电针刺激联合局部振动治疗对脊髓损伤并发下肢痉挛患者康复效果及血清BDNF、PDGF的影响

目的:探讨脊髓损伤(SCI)并发下肢痉挛患者经电针刺激联合局部振动治疗后的临床效果。方法:选取本院于2018年1月到2019年6月期间收治的SCI并发下肢痉挛患者90例,根据乱数表法将上述患者分为对照组(n=45)和研究组(n=45),对照组患者给予常规康复系统疗法治疗,研究组在对照组的基础上给予电针刺激联合局部振动治疗,比较两组患者临床疗效、相关量表评分、内收肌角、直腿抬高角以及血清BDNF、PDGF水平。结果:研究组治疗后的临床总有效率为91.11%(41/45),高于对照组的64.44%(29/45)(P0.05)。两组患者治疗后改良Barthel指数、血清BDNF、PDGF水平均升高,且研究组高于对照组(P0.05);改良Ashworth量表、临床痉挛指数评分降低,且研究组低于对照组(P0.05)。两组患者治疗后内收肌角、直腿抬高角均扩大,且研究组大于对照组(P0.05)。结论:电针刺激联合局部振动治疗SCI并发下肢痉挛患者,可有效促进患者康复,改善下肢痉挛,提高生活自理能力,同时还可有效改善血清BDNF、PDGF水平。     

Immune-associated biomarkers for early diagnosis of Parkinson’s disease based on hematological lncRNA–mRNA co-expression

Early stage diagnosis of Parkinson’s disease (PD) is challenging without significant motor symptoms. The identification of effective molecular biomarkers as a hematological indication of PD may help improve the diagnostic timelines and accuracy. In the present paper, we analyzed and compared the blood samples of PD and control (CTR) patients to identify the disease-related changes and determine the putative biomarkers for PD diagnosis. Based on the RNA sequencing analysis, differentially expressed genes (DEGs) were identified, and the co-expression network of DEGs was constructed using the weighted gene correlation network analysis (WGCNA). The analysis leads to the identification of 87 genes that were exclusively regulated in the PD group, whereas 66 genes were significantly increased and 21 genes were significantly decreased in contrast with the control group. The results indicate that the core lncRNA–mRNA co-expression network greatly changes the immune response in PD patients. Specifically, the results showed that Prader Willi Angelman Region RNA6 (PWAR6), LINC00861, AC83843.1, IRF family, IFIT family and calcium/calmodulin-dependent protein kinase IV (CaMK4) may play important roles in the immune system of PD. Based on the findings from the present study, future research aims at identifying novel therapeutic strategies for PD.     

Aldosterone enhances high phosphate–induced vascular calcification through inhibition of AMPK‐mediated autophagy

It remains unclear whether the necessity of calcified mellitus induced by high inorganic phosphate (Pi) is required and the roles of autophagy plays in aldosterone (Aldo)‐enhanced vascular calcification (VC) and vascular smooth muscle cell (VSMC) osteogenic differentiation. In the present study, we found that Aldo enhanced VC both in vivo and in vitro only in the presence of high Pi, alongside with increased expression of VSMC osteogenic proteins (BMP2, Runx2 and OCN) and decreased expression of VSMC contractile proteins (α‐SMA, SM22α and smoothelin). However, these effects were blocked by mineralocorticoid receptor inhibitor, spironolactone. In addition, the stimulatory effects of Aldo on VSMC calcification were further accelerated by the autophagy inhibitor, 3‐MA, and were counteracted by the autophagy inducer, rapamycin. Moreover, inhibiting adenosine monophosphate‐activated protein kinase (AMPK) by Compound C attenuated Aldo/MR‐enhanced VC. These results suggested that Aldo facilitates high Pi‐induced VSMC osteogenic phenotypic switch and calcification through MR‐mediated signalling pathways that involve AMPK‐dependent autophagy, which provided new insights into Aldo excess‐associated VC in various settings.     

Crystal Structures of GCN2 Protein Kinase C-terminal Domains Suggest Regulatory Differences in Yeast and Mammals

In response to amino acid starvation, GCN2 phosphorylation of eIF2 leads to repression of general translation and initiation of gene reprogramming that facilitates adaptation to nutrient stress. GCN2 is a multidomain protein with key regulatory domains that directly monitor uncharged tRNAs which accumulate during nutrient limitation, leading to activation of this eIF2 kinase and translational control. A critical feature of regulation of this stress response kinase is its C-terminal domain (CTD). Here, we present high resolution crystal structures of murine and yeast CTDs, which guide a functional analysis of the mammalian GCN2. Despite low sequence identity, both yeast and mammalian CTDs share a core subunit structure and an unusual interdigitated dimeric form, albeit with significant differences. Disruption of the dimeric form of murine CTD led to loss of translational control by GCN2, suggesting that dimerization is critical for function as is true for yeast GCN2. However, although both CTDs bind single- and double-stranded RNA, murine GCN2 does not appear to stably associate with the ribosome, whereas yeast GCN2 does. This finding suggests that there are key regulatory differences between yeast and mammalian CTDs, which is consistent with structural differences.     

Awareness,Treatment, Control of Diabetes Mellitus and the Risk Factors: Survey Results from Northeast China

Background

The awareness, treatment and control of diabetes mellitus (DM) can effectively reflect on the social status of diabetes conditions. Although several researchers have investigated the awareness, treatment and control rates of diabetes mellitus in China, little is known about their association with risk factors. This study aims to examine the relationship between risk factors and awareness, treatment and control of diabetes mellitus in northeast China.

Methods

A cross-sectional survey was conducted in 2012. Multistage stratified random cluster sampling design was used to select participants aged 18 to 79 years old. The analysis was based on a representative sample of 1,854 adult subjects. Multivariable logistic regression analysis was used to examine socio-demographic factors associated with the levels of awareness, treatment and control of diabetes mellitus.

Results

The awareness, treatment, and control rates of diabetes mellitus were 64.1%, 52.9% and 44.2%, respectively. In the multivariable logistic regression analysis, family history of diabetes was significantly positively associated with awareness (OR, 2.145; 95% CI, 1.600–2.875) and treatment (OR, 2.021; 95% CI, 1.559–2.619) of diabetes mellitus, while negatively associated with control (OR, 0.671; 95% CI, 0.529–0.951). Cigarette smokers and alcohol drinkers were less likely than non-smokers and non-drinkers to be aware of their blood glucose levels (OR, 0.895, 0.614; 95% CI, 0.659–1.216, 0.446–0.844, respectively). Participants who frequently exercise were more likely to be aware of their diabetic conditions than people who never or rarely exercise (OR, 2.003; 95% CI, 1.513–2.651).

Conclusions

We found that the awareness and treatment of diabetes mellitus were positively associated with age and were high in participants with a family history of diabetes and those who exercise frequently, but low for cigarette smokers and alcohol drinkers. Participants with a family history of diabetes had their diabetic condition poorly controlled.     

Association of Simple Anthropometric Indices and Body Fat with Early Atherosclerosis and Lipid Profiles in Chinese Adults

Objective

The discriminatory capability of different adiposity indices for atherosclerosis and lipid abnormalities remains uncertain. This study aimed to identify the best adiposity index for predicting early atherosclerosis and abnormal lipid profiles among anthropometric parameters and body fat measures in middle-aged and elderly Chinese.

Method

A total of 2,063 women and 814 men (57.6±5.2 y) were recruited for this community-based cross-sectional study. Body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were assessed. Body fat mass and its percentage values for the whole body and trunk were measured by bioelectrical impedance analysis (BIA). The intima-media thicknesses (IMTs) of the common carotid arteries (CCA), internal carotid arteries (ICA) and bifurcation (BIF) were determined via B-mode ultrasound. The fasting lipid profiles were assessed.

Results

With per SD increase of adiposity indices, the magnitude of the changes of IMT values and lipid profiles was more substantial for WC, WHR and WHtR in both genders. A multivariate logistic regression analysis indicated that WC, WHR and WHtR were more sensitive in predicting the presence of intima-media thickening at the three segments as well as the lipids disturbances in women and men. In general, BIA-derived measures have no added predictive value for IMT-thickening as opposed to those three traditional abdominal measures.

Conclusion

Our findings suggest that abdominal anthropometric measures including WC, WHR and WHtR are sensitive for discriminating carotid atherosclerosis and lipids abnormalities. WC is the best index because of its simplicity in routine use.     

Molecular mechanisms of two-component system RhpRS regulating type III secretion system in Pseudomonas syringae

Pseudomonas syringae uses the two-component system RhpRS to regulate the expression of type III secretion system (T3SS) genes and bacterial virulence. However, the molecular mechanisms and the regulons of RhpRS have yet to be fully elucidated. Here, we show that RhpS functions as a kinase and a phosphatase on RhpR and as an autokinase upon itself. RhpR is phosphorylated by the small phosphodonor acetyl phosphate. A specific RhpR-binding site containing the inverted repeat (IR) motif GTATC-N₆-GATAC, was mapped to its own promoter by a DNase I footprint analysis. Electrophoretic mobility shift assay indicated that P-RhpR has a higher binding affinity to the IR motif than RhpR. To identify additional RhpR targets in P. syringae, we performed chromatin immunoprecipitation followed by high-throughput DNA sequencing (ChIP-seq) and detected 167 enriched loci including the hrpR promoter, suggesting the direct regulation of T3SS cascade genes by RhpR. A genome-wide microarray analysis showed that, in addition to the T3SS cascade genes, RhpR differentially regulates a large set of genes with various functions in response to different growth conditions. Together, these results suggested that RhpRS is a global regulator that allows P. syringae to sense and respond to environmental changes by coordinating T3SS expression and many other biological processes.     

抗人血栓调节蛋白单克隆抗体的制备与鉴定

为了制备特异性抗人血栓调节蛋白(human thrombomodulin,hTM)的单克隆抗体(monoclonal antibody,McAb),利用脂质体Lipofectamine 2000将包含hTM全长cDNA序列的重组表达质粒pThr402转染CHO细胞,经G418筛选及相关鉴定后获得高效稳定表达hTM的CHO-TM5细胞株。将CHO-TM5细胞直接免疫Balb/c小鼠,应用杂交瘤技术,通过细胞ELISA (cellular enzyme-linked immunoabsorbent assay,CELISA)筛选出阳性克隆后,将杂交瘤细胞株腹腔注射Balb/c小鼠诱生腹水。用CELISA、流式细胞术、免疫组织化学染色法及免疫印迹法对所获McAb的特异性进行鉴定。我们获得了1株可稳定分泌抗hTM的McAb的杂交瘤细胞株NH-1,其亚型为IgGl,McAb腹水效价为1×10~(-6),腹水抗体含量为20 mg/ml。NH-1对相应抗原具有较高的组织特异性,在体内与正常组织的交叉反应少,对人脐静脉内皮细胞、CHO-TM5有特异性结合反应,说明NH-1可特异性识别天然的hTM分子,为进一步应用此McAb进行hTM生物学功能及临床意义研究提供了基础。