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Abstract Background Prior studies on the link between socioeconomic status (SES) and diabetic microvascular complications have been inconclusive. This study aimed to explore whether SES is associated with the risk of diabetic retinopathy (DR), nephropathy (DN) and diabetic peripheral neuropathy (DPN) using large prospective cohort. Methods SES was evaluated using education attainment (individual level), household income (household level), and Townsend deprivation index (TDI, neighborhood level). This study included 28,339 participants without DR, 29,951 without DN and 29,762 without DPN at baseline from the UK Biobank. Weighted Cox proportional hazard models were used to investigate the relationship between SES and the risk of diabetic microvascular complications. Results The median follow-ups of the DR, DN and DPN cohorts were 12.95, 12.89 and 13.02 years, respectively. In total, 3,177 (11.2%) participants developed DR, 4,418 (14.8%) developed DN and 1,604 (5.4%) developed DPN. After adjusting for confounders, higher education levels (DN: hazard ratios [HR] = 0.85; 95% CI, 0.82–0.89; P

Abstract Background Insulin resistance (IR) and metabolic syndrome (MetS) are significant global health challenges that increase the risk of various chronic diseases. The lymphocyte-to-high-density lipoprotein cholesterol ratio (LHR) has emerged as a novel inflammatory metabolic marker. The present study focused on evaluating the association between the LHR and both IR and MetS. Methods We analyzed data from 14,779 adults aged ≥ 20 years from the National Health and Nutrition Examination Survey (2007–2018). To investigate the relationship between LHR and both IR and MetS, we conducted multivariable logistic regression analyses. The reliability of the results was validated through both stratified and sensitivity analyses. Furthermore, we thoroughly examined possible nonlinear associations by implementing a restricted cubic spline in conjunction with a threshold effect analysis. Results Compared to the lowest LHR quartile, individuals in the highest quartile indicated significantly increased prevalence of IR (odds ratio = 3.72, 95% confidence intervals: 3.01–4.59) and MetS (odds ratio = 11.38, 95% confidence intervals: 8.85–14.63) in fully adjusted models. Subgroup analyses demonstrated that the association between the LHR and IR remained consistent across all subgroups, with no significant interaction effect observed. However, the association between LHR and MetS was more pronounced in female participants. Restricted cubic spline analyses revealed nonlinear associations between LHR and both IR and MetS. The threshold effect analyses identified inflection points at 0.055 for these non-linear relationships. Conclusions An elevated LHR was positively associated with the prevalence of IR and MetS, indicating its promising role in early screening and disease prevention through biological monitoring.

Abstract Purpose Our objective was to ascertain the most recent prevalence and trends of hyperuricemia among adolescents, stratified by sex and race/ethnicity subgroups, as well as to investigate potential risk factors associated with hyperuricemia in US adolescents. Methods Data were obtained from adolescents aged 12–17 years in the 1999–2018 NHANES cycles. Hyperuricemia for adolescents was defined as ≥ 5.5 mg/dL. The prevalence of hyperuricemia, along with 95% confidence intervals (CIs), was calculated for each four-year survey cycle, stratified by sex, race/ethnicity, body mass index (BMI), poverty income ratio (PIR), and parental education levels. Linear regression and logistic regression analyses were conducted independently to evaluate the linear trends in mean serum urate levels and the prevalence of hyperuricemia across the four-year cycles. Utilizing NHANES data from 2011 to 2018, we identified factors associated with mean serum urate levels and hyperuricemia through the application of linear regression and Poisson regression analyses. Results A total of 11 264 participants were included in the analysis. In 2015–2018, the overall hyperuricemia prevalence was 32.78%, 50.7% in males, and 13.51% in females. No significant trends were identified in the prevalence of hyperuricemia from 1999 to 2002 to 2015–2018. Between 2011 and 2018, hyperuricemia was significantly more prevalent among males compared to females (prevalence ratio [PR], 3.50 [95% CI, 2.83–4.33]), non-Hispanic Asians compared to non-Hispanic Whites (PR, 1.26 [95% CI, 1.04–1.53]), and individuals with overweight (PR, 1.63 [95% CI, 1.32–2.01]) or obesity (PR, 2.45 [95% CI, 2.08–2.88]) compared to those of normal weight. There was a stronger correlation between obesity and hyperuricemia among females (PR, 4.77 [95% CI, 3.08–7.39]) than in males (PR, 2.06 [95% CI, 1.82–2.34]). Furthermore, non-Hispanic Black adolescents with obesity exhibited higher PRs (PR, 3.40 [95% CI, 2.54–4.55]) for hyperuricemia in comparison to other ethnic groups. Conclusions This study has updated recent trends in hyperuricemia by sex and race/ethnicity among US adolescents. Our results suggest that hyperuricemia has a significant association with greater obesity in US adolescents, and the degree of correlation varies by sex and race/ethnicity.

BackgroundThe first-line treatment for polycystic ovary syndrome (PCOS) is lifestyle modification. However, it is currently unknown whether digital medicine can assist patients with PCOS in maintaining a healthy lifestyle while alleviating PCOS symptoms. ObjectiveThis study aims to evaluate the efficacy of WeChat-based digital intervention versus metformin treatment in women with PCOS and insulin resistance. MethodsA total of 80 women with PCOS and insulin resistance were recruited from an endocrinology clinic and randomly assigned to receive either a WeChat-based digital intervention (n=40, 50%) or metformin (n=40, 50%) for 12 weeks. The WeChat-based digital intervention consisted of 3 modules; a coach assisted the patients in using the intervention. The primary outcome was the change in a homeostatic model assessment for insulin resistance. At baseline and after the 12-week intervention, anthropometric parameters, menstruation frequency, sex hormone levels, metabolic factors, and body fat distribution were measured in the clinic. Furthermore, self-assessed web-based questionnaires on diet, exercise, sleep, anxiety, and depression were obtained. ResultsA total of 72 participants completed the follow-up (for a 90% follow-up rate), including 35 of 40 (88%) participants from the digital intervention group and 37 of 40 (93%) participants from the metformin group. The homeostatic model assessment for insulin resistance in the digital intervention group was significantly improved after 12 weeks of treatment with a mean change of –0.93 (95% CI –1.64 to –0.23), but no statistical difference was observed between the groups (least squares mean difference –0.20; 95% CI –0.98 to 0.58; P=.62). Both digital intervention and metformin treatment significantly improved menstruation frequency (digital intervention: P

Abstract Background Obesity is associated with elevated serum uric acid (SUA) levels and frequent gout flares. Losing weight can reduce the SUA level and gout flares. The effect of orlistat on SUA levels and gout flares in patients with overweight/obesity and hyperuricemia (HUA) has not been extensively studied. This study investigated the effects of orlistat on SUA levels and gout flares compared to placebo in overweight and obese patients with HUA. Methods A total of 72 Chinese patients with overweight/obesity and HUA were randomly divided into a placebo group (35, 48.6%) and an orlistat group (37, 51.4%); the trial lasted 12 weeks. The primary endpoints were the relative changes in body weight, the SUA level, and gout flares in the per-protocol population. Results Orlistat reduced the proportion of patients with gout flares (log-rank P = 0.023, hazard ratio = 0.31, 95% confidence interval 0.11–0.85). There was no significant difference in SUA level between the two groups. The average weight loss of the orlistat group was 2.85 kg, and the average weight loss of the placebo group was 0.76 kg. The weight loss in the orlistat group was significantly greater than that in the control group (P

Abstract Background The relationship between integrated lifestyles, mental status and their impact on overall well-being has attracted considerable attention. This study aimed to evaluate the association between lifestyle factors, depression and diabetic retinopathy (DR) in adults aged 18–64 years. Methods A cohort of 3482 participants diagnosed with diabetes was drawn from the National Health and Nutrition Examination Survey (NHANES) spanning the years 1999–2018. DR was defined based on self-reported diabetic retinopathy diagnoses by professional physicians, relying on Diabetes Interview Questionnaires. Subgroup analysis was employed to assess lifestyle and psychological factors between participants with DR and those without, both overall and stratified by diabetic duration. Continuous variables were analyzed using the student’s t test, while weighted Rao-Scott χ2 test were employed for categorical variables to compare characteristics among the groups. Results Of the 3482 participants, 767 were diagnosed with diabetic retinopathy, yielding a weighted DR prevalence of 20.8%. Patients with DR exhibited a higher prevalence of heavy drinking, depression, sleep deprivation, and insufficient physical activity compared to those without DR. Furthermore, multivariable logistic regression analysis revealed that sleeping less than 5 h (OR = 3.18, 95%CI: 2.04–4.95, p

Background: Ultrasound (US) has a high sensitivity in detecting monosodium urate (MSU) deposition in gout patients. However, the value of US in predicting gout flares has been reported only in a few monocentric studies. Objective: To investigate the association between gout flares in the previous year and US-detected MSU burden using two different US scores. Design: A retrospective study. Methods: Patients with gout were consecutively recruited to undergo musculoskeletal US examinations of their knees, ankles, and feet. The score derived from Outcome Measure in Rheumatology (hereinafter referred to as MSU score) and musculoskeletal US features-based (hereinafter referred to as MSKF score) were used to quantify the MSU burden of gout. Odds ratios for frequent gout flares were calculated. Results: We enrolled 1894 patients with gout (mean age: 45 years; gout duration: 5 years; males: 96.1%), experiencing a median of three flares over the past year. Of these, 428 (22.6%) patients reported frequent (⩾7) gout flares. The MSU and MSKF median scores were 6 and 9, respectively. For each five-point increase in MSU and MSKF score, the odds ratio of frequent gout flares increased 1.13-fold and 1.24-fold, respectively. The area under the curve (AUC) for the MSU and MSKF score was 0.635 [95% confidence interval (CI): 0.604–0.665] and 0.688 (95% CI: 0.659–0.718), respectively, (AUC difference 0.054, p value for AUC difference

Background & Aims: Liver regeneration is vital for the recovery of liver function after injury, yet the underlying mechanism remains to be elucidated. Forkhead box protein A3 (FOXA3), a member of the forkhead box family, plays important roles in endoplasmic reticulum stress sensing, and lipid and glucose homoeostasis, yet its functions in liver regeneration are unknown. Methods: Here, we explored whether Foxa3 regulates liver regeneration via acute and chronic liver injury mice models. We further characterised the molecular mechanism by chromatin immunoprecipitation sequencing and rescue experiments in vivo and in vitro. Then, we assessed the impact of Foxa3 pharmacological activation on progression and termination of liver regeneration. Finally, we confirmed the Foxa3–Cebpb axis in human liver samples. Results: Foxa3 is dominantly expressed in hepatocytes and cholangiocytes and is induced upon partial hepatectomy (PH) or carbon tetrachloride (CCl4) administration. Foxa3 deficiency in mice decreased cyclin gene levels and delayed liver regeneration after PH, or acute or chronic i.p. CCl4 injection. Conversely, hepatocyte-specific Foxa3 overexpression accelerated hepatocytes proliferation and attenuated liver damage in an CCl4-induced acute model. Mechanistically, Foxa3 directly regulates Cebpb transcription, which is involved in hepatocyte division and apoptosis both in vivo and in vitro. Of note, Cebpb overexpression in livers of Foxa3-deficient mice rescued their defects in cell proliferation and regeneration upon CCl4 treatment. In addition, pharmacological induction of Foxa3 via cardamonin speeded up hepatocyte proliferation after PH, without interfering with liver regeneration termination. Finally, Cebpb and Ki67 levels had a positive correlation with Foxa3 expression in human chronic disease livers. Conclusions: These data characterise Foxa3 as a vital regulator of liver regeneration, which may represent an essential factor to maintain liver mass after liver injury by governing Cebpb transcription. Impact and Implications: Liver regeneration is vital for the recovery of liver function after chemical insults or hepatectomy, yet the underlying mechanism remains to be elucidated. Herein, via in vitro and in vivo models and analysis, we demonstrated that Forkhead box protein A3 (FOXA3), a Forkhead box family member, maintained normal liver regeneration progression by governing Cebpb transcription and proposed cardamonin as a lead compound to induce Foxa3 and accelerate liver repair, which signified that FOXA3 may be a potential therapeutic target for further preclinical study on treating liver injury.

Multi-objective evolutionary algorithm based on decomposition (MOEA/D) has achieved great success in the field of evolutionary multi-objective optimization. It decomposes a multi-objective optimization problem into a number of scalar optimization sub-problems. Each sub-problem is optimized by using information from its neighboring sub-problems. Therefore, the neighborhood size of each sub-problem plays an important role in MOEA/D. Different neighborhood sizes are tested in this paper. Experimental results demonstrate that larger neighborhood size helps achieve better convergence and diversity with more CPU time and vice versa. MOEA/D uses constant neighborhood size during the whole process, and it is difficult to balance the convergence, diversity and running time. Therefore, this paper propose an algorithm based on MOEA/D. The algorithm adjusts the neighborhood size dynamically in different generations and different sub-problems to reduce the running time while the convergence and diversity of this algorithm are similar or better than other state-of-the-art algorithms. Compared to the original MOEA/D, experimental results show that adjusting the neighborhood size dynamically is a good way to reduce the running time significantly while maintaining the convergence and diversity. Furthermore, the algorithm proposed in this paper is compared with five state-of-the-art algorithms based on MOEA/D. The experimental results show that the proposed algorithm outperforms the others in efficiency while performs similarly in convergence and diversity.

Multi-objective evolutionary algorithm based on decomposition (MOEA/D) is effective to solve most multi-objective optimization problems (MOPs) in the past 20 years. However, the algorithm MOEA/D with constant weight vectors has bad performance in solving several MOPs with discontinuous Pareto front (PF). This paper analyses the limitations of the constant weight vectors in MOEA/D and explains the necessity of adjusting the weight vectors in the processing. This paper proposes a weight vector adjustment method for MOEA/D (MOEA/D-WVA). It deletes the weight vectors which have bad search direction, and adds some new weight vectors in the processing. Experimental studies are conducted on several MOPs with discontinuous PF to compare the MOEA/D-WVA with other state-of-the-art multi-objective optimization algorithms in solving those MOPs with complex PF. The results show MOEA/D-WVA performs better than other algorithms on those MOPs with discontinuous PF.

Endothelial dysfunction is a critical and initiating factor of the vascular complications of diabetes. Inflammation plays an important role in endothelial dysfunction regulated by epigenetic modifications. N6-methyladenosine (m6A) is one of the most prevalent epigenetic modifications in eukaryotic cells. In this research, we identified an m6A demethylase, fat mass and obesity-associated protein (FTO), as an essential epitranscriptomic regulator in diabetes-induced vascular endothelial dysfunction. We showed that enhanced FTO reduced the global level of m6A in hyperglycemia. FTO knockdown in endothelial cells (ECs) resulted in less inflammation and compromised ability of migration and tube formation. Compared with EC Ftofl/fl diabetic mice, EC-specific Fto-deficient (EC FtoΔ/Δ) diabetic mice displayed less retinal vascular leakage and acellular capillary formation. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) combined with RNA-Seq indicated that Tnip1 served as a downstream target of FTO. Luciferase activity assays and RNA pull-down demonstrated that FTO repressed TNIP1 mRNA expression by erasing its m6A methylation. In addition, TNIP1 depletion activated NF-κB and other inflammatory factors, which aggravated retinal vascular leakage and acellular capillary formation, while sustained expression of Tnip1 by intravitreal injection of adeno-associated virus alleviated endothelial impairments. These findings suggest that the FTO-TNIP1-NF-κB network provides potential targets to treat diabetic vascular complications.

The most critical aspect for photoelectrochemical (PEC) water splitting is the choice of suitable photoelectrode materials. The low efficiency of PEC water splitting photoanodes restricts their widespread deployment for large scale H2 production. Herein, WO3 with controlled structures was in situ hydrothermally grown on fluorine-doped tin oxide (FTO) glass substrates via simply using different orientation agents, i.e., citric acid for the sandwich structure and tartaric acid for nanoplates. By determining the electrochemically active surface area (ECSA), the sandwich structure is proven to be able to provide more active sites and a larger specific reaction surface area for PEC water splitting. In the citric acid derived WO3 sandwich structure, upon increasing the hydrothermal reaction time from 4 to 16 h, the dominating exposed facets were converted from the (200) crystal plane to the (002) crystal plane, while WO3 prepared from tartaric acid consistently yielded the (200) crystal plane. Moreover, the sandwich structured WO3 photoanode with intensively exposed (002) facets obtained hydrothermally in 12 h exhibited a photocurrent density of 3.16 mA cm-2 in aqueous Na2SO4 solution under AM 1.5 G illumination and an incident photon-to-current efficiency (IPCE) value of 79% at 400 nm at 1.23 V vs. RHE. To the best of our knowledge, this value is one of the most remarkable for pristine WO3 photoanodes. The excellent PEC performances of the resulting sample could be attributed to the 2-D nanoplates with superior crystallinity and exposed highly reactive (002) facets which facilitated the separation of photogenerated electron--hole pairs. [ABSTRACT FROM AUTHOR]

Abstract Objectives The objective of this study was to develop and validate a prediction model for renal urate underexcretion (RUE) in male gout patients. Methods Men with gout enrolled from multicenter cohorts in China were analyzed as the development and validation data sets. The RUE phenotype was defined as fractional excretion of uric acid (FEUA)

Polyoxometalate-based composite materials have recently attracted extensive attention due to their unique structural characteristics and physicochemical properties. In the present work, a flexible anti-UV blocker compatible with cotton fabric was prepared by simple covalent bond self-assembly of carboxyl group (−COOH) and phosphomolybdate. The resultant cotton fabrics were investigated and confirmed by FT-IR, PXRD and SEM-EDS, demonstrating the successful preparation of polyoxometalate-based composite fabric. The UV spectrum of as-designed composite fabric imparts excellent UV absorption capacity and the UPF value reaches 397.19, which is far superior to original cotton (7.09). Furthermore, the blocker was tested on the photosensitive material in direct UV irradiation, which proved its outstanding performance as a flexible, wearable, and visualized UV blocker. In addition, the experimental results confirmed that the prepared composite material exhibited an excellent and stable UV resistant performance (UPF: 100+) after 5 days UV aging irradiation and five times washing. The proposed fabrication strategy could promisingly endow polyoxometalate-based fiber materials with extensive applicability potential.

Optimal entry flight of hypersonic vehicles requires achieving specific mission objectives under complex nonlinear flight dynamics constraints. The challenge lies in rapid generation of optimal or near-optimal flight trajectories with significant changes in the initial flight conditions during entry. Deep Neural Networks (DNNs) have shown the capability to capture the inherent nonlinear mapping between states and optimal actions in complex control problems. This paper focused on comprehensive investigation and evaluation of a DNN-based method for three-dimensional hypersonic entry flight trajectory generation. The network is designed using cross-validation to ensure its performance, enabling it to learn the mapping between flight states and optimal actions. Since the time-consuming training process is conducted offline, the trained neural network can generate a single optimal control command in about 0.5 milliseconds on a PC, facilitating onboard applications. With the advantages in mapping capability and calculating speed of DNNs, this method can rapidly generate control action commands based on real-time flight state information from the DNN model. Simulation results demonstrate that the proposed method maintains a high level of accuracy even in scenarios where the initial flight conditions (including altitude, velocity, and flight path angle) deviate from their nominal values, and it has certain generalization ability.

Abstract Background Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GSD) often coexist in the general population owing to shared risk factors. This study explored the relationship between NAFLD and GSD in patients with type 2 diabetes. Methods We conducted a retrospective cross-sectional analysis of 4325 patients with type 2 diabetes. GSD and NAFLD were confirmed using ultrasonography. GSD was defined as either asymptomatic gallstones or previous cholecystectomy, and each was analyzed separately. Result There was no significant difference in the prevalence of GSD between patients with and without NAFLD (23.8% vs. 21.2%, P = 0.15). After case–control matching (1:1) of baseline data such as age, sex, duration of diabetes, and HbA1c between patients with and without NAFLD, there was still no significant difference in the prevalence of GSD (25.5% vs. 23.6%, P = 0.15). The prevalence of NAFLD in patients with asymptomatic gallstones was lower than that of patients without GSD (38.6% vs. 47.3%, P

BackgroundLiver-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).MethodsWe 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.ResultsSerum 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).ConclusionsFABP1 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.

Abstract Background Skeletal muscle atrophy and fibrosis are pathological conditions that contribute to morbidity in numerous conditions including aging, cachexia, and denervation. Muscle atrophy is characterized as reduction of muscle fiber size and loss of muscle mass while muscle fibrosis is due to fibroblasts activation and excessive production of extracellular matrix. Purinergic receptor P2Y2 has been implicated in fibrosis. This study aims to elucidate the roles of P2Y2 in sleketal muscle atrophy and fibrosis. Methods Primary muscle fibroblasts were isolated from wild type and P2Y2 knockout (KO) mice and their proliferating and migrating abilities were assessed by CCK-8 and Transwell migration assays respectively. Fibroblasts were activated with TGF-β1 and assessed by western blot of myofibroblast markers including α-SMA, CTGF, and collagen I. Muscle atrophy and fibrosis were induced by transection of distal sciatic nerve and assessed using Masson staining. Results P2Y2 KO fibroblasts proliferated and migrated significantly slower than WT fibroblasts with or without TGF-β1.The proliferation and ECM production were enhanced by P2Y2 agonist PSB-1114 and inhibited by antagonist AR-C118925. TGF-β1 induced fibrotic activation was abolished by P2Y2 ablation and inhibited by AKT, ERK, and PKC inhibitors. Ablation of P2Y2 reduced denervation induced muscle atrophy and fibrosis. Conclusions P2Y2 is a promoter of skeletal muscle atrophy and activation of fibroblasts after muscle injury, which signaling through AKT, ERK and PKC. P2Y2 could be a potential intervention target after muscle injury.

ObjectivePeripheral neuropathies (PNs) are a group of disorders that affect the peripheral nervous system. PN in gout has been scarcely described. This study is conducted to determine the prevalence and related risk factors of PN, as assessed by vibration perception threshold (VPT) in patients with gout.MethodsA total of 442 patients were included in the cross-sectional study. The VPT values were measured by using the Biothesiometer sensory quantitative tester on each patient. The VPT value of either limb higher than 15 V was considered abnormal and is considered to have PN. The univariate and multivariate logistic regression models were used to identify risk factors for PN in patients with gout.ResultsWe included 442 patients with gout, 97.5% men, 26.9% tophaceous gout, mean age 45.5 ± 15.2 years, and 7.4 ± 4.6 years of disease duration. The prevalence of PN in patients with gout was 11.1%. Patients in the abnormal VPT group were older, had a longer gout duration, and had significantly higher levels of waist circumference, waist-to-hip ratio, systolic blood pressure (SBP), and erythrocyte sedimentation rate (ESR), as compared to patients in the normal vibration group (P < 0.05). The univariate logistic regression analysis demonstrated that there was a significant association between abnormal VPT and age, duration of gout, SBP, C-reactive protein, ESR, presence of tophi, and estimated glomerular filtration rate (eGFR) in all the subjects (P < 0.05). The multivariate logistic regression analysis indicated that age (odds ratio, 1.094) and presence of tophi (odds ratio, 1.048) were independent risk factors for PN in patients with gout.ConclusionThe abnormal VPT was significantly correlated with age and presence of tophi in patients with gout and the VPT level may be useful as a screening tool for assessment of PN in gout.

Objectives.The effect of insulin therapy on coronary artery disease (CAD) remains controversial. This study aimed to analyze the association between insulin resistance and the morbidity of severe CAD in type 2 diabetes mellitus (T2DM). Methods. A total of 2044 T2DM patients aged ≥40 years were included in this cross-sectional observational study. Clinical information and laboratory results were collected from the medical records. Those who underwent percutaneous coronary intervention (PCI) were classified as severe CAD, while those who did not have a history of and were not suffering from CAD were classified as patients without CAD. Results. T2DM patients with severe CAD and without CAD had no significant differences in glycosylated hemoglobin A1c (8.55% ± 2.10% vs. 8.39% ± 1.77%, P=0.234). The proportion of insulin treatment was also similar between the two groups (56.85% vs. 53.65%, odds ratio = 1.138, P=0.310). In the patients without insulin treatment, the levels of fasting C peptide (FCP) correlated with severe CAD prevalence. FCP was categorized into 3 tertiles (

With the transformation of the national energy and power sector, the steady advancement of intelligent power grid construction and the continuous improvement of the Ubiquitous Power Internet of Things technology framework, it has further requirements for realizing state comprehensive awareness and efficient processing of information data, and has been widely used in power equipment. The infrared image recognition technology, which has been widely used in thermal fault diagnosis of power equipment, also requires deeper research. For traditional Intuitionistic Fuzzy C-means (IFCM) algorithm for image segmentation is sensitive to the clustering center lead to low final clustering precision and detail, the time complexity and the high shortage. The paper puts forward a kind of applicable to power equipment of the infrared image segmentation based on space distribution information of Intuitionistic Fuzzy clustering algorithm. Non-target objects with high intensity and uneven image intensity in infrared image have strong interference to image segmentation. The proposed algorithm can effectively suppress the interference. Firstly, the gaussian model is introduced into the global spatial distribution information of power equipment to improve the IFCM. Secondly, the spatial operator optimization membership function of local spatial information is used to solve the problem of edge blurring and uneven image intensity. Through experiments on the data set containing 300 infrared images of power equipment, the relative regional error rate is about 10%, which is less affected by the change of fuzzy factor m. The effectiveness and applicability of this algorithm are verified, which is obviously better than other comparison algorithms.

Objectives: To develop a tool which can evaluate the severity of the joint injury in individuals with gout and asymptomatic hyperuricaemia. Methods: This retrospective study included 616 male patients: 245 with asymptomatic hyperuricaemia and 371 with intercritical gout. All patients underwent ultrasonography of the knee, ankle and first metatarsophalangeal (MTP) joints. Ultrasound features that were significantly different between groups were entered into a binary logistic regression analysis to identify discriminative factors. The ultrasound signs were scored based on their odds ratios, which were then used to evaluate the severity of gout and asymptomatic hyperuricaemia. The performance of the ultrasound score was validated in an additional population including 163 patients with asymptomatic hyperuricaemia and 196 patients with gout. Results: Ultrasound signs were scored as follows: knee joint: synovial effusion, 2 points, tophus, 5 points; ankle joint: synovial effusion, 2 points, synovial hypertrophy, 5 points, tophus, 3 points, bone erosion, 7 points; and first MTP joint: double contour sign, 2 points, synovial hypertrophy, 3 points, tophus, 9 points, bone erosion, 4 points. The maximum possible total score was 42. The optimal cut-off score for gout was 6.5. The sensitivity, specificity and area under the receiver operating characteristic curve (AUC) were 86.9%, 75.2% and 0.878, respectively. The patients were stratified according to their ultrasound score (range 0–42). The prevalence of intercritical gout, tophi, and bone erosion increased with the increase of the score. In the validation population, 83.20% of 193 patients with gout had ultrasound scores above 6.5; 76.10% of 163 patients with asymptomatic hyperuricaemia had ultrasound scores under 6.5. Conclusion: The scoring system based on the differential ultrasound signs can effectively evaluate the severity of joint injury in individuals with gout and asymptomatic hyperuricaemia.

The relationship between thyroid hormones and serum urate is unclear. Our aim is to analyze the correlation between uric acid and thyroid hormones in gout patients and to explore the effect and mechanism of triiodothyronine on liver uric acid production. Eighty men patients with gout were selected to analyze the correlation between blood urate and thyroid function-related hormone levels. Stepwise multiple linear regression was used to analyze factors affecting blood urate in patients with gout. Levels of urate in serum, liver, and cell culture supernatant were measured after triiodothyronine treatment. Purine levels (adenine, guanine, and hypoxanthine) were also measured. Expression levels of Period2 and nucleotide metabolism enzymes were analyzed after triiodothyronine treatment and Period2-shRNA lentivirus transduction. Chromatin immunoprecipitation was used to analyze the effects of triiodothyronine and thyroid hormone receptor-β on Period2 expression. The results showed that in patients FT3 influenced the serum urate level. Furthermore, urate level increased in mouse liver and cell culture supernatant following treatment with triiodothyronine. Purine levels in mouse liver increased, accompanied by upregulation of enzymes involved in nucleotide metabolism. These phenomena were reversed in Period2 knockout mice. Triiodothyronine promoted the binding of thyroid hormone receptor-β to the Period2 promoter and subsequent transcription of Period2. Triiodothyronine also enhanced nuclear expression of Sirt1, which synergistically enhanced Period2 expression. The study demonstrated that triiodothyronine is independently positively correlated with serum urate and liver uric acid production through Period2, providing novel insights into the purine metabolism underlying hyperuricemia/gout pathophysiology.

Epidemiological research has shown that elevated serum urate concentration is a risk factor for the development of kidney disease; however, the mechanisms underlying this process have not yet been elucidated. To examine the role of urate in the kidney, we used Wistar rats to functionally disrupt expression of urate oxidase (UOX) by using the CRISPR/Cas9 system. In comparison to wild-type (WT) rats, serum urate levels spontaneously and persistently increased in UOX-KO rats, without showing a significant decrease in survival rate. Architecture and function of the kidneys in UOX-KO rats were impaired. Injury to the kidney resulted in increased interstitial fibrosis, macrophage infiltration, increased expression of NLRP3 and IL-1β, and activation of multiple cell-signaling pathways associated with autophagy, such as AMPK, p38 MAPK, ERK and JNK pathways. Inhibition of autophagy with the PI3K inhibitor 3-MA abrogated the development of kidney damage and attenuated renal fibrosis, macrophage infiltration, and expression of NLRP3 and IL-1β in injured kidneys. In conclusion, the UOX-KO rat is a great model to study hyperuricemia-related diseases. Hyperuricemia-induced autophagy and NLRP3-dependent inflammation are critically involved in the development of renal damage and, therefore, highlight the inhibition of autophagy and inflammation in search of therapeutic strategies to treat uric acid nephropathy.

The aim of this study was to solve the frequently occurring rotor-stator rub-impact fault in aero-engines without causing a significant reduction in efficiency. We proposed a fault mitigation scheme, using shape memory alloy (SMA) wire, whereby the tip clearance between the rotor and the stator is adjusted. In this scheme, an acoustic emission (AE) sensor is utilized to monitor the rub-impact fault. An active control actuator is designed with pre-strained two-way SMA wires, driven by an electric current via an Arduino control board, to mitigate the rub-impact fault once it occurs. In order to investigate the feasibility of the proposed scheme, a series of tests on the material properties of NiTi wires, including heating response rate, ultimate strain, free recovery rate, and restoring force, were carried out. A prototype of the actuator was designed, manufactured, and tested under various conditions. The experimental result verifies that the proposed scheme has the potential to mitigate or eliminate the rotor-stator rub-impact fault in aero-engines.

Abstract The chloride/phosphate ratio (Cl/PO4) has been suggested to have a role in primary hyperparathyroidism (PHPT), but the associations between Cl/PO4 combined with ALP level and PHPT has not been well-studied. Our aim was to investigate the predictive value of combination Cl/PO4 with ALP for PHPT. A cross-sectional retrospective analysis was conducted to examine 172 patients diagnosed with PHPT categorized into two groups: normocalcaemic primary hyperparathyroidism (NPHPT) group and hypercalcaemia PHPT group. We found that Cl/PO4 levels and ALP levels in the NPHPT and hypercalcaemia PHPT group were both significantly higher than normal controls. Cl/PO4 and ALP levels were an independent risk factor for PHPT. Cl/PO4 combined with ALP increased the receiver-operating characteristic curves (ROC-AUC) and the diagnostic value in NPHPT and hypercalcaemia PHPT group (0.913; 95% CI, 0.744–1.000 and 0.932; 95% CI, 0.897–0.966, respectively), specificity of 92.8% and sensitivity of 98%. In conclusion, combination Cl/PO4 with ALP might be a low-cost, simple, available predictive marker of PHPT in Chinese individuals, particularly Chinese remote region where the method used to measure PTH cannot be done. Moreover, due to serum calcium level in NPHPT, Cl/PO4 combined with ALP level measurement have great potential to predict significant occurrence of NPHPT.

Abstract Previous studies have discussed the relationship between simple renal cysts (SRC) and serum uric acid level in healthy individuals. We performed a cross-sectional study to evaluate the association between serum uric acid level and fractional excretion of uric acid (FEUA) and simple renal cysts in males and postmenopausal females with type 2 diabetes. The overall prevalence of SRC was 18.1% in our population. SRC prevalence was significantly higher in hyperuricemic than normouricemic subjects (27.3% vs. 16.8%, P

Abstract Background Recent studies highlight a negative association between total bilirubin concentrations and albuminuria in patients with type 2 diabetes mellitus. Our study evaluated the relationship between bilirubin concentrations and the prevalence of diabetic nephropathy (DN) in Chinese patients with type 1 diabetes mellitus (T1DM). Methods A total of 258 patients with T1DM were recruited and bilirubin concentrations were compared between patients with or without diabetic nephropathy. Multiple stepwise regression analysis was used to examine the relationship between bilirubin concentrations and 24 h urinary microalbumin. Binary logistic regression analysis was performed to assess independent risk factors for diabetic nephropathy. Participants were divided into four groups according to the quartile of total bilirubin concentrations (Q1, 0.20–0.60; Q2, 0.60–0.80; Q3, 0.80–1.00; Q4, 1.00–1.90 mg/dL) and the chi-square test was used to compare the prevalence of DN in patients with T1DM. Results The median bilirubin level was 0.56 (interquartile: 0.43–0.68 mg/dL) in the DN group, significantly lower than in the non-DN group (0.70 [interquartile: 0.58–0.89 mg/dL], P

The highly nonlinear and coupling characteristics of a flexible air-breathing hypersonic vehicle create great challenges to its flight control design. A unique parameter adaptive nonsingular terminal sliding mode method is proposed for longitudinal control law design of a flexible coupling air-breathing hypersonic vehicle. This method uses adaptive reaching law gain instead of the additional adaptive compensation term to handle the uncertainty to improve robustness. The stability of the close loop system is proved via a Lyapunov way. The longitudinal tracking control law for velocity and angle of attack is designed based on a rigid dynamic model of a flexible air-breathing hypersonic vehicle. A strong coupling model of the same vehicle, considering aerodynamic-scramjet engine-flight dynamic-elastic couplings, is established as the verification platform of the designed control law. The remarkable differences of flight dynamic characteristics between this strong coupling model and the rigid body model can be seen, which mean the controller needs to endure very great uncertainty, unmodeled dynamics, and other types of internal disturbance. Simulation results based on the coupling model demonstrate that the designed control law has good performance and acceptable robustness.

This paper presents a localization model employing convolutional neural network (CNN) and Gaussian process regression (GPR) based on Wi-Fi received signal strength indication (RSSI) fingerprinting data. In the proposed scheme, the CNN model is trained by a training dataset. The trained model adapts to complex scenes with multipath effects or many access points (APs). More specifically, the pre-processing algorithm makes the RSSI vector which is formed by considerable RSSI values from different APs readable by the CNN algorithm. The trained CNN model improves the positioning performance by taking a series of RSSI vectors into account and extracting local features. In this design, however, the performance is to be further improved by applying the GPR algorithm to adjust the coordinates of target points and offset the over-fitting problem of CNN. After implementing the hybrid model, the model is experimented with a public database that was collected from a library of Jaume I University in Spain. The results show that the hybrid model has outperformed the model using k-nearest neighbor (KNN) by 61.8%. While the CNN model improves the performance by 45.8%, the GPR algorithm further enhances the localization accuracy. In addition, the paper has also experimented with the three kernel functions, all of which have been demonstrated to have positive effects on GPR.

The overproduction of mitochondrial reactive oxygen species (ROS) plays a key role in the pathogenesis of diabetic nephropathy (DN). However, the underlying molecular mechanism remains unclear. Our aim was to investigate the role of PGC-1α in the pathogenesis of DN. Rat glomerular mesangial cells (RMCs) were incubated in normal or high glucose medium with or without the PGC-1α-overexpressing plasmid (pcDNA3-PGC-1α) for 48 h. In the diabetic rats, decreased PGC-1α expression was associated with increased mitochondrial ROS generation in the renal cortex, increased proteinuria, glomerular hypertrophy, and higher glomerular 8-OHdG (a biomarker for oxidative stress). In vitro, hyperglycemia induced the downregulation of PGC-1α, which led to increased DRP1 expression, increased mitochondrial fragmentation and damaged network structure. This was associated with an increase in ROS generation and mesangial cell hypertrophy. These pathological changes were reversed in vitro by the transfection of pcDNA3-PGC-1α. These data suggest that PGC-1α may protect DN via the inhibition of DRP1-mediated mitochondrial dynamic remodeling and ROS production. These findings may assist the development of novel therapeutic strategies for patients with DN.

We present the design, fabrication, and experimental characterization of a modified two-dimensional Luneburg lens based on bulk metamaterials. The lens is composed by a number of concentric layers. By varying the geometric dimensions of unit cells in each layer, the gradient refractive index profile required for the modified Luneburg lens can be achieved. The cylindrical waves generated from a point source at the focus point of the lens could be transformed into plane waves as desired in the microwave frequency. The proposed modified Luneburg lens can realize wide-angle beam scanning when the source moves along the circumferential direction inside the lens. Numerical and experimental results validate the performance of the modified Luneberg lens.

OBJECTIVE:The objective of this study was to evaluate the trend and prevalence of prediabetes and diabetes among high-risk adults in Shanghai from 2002 to 2012. METHODS:From 2002 to 2012, 10043 subjects with known risk factors for diabetes participated in the diabetes-screening project at the Shanghai Sixth People's Hospital of Shanghai Jiao Tong University. All participants were asked to complete a nurse-administered standard questionnaire concerning age, sex, smoking status, and personal and family histories of diabetes, cardiovascular disease, stroke, hypertension and other diseases. The participants' body mass index scores, blood pressures and blood glucose levels at 0, 30, 60, 120 and 180 min were measured in response to a 75 g oral glucose tolerance test. RESULTS:The overall prevalence of diabetes increased from 27.93% to 34.78% between 2002 and 2012 in high-risk subjects. The study also showed that the prevalence increased much faster in male compared to female subjects. Specifically, an increased rate was seen in middle-aged men, with no change observed in middle-aged females over the eleven-year period. CONCLUSION:This study showed that sex, age, parental diabetic history, and being overweight were associated with an increased risk for diabetes in high-risk people. Therefore, as prediabetes and diabetes are highly prevalent in people with multiple diabetes risk factors in Shanghai, screening programs targeting these individuals may be beneficial.

A simple approach is formulated to predict the elastic, kinematic pile bending during harmonic or transient excitation for a circular pile (rather than a simplified thin strip). The kinematic response of a pile embedded in two-layer soil is resolved in the frequency domain caused by the upward propagation of shear waves from the underlying bedrock. The simplified approach is generally valid to nonhomogeneous soil profiles, in light of the good comparison with the dynamic FE method and BDWF solution. It employs the soil-displacement-influence coefficients Is to consider the pile-soil interaction (resembling the spring constant kx in the BDWF) and provides conservative estimations of maximum kinematic bending moments at the soil-layer interface (with a sharper stiffness contrast). The accuracy of the approach may be improved by incorporating the interaction of soil into the soil-displacement-influence coefficients Is for such cases with Vb/Va

Based on the hypothesis that the penetration of a single pile can be simulated by a series of spherical cavity expansions, this paper presents an analytical solution of cavity expansion near the sloping ground. Compared with the cavity expansion in the half-space, the sloping free boundary has been taken into account as well as the horizontal free boundary. The sloping and horizontal free surfaces are considered by the introduction of a virtual image technique, the harmonic function, and the Boussinesq solution. The results show that the sloping free boundary and the variation of the inclination angle have pronounced influences on the distribution of the stress and displacement induced by the spherical cavity expansion. The present solution provides a simplified and realistic theoretical method to predict the soil behaviors around the spherical cavity near the sloping ground. The approach can also be used for the determination of the inclination angle of the slope according to the maximum permissible displacement.

BACKGROUND: Low vitamin D levels can be associated with albuminuria, and vitamin D analogs are effective anti-proteinuric agents. The aim of this study was to investigate differences in vitamin D levels between those with micro- and those with macroalbuminuria, and to determine whether low dose cholecalciferol increases vitamin D levels and ameliorates albuminuria. METHODS: Two studies were performed in which 25-OH vitamin D(3) (25(OH)D(3)) concentrations were determined by electrochemiluminescence immunoassay: 1) a cross-sectional study of patients with type 2 diabetes mellitus (T2DM) (n = 481) and healthy controls (n = 78); and 2) a longitudinal study of T2DM patients with albuminuria treated with conventional doses, 800 IU, of cholecalciferol for 6 months (n = 22), and a control group (n = 24). RESULTS: 1) Cross-sectional study: Compared to controls and T2DM patients with normoalbuminuria, serum 25(OH)D(3) concentrations were significantly lower in patients with macro-albuminuria, but not in those with micro-albuminuria. Serum 25(OH)D(3) levels were independently correlated with microalbuminuria. 2) Longitudinal study: Cholecalciferol significantly decreased microalbuminuria in the early stages of treatment, in conjunction with an increase in serum 25(OH)D(3) levels. CONCLUSIONS: Low vitamin D levels are common in type 2 diabetic patients with albuminuria, particularly in patients with macroalbuminuria, but not in those with microalbuminuria. Conventional doses of cholecalciferol may have antiproteinuric effects on Chinese type 2 diabetic patients with nephropathy.

OBJECTIVE: To test the hypothesis that a microalbuminuria (MA) threshold can help predict the risk for the development of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM)_ patients. DESIGN: We conducted a cross-sectional study of 4739 subjects with T2DM and a prospective study of 297 subjects with T2DM in China respectively. METHODS: Clinical and laboratory data were collected and biologic risk factors associated with any DR were analysed. RESULTS: In the cross-sectional study, we found that MA was an independent risk factor for DR development; further, when the patients were divided into MA deciles, odds ratio (ORs) of DR for the patients in the sixth MA decile (10.7 mg/24 h) was 1.579-fold (1.161-2.147) compared to that for patients in the first MA decile. Furthermore, the OR of DR increased with a gradual increase in MA levels. Similarly, in the prospective study, during a mean follow-up of 4.5 years, we found that 51 patients (29.0%) of the 176 subjects with high MA level (10.7-30 mg/24 h) developed DR, while 17 patients (14.1%) of the 121 subjects with lower MA (