Remediation of 2,4-dichlorophenol-contaminated soil by electrokinetic delivery of persulfate technology.

2,4-Dichlorophenol (2,4-DCP) is difficult to degrade rapidly in the environment due to its stable chemical properties, so it was easy to lead to serious chlorophenol pollution in soil. Consequently, a remediation method which is efficient, safe, and economical is required. In this study, electrokinetic (EK) remediation was used to transfer sodium persulfate (Na2S2O8) into soil to degrade 2,4-DCP, and the effect of several factors (including the addition location of Na2S2O8, applied voltage, and running time) on the remediation efficiency was explored. The concentration of Na2S2O8, residual efficiency of 2,4-DCP and distribution characteristics of pH, and electrical conductivity were analyzed. The results showed that the cathode was the optimal position to add Na2S2O8. Under this condition, Na2S2O8 was uniformly distributed in the whole soil column through electromigration. The optimal removal efficiency of 2,4-DCP in soil by adding Na2S2O8 was approximately 26% when the voltage gradient was 1.0 V/cm and the operating time was 9 days, which was mainly due to the degradation of S2O82-.

The MT1 receptor as the target of ramelteon neuroprotection in ischemic stroke.

Stroke is the leading cause of death and disability worldwide. Novel and effective therapies for ischemic stroke are urgently needed. Here, we report that melatonin receptor 1A (MT1) agonist ramelteon is a neuroprotective drug candidate as demonstrated by comprehensive experimental models of ischemic stroke, including a middle cerebral artery occlusion (MCAO) mouse model of cerebral ischemia in vivo, organotypic hippocampal slice cultures ex vivo, and cultured neurons in vitro; the neuroprotective effects of ramelteon are diminished in MT1-knockout (KO) mice and MT1-KO cultured neurons. For the first time, we report that the MT1 receptor is significantly depleted in the brain of MCAO mice, and ramelteon treatment significantly recovers the brain MT1 losses in MCAO mice, which is further explained by the Connectivity Map L1000 bioinformatic analysis that shows gene-expression signatures of MCAO mice are negatively connected to melatonin receptor agonist like Ramelteon. We demonstrate that ramelteon improves the cerebral blood flow signals in ischemic stroke that is potentially mediated, at least, partly by mechanisms of activating endothelial nitric oxide synthase. Our results also show that the neuroprotection of ramelteon counteracts reactive oxygen species-induced oxidative stress and activates the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway. Ramelteon inhibits the mitochondrial and autophagic death pathways in MCAO mice and cultured neurons, consistent with gene set enrichment analysis from a bioinformatics perspective angle. Our data suggest that Ramelteon is a potential neuroprotective drug candidate, and MT1 is the neuroprotective target for ischemic stroke, which provides new insights into stroke therapy. MT1-KO mice and cultured neurons may provide animal and cellular models of accelerated ischemic damage and neuronal cell death.

The efficacy and safety of beinaglutide alone or in combination with insulin glargine in Chinese patients with type 2 diabetes mellitus who are inadequately controlled with oral antihyperglycemic therapy: A multicenter, open-label, randomized trial.

BACKGROUND: To compare glycemic control in Chinese patients with type 2 diabetes mellitus (T2DM) whose blood glucose levels were inadequately controlled with oral antidiabetic drugs after beinaglutide alone or combined with insulin glargine (IGlar). METHODS: In this 16-week multicenter, randomized clinical trial, 68 participants randomly received beinaglutide or IGlar for 8 weeks, then the two drugs in combination for 8 weeks. The primary outcomes were the proportion of individuals achieving their glycemic target and the change in glucose variability as measured with a continuous glucose monitoring system from baseline to 8 and 16 weeks. RESULTS: Both the beinaglutide and IGlar groups showed increased proportions achieving their glycemic target at 8 weeks, and the combination augmented the proportion reaching the glycated hemoglobin target from 25.42% at 8 weeks to 40.68% at 16 weeks. The beinaglutide group showed a significant reduction in body weight, body mass index, waist circumference, and systolic blood pressure. Beinaglutide elevated high-density lipoprotein cholesterol by 0.08 mmol/L (95% confidence interval [CI], 0.00-0.16), and diminished low-density lipoprotein cholesterol by 0.21 mmol/L (95% CI, 0.05-0.48), whereas IGlar showed no effect. Though IGlar was more efficient in lowering fasting plasma glucose than beinaglutide at comparable efficacies (to -1.57 mmol/L [95% CI, -2.60 to -0.54]), this difference was abolished in patients whose fasting C-peptide was ≥0.9 ng/mL. CONCLUSION: Beinaglutide exhibited a favorable hypoglycemic effect on patients with T2DM, and in combination with IGlar, glucose level was further decreased. Low fasting C-peptide in patients may reduce the glycemic response to beinaglutide therapy. We recommend that C-peptide levels be evaluated when using or switching to the novel glucagon-like peptide-1 receptor agonists beinaglutide. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03829891.

Association between Severity of Diabetic Retinopathy and Cardiac Function in Patients with Type 2 Diabetes.

Background: The purpose of this research was to assess the relationship between the severity of diabetic retinopathy (DR) and indexes of left ventricle (LV) structure and function in type 2 diabetes mellitus (T2DM). Methods: Retrospective analysis of 790 patients with T2DM and preserved LV ejection fraction. Retinopathy stages were classified as no DR, early nonproliferative DR, moderate to severe nonproliferative DR, or proliferative DR. The electrocardiogram was used to assess myocardial conduction function. Echocardiography was used to evaluate myocardial structure and function. Results: Patients were divided into three groups based on the DR status: no DR group (NDR, n = 475), nonproliferative DR group (NPDR, n = 247), and proliferative DR group (PDR, n = 68). LV interventricular septal thickness (IVST) increased significantly with more severe retinopathy (NDR: 10.00 ± 1.09; NPDR: 10.42 ± 1.21; and PDR: 10.66 ± 1.58; P < 0.001). Multivariate logistic regression analysis showed that the significant correlation of IVST persisted between subjects with no retinopathy and proliferative DR (odds ratio = 1.35, P = 0.026). Indices of myocardial conduction function were assessed by electrocardiogram differences among groups of retinopathy (all P < 0.001). In multiple-adjusted linear regression analyses, the increasing degree of retinopathy was closely correlated with heart rate (ß = 1.593, P = 0.027), PR interval (ß = 4.666, P = 0.001), and QTc interval (ß = 8.807, P = 0.005). Conclusion: The proliferative DR was independently associated with worse cardiac structure and function by echocardiography. Furthermore, the severity of retinopathy significantly correlated with abnormalities of the electrocardiogram in patients with T2DM.

Design, synthesis, and biological evaluation of pyrido[2,3-d]pyrimidine and thieno[2,3-d]pyrimidine derivatives as novel EGFRL858R/T790M inhibitors.

EGFR mutations have been identified in 20,000 reported NSCLC (non-small cell lung cancer) samples, and exon 19 deletions and L858R mutations at position 21, known as "classical" mutations, account for 85-90% of the total EGFR (epidermal growth factor receptor) mutations. In this paper, two series of EGFR kinase inhibitors were designed and synthesised. Among them, compound B1 showed an IC50 value of 13 nM for kinase inhibitory activity against EGFRL858R/T790M and more than 76-fold selectivity for EGFRWT. Furthermore, in an in vitro anti-tumour activity test, compound B1 showed an effective anti-proliferation activity against H1975 cells with an IC50 value of 0.087 µΜ. We also verified the mechanism of action of compound B1 as a selective inhibitor of EGFRL858R/T790M by cell migration assay and apoptosis assay.

Association between triglyceride glucose index and subclinical left ventricular systolic dysfunction in patients with type 2 diabetes.

BACKGROUND: The triglyceride glucose (TyG) index has been considered a new biomarker for the diagnosis of angiocardiopathy and insulin resistance. However, the association of the TyG index with subclinical left ventricular (LV) systolic dysfunction still lacks comprehensive exploration. This study was carried out to examine this relationship in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 150 T2DM patients with preserved LV ejection fraction (LVEF ≥ 50%) from June 2021 to December 2021 were included in this study. The subclinical LV function was evaluated through global longitudinal strain (GLS), with the predefined GLS < 18% as the cutoff for subclinical LV systolic dysfunction. The TyG index calculation was obtained according to ln (fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2), which was then stratified into quartiles (TyG index-Q). RESULTS: Analyses of clinical characteristics in the four TyG indexes-Q (Q1 (TyG index ≤ 8.89) n = 38, Q2 (8.89 < TyG index ≤ 9.44) n = 37, Q3 (9.44 < TyG index ≤ 9.83) n = 38, and Q4 (TyG index > 9.83) n = 37) were conducted. A negative correlation of the TyG index with GLS (r = -0.307, P < 0.001) was revealed according to correlation analysis. After gender and age were adjusted in multimodel logistic regression analysis, the higher TyG index (OR 6.86; 95% CI 2.44 to 19.30; P < 0.001, Q4 vs Q1) showed a significant association with GLS < 18%, which was still maintained after further adjustment for related clinical confounding factors (OR 5.23, 95% CI 1.12 to 24.51, p = 0.036, Q4 vs Q1). Receiver operator characteristic analysis indicated a diagnostic capacity of the TyG index for GLS < 18% (area under curve: 0.678; P < 0.001). CONCLUSIONS: A higher TyG index had a significant association with subclinical LV systolic dysfunction in T2DM patients with preserved ejection fraction, and the TyG index may have the potential to exert predictive value for myocardial damage.

Assessment of subclinical left ventricular systolic dysfunction in patients with type 2 diabetes: Relationship with HbA1c and microvascular complications.

BACKGROUND: We aimed to examine the association between glycated hemoglobin (HbA1c), microvascular complications, and subclinical left ventricular (LV) systolic dysfunction, and to determine the strength of the correlation in asymptomatic patients with type 2 diabetes mellitus (T2DM). METHODS: Global longitudinal strain (GLS) was employed to assess the subclinical LV function of 152 enrolled T2DM patients with preserved LV ejection fraction, with the cutoff for subclinical LV systolic dysfunction predefined as GLS < 18%. RESULTS: According to univariate analysis, the reduced GLS exhibited association with the clinical features including HbA1c, triglyceride, systolic blood pressure, fasting glucose, heart rate, diabetic retinopathy, and urinary albumin creatinine ratio (UACR) (all p < .05). After the factors of gender, age, and related clinical covariables adjusted, multiple logistic regression analysis revealed the HbA1c (odds ratio [OR] 1.66; 95% confidence interval [CI] 1.30-2.13; p < .001), UACR (OR 2.48; 95% CI 1.12-5.47; p = .025) and triglyceride (OR 1.84; 95% CI 1.12-3.03; p = .017) as the independent risk factors for the reduced GLS. Receiver operating characteristic curve showed a predictive value of the HbA1c for the subclinical LV systolic dysfunction (area under curve: 0.74; p < .001). CONCLUSIONS: In asymptomatic T2DM patients, subclinical LV systolic dysfunction was associated with HbA1c, diabetic complications, and triglyceride. More prominently, HbA1c may exert a prognostic significance for the progression of myocardial damage.

Association of peripheral neuropathy with subclinical left ventricular dysfunction in patients with type 2 diabetes.

OBJECTIVES: The impacts of diabetic peripheral neuropathy (DPN) on clinical manifestations of left ventricular (LV) function in patients suffering from type 2 diabetes mellitus (T2DM) and the preserved LV ejection fraction (LVEF) lack a full evaluation. This study was carried out to investigate the correlation of peripheral neuropathy with subclinical LV systolic dysfunction, accompanied by the exploration of the relevant clinical features of peripheral neuropathy in these patients. METHODS: A retrospective analysis was conducted depending on the data of 101 consecutive inpatients with T2DM and preserved LVEF (all ≥ 50 %), without coronary artery disease and other histories of heart disease. All subjects received both a nerve conduction assessment and a speckle-tracking echocardiography examination. Global longitudinal strain (GLS) was conducted to assess the subclinical LV systolic function. RESULTS: Forty-six (46 %) patients were diagnosed as DPN according to electrophysiological examination and clinical assessment. A significant difference was revealed in GLS between patients with and without DPN (16.5 ± 2.8 vs. 19.3 ± 3.4, p < 0.001). Multiple logistic regression analysis indicated GLS as one of the independent determinative factors for DPN (odds ratio, 0.68; P < 0.001). In addition, motor-sensory nerve conduction exhibited a significant positive correlation with GLS, which may not be revealed between the types of peripheral nerve damage. CONCLUSIONS: Despite the preserved LVEF, the subclinical LV myocardial dysfunction may have occurred in T2DM patients with DPN. Peripheral nerve conduction was significantly correlated with GLS. An early assessment of nerve conduction may exert a dual warning significance for the progression of subclinical LV dysfunction in asymptomatic patients with T2DM.

Design, synthesis and antibacterial activity of novel pleuromutilin derivatives with thieno[2,3-d]pyrimidine substitution.

A series of novel pleuromutilin derivatives with substituted thienopyrimidines were designed, synthesized, and evaluated for antibacterial act ivity. In this study, the activities of these compounds were investigated using the inhibition circle test, the minimum inhibitory concentration (MIC) test, real-time growth curves, time-kill kinetic assays, cytotoxicity assays, and molecular docking. Most of the tested compounds exhibited moderate antibacterial activity against Staphylococcus aureus, Streptococcus agalactiae, and Escherichia coli. Compound A11 was the most active and displayed bacteriostatic activities against methicillin-resistant S. aureus, with MIC values as low as 0.00191 µg/mL, which is 162 and 32 times lower than that of the marketed antibiotics tiamulin and retapamulin, respectively. Furthermore, the mechanism of action of A11 was confirmed by molecular docking studies.

Corrigendum: Pioglitazone for NAFLD Patients With Prediabetes or Type 2 Diabetes Mellitus: A Meta-Analysis.

[This corrects the article DOI: 10.3389/fendo.2021.615409.].

Pd-Catalyzed Rearrangement Reaction of N-Tosylhydrazones Bearing Allyl Ethers Into Trans-Olefin-Substituted Sulfonylhydrazones.

A novel and efficient rearrangement of N-tosylhydrazones bearing allyl ethers into trans-olefin-substituted sulfonylhydrazones is proposed. The reaction involves breakage of the C-O bond and formation of the C-N bond. The reaction can be extended to a wide range of substrates, and the target products can be synthesized smoothly, regardless of the presence of electron-donating and electron-withdrawing groups. The proposed strategy is a new direction in the field of rearrangement reactions.

Design, synthesis and biological evaluation of aminopyrimidine derivatives bearing a 4,5,6,7-tetrahydrothieno [3,2-c]pyridine as potent EGFR inhibitors.

To resolve the problem of drug resistance caused by epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer, we used the principle of collocation to design and synthesize a series of aminopyrimidine derivatives with 4,5,6,7-tetrahydrothieno [3,2-c]pyridine side chains (according to the binding mode of AZD9291 to EGFRT790M) for use as EGFRL858R/T790M kinase inhibitors. The most promising compound A12, a non-covalently bound reversible inhibitor, showed excellent kinase inhibitory activity against EGFRL858R/T790M, with an IC50 value of 4.0 nM and more than 42-fold selectivity for EGFRWT (IC50 = 170.0 nM). Moreover, compound A12 showed strong anti-proliferative activity against H1975 cells, with IC50 value of 0.086 µΜ. Additionally, the effective inhibition of cell migration and the promotion of apoptosis by A12 verified its mechanism of action, as a selective inhibitor of EGFRL858R/T790M.

Pioglitazone for NAFLD Patients With Prediabetes or Type 2 Diabetes Mellitus: A Meta-Analysis.

Objective: To systematically evaluate the effects of pioglitazone in the treatment of patients with prediabetes or T2DM combined with NAFLD. Methods: The Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and ClinicalTrials databases were searched until August 2020 for publications written in English. Two reviewers independently assessed study eligibility, continuous data extraction, independent assessment of bias risk, and graded the strength of evidence. Our primary outcomes were the individual number of patients with improvement of at least 1 point in each of the histological parameters. Baseline characteristic data, such as BMI, weight, total body fat, fasting plasma glucose and fasting plasma insulin, and liver biological indicators, such as triglyceride level, HDL cholesterol level, plasma AST, and plasma ALT, were used as secondary outcomes. Results: A total of 4 studies were included. Compared with placebo, pioglitazone significantly improved steatosis grade, inflammation grade and ballooning grade, while in the fibrosis stage, there was no significant improvement in pioglitazone compared with placebo. In addition, pioglitazone can also improve blood glucose and liver function. Conclusion: Pioglitazone can significantly improve the histological performance of the liver and insulin sensitivity. Additionally, it can significantly reduce fasting blood glucose, glycosylated hemoglobin, plasma AST, ALT and other liver biological indicators. Due to the lack of relevant randomized controlled trials and short intervention times, long-term studies are still needed to verify its efficacy and safety. Systematic Review Registration: [PROSPERO], identifier [CRD42020212025].

Efficacy of Various Hypoglycemic Agents in the Treatment of Patients With Nonalcoholic Liver Disease With or Without Diabetes： A Network Meta-Analysis.

Objective: To comprehensively evaluate and compare the therapeutic effects of various hypoglycemic agents in NAFLD patients with or without diabetes. Methods: All literature from the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Clinical Trials was searched, and the language was limited to English. Two reviewers independently assessed study eligibility, continuous data extraction, and independent assessment of bias risk. Our primary outcomes were alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride levels, while our secondary outcomes were high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels, body weight, BMI, and fasting glucose and glycosylated hemoglobin (HbA1c) levels. Results: The review identified 20 eligible trials that met the inclusion criteria. We found that, compared to other drugs, thiazolidinediones, especially pioglitazone, had a greater effect on the levels of ALT (-8.01 (95% CI -14.3 to 2.02)) and AST (-5.0 (95% CI -9.21 to -1,22)) and other biological indicators, but they were also associated with an increased risk of weight gain (3.62 (95% CI 2.25 to 4.99) and increased BMI (0.59 (95% Cl -0.13 to 1.29). GLP1 RAs and metformin also had better therapeutic effects than other drugs as measured by the levels of ALT (liraglutide: -9.36 (95% Cl -18 to -0.34), metformin: -2.84 (95% CI -11.09 to 5.28)) and AST (liraglutide: -5.14 (95% CI -10.69 to 0.37), metformin: -2.39 (95% CI -7.55, 2.49)) and other biological indicators. Conclusion: Despite the significant risk of weight gain, thiazolidinediones, especially pioglitazone, are beneficial in normalizing liver and glucose metabolism in NAFLD patients. In clinical practice, we believe that GLP1 RAs such as liraglutide and exenatide or metformin can be used in combination to offset the risk of weight gain associated with thiazolidinediones. However, long-term studies are still needed to verify the efficacy and safety of individual hypoglycemic agents. Systematic Review Registration: [PROSPERO], identifier [CRD42020212025].

The Fecal Microbiota Is Already Altered in Normoglycemic Individuals Who Go on to Have Type 2 Diabetes.

Objective: Mounting evidence has suggested a link between gut microbiome characteristics and type 2 diabetes (T2D). To determine whether these alterations occur before the impairment of glucose regulation, we characterize gut microbiota in normoglycemic individuals who go on to develop T2D. Methods: We designed a nested case-control study, and enrolled individuals with a similar living environment. A total of 341 normoglycemic individuals were followed for 4 years, including 30 who developed T2D, 33 who developed prediabetes, and their matched controls. Fecal samples (developed T2D, developed prediabetes and controls: n=30, 33, and 63, respectively) collected at baseline underwent metagenomics sequencing. Results: Compared with matched controls, individuals who went on to develop T2D had lower abundances of Bifidobacterium longum, Coprobacillus unclassified, and Veillonella dispar and higher abundances of Roseburia hominis, Porphyromonas bennonis, and Paraprevotella unclassified. The abundance of Bifidobacterium longum was negatively correlated with follow-up blood glucose levels. Moreover, the microbial Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of carbohydrate metabolism, methane metabolism, amino acid metabolism, fatty acid metabolism, and membrane transport were changed between the two groups. Conclusions: We found that fecal microbiota of healthy individuals who go on to develop T2D had already changed when they still were normoglycemic. These alterations of fecal microbiota might provide insights into the development of T2D and a new perspective for identifying individuals at risk of developing T2D.

Status of Analgesic Drugs and Quality of Life Results for Diabetic Peripheral Neuropathy in China.

Objective: The purpose of this study is to describe the current clinical situation of patients with painful diabetic peripheral neuropathy (DPN) and related anxiety, depression, and the quality of life of patients in mainland China, and to report the current status of the use of analgesics. Methods: Between June 15, 2021, and October 15, 2021, a total of 401 participants participated in the study. Recruitment was carried out using a multi-level sampling method. Participants' demographics, medical history, analgesic use, Michigan Symptom Score (MNSI), Numerical Rating Scale (NRS) pain score, Patient Health Questionnaire 9 (PHQ-9) score, Generalized Anxiety Disorder 7 (GAD) -7) Score, quality of life score (SF-12) and diabetes treatment status were collected. Results: Among the participants, there were 236 male patients and female patients. Participants were 322 patients over 40 years old. Regarding the use of analgesics: 132 patients reported using analgesics, 221 patients reported not using analgesics, and 48 patients reported having used analgesics. The results of the scale showed that the scores of NRS, GAD-7, PHQ-9 and SF-12 were 5.12 ± 2.15, 6.33 ± 3.67, 8.46 ± 4.07 and 47.84 ± 19.92 for patients who used analgesics, Compared with patients who did not use analgesics (NRS: 1.99 ± 1.7, GAD-7: 1.81 ± 2.81, PHQ-9: 3.13 ± 4.10, SF-12: 78.34 ± 21.66) there are significant differences (p< 0.001). In addition, patients' NRS scores are also closely related to GAD-7, PHQ-9 and SF-12 scores. Conclusion: The severity of symptoms, mental status and quality of life of patients who used analgesics were more severe than those of patients who did not use analgesics. Pregabalin is still the preferred analgesic for patients with painful DPN, and the use of opioids in my country is extremely low, which is consistent with current international guidelines. Age, diabetic duration, DPN duration, PHQ-9 score, GAD-7 score and SF-12 scores are closely related to NRS pain scores. In addition, there are still a considerable number of patients who have not used analgesics due to financial burdens and other reasons, suggesting that China still has insufficient pain management in DPN patients.

Integrated Skin Transcriptomics and Serum Multiplex Assays Reveal Novel Mechanisms of Wound Healing in Diabetic Foot Ulcers.

Nonhealing diabetic foot ulcers (DFUs) are characterized by low-grade chronic inflammation, both locally and systemically. We prospectively followed a group of patients who either healed or developed nonhealing chronic DFUs. Serum and forearm skin analysis, both at the protein expression and the transcriptomic level, indicated that increased expression of factors such as interferon-γ (IFN-γ), vascular endothelial growth factor, and soluble vascular cell adhesion molecule-1 were associated with DFU healing. Furthermore, foot skin single-cell RNA sequencing analysis showed multiple fibroblast cell clusters and increased inflammation in the dorsal skin of patients with diabetes mellitus (DM) and DFU specimens compared with control subjects. In addition, in myeloid cell DM and DFU upstream regulator analysis, we observed inhibition of interleukin-13 and IFN-γ and dysregulation of biological processes that included cell movement of monocytes, migration of dendritic cells, and chemotaxis of antigen-presenting cells pointing to an impaired migratory profile of immune cells in DM skin. The SLCO2A1 and CYP1A1 genes, which were upregulated at the forearm of nonhealers, were mainly expressed by the vascular endothelial cell cluster almost exclusively in DFU, indicating a potential important role in wound healing. These results from integrated protein and transcriptome analyses identified individual genes and pathways that can potentially be targeted for enhancing DFU healing.

Greater macrovascular and microvascular morbidity from type 2 diabetes in northern compared with southern China: A cross-sectional study.

AIMS/INTRODUCTION: There are substantial differences in genes, diet, culture and environment between the northern and southern Chinese populations, which might influence treatment strategy and screening policy. We studied the differences in type 2 diabetes and diabetic complications between northern and southern China. MATERIALS AND METHODS: We carried out a cross-sectional survey using data from the China Cardiometabolic Registries on blood pressure, blood lipids and blood glucose in 25,398 Chinese type 2 diabetes patients. Macrovascular, microvascular and other complications were collected by self-report or medical records, and then divided into the northern and southern groups by the boundary of the Yangtze River. RESULTS: Northern patients were younger, and had heavier weight, greater body mass index and waist circumference, higher blood pressure, higher total cholesterol, higher low-density lipoprotein cholesterol, and higher hemoglobin A1C. The prevalence of cardiovascular, cerebrovascular and macrovascular complications were 1.76-fold, 1.24-fold and 1.47-fold more in northern than that in southern Chinese patients. In addition, the prevalence of diabetic nephropathy, retinopathy, neuropathy and microvascular complications in northern Chinese patients also increased. When stratified by age, the difference in both cardiovascular disease and ischemic stroke morbidity became significant, even in the 35-44 years age group. CONCLUSIONS: More macrovascular and microvascular complications were found in northern compared with southern patients, and the largest difference also appeared in the younger age groups <55 years, which might be meaningful to a screening and treatment strategy according to geographic differences.

Efficacy and safety of a needle-free injector in Chinese patients with type 2 diabetes mellitus treated with basal insulin: a multicentre, prospective, randomised, crossover study.

Objective: To evaluate the efficacy and safety of a needle-free injector in Chinese patients with type 2 diabetes mellitus treated with basal insulin. Methods: 62 patients with type 2 diabetes were enrolled in a multicenter, randomised, prospective, open-label, crossover study. All patients received subcutaneous insulin glargine administered by a needle-free injector or a glargine pen for 7 ~ 14 days, and were then crossed over after wash out. Results: Patients in the insulin needle-free injector (NFI) and glargine pen (GP) groups achieved similar fasting blood glucose control . However, the dosage of insulin required to achieve the target FBG level in the NFI group was lower than in the GP group (16.14 ± 5.13 U/day vs 19.25 ± 6.20 U/day, respectively; p = 0.0046). This difference was more significant in patients who received higher insulin dosages compared with those receiving lower dosages. Use of the needle-free injector was also associated with significantly less pain (p < 0.001) and less fear of injection (p < 0.001) than glargine pens. Conclusion: The use of a needle-free injector can significantly lower the dosage of insulin required to achieve good glycemic control and reduce topical adverse reactions and the fear of injections as well, which help to improve patient compliance. Clinical Trial Registration Number KY20172077-1; NCT03420040.

Amelioration of prediabetes-induced changes of dendritic structural plasticity.

Accumulating evidence suggests that the diabetes-induced cognitive dysfunction can be alleviated when exposed to the enriched environment. However, the impact of the changes of the hippocampal plasticity on the cognitive decline and the possible effect of an enriched environment in prediabetes are still not clearly documented. To explore the effect of enriched environment for prediabetes-induced changes of dendritic structural plasticity in hippocampus pyramidal and cognitive deficits, the praxiology experiments for evaluating of anxiety, spatial learning and memory of prediabetic Wistar were performed, and then the dendritic spine density was assessed in the hippocampal CA1 pyramidal neuronal region. The prediabetic rats demonstrated a hyper-anxiety like behavior and significantly decreased spatial learning abilities and memory deficits. Exposing prediabetic rats to an enriched environment appeared to significantly mitigate the above changes in a time-dependent manner. The enriched environment also restored the density of the hippocampal dendritic spine which was significantly reduced in prediabetic rats. We found that the enriched environment was beneficial in overcoming the prediabetes-induced cognitive disorders and diminished dendritic plasticity of hippocampus pyramidal.