Use of bomb pulse carbon-14 to age senile plaques and neurofibrillary tangles in Alzheimer's disease.

The time course of formation of neurofibrillary tangles (NFT) and senile plaques (SP) in Alzheimer's disease (AD) brain is unknown. Above ground nuclear weapons testing in the late 1950s and early 1960s led to significantly increased levels of 14C in the atmosphere and carbon cycle. Because the amyloid beta peptide of SP and paired helical filaments of NFT, once formed, are relatively resistant to degradation, 14C levels observed in SP and NFT should reflect their year of formation. The purpose of this study was to develop a method to determine whether 14C levels could be used to define NFT and SP ages. Using accelerator mass spectrometry to measure bomb-pulse 14C levels, we determined the average age of formation of isolated SP and NFT fractions in bulk brain samples of 6 AD subjects. Although preliminary, the results demonstrate that it is possible to use bomb pulse 14C to determine the average year of formation of NFT and SP in the brain in AD. In addition, the data show that these structures, once formed, have a much slower carbon turnover rate than normal brain and are not in a formation/enzymatic degradation equilibrium.     

Regulation of Toll-like receptor-mediated inflammatory response by microRNA-152-3p-mediated demethylation of MyD88 in systemic lupus erythematosus

Objective

microRNAs (miRNAs) play critical roles in embryogenesis, cell differentiation and the pathogenesis of several human diseases, including systemic lupus erythematosus (SLE). Toll-like receptors (TLRs) are also known to exert crucial functions in the immune response activation occurring in the pathogenesis of autoimmune diseases like SLE. Herein, the current study aimed to explore the potential role of miR-152-3p in TLR-mediated inflammatory response in SLE.

Methods

We determined the miR-152-3p expression profiles in CD4⁺ T cells and peripheral blood mononuclear cells (PBMCs) harvested from patients with SLE and healthy controls, and analyzed the correlation between miR-152-3p expression and clinicopathological parameters. CD70 and CD40L expression patterns in CD4⁺ T cells were assessed by RT-qPCR and flow cytometry. ChIP was adopted to determine the enrichment of DNA methyltransferase 1 (DNMT1) in the promoter region of myeloid differentiation factor 88 (MyD88).

Results

The obtained findings revealed that miR-152-3p was highly-expressed in CD4⁺ T cells and PBMCs of patients with SLE, and this high expression was associated with facial erythema, joint pain, double-stranded DNA, and IgG antibody. DNMT1 could be enriched in the MyD88 promoter, and miR-152-3p inhibited the methylation of MyD88 by targeting DNMT1. We also found that silencing miR-152-3p inhibited MyD88 expression not only to repress the autoreactivity of CD4⁺ T cells and but also to restrain their cellular inflammation, which were also validated in vivo.

Conclusion

Our study suggests that miR-152-3p promotes TLR-mediated inflammatory response in CD4⁺ T cells by regulating the DNMT1/MyD88 signaling pathway, which highlights novel anti-inflammatory target for SLE treatment.

     

脑卒中患者生活质量量表的编制及试测

为获取适合中国文化背景及脑卒中患者实际情况的生活质量评定工具,本研究根据量表编制的理论与方法,参考国外相关量表,在调查研究脑卒中患者的基础上,编制了《脑卒中患者生活质量量表》。量表包含5个方面:工作及经济状况、家务活动、家庭关系、户外及休闲活动、心理状态,共计25项,评定耗时约20～30min。并采用该量表对22例脑卒中患者进行了初步测试,结果显示:量表的信度、效度基本满足心理测验要求。初步估计了脑卒中患者病后1～3周内的生活质量得分区间。     

卡培他滨引起急性肾衰竭

1名94岁男性直肠腺癌患者接受卡培他滨化疗。在第3周期给予卡培他滨1500mg,2次/d,用药12d后,患者出现嗜睡、心慌、发热,血Cr由145μmol/L上升到173μmol/L,BUN由10.9mmol/L上升到27.4mmol/L,立刻停药。6d后,SCr310μmol/L,BUN62.5mmol/L。给予复方α-酮酸、利尿剂、低蛋白饮食等治疗,SCr及BUN逐渐下降。4个月后复查,SCr及BUN恢复正常。     

Bibliometric and altmetric analysis of research relating to antiphospholipid syndrome based on VOS viewer (2011–2021)

Clinical Rheumatology - Antiphospholipid syndrome is an autoimmune disorder characterized by recurrent vascular thrombosis and pregnancy losses in the presence of persistently positive...     

Activation of protein kinase C modulates BACE1-mediated beta-secretase activity

beta-Site APP cleavage enzyme 1 (BACE1) is the beta-secretase responsible for generating amyloid-beta (A beta) peptides in Alzheimer's disease (AD). Previous studies suggest that activation of protein kinase C (PKC) modulates the beta-secretase-mediated cleavage of APP and reduces the production of A beta. The mechanism of PKC-mediated modulation of beta-secretase activity, however, remains elusive. We report here that activation of PKC modulated beta-secretase activity through either suppressing the accumulation or promoting the translocation of BACE1 protein in a cell type-dependent manner. We found that activation of PKC suppressed the accumulation of BACE1 protein in fibroblasts through an enhancement of intracellular protease activities. In neurons, activation of PKC did not alter the expression level of BACE1, but led to more BACE1 translocated to the cell surface, resulting in a decreased cleavage of APP at the beta1 site. Together, Our findings provide novel mechanisms of PKC-mediated modulation of beta-secretase activity, suggesting that alteration of the intracellular trafficking of BACE1 may serve as a useful therapeutic strategy to lower the production of A beta in AD.     

Molecular Characterization of the Enterohemolysin Gene (ehxA) in Clinical Shiga Toxin-Producing Escherichia coli Isolates

Shiga toxin (Stx)-producing Escherichia coli (STEC) is an important foodborne pathogen with the ability to cause bloody diarrhea (BD) and hemolytic uremic syndrome (HUS). Little is known about enterohemolysin-encoded by ehxA. Here we investigated the prevalence and diversity of ehxA in 239 STEC isolates from human clinical samples. In total, 199 out of 239 isolates (83.26%) were ehxA positive, and ehxA was significantly overrepresented in isolates carrying stx_2a + stx_2c (p < 0.001) and eae (p < 0.001). The presence of ehxA was significantly associated with BD and serotype O157:H7. Five ehxA subtypes were identified, among which, ehxA subtypes B, C, and F were overrepresented in eae-positive isolates. All O157:H7 isolates carried ehxA subtype B, which was related to BD and HUS. Three ehxA groups were observed in the phylogenetic analysis, namely, group Ⅰ (ehxA subtype A), group Ⅱ (ehxA subtype B, C, and F), and group Ⅲ (ehxA subtype D). Most BD- and HUS-associated isolates were clustered into ehxA group Ⅱ, while ehxA group Ⅰ was associated with non-bloody stool and individuals ≥10 years of age. The presence of ehxA + eae and ehxA + eae + stx₂ was significantly associated with HUS and O157:H7 isolates. In summary, this study showed a high prevalence and the considerable genetic diversity of ehxA among clinical STEC isolates. The ehxA genotypes (subtype B and phylogenetic group Ⅱ) could be used as risk predictors, as they were associated with severe clinical symptoms, such as BD and HUS. Furthermore, ehxA, together with stx and eae, can be used as a risk predictor for HUS in STEC infections.     

儿童专科门诊电子病历系统的建设实践

目的充分发挥信息化技术优势,提升儿童专科门诊医疗质量和医生工作效率.方法结合儿童专科门诊业务和病历特点,运用自主研发优势,建设儿童专科门诊电子病历系统.结果儿童专科门诊电子病历系统有效提升了门诊医疗质量,提高了医生工作效率.结论充分考虑临床业务特点的信息系统可以更好地服务医疗.     

丙型肝炎病毒与荧光素酶融合基因细胞模型的初步建立

Objective　To establish HCV cell culture model which is easy to measure. Methods　Controllable retroviral vector with fusion gene of hepatitis C virus (HCV) cDNA and luciferase (luc) reporter gene was constructed by molecular cloning technique, the transfection of this retroviral vector in a human hepatic carcinoma cell (HHCC) line was performed by lipofectAMINE and then luciferase activity in the cellular lysate was measured by scintillation counter. Results　 ① Fusion gene of the HCV 5′ NCR-C region and luciferase reporter gene identified by restriction endonuclease cleavage have been cloned into pBPSTR1 vector. ② The luciferase activity could maintain up to 20 days at least, and could be increased by puromycin treatment and regulated by tetracycline. Conclusion　A cell model for expression of HCV C-E1 and luciferase genes was established for gene therapy studies against HCV C-E1 sequences.