Impaired skin wound healing is one of the main diabetic complications. However, the current treatment strategy is limited. Glycerol 3-phosphate dehydrogenase (mGPDH), as a component of the respiratory chain, plays an important role in cellular bioenergetics. Here, we identified that mGPDH deficiency promotes fibroblast extracellular matrix (ECM) secretion and accelerates diabetic wound healing. Specifically, mGPDH expression was significantly increased. By contrast, a lack of mGPDH promoted fibroblast migration and ECM secretion and remodelling. Mechanistically, mGPDH deficiency promotes fibroblast expression of ECM-related proteins by increasing silent information regulator 1 (SIRT1) activity and thereby the level of cellular-myelocytomatosis viral oncogene (c-Myc) deacetylation was increased, which in turn activates the transforming growth factor beta 1 (TGF-β1) signalling pathway. In mice, the mGPDH knockout of adeno-associated virus promotes collagen deposition and ECM remodelling in diabetic skin wounds. Together, our results showed that mGPDH deficiency is a potential therapeutic target for diabetic wound healing.Funding: This work was supported by the Chongqing Natural Science Foundation (Outstanding Youth Foundation) No. cstc2020jcyj-jqX0017 to M.L., Chongqing Young and Middle-aged High-end Talents Endocrine Pituitary and Gonadal Disease Studio Project to M.L.,Chongqing Young and Middle-aged High-end Talents Project to M.L., and Army Medical University Incubation Project No. 2022XQN35 to L.Z.Declaration of Interest: We declare that are no potential conflicts of interest relevant to this article.Ethical Approval: All studies involving mice were conducted in strict accordance with protocols approved by the Experimental Animal Welfare and Ethics Committee of the Army Medical University (AMUWEC20210019) and were performed according to the guidelines of the NIH (USA).

Background. Non-standardized insulin injection has an impact on the efficacy of glucose control.Objectives. The aim of the study was to explore the effectiveness of a nursing project in improving the insulin self-injection accuracy of diabetes mellitus patients.Materials and methods. A total of 200 type 2 diabetes patients who received insulin therapy with an insulin pen were recruited at the First Affiliated Hospital of Army Medical University (Chongqing, China). Patients were randomly assigned to a control (n = 100) or intervention (n = 100) group. Conventional health education was conducted in the control group, while a nursing project and conventional health education were undertaken in the intervention group. The following parameters were analyzed between the 2 groups: standardized insulin pen use at admission and discharge, glycosylated hemoglobin (HbA1c), time in range (TIR), and adipose hyperplasia incidence rate 6 months after discharge.Results. Concerning standardized insulin self-injection, the intervention group was superior to the control group, and the difference between the 2 groups was statistically significant (p < 0.05). The HbA1c levels (p = 0.000), TIR (p = 0.005) and adipose hyperplasia incidence rate 6 months after discharge (p = 0.000) all improved in the intervention group compared to the control group.Conclusions. The application of the nursing project effectively improved the efficacy of glucose control in diabetes mellitus patients.

Currently, the treatment of diabetic wounds in clinical practice is still unsatisfactory due to the risks of oxidative damage and bacterial infection during the healing process. An optimal wound dressing should exhibit robust capabilities in scavenging reactive oxygen species (ROS) and combatting bacterial growth. In this study, we utilized borax as a crosslinker and prepared a pH/glucose dual-responsive composite hydrogel based on poly(vinyl alcohol) (PVA), sodium alginate (SA), and tannic acid (TA). This hydrogel, loaded with cerium dioxide, serves as an effective ROS scavenger, promoting wound closure by reducing the level of ROS in the wound area. Additionally, the hydrogel can release the antibacterial drug ofloxacin in response to the low pH and high glucose microenvironment in infected wounds. Results from skin defect model in diabetic mice demonstrated this ROS-scavenging and antibacterial hydrogel can suppress inflammation and accelerate wound healing. In summary, our work provides a new perspective on a local and stimulus-responsive drug delivery strategy for treating diabetic wounds.

A systematic review and meta-analysis was conducted in an attempt to systematically collect and evaluate the associations of epidemiological, comorbidity factors with the severity and prognosis of coronavirus disease 2019 (COVID-19). The systematic review and meta-analysis was conducted according to the guidelines proposed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Sixty nine publications met our study criteria, and 61 studies with more than 10,000 COVID-19 cases were eligible for the quantitative synthesis. We found that the males had significantly higher disease severity (RR: 1.20, 95% CI: 1.13-1.27, P <0.001) and more prognostic endpoints. Older age was found to be significantly associated with the disease severity and six prognostic endpoints. Chronic kidney disease contributed mostly for death (RR: 7.10, 95% CI: 3.14-16.02), chronic obstructive pulmonary disease (COPD) for disease severity (RR: 4.20, 95% CI: 2.82-6.25), admission to intensive care unit (ICU) (RR: 5.61, 95% CI: 2.68-11.76), the composite endpoint (RR: 8.52, 95% CI: 4.36-16.65,), invasive ventilation (RR: 6.53, 95% CI: 2.70-15.84), and disease progression (RR: 7.48, 95% CI: 1.60-35.05), cerebrovascular disease for acute respiratory distress syndrome (ARDS) (RR: 3.15, 95% CI: 1.23-8.04), coronary heart disease for cardiac abnormality (RR: 5.37, 95% CI: 1.74-16.54). Our study highlighted that the male gender, older age and comorbidities owned strong epidemiological evidence of associations with the severity and prognosis of COVID-19.

Objective Circulating miR-146a is aberrantly expressed in patients with type 2 diabetes (T2D), probably resulting from gene polymorphisms. However, the role of polymorphism rs2910164 in T2D pathogenesis remains controversial. Thus, we designed a meta-analysis to investigate the association between rs2910164 and T2D. Methods PubMed and Embase were searched for eligible papers in English published through September 2, 2019. Random or fixed effect models were used to determine risk estimates according to heterogeneities. Results Four studies, involving 2,069 patients and 1,950 controls, were included. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size. The pooled ORs and 95% CIs were 1.501 (0.887-2.541), 1.102 (0.931-1.304), 1.276 (0.900-1.811), 1.204 (0.878-1.652), 1.238 (0.880-1.740), and 1.350 (0.904-2.016) under the homozygote, heterozygote (CG vs. GG and CC vs. CG), dominant, allele, and recessive models, respectively. Heterogeneity was detected in most genetic models, with subgroup analyses performed by ethnicity, genotyping method, and disease duration. The co-dominant model was determined to be the most appropriate genetic model. Conclusions Our findings suggested that polymorphism rs2910164 is not correlated with T2D susceptibility. However, the results should be interpreted with caution because of confounding factors.

Conflicts of interest: No potential conflicts of interests are declared. of the crude drug Fu Zi, otherwise known as Radix Aconiti Lateralis Praeparata (1). It contains aconitine-type alkaloids, and has been used to alleviate severe pain and to treat rheumatic diseases from ancient times (2). Many aconite poisoning cases have been reported, most resulting from oral use, producing systemic symptoms (3). Here, we report a case of dry gangrene of the left leg caused by the topical use of a home-prepared aconite tincture (Fig. 1).

Objective:To investigate the efficacy of Trimetazidine in 156 patients with diabetic cardiomyopathy.Methods:156 patients were randomly divided into Trimetazidine treatment group (n =81) and the control group (n =75),both received conventional medical treatment.Treatment group received further Trimetazidine treatment.Blood glucose,HbA1 C,blood lipids (total cholesterol,triglycerides,LDL,HDL),E/A ratio,ECG QT dispersion,High-sensitive C-reactive protein(HsCRP)and TNF-αwere tested before and after treatment.Results:Compared with before treatment,blood glucose,total cholesterol,triglycerides,LDL,HDL were improved significantly in both group after treatment (P ＜ 0.05);in treatment group,total cholesterol,triglycerides,LDL,HDL improved much more than control group(P ＜0.05);QT dispersion decreased compared with before treatment(P ＜ 0.05),of which treatment decreased much more tan control group (P ＜ 0.05);E/A ratio improved compared with before treatment(P ＜ 0.05),of which treatment group improved much more than control group (P ＜ 0.05);HsCRP and TNF-αdecreased compared with before treatment(P ＜ 0.05),of which HsCRP and TNF-α improvement were more obvious compared with control group (P ＜ 0.05).Conclusion:Trimetazidine can assist the treatment of diabetic cardiomyopathy.

Zinc transporter 8 (ZnT8) is exclusively expressed in the pancreatic islet and is essential for insulin crystallization, hexamerization and secretion. Tumor necrosis factor α-induced protein-3 (TNFAIP3) is a zinc finger protein that serves a major role in the negative feedback regulation of NF-κB signaling in response to multiple stimuli, and is a central regulator of immunopathology. Although the role of TNFAIP3 in diabetes has been extensively studied, its effect on ZnT8 has not been fully elucidated. The present study aimed to verify whether proinflammatory cytokines, tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β), are able to affect ZnT8 expression in islet cells. In addition, the study aimed to determine the effect of TNFAIP3 overexpression on cytokine-altered ZnT8 activity, considering its effect on NF-κB signaling. Cell-based studies using NIT-1 cells overexpressing TNFAIP3 were used to assess the effect of cytokines on ZnT8 and NF-κB activation, as well as the effect of TNFAIP3 on ZnT8 expression. Western blot analysis and immunofluorescence staining were employed to determine the protein expression and NF-κB activation, respectively. The results indicated that cytokine stimulation led to TNFAIP3 upregulation, ZnT8 downregulation and NF-κB activation. Furthermore, TNFAIP3 overexpression protected ZnT8 from cytokine-induced downregulation. In conclusion, the current results suggest that inflammation or TNFAIP3 dysfunction may be involved in the pathogenesis of diabetes via ZnT8 expression, besides from islet cell apoptosis. In addition, restricting inflammation and enhancing TNFAIP3 expression may exert a positive effect in diabetes prevention, treatment and pancreatic cell transplantation.

OBJECTIVE:Secreted frizzled-related protein 5 (sfrp5), like adiponectin, has been identified as a novel insulin-sensitising and anti-inflammatory adipokine. Our objective was to determine whether differences of circulating plasma sfrp5 concentration exist among type 2 diabetes (T2D), latent autoimmune diabetes in adults (LADA) and healthy population.METHODS:Enzyme-linked immuno sorbent assay was employed to detect the circulating sfrp5 level in plasma, and other lab tests such as fasting glucose and creatinine were also examined. Correlation analysis between sfrp5 and characteristics of subjects was conducted IBM SPSS Statistics and GraphPad Prism.RESULTS:Circulating sfrp5 level was significantly decreased in T2D and LADA patients plasma compared with that in healthy control (14.14±11.91ng/mL, 14.82±11.27ng/mL, 22.98±12.36ng/mL, respectively), although no differences was observed between LADA and T2D groups. Furthermore, we found sfrp5 was correlated with homeostasis model assessment of insulin resistance (HOMA-IR), diabetes duration and BMI. Finally we found sfrp5 was still negatively correlated with HOMA-IR after being adjusted for disease duration and BMI(r= -0.315, P< 0.05).CONCLUSIONS:Our results support a role for SFRP5 as a protective factor in the pathogenesis of autoimmune diabetes and facilitate a novel aspect for diabetes research.

BACKGROUND:Type 1 diabetes mellitus is an autoimmune disease, and islet autoantibodies secreted by auto-reactive plasma cells are diagnostic indicators of the immune processes. Autoantibodies to zinc transporter 8 (ZnT8) have been identified as a novel reliable biomarker for the prediction, diagnosis, monitoring, and prognosis of autoimmune diabetes, complementing the panel of existing diagnostic autoantibodies. Although the enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay are the most frequently used testing methods, they do not allow simultaneous detection of multiple autoantibodies. Another obstacle is the cost of ZnT8 production for antibody assays. This study aimed to develop a cost-effective expression system for the production of two ZnT8 C-terminal fragments containing main ZnT8 antigen epitopes and establish an improved reliable and rapid assay for the detection of anti-ZnT8 antibodies with a potential to simultaneously measure multiple autoantibodies.METHODS:The coding codons of the human ZnT8 were optimized for prokaryotic expression and the mutation was achieved using site-directed mutagenesis. A total of 42 newly diagnosed type 1 diabetes patients (16 males and 26 females) and 100 healthy controls (57 males and 43 females) were enrolled for sera. The dot immunogold filtration assay (DIGFA) was evaluated by comparing with ELISA as the "gold standard".RESULTS:Two ZnT8 antigens (arginine and tryptophan ZnT8 at position 325) were successfully produced. We established a rapid DIGFA method for the simultaneous detection of anti-ZnT8 antibodies, with the sensitivity, specificity, accuracy, Youden index, and positive and negative likelihood ratio being 64.3%, 96.4%, 85.7%, 0.607, 18.0, and 0.370, respectively, and the results did not significantly differ from those for ELISA (p = 0.22).CONCLUSIONS:These results demonstrate that the pColdII expression system is suitable for the production of bioactive ZnT8 antigens and that DIGFA can be a rapid, reliable, and highly specific method for the detection of ZnT8 antibodies, which can be potentially applied to identify a panel of diabetes-specific autoantibodies simultaneously.

Background Accumulating but inconsistent data about the role of rs13266634 variant of SLC30A8 in type 2 diabetes have been reported, partly due to small sample sizes and non-identical ethnicity. Material/Methods We searched PubMed and Cochrane Library to identify eligible studies and extract data of baseline characteristics, genotype count, odds ratio (OR), and 95% confidence interval (CI). Both adjusted OR with 95% CI and genotype counts were employed to assess the association. Genotype data were further pooled to provide estimates under different genetic models and the most appropriate model was determined. Sensitivity and cumulative analysis were conducted to assure the strength of results. Results Fifty-five datasets of 39 studies (including 38 of 24 with genotype count) were included. Significant associations were found in allelic contrasts using adjusted ORs and raw genotype count, respectively, overall in Asian and European populations (overall: OR=1.147/1.157, 95% CI 1.114–1.181/1.135–1.180; Asian: OR=1.186/1.165, 95% CI 1.150–1.222/1.132–1.198; European: OR=1.100/1.151, 95% CI 1.049–1.153/1.120–1.183; All p=0.00), but not in African populations (African: OR=1.255/1.111, 95% CI 0.964–1.634/0.908–1.360, p=0.091/0.305). Further analysis with genotype count under different genetic models all showed that individuals with CC genotype had 33.0% and 16.5% higher risk of type 2 diabetes than those carrying TT and CT genotypes, respectively, under the most likely codominant model. Cumulative analysis indicated gradually improved precision of estimation after studies accumulated. Conclusions Our results suggest that rs13266634 may be an important genetic factor of type 2 diabetes risk among Asian and European but not African populations.

Aims A20 is a negative regulator of nuclear factor kappa B activation and the central gatekeeper in inflammation and immunity. While its role in type 1 diabetes has been widely studied, its expression level in immune cells from type 2 diabetes (T2D) and latent autoimmune diabetes in adult (LADA) patients remains unclear. This study aimed to clarify whether the expression of A20 is altered in patients with T2D or LADA. Methods Quantitative real-time polymerase chain reaction and western blotting were utilized to determine the expression of A20 mRNA and protein respectively in peripheral blood mononuclear cells (PBMCs) from patients with T2D (n = 36) or LADA (n = 17) and sex- and age-matched healthy controls (n = 34). Results The mRNA and protein expression of A20 in PBMCs from T2D and LADA patients was significantly decreased compared with healthy controls (P < 0.05). Furthermore, A20 mRNA and protein expression was significantly lower in newly diagnosed T2D patients (≤1 year since diagnosis) than in patients with a long T2D duration (>1 year since diagnosis) (P < 0.05). Conclusions Our results suggest that decreased expression of A20 in PBMCs may be involved in the pathogenesis of diabetes, and targeting A20 may offer a potential therapeutic tool in the treatment of diabetes.

目的 构建联合检测糖尿病自身抗体的斑点金免疫渗滤法(dot immunogold filtration assay,DIGFA).方法 将重组人胰岛素、谷氨酸脱羧酶、蛋白酪氨酸磷酸酶和锌转运体8抗原点样于硝酸纤维素膜上,制备胶体金标记链霉亲和素作为显色探针,建立斑点金免疫渗滤法检测1型糖尿病(type 1 diabetes,T1DM)患者外周血中相应的自身抗体,并对方法性能开展评估.结果 DIGFA法检测42例T1DM敏感性66.7％,检测100例健康对照特异性97％.与ELISA法相比对T1DM自身抗体检出率无显著差异(P＞0.05).3个批次的免疫渗滤装置检测结果一致,4℃保存10周内检测性能稳定.结论 本研究构建的斑点金免疫渗滤法准确、快速、简便,为联合检测糖尿病自身抗体提供了一种高效的新途径.

Aims: To examine whether overexpression of peroxisome proliferator activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) can prevent apoptosis in adipose-derived stem cells (ASCs) by reducing reactive oxygen species (ROS) production and enhancing mitochondrial function in a diabetic environment.Methods: After the isolation, expansion and characterisation of rat ASCs, we overexpressed PGC-1 alpha in ASCs using an adenoviral vector encoding green fluorescent protein (GFP) or PGC-1 alpha and tested the apoptotic effect under conditions of high glucose, hypoxia and serum deprivation. The production of intracellular ROS and mitochondrial ROS was evaluated using dihydroethidium and CM-H(2)XRos fluorescent probes.Results: Under conditions of high glucose, hypoxia and serum deprivation, the overexpression of PGC-1 alpha in ASCs decreased apoptosis and led to an increased survival rate. The ASCs modified with PGC-1 alpha produced lower intracellular and mitochondrial ROS. The mitochondrial morphology and structure in the PGC-1 alpha-ASC group remained relatively complete compared with the control group.Conclusions: These results reveal a crucial protective role for PGC-1 alpha in the treatment of diabetes mellitus and its complications using stem cells therapy. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

OBJECTIVE:To determine the association of systemic lupus erythematosus (SLE) with single-nucleotide polymorphisms (SNP) in the TNIP1 gene and compare the expression of this gene in cases and controls from a Chinese Han population in this replication study.METHODS:Matrix-assisted laser desorption ionization time-of-flight mass spectrometry was used to genotype 19 SNP in TNIP1 in Chinese Han patients with SLE (n = 341) and controls (n = 356). Genotypes were analyzed by codominant, dominant, and recessive models. Analysis of allele frequencies and linkage disequilibrium was also performed. Western blotting and qRT-PCR were used to measure the expression of these genes in peripheral blood mononuclear cells of SLE cases and controls.RESULTS:Seven SNP loci were significantly associated with SLE in our population (p < 0.05 for all comparisons). Two TNIP1 gene haplotypes (ATTGCGC and GTCCTAT) were associated with SLE (p = 0.0246 and p = 0.0024, respectively). Western blotting and qRT-PCR results provide evidence that patients with SLE had significantly reduced expression of TNIP1/ABIN-1 relative to controls.CONCLUSION:Analysis of SNP in the TNIP1 gene and expression of this gene in peripheral blood lymphocytes indicated these SNP were associated with the occurrence of SLE in Han Chinese patients. Future studies should examine the roles of these SNP in the pathogenesis of SLE.

以我校为例,指出如今高等医学院校的高等数学教育中普遍存在的两个方面的问题,并对我校高等数学课程体系的改革提出一些设想,和准备采取的一些措施。

Background Bacteriophages (phages) are widespread in the environment and play a crucial role in the evolution of their bacterial hosts and the emergence of new pathogens. Results LSB-1, a reference coliphage strain, was classified as a member of the Podoviridae family with a cystic form (50 ± 5 nm diameter) and short tail (60 ± 5 nm long). The double stranded DNA was about 30 kilobase pairs in length. We identified its host range and determined the gp17 sequences and protein structure using shotgun analysis and bioinformatics technology. Conclusions Coliphage LSB-1 possesses a tailspike protein with endosialidase activity which is probably responsible for its specific enteroinvasive E.coli host range within the laboratory.

Conjugate gradient methods with a certain kind of Property under an Armijo-type line search were investigated.These methods include the well-known PRP method as a special case,and the global convergence of the methods is proved.Preliminary numerical results show that these methods are efficient.

以L-丙氨酸缓冲液为发芽剂,结合芬顿反应原理,观察发芽-氧化损伤效应对芽胞的杀灭效果,以期为新型炭疽疫源地净化方法的深入研究奠定基础.以腊样芽胞为试验菌,采用透射电镜、激光扫描共聚焦显微镜、活菌计数等方法观察芽胞发芽过程的超微结构、核酸含量变化,以及在芬顿反应的联合作用下发芽体的活性变化.在20～30 min的发芽过程中,芽胞核心密度降低,核心与皮质、皮质与外壁之间界限模糊,芽胞外壁和芽胞衣有破裂,通透性增加,进一步有皮质消失、细胞核与细胞质融合、细胞膜基本形成的现象;发芽体荧光强度不断增加,显示菌体中核酸的活性和含量不断增加;发芽体对化学因子的抗力明显下降,H2O2浓度为0.20 mol/L的Fenton反应系统作用60 min时,发芽体灭活可达到3.016个对数级.诱导发芽和反应的联合处理程序可显著提高芽胞的灭活水平.

We in this note drop a Lipschitz constant in a Grippo–Lucidi-type step length rule recently proposed by Shi and Shen [Z. Shi, J. Shen, Convergence of PRP method with new nonmonotone line search, Applied Mathematics and Computation 181(1) (2006) 423–431], and the original convergence remains valid.