivation of the Akt/mTOR/S6K pathway and impairment of muscle growth. CONCLUSIONS/INTERPRETATION: Our results identified a previously unrecognised role of miR-193b in muscle function and mass that could be a potential therapeutic target for treating sarcopenia.

Cholecystectomy is associated with dysglycaemia: Cross-sectional and prospective analyses.

Cholecystectomy has been reported to be associated with increased risk of diabetes in cross-sectional studies. In the current study, we performed both cross-sectional and prospective analyses to examine the association between cholecystectomy and dysglycaemia in Chinese community-dwelling adults. A total of 1612 participants (n = 1564 without cholecystectomy and n = 48 with cholecystectomy) were evaluated for glycaemic status (according to the World Health Organization (WHO) 1999 criteria) and then followed up over ~3.2 years. Percent changes (Δ) in fasting blood glucose and HbA1c from baseline at the follow-up visit were calculated to define glycaemic control as stable (-10% ≤ Δ < 10%), improved (Δ < -10%), or worsened (Δ ≥ 10%). The baseline cross-sectional analyses indicated that cholecystectomy was associated with an increased risk of both prediabetes and diabetes, while the prospective analysis indicated that cholecystectomy was also associated with a greater risk of deterioration in glycaemic control (ΔFPG ≥10% and ΔHbA1c ≥10%) (P < 0.05 for each, both before and after adjusting for potential confounding covariates). These observations suggest that individuals in the Chinese community-dwelling population who have undergone cholecystectomy are at increased risk of dysglycaemia. Further studies are warranted to both delineate the underlying mechanisms and to clarify whether more intense surveillance for future development of diabetes is needed in this group.

The elevation of serum uric acid depends on insulin resistance but not fasting plasma glucose in hyperuricaemia.

OBJECTIVES: The association between serum uric acid (SUA) and fasting plasma glucose (FPG) has not been fully outlined, in particular in hyperuricaemic population. This study aimed to address this issue, along with the exploration of the role of insulin resistance that was assessed by triglyceride-and-glucose (TyG) index. METHODS: A total of 16,297 participants without known diabetes from the SENSIBLE and SENSIBLE-Addition studies were included in the present analysis. Hyperuricaemia was defined as SUA ≥6 mg/dL. Generalised addictive model was applied to establish the relationship of SUA with FPG, and mediation analysis was performed to assess how insulin resistance affected the relationship. RESULTS: SUA showed an inverted U-shaped association with FPG, with the turning point of FPG at 6.1 mmol/L and 7.5 mmol/L in normouricaemic and hyperuricaemic participants, respectively. However, the significant relationship between SUA and FPG disappeared in hyperuricaemic participants (form B=3.3, 95% CI: 0.6-5.9, p=0.016 to B= -0.2, 95% CI: -3.1-2.7, p=0.894), and attenuated in normouricaemic participants (from B=9.8, 95% CI: 8.0-11.7, p<0.001 to B=7.3, 95% CI: 5.3-9.2, p<0.001) after controlling for TyG index. In the ascending segment, the relationship between SUA and FPG was partially mediated by TyG index in normouricaemic participants, but fully in hyperuricaemic participants. CONCLUSIONS: SUA had an inverted U-shaped relationship with FPG, and their positive relationship was fully mediated by insulin resistance in participants with hyperuricaemia but not those without.

Tea consumption and risk of diabetes in the Chinese population: a multi-centre, cross-sectional study.

The aim of the present study was to explore the influence of tea consumption on diabetes mellitus in the Chinese population. This multi-centre, cross-sectional study was conducted in eight sites from south, east, north, west and middle regions in China by enrolling 12 017 subjects aged 20-70 years. Socio-demographic and general information was collected by a standardised questionnaire. A standard procedure was used to measure anthropometric characteristics and to obtain blood samples. The diagnosis of diabetes was determined using a standard 75-g oral glucose tolerance test. In the final analysis, 10 825 participants were included and multiple logistic models and interaction effect analysis were applied for assessing the association between tea drinking with diabetes. Compared with non-tea drinkers, the multivariable-adjusted OR for newly diagnosed diabetes were 0·80 (95 % CI 0·67, 0·97), 0·88 (95 % CI 0·71, 1·09) and 0·86 (95 % CI 0·67, 1·11) for daily tea drinkers, occasional tea drinkers and seldom tea drinkers, respectively. Furthermore, drinking tea daily was related to decreased risk of diabetes in females by 32 %, elderly (>45 years) by 24 % and obese (BMI > 30 kg/m2) by 34 %. Moreover, drinking dark tea was associated with reduced risk of diabetes by 45 % (OR 0·55; 95 % CI 0·42, 0·72; P < 0·01). The results imply that drinking tea daily was negatively related to risk of diabetes in female, elderly and obese people. In addition, drinking dark tea was associated with decreased risk of type 2 diabetes mellitus.

Association Between Cardiorespiratory Fitness and Risk of Heart Failure: A Meta-Analysis.

BACKGROUND: Evidence emerges that cardiorespiratory fitness (CRF) might be implicated in the development of heart failure (HF). This meta-analysis aimed to quantify the association between CRF exposed at baseline and HF risk with dose-response analysis and to assess whether CRF changes over time are correlated with alterations in HF risk. METHODS AND RESULTS: Cohort studies that assessed the association between CRF and risk of HF in subjects without baseline HF were included. Study-specific multivariate-adjusted relative risks (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Ten studies from 8 articles were included, enrolling 8987 incident HF cases from 154,598 participants. The RR of HF per 1-metabolic equivalent (MET) higher CRF at baseline was 0.82 (95% CI 0.80-0.84) in the overall population. The RRs were similar in men (0.82, 95% CI 0.80-0.85) and women (0.81, 95% CI 0.78-0.84), and remained minorly changed in patients with existing diabetes, hypertension, or cardiovascular disease at entry. No evidence of a nonlinear relationship between CRF at baseline and risk of HF was observed (Pnonlinearity = .18). The RR of HF per 1-MET increase in CRF over time was 0.79 (95% CI 0.67-0.93), and the measurement of CRF provided incremental value to the prediction of HF beyond conventional models. CONCLUSIONS: High or increased CRF resulted in reduced risk of HF in a dose-dependent manner, supporting the necessity to increase CRF to prevent HF in clinical practice.

OCT1-Mediated Metformin Uptake Regulates Pancreatic Stellate Cell Activity.

BACKGROUND/AIMS: Metformin treatment is reported to be associated with a lower incidence of and mortality from pancreatic cancer (PC) in type 2 diabetes patients. Activated pancreatic stellate cells (PSCs) are key stroma cells responsible for pancreatic fibrogenesis and PC progression. However, little research is about the influence of metformin on PSCs. Given the potential beneficial effects of metformin on PC, pancreatic tumour stroma is an important target for new therapeutics. We observed the effects of metformin on PSCs. We investigated the effects of metformin on human PSCs proliferation and the production of extracellular matrix (ECM) proteins. METHODS: Cells were cultured with different concentrations of metformin (0-10 mmol/L). Cell proliferation was determined by immunofluorescence staining for nuclear Ki67 labelling. ECM production was studied by quantitative real-time polymerase chain reaction, immunoblotting and immunofluorescence microscopy. Adenosine monophosphate-activated protein kinase (AMPK), an important regulatory molecule responsible for metformin action, and the organic cation transporter member 1 (OCT1), which is believed to be the most important transporter for the pharmacological action of metformin, were investigated for their possible involvements in metformin-induced proliferation and ECM production. RESULTS: Our results showed that metformin inhibited PSCs proliferation and decreased the production of ECM proteins by activation of AMPK phosphorylation. Silencing of OCT1 expression resulted in a reduction in the effects of metformin on PSCs activity. CONCLUSIONS: Collectively, the data indicate that OCT1 may contribute to uptake metformin and regulate PSCs activity. OCT1 is a target of metformin in regulating PSCs activity.

Exercise training and endothelial function in patients with type 2 diabetes: a meta-analysis.

BACKGROUND AND AIMS: Exercise training is considered a cornerstone in the management of type 2 diabetes, which is associated with impaired endothelial function. However, the association of exercise training with endothelial function in type 2 diabetes patients has not been fully understood. This meta-analysis aimed to investigate their associations with focus on exercise types. METHODS: Databases were searched up to January 2018 for studies evaluating the influences of exercise training with durations ≥ 8 weeks on endothelial function assessed by flow-mediated dilation (FMD) among type 2 diabetes patients or between type 2 diabetics and non-diabetics. Data were pooled using random-effects models to obtain the weighted mean differences (WMDs) and 95% confidence intervals (CIs). RESULTS: Sixteen databases were included. Exercise training resulted in an overall improvement in FMD by 1.77% (95% CI 0.94-2.59%) in type 2 diabetes patients. Specifically, both aerobic and combined aerobic and resistance exercise increased FMD by 1.21% (95% CI 0.23-2.19%) and 2.49% (95% CI 1.17-3.81%), respectively; but resistance exercise only showed a trend. High-intensity interval aerobic exercise did not significantly improve FMD over moderate-intensity continuous exercise. Notably, the improvement in FMD among type 2 diabetes patients was smaller compared with non-diabetics in response to exercise training (WMD - 0.72%, 95% CI - 1.36 to - 0.08%) or specifically to aerobic exercise (WMD - 0.65%, 95% CI - 1.31 to 0.01%). CONCLUSIONS: Exercise training, in particular aerobic and combined exercise, improves endothelial function in type 2 diabetes patients, but such an improvement appears to be weakened compared with non-diabetics. Trial registration PROSPERO CRD42018087376.

Circulating irisin in patients with polycystic ovary syndrome: a meta-analysis.

There is growing interest in exploring circulating (plasma/serum) irisin in polycystic ovary syndrome (PCOS) patients. This meta-analysis aimed to summarize the evidence assessing circulating irisin changes in this population. A systematic search was conducted in three databases: PubMed, Cochrane Library and Web of Science, for studies reporting irisin in PCOS patients compared with healthy controls or stratified by body mass index (BMI), or assessing irisin response to hyperinsulinemia. Effect sizes (Cohen's d with 95% confidence intervals [CI]) were calculated using random-effects models. Eight studies with 918 PCOS patients and 528 healthy controls were included. Results showed that circulating irisin was higher in PCOS patients than in overall healthy controls (d = 0.37, 95% CI 0.05 to 0.70), but not compared with BMI-matched or age- and BMI-matched controls. Circulating irisin was higher in PCOS patients with higher BMI than lower (d = 0.36, 95% CI 0.16 to 0.56). Circulating irisin decreased 2 h later in response to euglycemic hyperinsulinemia in PCOS patients with a larger magnitude than healthy controls (d = -0.32, 95% CI -0.53 to -0.11). In summary, with adjustment for BMI, circulating irisin in PCOS patients seems comparable to healthy controls, but its response to hyperinsulinemia might be impaired.

Step counter use in type 2 diabetes: a meta-analysis of randomized controlled trials.

BACKGROUND: While step counter use has become popular among type 2 diabetes (T2D) patients, its effectiveness in increasing physical activity (PA) and improving glycemic control has been poorly defined. The aim of this meta-analysis of randomized controlled trials (RCTs) was to evaluate the association of step counter use with PA and glycemic control in T2D patients. METHODS: Articles were identified by searches of PubMed, Web of Science and Cochrane Library from January 1994 to June 2013. RCTs in the English language were included, if they had assessed the effectiveness of step counters as motivating and monitoring tools in T2D patients, with reported changes in steps per day (steps/d) or glycosylated hemoglobin A1c (HbA1c), or both. Data were independently collected by 2 authors and overall estimates were made by a random-effects model. RESULTS: Of the 551 articles retrieved, 11 RCTs were included. Step counter use significantly increased PA by 1,822 steps/d (7 studies, 861 participants; 95% confidence interval (CI): 751 to 2,894 steps/d) in patients with T2D. Step counter use with a PA goal showed a bigger increase in PA (weighted mean difference (WMD) 3,200 steps/d, 95% CI: 2,053 to 4,347 steps/d) than without (WMD 598 steps/d, 95% CI: -65 to 1,260 steps/d). Further subgroup analysis suggested step counter use with a self-set PA goal (WMD 2,816 steps/d, 95% CI: 1,288 to 4,344 steps/d) made no difference in increasing PA from a 10,000 steps/d goal (WMD 3,820 steps/d, 95% CI: 2,702 to 4,938 steps/d). However, no significant HbA1c change was observed by step counter use (10 studies, 1,423 participants; WMD 0.02%, 95% CI: -0.08% to 0.13%), either with (WMD 0.04%, 95% CI: -0.21% to 0.30%) or without a PA goal (WMD 0.01%, 95% CI: -0.10% to 0.13%). CONCLUSIONS: Step counter use is associated with a significant increase in PA in patients with T2D. However, evidence regarding its effect in improving glycemic control remains insufficient. TRIAL REGISTRATION: PROSPERO CRD42013005236.

Combined use of Anlotinib with chemotherapy in patients with advanced ovarian cancer: a real-world cohort study and meta-analysis.

Background: Anlotinib is a novel oral small-molecule receptor tyrosine kinase inhibitor. However, the efficacy and safety of its combined use with chemotherapy remain unclear in patients with advanced ovarian cancer. Objectives: To assess the efficacy and safety of the combined use of Anlotinib with chemotherapy in patients with advanced ovarian cancer. Design: A multi-center retrospective real-world analysis and a meta-analysis. Data sources and methods: We enrolled patients with advanced ovarian cancer who received a combination therapy of Anlotinib and chemotherapy from 15 medical centers. We also searched electronic databases for studies assessing the efficacy and safety of the combined use of Anlotinib with chemotherapy in patients with ovarian cancer. The outcomes of interest included objective response rate (ORR), disease control rate (DCR), and median progression-free survival (mPFS). Results: A total of 71 patients, who were predominantly recurrent cases, were included in the real-world study. The ORR and DCR of the included patients were 40.8% and 76.1%, respectively; and their mPFS was 4.6 months. The log-rank test showed that previous antiangiogenic therapy was related to a longer mPFS (p < 0.05). Five studies in total were eligible for meta-analysis. The random-effects meta-analysis model showed that the ORR, DCR, and mPFS were 33.8% [95% confidence interval (CI) 22.7-44.8% from four studies], 90.6% (95% CI 73.6-99.9% from five studies), and 6.6 months (95% CI 4.9-8.4 months from five studies). The most common adverse events were hand-foot syndrome and hypertension. Conclusion: The combined use of Anlotinib with chemotherapy showed potential in treating patients with advanced ovarian cancer, with a tolerable safety profile.

Muscle Quality in Relation to Prediabetes Phenotypes: A Population-Based Study With Mediation Analysis.

CONTEXT: Prediabetes is associated with an increased risk of physical disability, yet no studies have assessed the extent to which muscle quality, a measure reflecting muscle functionality, was altered in prediabetes and its specific phenotype. OBJECTIVE: We evaluated their associations in a general US population with mediation analysis. METHODS: This was a cross-sectional study based on the National Health and Nutrition Examination Survey 2011-2014. Participants with prediabetes were stratified as having an isolated defect (impaired fasting glucose [IFG], impaired glucose tolerance [IGT], or impaired hemoglobin A1c [IA1c]), 2 defects (IFG + IGT, IFG + IA1c, or IGT + IA1c), or all defects (IFG + IGT + IA1c). Muscle quality was calculated as dominant grip strength divided by dominant arm muscle mass measured by dual-energy X-ray absorptiometry. RESULTS: We included 2351 participants (938 with prediabetes and 1413 with normoglycemia). Despite higher grip strength and larger arm muscle mass, arm muscle quality was lower in prediabetes and all prediabetes phenotypes (except for IGT) than normoglycemia (all P < .04), and was unrelated to prediabetes awareness. Arm muscle quality was decreased and the odds of low arm muscle quality was increased in prediabetes with increasing numbers of glucometabolic defects (both P < .001), with insulin resistance being the predominant mediator. HbA1c-defined prediabetes (IA1c) had lower arm muscle quality and higher odds of low arm muscle quality than blood glucose-defined prediabetes (IFG, IGT, or IFG + IGT). CONCLUSION: Muscle quality was impaired in prediabetes and its specific phenotype. Relative to blood glucose, elevated HbA1c might be a better predictor of reduced muscle quality.

Performance of different machine learning algorithms in identifying undiagnosed diabetes based on nonlaboratory parameters and the influence of muscle strength: A cross-sectional study.

AIMS/INTRODUCTION: Machine learning algorithms based on the artificial neural network (ANN), support vector machine, naive Bayesian or logistic regression model are commonly used to identify diabetes. This study investigated which approach performed the best and whether muscle strength provided any incremental benefit in identifying undiagnosed diabetes in Chinese adults. METHODS: This cross-sectional study enrolled 4,482 eligible participants from eight provinces in China, who were randomly divided into the training dataset (n = 3,586) and the testing dataset (n = 896). Muscle strength was assessed by handgrip strength and the number of chair stands in the 30-s chair stand test. An oral glucose tolerance test was used to ascertain undiagnosed diabetes. The areas under the curve (AUCs) were calculated accordingly and compared with each other. RESULTS: Of the included participants, 233 had newly diagnosed diabetes. All the four machine learning algorithms, which were developed based on nonlaboratory parameters, showed acceptable discriminative ability in identifying undiagnosed diabetes (all AUCs >0.70), with the ANN approach performing the best (AUC 0.806). Adding handgrip strength or the 30-s chair stand test to this approach did not increase the AUC further (P = 0.39 and 0.26, respectively). Furthermore, compared with the New Chinese Diabetes Risk Score, the ANN approach showed a larger AUC in identifying undiagnosed diabetes (Pcomparison < 0.01), regardless of the addition of handgrip strength or the 30-s chair stand test. CONCLUSIONS: The ANN approach performed the best in identifying undiagnosed diabetes in Chinese adults; however, the addition of muscle strength might not improve its efficacy.

Can the postload-fasting glucose gap be used to determine risk of developing diabetes in chinese adults: A prospective cohort study.

OBJECTIVE: To evaluate the relationship between fasting plasma glucose (FPG) and 2-hour postload plasma glucose (2hPG) measured during an oral glucose tolerance test, and the risk of developing diabetes in Chinese adults. METHODS: We followed 3,094 participants without diabetes, categorizing them based on their oral glucose tolerance test (OGTT) results into low post load (2hPG ≤ FPG) and high post load (2hPG > FPG) at baseline. We monitored the incidence of diabetes, incidence of prediabetes, disease progression from prediabetes to diabetes and disease reversal from prediabetes to normal glucose tolerance (NGT) over an average of 3.2 years of follow-up. After the Schoenfeld residual test, Cox's time-varying covariate (Cox-TVC) models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) to compare the different clinical events between low and high post load groups. RESULTS: In the cohort study, of the 3,094 participants, 702 (22.7 %) had low post load (2hPG ≤ FPG, mean postload-fasting gap: -0.8 ± 0.7 mmol/L) and 2,392 (77.3 %) had high post load (2hPG > FPG, mean postload-fasting gap: 1.8 ± 1.2 mmol/L). Over 3.2 ± 0.2 years of follow-up, 282 (9.1 %) developed diabetes. In the low post load group, the incidence rates per 1,000 person-years were: diabetes was 7.9, prediabetes was 70.0, disease progression from prediabetes to diabetes was 23.4 and disease reversal to NGT was 327.2. For the high post load group, incidence rates for diabetes was 13.9, prediabetes was 124.3, disease progression was 59.5 and disease reversal was 238.6 per 1,000 person-years. Participants with high post load showed higher incidence rates of diabetes, prediabetes, and progression from prediabetes to diabetes compared to those with low post load. HRs were significantly higher for incident diabetes and prediabetes, and disease progression from prediabetes to diabetes, whereas disease reversal was lower. CONCLUSION: The risk of developing prediabetes/diabetes after 3.2 years of follow-up was higher in the participants with high post load. It suggested that postload-fasting gap may be a simple tool to predict the risk of developing prediabetes, diabetes or reversal to NGT.

Circulating irisin in nonalcoholic fatty liver disease: an updated meta-analysis.

INTRODUCTION: Exogenous administration of recombinant irisin may reverse hepatic steatosis and steatohepatitis. However, it remains controversial as to whether nonalcoholic fatty liver disease (NAFLD) shows reduced circulating (serum/plasma) irisin levels. A meta-analysis was conducted to address this issue. MATERIAL AND METHODS: A literature search of databases was performed up to June 2021. Observational studies that reported circulating irisin in NAFLD ascertained by any methods (e.g. ultrasonography or magnetic resonance) and compared with any controls were eligible for inclusion. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were obtained using a random-effects meta-analysis model. RESULTS: Eleven studies enrolling 1277 NAFLD cases and 944 non-NAFLD controls were included. The approaches used for NAFLD ascertainment included ultrasonography (4 studies), magnetic resonance (3 studies), and liver biopsy (5 studies). Meta-analysis showed that circulating irisin in NAFLD was comparable to any non-NAFLD controls (10 studies with 11 datasets; SMD -0.09, 95% CI: -0.48 to 0.29), including the body mass index (BMI)-matched and lean controls (both p ≥ 0.80). Restricting studies to NAFLD ascertained by magnetic resonance or liver biopsy rather than ultrasonography showed that serum irisin was reduced in NAFLD (5 studies, SMD -0.63, 95% CI: -1.14 to -0.13). Meta-analysis also suggested that circulating irisin did not differ between mild and moderate-to-severe NAFLD (7 studies; SMD 0.02, 95% CI: -0.25 to 0.30), and this association was not significantly moderated by study location (Europe versus Asia). CONCLUSIONS: Circulating irisin in NAFLD did not differ from any non-NAFLD controls and was unlikely to be affected by disease severity or racial-ethnic difference.