Molecular Surface of JZTX-V (β-Theraphotoxin-Cj2a) Interacting with Voltage-Gated Sodium Channel Subtype NaV1.4

Voltage-gated sodium channels (VGSCs; Na_V1.1–Na_V1.9) have been proven to be critical in controlling the function of excitable cells, and human genetic evidence shows that aberrant function of these channels causes channelopathies, including epilepsy, arrhythmia, paralytic myotonia, and pain. The effects of peptide toxins, especially those isolated from spider venom, have shed light on the structure–function relationship of these channels. However, most of these toxins have not been analyzed in detail. In particular, the bioactive faces of these toxins have not been determined. Jingzhaotoxin (JZTX)-V (also known as β-theraphotoxin-Cj2a) is a 29-amino acid peptide toxin isolated from the venom of the spider Chilobrachys jingzhao. JZTX-V adopts an inhibitory cysteine knot (ICK) motif and has an inhibitory effect on voltage-gated sodium and potassium channels. Previous experiments have shown that JZTX-V has an inhibitory effect on TTX-S and TTX-R sodium currents on rat DRG cells with IC₅₀ values of 27.6 and 30.2 nM, respectively, and is able to shift the activation and inactivation curves to the depolarizing and the hyperpolarizing direction, respectively. Here, we show that JZTX-V has a much stronger inhibitory effect on Na_V1.4, the isoform of voltage-gated sodium channels predominantly expressed in skeletal muscle cells, with an IC₅₀ value of 5.12 nM, compared with IC₅₀ values of 61.7–2700 nM for other heterologously expressed Na_V1 subtypes. Furthermore, we investigated the bioactive surface of JZTX-V by alanine-scanning the effect of toxin on Na_V1.4 and demonstrate that the bioactive face of JZTX-V is composed of three hydrophobic (W5, M6, and W7) and two cationic (R20 and K22) residues. Our results establish that, consistent with previous assumptions, JZTX-V is a Janus-faced toxin which may be a useful tool for the further investigation of the structure and function of sodium channels.     

Association between Serum Vitamin A,Blood Lipid Level and Dyslipidemia among Chinese Children and Adolescents

Background: To study the relationship between serum vitamin A (VA) level and blood lipid profiles in children and adolescents aged 6–18 years, as well as the effect of VA on dyslipidemia. Methods: The project adopted a multistage stratified cluster sampling method. The Food Frequency Questionnaire (FFQ) was used to obtain dietary factors data. Blood samples of subjects were taken via venipuncture. Generalized linear models were used to explore the correlation be-tween VA and biochemical indicators, as well as stratified and inter-actions analysis to explore the influence of confounders on these relationships. Generalized linear models were constructed to explore the association between VA and blood lipids. Restricted cubic splines were used to characterize dose–response associations between serum VA and dyslipidemia based on logistic regression. Results: Serum VA was positively correlated with TC, TG and HDL-C (p < 0.05), but these associations were influenced by age (p < 0.05). The adjusted odds ratio (OR) values of VA for hypercho lesterolemia, hypertriglyceridemia, mixed hyperlipidemia and low high-density lipoprotein cholesterolemia were 3.283, 3.239, 5.219 and 0.346, respectively (p < 0.01). Meanwhile, significant age interactions affected the relationship between VA and TC, as well as TG and LDL-C (p < 0.01). Conclusion: Serum VA was positively correlated with blood lipids, but these associations were influenced by age. VA was a risk factor for dyslipidemias, such as hypercholesterolemia, hypertriglyceridemia and mixed hyperlipidemia, but was a protective factor for low high-density lipoprotein cholesterolemia.     

莫西沙星短程治疗社区获得性肺炎

目的评价莫西沙星短程治疗社区获得性肺炎(CAP)的疗效及安全性。方法87例轻中度CAP患者随机分为两组。对照组(传统疗程组)予莫西沙星静脉治疗10 d;短程治疗组予莫西沙星静脉治疗5 d。结果①对照组和短程治疗组痊愈率分别为68.2%(30/44)和65.1%(28/43),临床有效率分别为90.9%(40/44)和88.4%(38/43),细菌清除率分别为88.2%(30/34)和87.9%(29/33);这三个指标中,两组间比较差异均无统计学意义。②对照组和短程治疗组不良反应发生率分别为9.1%(4/44)和7.0%(3/43),两组间比较差异无统计学意义。结论莫西沙星短程治疗社区获得性肺炎效果与莫西沙星传统疗程治疗相似,较安全。     

中职学生自我概念、社会支持与心身症状的关系

目的探讨中职学生自我概念、社会支持与心身症状间的关系。方法采用自我概念描述问卷和自编的中职学生社会支持评定问卷测查2012名中职学生（男972人,女1040人）。结果自我概念的各因子与社会支持的各因子、症状总均分间存在一定的相关;自我概念的非学业自我与一般自我、社会支持的主观支持、支持利用度只能解释中职学生的心理健康状况的22%的变异。结论自我概念和社会支持对中职学生的心理健康均产生影响。     

肿瘤的化学治疗——ⅩⅩⅩⅨ.2-甲基-5-双(β-氯乙基)氨基苯丙氨酸及2-双(β-氯乙基)氨甲基-5-硝基苯丙氨酸的合成

本文报道在间位溶肉瘤素氮芥基的对位引入一个甲基,合成了2-甲基-5-双(β-氯乙基)氨基苯丙氨酸(Ⅳ,AT-1420),希望甲基的引入,通过其推电子效应,增加氮芥基中氯原子的活泼性,从而增加抗癌效力。药理试验结果表明,化合物Ⅳ对艾氏癌实体型有明显的抑制作用。从合成化合物Ⅳ的中间体(Ⅶ)出发,为抗癌新药消瘤芥(AT-1258,Ⅴ)提供了一条有用的工艺生产路线。     

The HUDSEN Atlas: a three-dimensional (3D) spatial framework for studying gene expression in the developing human brain

We are developing a three-dimensional (3D) atlas of the human embryonic brain using anatomical landmarks and gene expression data to define major subdivisions through 12 stages of development [Carnegie Stages (CS) 12-23; approximately 26-56 days post conception (dpc)]. Virtual 3D anatomical models are generated from intact specimens using optical projection tomography (OPT). Using MAPAINT software, selected gene expression data, gathered using standard methods of in situ hybridization and immunohistochemistry, are mapped to a representative 3D model for each chosen Carnegie stage. In these models, anatomical domains, defined on the basis of morphological landmarks and comparative knowledge of expression patterns in vertebrates, are linked to a developmental neuroanatomic ontology. Human gene expression patterns for genes with characteristic expression in different vertebrates (e.g. PAX6, GAD65 and OLIG2) are being used to confirm and/or refine the human anatomical domain boundaries. We have also developed interpolation software that digitally generates a full domain from partial data. Currently, the 3D models and a preliminary set of anatomical domains and ontology are available on the atlas pages along with gene expression data from approximately 100 genes in the HUDSEN Human Spatial Gene Expression Database (http://www.hudsen.org). The aim is that full 3D data will be generated from expression data used to define a more detailed set of anatomical domains linked to a more advanced anatomy ontology and all of these will be available online, contributing to the long-term goal of the atlas, which is to help maximize the effective use and dissemination of data wherever it is generated.     

毒鼠强中毒治疗方法的对比分析

目的 分析不同治疗方案在治疗毒鼠强中毒(ATI)中的作用，探索最佳的治疗方法。方法 回顾性统计近十年问我院67例ATI患者的治疗及住院情况，按治疗方法不同分为ABC三组，对比分析其死亡率及并发症等情况。结果 三种治疗方法中，C法死亡率最低(13．33％)，B方法(55．56％)死亡率高于C法但低于A法(28．00％)，三者间有明显差异。结论 综合早期洗胃排毒、有效抗惊厥、抗毒鼠强毒性作用、应用特异性解毒药物，尤其是二巯基丙磺酸钠的使用，可明显降低死亡率、减少并发症。     

负性心理暗示对不同年级和专业医学生身心健康影响的比较研究

负性心理暗示对于医学生身心健康的影响可以通过症状自评量表进行分析研究。本文应用症状自评量表对甘肃省某医学院校学生进行调查,初步分析负性心理暗示对不同年级和专业医学生影响的差异,为有针对性地提出心理干预措施,降低或消除负性心理暗示对医学生身心健康的影响提供一定的参考依据。     

Histone acetyltransferase inhibitor C646 reverses epithelial to mesenchymal transition of human peritoneal mesothelial cells via blocking TGF-β1/Smad3 signaling pathway in vitro

Peritoneal fibrosis resulting from long-term peritoneal dialysis is a major cause of failure of peritoneal ultrafiltration function and main reason of dropout from peritoneal dialysis. Epithelial-mesenchymal transition (EMT) of peritoneal mesochelial cells (HPMCs) is a major contributor of peritoneal fibrosis. Recently, the association between histone acetylation and kinds of fibrosis including liver, lung and kidney fibrosis is well established. Thus, in this study we tried to profile whether histone acetylation is also operates EMT process in HPMCs and what’s the regulatory mechanism. We established an EMT model of HPMCs through high glucose treatment. And hyperacetylation of H3 histone was found using western blot in EMT model. After treated with C646, a histone acetyltransferase (HAT) inhibitor, high glucose-induced EMT in HPMCs was counteracted. To further understand the molecular mechanism of C646 rescues high glucose-induced EMT, CHIP-qPCRwas used to examine the modulation of histone H3 acetylation at promoters of series signaling target genes. We found that the H3 acetylation level at TGF-β1 gene promoter was down-regulation by C646 treatment. Moreover, we also found that TGF-β1/Smad3 signaling was blocked. Hence, our results suggest that histone H3 acetylation activated TGF-β1/Smad3 signaling during EMT of HPMCs, and C646 can rescue the mesenchymal phenotype transition. These findings may provide a novel pathogenic mechanism and therapeutic target for peritoneal fibrosis.     

标本溶血对18项常规生化指标检验结果的影响

目的定量测定分析溶血对18项血清常规生化指标检测结果的影响,探讨其干扰机制。方法选取甘肃省平凉市人民医院门诊健康体检正常者300例作为研究对象,采用日本(希森美康)SYSMEX-XT4000i全自动血细胞分析仪测定溶血标本其血清血红蛋白(Hb)的含量作为判定溶血的程度。采用德国罗氏P800型全自动生化分析仪检测正常血清标本和溶血标本中ALT、AST、LDH、GGT、CHOL、TG、Scr、ALP、GLU、SUA、CK、BUN、TB、DB、TP、ALB、K+、Ca2+18项生化指标的含量。结果轻度溶血(0.3~3 g/L),血清中CHOL、CK、ALB增高(P<0.05);AST、LDH、K+显著升高(P<0.01);GGT、ALP、TB、DB降低(P<0.05);ALT、TG、Scr、GLU、BUN、TP、SUA、Ca2+无显著性变化(P>0.05)。重度溶血(Hb﹥3.0/L),血清中CHOL、ALB、TP增高(P<0.05);ALT、AST、LDH、CK、K+显著升高(P<0.01);GGT、TB、降低(P<0.05);ALP、DB显著降低(P<0.01);TG、Scr、GLU、BUN、SUA、Ca2+无显著性变化(P>0.05)。结论针对临床血液标本溶血前后及不同溶血程度生化检测结果进行定量测定分析,比较标本溶血对不同检测项目影响程度的大小,探讨其干扰机制,对提高临床生化检验的准确性和可靠性具有重要参考价值。