Myosteatosis is associated with coronary artery calcification in patients with type 2 diabetes.

BACKGROUND: Myosteatosis, rather than low muscle mass, is the primary etiologic factor of sarcopenia in patients with type 2 diabetes mellitus (T2DM). Myosteatosis may lead to a series of metabolic dysfunctions, such as insulin resistance, systematic inflammation, and oxidative stress, and all these dysfunctions are closely associated with the acceleration of T2DM and atherosclerosis. AIM: To investigate the association between myosteatosis and coronary artery calcification (CAC) in patients with T2DM. METHODS: Patients with T2DM, who had not experienced major cardiovascular events and had undergone both abdominal and thoracic computed tomography (CT) scans, were included. The mean skeletal muscle attenuation was assessed using abdominal CT images at the L3 level. The CAC score was determined from thoracic CT images using the Agatston scoring method. Myosteatosis was diagnosed according to Martin's criteria. Severe CAC (SCAC) was defined when the CAC score exceeded 300. Logistic regression and decision tree analyses were performed. RESULTS: A total of 652 patients with T2DM were enrolled. Among them, 167 (25.6%) patients had SCAC. Logistic regression analysis demonstrated that myosteatosis, age, duration of diabetes, cigarette smoking, and alcohol consumption were independent risk factors of SCAC. Myosteatosis was significantly associated with an increased risk of SCAC (OR = 2.381, P = 0.003). The association between myosteatosis and SCAC was significant in the younger patients (OR = 2.672, 95%CI: 1.477-4.834, P = 0.002), but not the older patients (OR = 1.456, 95%CI: 0.863-2.455, P = 0.188), and was more prominent in the population with lower risks of atherosclerosis. The decision tree analyses prioritized older age as the primary variable for SCAC. In older patients, cigarette smoking was the main contributing factor for SCAC, while in younger patients, it was myosteatosis. CONCLUSION: Myosteatosis is a novel risk factor for atherosclerosis in patients with T2DM, especially in the population with younger ages and fewer traditional risk factors.

Fluorinated carbon as high-performance cathode for aqueous zinc primary batteries.

Fluorinated carbon (CFx) has been extensively served as promising positive electrode material for lithium primary batteries due to its high energy density. However, there are comparatively far less reports about the use of CFx on other battery systems, let alone on the research of aqueous batteries. Herein in this study, we employed CFx as the cathode active for aqueous zinc batteries for the first time and systematically investigated its electrochemical behavior under a series of aqueous zinc-ion electrolytes. As is discovered that the F/C ratio (the x value in CFx) of CFx have significant effects on the electrochemical performance of aqueous Zn/CFx batteries. Specifically, CF0.85 exhibits excellent electrochemical property with delivering a remarkable discharge capacity of 503 mA h g-1 and energy density of 388 W h kg-1 (at a current rate of 30 mA g-1 under temperature of 25 °C), much better than several other CFx electrode with F/C ratio of 0.70, 0.95, and 1.10, respectively. Besides, it also exhibits decent temperature performance with discharge capacities of 550 mA h g-1 at 50 °C and 460 mA h g-1 at 0 °C under current density of 30 mA g-1. Furthermore, the electrochemical discharge mechanism based on conversion reaction was further uncovered by applying XPS, XRD, SEM and EDS elemental analysis characterization techniques. In conclusion, these results demonstrate the potential application value of CFx in aqueous zinc primary batteries.

Functional investigation of a novel ANKRD11 frameshift variant identified in a Chinese family with KBG syndrome.

KBG syndrome is a rare autosomal dominant condition characterized by multisystem developmental disorder, primarily caused by loss-of-function variants in ankyrin repeat domain-containing protein 11 (ANKRD11). Approximately 80 % of ANKRD11 variants associated with KBG syndrome, are frameshift and nonsense variants. Current insight into the pathogenesis of KBG syndrome resulting from ANKRD11 truncating variants remains limited. Here, we presented two members from a non-consanguineous Chinese pedigree both exhibiting characteristics fitting the KBG syndrome-associated phenotypic spectrum. Whole-exome sequencing identified a novel heterozygous frameshift variant in ANKRD11 (NM_013275.6, c.2280_2281delGT, p.Y761Qfs*20) in the proband. Sanger sequencing confirmed that the variant was inherited from her mother and co-segregated with KBG syndrome phenotype. In vitro functional assays revealed that the frameshift variant escaped nonsense-mediated mRNA decay, and resulting in a truncated protein with significantly increased expression levels compared to full-length ANKRD11. Immunofluorescence results demonstrated that truncated protein was predominantly expressed in the nucleus of HEK293 cells, while wild-type ANKRD11 was equally distributed in both the nucleus and cytoplasm. Moreover, the truncated protein significantly reduced CDKN1A/P21-promoter luciferase activity in comparison to wild-type ANKRD11 protein, as well as a remarkably decrease in the endogenous CDKN1A/P21 mRNA level in HEK293 cells. These findings suggest a loss of transcriptional activation function and potentially a dominant-negative mechanism. Overall, our study expands the mutational spectrum of ANKRD11 gene and provides new insights into the pathogenic mechanism of KBG syndrome caused by ANKRD11 truncating variants.

Identification and functional analysis of first heterozygous frameshift mutation in the GHRH gene in a Chinese boy with isolated growth hormone deficiency.

BACKGROUND: Isolated growth hormone deficiency (IGHD) is a rare genetically heterogeneous disorder caused primarily by mutations in GH1 and GH releasing hormone receptor (GHRHR). The aim of this study was to identify the molecular etiology of a Chinese boy with IGHD. METHODS: Whole-exome sequencing, sanger sequencing and bioinformatic analysis were performed to screen for candidate mutations. The impacts of candidate mutation on gene expression, intracellular localization and protein function were further evaluated by in vitro assays. RESULTS: A novel heterozygous frameshift mutation in the GHRH gene (c.91dupC, p.R31Pfs*98) was identified in a Chinese boy clinically diagnosed as having IGHD. The mutation was absent in multiple public databases, and considered as deleterious using in silico prediction, conservative analysis and three-dimensional homology modeling. Furthermore, mRNA and protein expression levels of mutant GHRH were significantly increased than wild-type GHRH (p < 0.05). Moreover, mutant GHRH showed an aberrant accumulation within the cytoplasm, and obviously reduced ability to stimulate GH secretion and cAMP accumulation in human GHRHR-expressing pituitary GH3 cells compared to wild-type GHRH (p < 0.05). CONCLUSION: Our study discovered the first loss-of function mutation of GHRH in a Chinese boy with IGHD and provided new insights on IGHD pathogenesis caused by GHRH haploinsufficiency.

Clinical Manifestations, Genetic Variants and Therapeutic Evaluation in Sporadic Chinese Patients with Idiopathic Hypogonadotropic Hypogonadism.

Purpose: Genetic factors account for a large proportion of idiopathic hypogonadotropic hypogonadism (IHH) etiologies, although not necessarily a complete genetic basis. This study aimed to characterize the clinical presentations, genetic variants, and therapeutic outcomes of patients with sporadic IHH, which may be helpful for genetic counseling and treatment decisions. Patients and Methods: Eleven Chinese patients with IHH were retrospectively analyzed. Rare genetic variants were evaluated using whole-exome sequencing and bioinformatics analysis and were further classified according to the ACMG-AMP guidelines. The therapeutic responses of patients were further evaluated. Results: Six heterozygous variants of SOX10, WDR11, PROKR2, CHD7 and FGF17 were detected in five Kallmann syndrome (KS) patients, whereas two heterozygous variants of CHD7 and PROKR2 were detected in two normosmic IHH (nIHH) patients. Among these variants, a novel likely pathogenic variant in the SOX10 (c.429-1G>C) was considered to cause the KS phenotype in patient 02, and two potential variants of uncertain significance (VUS) in CHD7 (c.3344G>A and c.7391A>G) possibly contributed to the KS phenotype in patient 05 and the nIHH phenotype in patient 07, which need to be confirmed by further evidence. Additionally, long-term testosterone or estradiol replacement treatment effectively improved the development of sexual characteristics in patients with IHH. Conclusion: Next-generation sequencing is a powerful tool for identifying the molecular etiology and early diagnosis of IHH. Efficient therapeutic outcomes strongly indicate a need for timely treatment.

Serum triglyceride glucose index is a valuable predictor for visceral obesity in patients with type 2 diabetes: a cross-sectional study.

BACKGROUND: Since the triglyceride glucose (TyG) index can reflect insulin resistance, it has been proven to be an efficient predictor of glycolipid-metabolism-related diseases. Therefore, this study aimed to investigate the predictive value of the TyG index for visceral obesity (VO) and body fat distribution in patients with type 2 diabetes mellitus (T2DM). METHODS: Abdominal adipose tissue characteristics in patients with T2DM, including visceral adipose area (VAA), subcutaneous adipose area (SAA), VAA-to-SAA ratio (VSR), visceral adipose density (VAD), and subcutaneous adipose density (SAD), were obtained through analyses of computed tomography images at the lumbar 2/3 level. VO was diagnosed according to the VAA (> 142 cm2 for males and > 115 cm2 for females). Logistic regression was performed to identify independent factors of VO, and receiver operating characteristic (ROC) curves were used to compare the diagnostic performance according to the area under the ROC curve (AUC). RESULTS: A total of 976 patients were included in this study. VO patients showed significantly higher TyG values than non-VO patients in males (9.74 vs. 8.88) and females (9.59 vs. 9.01). The TyG index showed significant positive correlations with VAA, SAA, and VSR and negative correlations with VAD and SAD. The TyG index was an independent factor for VO in both males (odds ratio [OR] = 2.997) and females (OR = 2.233). The TyG index ranked second to body mass index (BMI) for predicting VO in male (AUC = 0.770) and female patients (AUC = 0.720). Patients with higher BMI and TyG index values showed a significantly higher risk of VO than the other patients. TyG-BMI, the combination index of TyG and BMI, showed significantly higher predictive power than BMI for VO in male patients (AUC = 0.879 and 0.835, respectively) but showed no significance when compared with BMI in female patients (AUC = 0.865 and 0.835, respectively). CONCLUSIONS: . TyG is a comprehensive indicator of adipose volume, density, and distribution in patients with T2DM and is a valuable predictor for VO in combination with anthropometric indices, such as BMI.

Occurrence Behaviors of As/Sb/Bi in Copper Anode Slime and Their Separation by Compound Leaching Followed by Stepwise Precipitation.

Copper anode slime is the main raw material for the extraction of rare and precious metals. However, the recovery of rare and precious metals still faces great challenges due to the variety of impurities and the complex occurrence phase. In view of this, this research focuses on the occurrence mineral phases of arsenic, antimony, and bismuth in copper anode slime, and the process consisting of chloride leaching and selective precipitation of arsenic and bismuth is proposed. The results show that in copper anode slime, As mainly exists in the form of arsenate, while Sb and Bi exist in the form of oxides. The arsenate and oxides of Sb and Bi can be effectively leached by using the compound leaching process in the chloride system. The leaching efficiencies of As, Sb, Bi, and Cu can reach 92.72, 99.98, 89.13, and 90.31%, respectively, using a H2SO4 concentration of 4 mol/L and a NaCl concentration of 120 g/L with a liquid-solid ratio of 10:1 at 70 °C for 2 h. After compound leaching, more than 98% of Sb and Bi can be separated by stepwise selective precipitation in the form of Sb4O5Cl2 and BiOCl by controlling the H+ concentration at 0.8 g/L and 0.2 g/L, respectively. After separation of Sb and Bi, the As-containing solution can be further treated by mature arsenic solidification technology. The copper-containing solution for removing arsenic, antimony, and bismuth can be returned to the electrolysis process for copper recovery. The proposed process realizes the effectively and environmentally friendly separation of As, Sb, Bi, and Cu from copper anode slime.

Association between the ratio of serum creatinine to cystatin C and bone mineral density in Chinese older adults patients with type 2 diabetes mellitus.

Background: The ratio of creatinine to cystatin C (Cre/CysC), a marker of muscle function and muscle mass, can be used to predict sarcopenia in different populations. Since sarcopenia is closely associated with osteoporosis, this study investigated the association between Cre/CysC and bone mineral density (BMD) in patients with type 2 diabetes mellitus (T2DM). Method: This cross-sectional study included 391 Chinese patients with T2DM. General information, biochemical indicators, and the BMD of lumbar spine (LS), femoral neck (FN), and total hip (TH) were measured. Results: Pearson correlation analysis showed that Cre/CysC was significantly positively correlated with the BMD of LS (r = 0.170, p = 0.001), FN (r = 0.178, p < 0.001), and TH (r = 0.205, p < 0.001). The results of stepwise linear regression suggested that Cre/CysC was the only biochemical predictor of the BMD at three sites (LS: ß = 0.137, p = 0.01; FN: ß = 0.097, p = 0.038; TH: ß = 0.145, p = 0.002). Conclusion: In older patients with T2DM, high Cre/CysC value is independently positively associated with BMD and hence, Cre/CysC may serve as a valuable marker of osteoporosis.

Real-world study of antiresorptive-related osteonecrosis of jaw based on the US food and drug administration adverse event reporting system database.

Objective: This study aims to explore the risk signals of osteonecrosis of the jaw induced by antiresorptive drugs and provide references for the clinical safety application. Method: According to the FDA's Adverse Event Reporting System (FAERS), from January 2004 to September 2021, we chose "Osteonecrosis of the jaw (10064658)" and "Exposed bone in jaw (10071014)" as preferred terms, "antiresorptive drugs" as the target drugs, and primary suspect drug as the drug role code in the dataset. We evaluated the association between drugs and adverse events by using reporting odds ratio (ROR) based on disproportionality analysis. We took the High-Level Terms (HLT) of MedDRA® as the classification level of indications to calculate ROR to compare the signal difference of ONJ in different indications. In addition, patients with antiresorptive-induced osteonecrosis of the jaw and the time of onset of the condition following different antiresorptive medications were collected for the study. Results: The FAERS contained 18,421 reports relating to jaw osteonecrosis from January 2004 to September 2021. A total of eight antiresorptive agents were included in the analysis. From high to low, the ROR of ONJ induced by antiresorptive agents (regardless of indication) is pamidronate (ROR = 494.8), zoledronic acid (ROR = 431.9), denosumab (ROR = 194.8), alendronate (ROR = 151.2), risedronate (ROR = 140.2), etidronic acid (ROR = 64.5), ibandronate (ROR = 40.8), and romosozumab (ROR = 6.4). HLT ROR values for "metabolic bone disorders" were the lowest for each drug, while HLT ROR values were high for "tumor-related indications," including breast and nipple neoplasms malignant, plasma cell myelomas, and prostatic neoplasms malignant. The onset time for osteonecrosis of the jaw as median (Q1, Q3), osteoporosis-related indications, and the onset time for ONJ were 730 (368, 1268), 489.5 (236.3, 909.8), 722.5 (314, 1055), 761 (368, 1720), and 153 (50, 346) for zoledronic acid, denosumab, ibandronate, risedronate, and romosozumab, respectively. Cancer-related indications: the onset time for ONJ were 680.5 (255.3, 1283), 488 (245, 851), and 696.5 (347, 1087) for zoledronic acid, denosumab, and pamidronate, respectively. Conclusion: When antiresorptive drugs are used for metastasis, they have the largest risk signal, followed by malignancy, and the smallest is osteoporosis. The onset time of ONJ may not be related to the indications. The onset time of ONJ for BPs was about 2 years, denosumab about 1.3 years, and romosozumab less than 1 year, which may be related to sequential treatment. When used according to the instructions, the risk of ONJ caused by denosumab was higher than that of zoledronic acid, regardless of the indication. Based on these findings, researchers will continue to monitor and identify risk factors.

Association Between the Growth Hormone/Insulin-Like Growth Factor-1 Axis and Muscle Density in Children and Adolescents of Short Stature.

Objective: To evaluate the association between the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis and muscle density in children and adolescents of short stature. Methods: Participants were children and adolescents of short stature hospitalized in the Affiliated Hospital of Jining Medical University between January 2020 and June 2021. All participants had CT scan images available. We performed an analysis of the images to calculate the muscle density or skeletal muscle attenuation (SMA), skeletal muscle index (SMI), and fat mass index (FMI). Bioelectrical impedance analysis (BIA) was used to ensure that chest CT is a credible way of evaluating body composition. Results: A total of 297 subjects were included with the mean age of 10.00 ± 3.42 years, mean height standard deviation score (SDS) of -2.51 ± 0.53, and mean IGF-1 SDS of -0.60 ± 1.07. The areas of muscle and fat tissues at the fourth thoracic vertebra level in the CT images showed strong correlation with the total weights of the participants (R2  = 0.884 and 0.897, respectively). The peak of GH was negatively associated with FMI (r = - 0.323, P <.01) and IGF-1 SDS was positively associated with SMI (r = 0.303, P <.01). Both the peak GH and IGF-1 SDS were positively associated with SMA (r = 0.244, P <.01 and r = 0.165, P <.05, respectively). Multiple stepwise linear regression analysis demonstrated that the GH peak was the predictor of FMI (ß = - 0.210, P < .01), the IGF-1 SDS was the predictor of SMI (ß = 0.224, P < .01), and both the peak GH and IGF-1 SDS were predictors of SMA (ß = 0.180, P < .01 and ß = 0.222, P < .01). Conclusions: A chest CT scan is a credible method of evaluating body composition in children and adolescents of short stature. In these patients, peak GH and IGF-1 SDS are independent predictors of muscle density and the GF/IGF-1 axis may regulate body composition through complex mechanisms.

The effects of glucagon-like peptide-1 receptor agonists on adipose tissues in patients with type 2 diabetes: A meta-analysis of randomised controlled trials.

AIMS: Glucagon­like peptide 1 receptor agonist (GLP-1RA) treatment can improve adipose distribution. We performed this meta-analysis to investigate whether GLP-1RAs preferentially reduce visceral adipose tissue (VAT) over subcutaneous adipose tissue (SAT) in patients with type 2 diabetes. MATERIALS AND METHODS: We searched MEDLINE and the Cochrane Library for randomised controlled trials explicitly reporting changes in VAT and SAT. A random-effects model was performed to estimate the weighted mean difference (MD) for VAT and SAT. Heterogeneity among the studies was assessed using I2 statistics, and publication bias was assessed using Egger's tests. Meta-regression was performed to identify the correlation between changes in adipose tissues and changes in body weight and glycated haemoglobin level. RESULTS: Ten trials with 924 patients were enrolled in the meta-analysis. GLP-1RA treatment led to similar absolute area (cm2) reductions in VAT (MD -21.13 cm2, 95% CI [-29.82, -12.44]) and SAT (MD -22.89 cm2, 95% CI [-29.83, -15.95]). No significant publication bias was detected, and this result was stable in the sensitivity and subgroup analyses. Moreover, GLP-1RA treatment resulted in a greater reduction in VAT and SAT in the subgroup with a greater reduction in body weight. The absolute area reduction in VAT was significantly correlated with the reduction in body weight (r = 6.324, p = 0.035). CONCLUSIONS: GLP-1RA treatment leads to significant and similar absolute reductions in VAT and SAT, and the reduction in adipose tissues may be correlated with the reduction in body weight.

Cre/CysC ratio may predict muscle composition and is associated with glucose disposal ability and macrovascular disease in patients with type 2 diabetes.

INTRODUCTION: Since the ratio of creatinine to cystatin C (Cre/CysC) can reflect muscle volume, it has been proven to be a predictor of sarcopenia in patients with or without diabetes. Here, we investigated the predictive value of Cre/CysC for the skeletal muscle composition and its correlations with glucose disposal ability and diabetic complications in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The skeletal muscle index (SMI) and mean skeletal muscle attenuation (MMA) values of 193 patients with type 2 diabetes were obtained through analyses of CT images at the lumbar 3 level. RESULTS: Serum Cre/CysC was significantly correlated with both the SMI (r=0.375, p<0.001) and MMA (r=0.378, p<0.001). Multiple stepwise linear regression analysis demonstrated that Cre/CysC was the only biochemical predictor of the SMI (ß=0.48 (95% CI 0.02 to 0.94)) and MMA (ß=0.57 (95% CI 0.14 to 1.01)). Furthermore, the fat mass index (FMI) was significantly associated with the MMA (r=-0.481, p<0.001) but not the SMI (r=0.101, p=0.164). In the diabetic complications analysis, Cre/CysC was significantly lower in patients with cardiovascular disease (95% CI (-1.47 to -0.22), p=0.008) and lower extremity arterial disease (95% CI (-1.44 to -0.29), p=0.004). Moreover, in the 100 g steamed bun test, Cre/CysC was significantly correlated with glucose levels at 60 min (r=-0.162, p=0.045), 120 min (r=-0.287, p<0.001) and 180 min (r=-0.313, p<0.001). CONCLUSIONS: Cre/CysC may be a valuable predictor of skeletal muscle composition in type 2 diabetes. Patients with a higher Cre/CysC may have a better ability to dispose of postprandial glucose and are at a lower risk of macrovascular disease.

The Remission Rate of Type 2 Diabetes Outpatients with Premixed Insulin: The Result of a 5-Year Prospective Study.

The aim of the study was to evaluate the remission rate with short-term premixed insulin therapy in newly diagnosed type 2 diabetes outpatients and investigate predictors contributing to the remission rate. A 5-year prospective study was conducted with a total of 170 patients enrolled. Patients were treated with premixed insulin monotherapy or insulin in combination with one or two oral drugs. After glucose levels were well controlled, insulin and oral drugs were discontinued in a stepwise manner. The prolonged and partial remission rates were calculated and the possible factors contributing to remission were also analyzed. A total of 164 subjects completed the research study. The prolonged remission, partial remission and non-remission rates at the 5-year follow-up were 9.8, 59.8, and 30.5%, respectively. The remission rate was negatively correlated with disease duration (r=0.39). The combined rate of remission (prolonged and partial remission) significantly decreased when the duration was longer than 16 days, and reduced to approximately 50% after 1 month. Moreover, 75% of prolonged remission patients had duration of < 16 days. At the 5-year follow-up, the prolonged remission rate was 9.8% and the partial remission rate was 59.8%. Furthermore, the duration after diagnosis is an independent predictor of remission rate, and initiation of short-term premixed insulin therapy within the first 16 days of diabetes diagnosis is very important for remission. This is the first study to evaluate the remission rate associated with short-term premixed insulin therapy in recently diagnosed type 2 diabetes outpatients. At the 5-year follow-up, the prolonged remission rate was 9.8% and the partial remission rate was 59.8%. The duration of diabetes was identified as an independent predictor of drug-free remission. The initiation of short-term premixed insulin therapy within 15 days of diabetes onset is particular importance for remission.

Extraction of Li and Co from industrially produced Li-ion battery waste - Using the reductive power of waste itself.

Industrially produced spent lithium-ion batteries (LIBs) waste contain not only strategic metals such as cobalt and lithium but also impurity elements like copper, aluminum and iron. The current work investigates the distribution of the metallic impurity elements in LIBs waste, and their influence on the acid dissolution of target active materials. The results demonstrate that the presence of these, naturally reductive, impurity elements (e.g. Cu, Al, and Fe) can substantially promote the dissolution of active materials. Through the addition of Cu and Al-rich larger size fractions, the extraction efficiencies of Co and Li increased up to over 99%, to leave a leach residue that is rich in graphite. By this method, the use of high cost reductants like hydrogen peroxide or ascorbic acid could be avoided. More importantly, additional Co and Li associated with the Cu and Al electrode materials could be also recovered. This novel approach contributes not only to improved reduction efficiency in LIBs waste leaching, but also to improved total recovery of Co and Li from LIBs waste, even from the larger particle size fractions, which are typically lost from circulation.

The role of atorvastatin on the restenosis process post-PTA in a diabetic rabbit model.

BACKGROUND: Restenosis remains to be a major limitation of percutaneous transluminal angioplasty (PTA) for diabetic patients with peripheral vascular disease (PVD). Despite of stations routine implements to prevent such progress, its exact effect is unclear. METHODS AND RESULTS: In our study, balloon was successfully implanted in the iliac artery of atherosclerotic rabbit. Patency of the narrowed artery was interrogated using ultrasound. Atorvastatin or vehicle was administered orally to rabbits from day 0 to day 28 after double-injury surgery. On day 7, day 14, and day 28, restenotic arteries were harvested and processed for histopathlogical analysis. Our data show that, after double-injury surgery, the intima was composed mostly by SMCs at all time course in rabbits undergoing surgery process. Significant increases in stenosis rates were noted from day 7 to day 14 (from 21 ± 5.85 % to 60.93 ± 12.46 %). On day 28 after double-injury surgery, severe restenosis was observed and daily administration of atorvastatin cannot prevent restenosis' formation (88.69 ± 3.71 % vs. 90.02 ± 3.11 %, P > 0.05). The PCNA index and SMCs proliferation were correlated with the scores of the vascular pathology. CONCLUSIONS: Our results indicate that double-injury model can mimic clinical restenosis, based on this model, atorvastatin showed no therapeutic effect on restenosis process in diabetic rabbits after PTA.

Association of chemokine ligand 5/chemokine receptor 5 gene promoter polymorphisms with diabetic microvascular complications: A meta-analysis.

AIMS/INTRODUCTION: Chemokine ligand 5 (CCL5) is a member of the CC-chemokine family expressed in various organs. It contributes to the migration of monocytes/macrophages into injured vascular walls by binding with its receptor chemokine receptor 5 (CCR5). Many studies have accessed the association between CCL5/CCR5 gene promoter polymorphisms and diabetic microvascular complications (DMI). However, the results are conflicting and inconclusive. The aim of the present study was to evaluate the association more precisely. MATERIALS AND METHODS: Trials were retrieved through PubMed, Embase, Medline, China National Knowledge Infrastructure, Web of Science and Cochrane database without restrictions on language. The pooled odds ratio (OR) and 95% confidence interval (CI) were used to describe the strength of association with DMI. RESULTS: Data were obtained from 11 case-control studies that included 2,737 DMI patients and 2,435 diabetic control subjects. In the overall analysis, the CCL5-403 G/A and CCL5-28 C/G gene polymorphisms were not significantly associated with the risk of DMI. However, CCR5-59029 G/A was an independent risk factor of DMI in a dominant model (OR 1.77, 95% CI 1.06-2.97). Subgroup analysis showed that the risk of the CCR5 59029A-positive genotype was significant in Asians (OR 2.08, 95% CI 1.68-2.57). In addition, the CCR5 59029A-positive genotype was associated with increased risk of albuminuria. CONCLUSIONS: There were no associations of CCL5 gene promoter polymorphism with the risk of DMI. However, the 59029A polymorphism in CCR5 might affect individual susceptibility for DMI.

Tumour Risk with Once-Weekly Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes Mellitus Patients: A Systematic Review.

BACKGROUND AND OBJECTIVE: Once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a novel class of injectable antidiabetic drugs. Previous studies indicated that GLP-1RAs (exenatide and liraglutide) might increase the incidence of pancreatitis and pancreatic cancer. Here, we evaluated the clinical safety of once-weekly GLP-1RAs with respect to tumour risk. METHODS: Relevant studies were selected from ClinicalTrials.gov. Randomized controlled trials that reported the incidences of neoplasms were included in our research. Outcomes were calculated as the risk ratio using the Mantel-Haenszel method and fixed-effects model. RESULTS: Our analysis included 26 randomized controlled trials with 16,090 patients. Once-weekly GLP-1RAs did not increase the risk for tumours compared with other antidiabetic drugs [risk ratio (RR), 1.02; 95 % confidence interval (CI), 0.74-1.41; p = 0.91]; this finding was independent of the type of GLP-1RA administered (albiglutide, exenatide extended-release and dulaglutide) and duration of the trials (limited to ≥52 weeks). Subgroup analyses revealed that once-weekly GLP-1RAs did not increase tumour risk compared with placebos, exenatide and liraglutide, insulin or oral drugs. Additionally, once-weekly GLP-1RAs did not increase tumour risk in any tissue. CONCLUSIONS: Compared with other antidiabetic drugs, once-weekly GLP-1RAs did not increase the risk for any tumour, and this finding was independent of the type of GLP-1RA administered and treatment duration. However, our study had many limitations, and further longer term trials with larger samples should be conducted in future to confirm our results.

Hyperglycemia has no effect on development of restenosis after percutaneous transluminal angioplasty (PTA) in a diabetic rabbit model.

It is well known that hyperglycemia is a trigger of atherosclerosis in patients with diabetes mellitus. However, the role of hyperglycemia in restenosis remains unclear. In this study, we investigated the effects of hyperglycemia on restenosis. Stenosis was evaluated in two sets of diabetic rabbit models: i) diabetic restenosis versus nondiabetic restenosis and ii) diabetic atherosclerosis versus nondiabetic atherosclerosis. Our results indicated that there was no difference in rates of stenosis between the diabetic and the nondiabetic groups in restenosis rabbit models. However, the incidence of stenosis was significantly higher in the diabetic atherosclerosis group compared with the nondiabetic atherosclerosis group. Similarly, the intima-media thickness and cell proliferation rate were significantly increased in the diabetic atherosclerosis group compared with the nondiabetic atherosclerosis group, but there was no difference between the diabetic restenosis and the nondiabetic restenosis groups. Our results indicate that hyperglycemia is an independent risk factor for atherosclerosis, but it has no evident effect on restenosis. These findings indicate that the processes of atherosclerosis and restenosis may involve different pathological mechanisms.

Glucagon-like peptide 1 receptor agonist therapy is more efficacious than insulin glargine for poorly controlled type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND: The aim of the present study was to compare the reported efficacy and safety of glucagon-like peptide-l receptor agonist (GLP-1RA) and insulin glargine (IGlar) for poorly controlled type 2 diabetes. METHODS: Medline, EMBASE, Cochrane Library, and clinicaltrials.gov were carried out. References and cited papers of relevant articles were also checked. RESULTS: Seven trials met the inclusion criteria. GLP-1RA showed equivalent or superior efficacy to IGlar for reducing hemoglobin A1c (HbA1c), with a greater proportion of patients achieving HbAlc<7%. GLP-1RA also favored decreased body weight, total cholesterol (TC), low-density lipoprotein (LDL), and systolic blood pressure (SBP). Serious adverse events were uncommon and not significantly different. More patients taking GLP-1RA experienced gastrointestinal complications: nausea, diarrhea, and vomiting. Severe hypoglycemia events were rare, and minor hypoglycemia was less common for GLP-1RA. CONCLUSIONS: GLP-1RA showed greater efficacy compared to IGlar for type 2 diabetes, and it may also prove beneficial for other diabetes-associated characteristics, including obesity, hypertension, and hyperlipidemia.

Promotion effect of KMnO 4 on the oxidation of As(III) by air in alkaline solution.

The mechanism of oxidation of As(III) in alkaline solution by air with promotion effect of KMnO4 was studied. The experimental results indicated that the superstoichiometric oxidation of As(III) by KMnO4 could be attributed to the catalytic effect of reductive product of KMnO4. The XRD and XPS results demonstrated that the catalyst was nascent MnO2 rich in potassium. The results also showed that the mole ratio of Mn/As and the initial pH had significant effects on the oxidation of As(III). The time for the oxidation by air was less than 2h with the mole ratio of Mn/As less than 1/10.5 and the initial pH higher than 13. The kinetics of the catalytic oxidation of arsenic was interpreted using the pseudo first order reaction, and the apparent active energy was about 15.01 kJ/mol. The study suggested that the initial oxidation was firstly dominated by the direct oxidation of KMnO4 followed by the catalytic oxidation with the nascent MnO2.