Association between early glycemic management and diabetes complications in type 1 diabetes mellitus: A retrospective cohort study

AimsTo investigate the association between early HbA1c levels near diagnosis and future glycemic management, and analyzed risk factors of complications in people with T1DM.MethodsThis retrospective cohort study included 201 children and adolescents with T1DM. Patient data including sex, age at diagnosis, duration of disease, HbA1c levels, HbA1c variability during the follow-up period, and diabetes complications and comorbidities were collected.ResultsThe mean follow-up period of patients was 16.4 years. HbA1c levels in all three examined time points after diagnosis (first year, second year, and first two years) were significantly associated with recent HbA1c level, and second-year HbA1c was most closely correlated with recent HbA1c level. Elevated second-year HbA1c was a risk factor of diabetic ketoacidosis (DKA) and retinopathy, and increased variability of HbA1c was significantly related to various microvascular complications. When HbA1c is stratified into quartiles, the subjects of each quartile trend to stay within that quartile over the follow-up period.ConclusionsEarly HbA1c levels were closely associated with recent HbA1c levels and diabetes complications in patients with T1DMs. Strict glucose management after diagnosis and reducing variability of HbA1c may prevent future diabetes complications and comorbidities.     

Renal tubular acidosis and associated factors in patients with primary Sjögren’s syndrome: a registry-based study

Clinical Rheumatology - To investigate the clinical features and factors associated with primary Sjögren’s syndrome (pSS)–associated renal tubular acidosis (RTA). This...     

The involvement of ERK/CREB/Bcl-2 in depression-like behavior in prenatally stressed offspring rats

A number of studies reveal that prenatal stress (PS) may induce an increased vulnerability to depression in offspring. Some evidences indicate that extracellular signal-regulated kinase (ERK)-cyclic AMP responsive element binding protein (CREB) signal system may play an important role in the molecular mechanism of depression. In the present study, we examined the effects of prenatal restraint stress on depression-like behavior in one-month offspring Sprague-Dawley rats and expression of ERK2, CREB, B-cell lymphoma-2 (Bcl-2) mRNA in the hippocampus, prefrontal cortex and striatum to explore the potential role of ERK–CREB pathway in mediating the behavioral effects of PS exposure. Our findings demonstrated that PS increased immobility time in forced swimming test and decreased expression of ERK2, CREB, Bcl-2 mRNA in the hippocampus and prefrontal cortex of juvenile offspring rats except for CREB in hippocampus of male offspring. Changes induced by PS were partly prevented by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist. These findings suggested that the ERK–CREB system might be related with the depression-like behavior in juvenile offspring rats subjected to PS, in which NMDA receptors might be involved.     

Combined effect of TNF-α and cyclic stretching on gene and protein expression associated with mineral metabolism in cementoblasts

ObjectiveThis work aims to investigate how the combination of TNF-α and cyclic stretching affects the expression of gene and protein associated with mineral metabolism in cementoblasts in vitro.DesignCementoblasts were cyclically stretched using the Flexcell tension system 4000 in the presence of 10 ng/ml TNF-α. Subsequently, the gene and protein expression CAP, Col I, BSP, OPG, RANKL and RUNX2 were detected using RT- PCR and ELISA/Western immunoblotting methods, respectively.ResultsCyclic stretching alone enhanced CAP, Col I, OPG, RANKL and RUNX2 expression in an amplitude manner, while decreased BSP expression. Expression of all these proteins was attenuated in the presence of TNF-α whether the cells were exposed to cyclic stretching or not. The ratio of RANKL/OPG was increased at any stimulation.ConclusionThis results suggest that TNF-α affected the regulation of gene and protein expression induced by mechanical stimulation in cementoblasts. This may suppress anabolism and promote catabolism of cementum. It suggests that inflammatory cytokine may impair the cementum remodeling under mechanical stimulation.     

Hypermethylation of Death-Associated Protein Kinase (DAPK1) and its association with oral carcinogenesis - An experimental and meta-analysis study

ObjectivesThe value of abnormal DNA methylation of DAPK1 promoter and its association with various cancers have been suggested in the literature. To establish the significance of DNA methylation of DAPK1 promoter in oral squamous cell carcinoma (OSCC), we a) performed a case-control study, b) evaluated published data for its utility in the diagnosis and prognosis of OSCC and c) identified the association of DAPK1 gene expression with promoter DNA methylation status.DesignBisulfite gene sequencing of DAPK1 promoter region was performed on non-malignant and malignant oral samples. Further, using a systematic search, 330 publications were retrieved from PubMed, Scopus, and Google Scholar and 11 relevant articles were identified.ResultsSignificant association of DAPK1 promoter methylation with OSCC (p < 0.0001) was observed in the case-control study. The studies chosen for meta-analysis showed prognostic and predictive significance of DAPK1 gene promoter, despite defined inconsistencies in few studies. Overall, we obtained a statistically significant (p-value < 0.001) association for both sensitivity and specificity of DAPK1 DNA promoter methylation in oral cancer cases, without publication bias.ConclusionDNA hypermethylation of DAPK1 gene promoter is a promising biomarker for OSCC prediction/prognostics and suggests further validation in large distinct cohorts to facilitate translation to clinics.     

Fasudil mediates cell therapy of EAE by immunomodulating encephalomyelitic T cells and macrophages

Although Fasudil has shown therapeutic potential in EAE mice, the mechanism of action are still not fully understood. Here, we examined the immunomodulatory effect of Fasudil on encephalitogenic mononuclear cells (MNCs), and tested the therapeutic potential of Fasudil‐treated MNCs in active EAE. Fasudil inhibited expression of CCL20 on T cells and migration of T cells, decreased CD4⁺IFN‐γ⁺ and CD4⁺IL‐17⁺ T cells, but increased CD4⁺IL‐10⁺ and CD4⁺TGF‐β⁺ T cells. Fasudil reduced expression of CD16/32 and IL‐12, while elevating expression of CD206, CD23, and IL‐10. Fasudil also decreased levels of iNOS/NO, enhanced levels of Arg‐1, and inhibited the TLR‐4/NF‐κB signaling and TNF‐α, shifting M1 macrophage to M2 phenotype. These modulatory effects of Fasudil on T cells and macrophages were not altered by adding autoantigen MOG_35–55 to the culture, i.e., autoantigen‐independent. Further, we observed that, in vitro, Fasudil inhibited the capacity of encephalitogenic MNCs to adoptively transfer EAE and reduced TLR‐4/p‐NF‐κB/p65 and inflammatory cytokines in spinal cords. Importantly, Fasudil‐treated encephalitogenic MNCs exhibited therapeutic potential when injected into actively induced EAE mice. Together, our results not only provide evidence that Fasudil mediates the polarization of macrophages and the regulation of T cells, but also reveal a novel strategy for cell therapy in MS.     

产超广谱β-内酰胺酶多重耐药的肺炎克雷伯菌相关基因研究

目的 了解山西地区五家医院多重耐药的肺炎克雷伯菌（Klebsiella pneumoniae,KP）的耐药特点,并研究其产超广谱β-内酰胺酶（extended spectrum β-lactamaes,ESBLs）多重耐药的KP相关基因的流行情况.方法 收集2010年1月-2012年12月山西地区五家医院临床标本中分离的KP2516株,采用药敏试验（K-B法）和ESBLs确证实验筛选多重耐药的KP,采用PCR法扩增ESBLs多重耐药的KP相关基因,选取阳性产物进行测序并在Genbank进行分析.结果 2516株KP中,筛选出40株产ESBLs的多重耐药KP.PCR法基因扩增检测出40株blaTEM型,1株SHV型和4株KPC型;检测出染色体介导的GyrA型32株,质粒介导的qnrA型8株,qnrB型15株,以及qnrS型2株;没有检出金属酶NDM-1基因.结论 多重耐药的KP耐药机制非常复杂,多重耐药菌株的出现导致同一菌株中同时携带几种基因.因此,应加强临床病例的监测,合理使用抗菌药物,减少泛耐药菌株的传播.