RASopathies在矮小症中的研究进展

RASopathies是一组由于Ras/丝裂原激活蛋白激酶(Ras/mitogen activated protein kinase,MAPK)通路中的组分或调节因子的编码基因发生突变引起的一系列疾病。Ras/MAPK通路在调控细胞发育过程中发挥重要作用，因此RASopathies涉及疾病众多，且临床表现相互重叠，诊断难度大。其中，矮小症是RASopathies最常见的临床表现之一，但导致矮小症的机制有待进一步探索，且生长激素治疗RASopathies的效果差异较大。本文就RASopathies及其在矮小症中的研究进展作一综述。     

肝纤维化发生及逆转途径的研究进展

肝纤维化是慢性或持续性肝损伤的最终共同途径,晚期常会进展为肝硬化和肝癌而危及生命。来自动物模型和临床的证据表明,当病原体被去除时,肝纤维化会消退,这与激活的肌成纤维细胞的消除和纤维瘢痕的吸收有关,所以了解肝纤维化消退的机制可以帮助确定治疗新的肝纤维化治疗靶点。本文主要讲述了肝纤维化的损伤机制,以及在应对肝纤维化的可逆性上,从细胞外基质的平衡,肝星状细胞的凋亡和失活、各种免疫细胞以及不同细胞信号通路,自噬等方面简要介绍如何协调和解决肝纤维化,以期为肝纤维化相关疾病的治疗和进一步研究提供理论指导。     

腺病毒介导的Hes1基因抑制肝细胞癌细胞的增殖与迁移CSCD

目的探讨Hes1基因对肝细胞癌细胞系Hep1-6细胞增殖、迁移与侵袭的影响。方法通过重组腺病毒载体介导Hes1基因在Hep1-6细胞系中过表达,随后测定细胞克隆形成率、增殖速率及体外迁移与侵袭能力的改变。结果Hep1-6细胞分别感染Ad-Hes1和阴性对照Ad-GFP后,感染Ad-Hes1的细胞系克隆形成数显著少于对照组(P<0.001);感染病毒6天后,CCK-8检测感染Ad-Hes1的细胞系在OD450 nm的吸光度值显著低于对照组(P<0.01);感染Ad-Hes1的细胞系24 h和48 h的划痕愈合率显著低于对照组(P<0.001);感染Ad-Hes1的细胞系在Transwell小室培养48 h后迁移进入Transwell下室的细胞数量显著低于对照组(P<0.001);感染Ad-Hes1的细胞系在铺有Matrigel基质胶的Transwell小室培养48 h后侵袭进入Transwell下室的细胞数量显著低于对照组(P<0.01)。结论Hes1有抑制Hep1-6细胞增殖、迁移与侵袭的作用。     

江苏地区1260名精神科女护士主观幸福感的调查研究

目的 了解江苏地区精神专科医院临床女护士主观幸福感的现状及影响因素,为提高精神专科医院的管理水平提供参考依据。方法 采用中文版的“总体幸福感量表”和自制的“一般情况调查表”对江苏省不同地区的6所精神专科医院1260名女护士进行调查。 结果 被调查对象主观幸福感前18项总分为(67.89±14.09)分,处于中等幸福感49～72分之间,但显著低于全国女性常模(71.00±18.00)分,两者比较,t =-2.768,差异有统计学意义(P<0.01)；经回归分析,其主要影响因素有对职业伤害的担心程度、家庭的支持程度、收入状况、医院支持系统的满意度,差异均有统计学意义(P<0.01或P<0.05)。结论 江苏地区的精神科女护士主观幸福感总体处于中等水平但显著低于全国女性常模,提高其主观幸福感可以从减少精神科护士的职业伤害、关注家庭方面影响、建立合理的薪酬体系和高效的医院支持系统4个方面努力。     

Evidence of association between single-nucleotide polymorphisms in lipid metabolism-related genes and type 2 diabetes mellitus in a Chinese population

Background: Type 2 diabetes mellitus (T2DM) is a complex chronic metabolic disorder triggered by insulin resistance in peripheral tissues. Evidence has shown that lipid metabolism and related genetic factors lead to insulin resistance. Hence, it is meaningful to investigate the association between single-nucleotide polymorphisms (SNPs) in lipid metabolism-related genes and T2DM.Methods: A total of 1,194 subjects with T2DM and 1,274 Non-diabetic subjects (NDM) were enrolled. Five SNPs in three genes (rs864745 in JAZF1, rs35767 in IGF1, and rs4376068, rs4402960, and rs6769511 in IGF2BP2) that contribute to insulin resistance involving lipid metabolism were genotyped using the MassArray method in a Chinese population.Results: The allele and genotypes of rs6769511 in IGF2BP2 were associated with T2DM (P=0.009 and P=0.002, respectively). In inheritance model analysis, compared with the T/T-C/T genotype, the C/C genotype of rs6769511 in IGF2BP2 was a risk factor for the development of T2DM (P<0.001, odds ratio [OR] =1.76; 95% confidence interval [CI]: 1.29-2.42). Haplotype analysis revealed associations of the rs4376068-rs4402960-rs6769511 haplotypes in IGF2BP2 with the development of T2DM (P=0.015). Additionally, rs4376068C-rs4402960T-rs6769511C was a risk haplotype for T2DM (OR=1.179; 95% CI: 1.033-1.346).Conclusion: The rs6769511 in IGF2BP2 was associated with T2DM susceptibility, and the rs4376068-rs4402960-rs6769511 haplotypes in IGF2BP2 was associated with the development of T2DM in a Chinese population.     

三维超声自由解剖成像技术对早期宫角与间质部妊娠的诊断价值

【摘要】 目的 探讨三维经阴道超声自由解剖成像技术(3DTVUOT)对早期宫角妊娠(CP)与间质部妊娠(ITP)的定性诊断价值。 方法 回顾性分析35例CP和36例ITP患者的临床资料。均因临床疑诊早期CP或ITP被序贯予以二维经阴道超声(2DTVU)和3DTVUOT检查，对妊娠病灶与宫腔的相通情况、病灶周围肌层完整性和厚度情况等进行比较分析；以手术 病理结果作为诊断金标准，对两种检查方法应用于CP和ITP定性诊断中的敏感性、特异性及准确性进行比较。 结果 CP患者的妊娠病灶与宫腔相通率(9143％)高于ITP(833％),病灶周围包绕肌层的厚度(608±135） mm高于ITP (195±058）mm,完整性(100％)亦高于ITP的(7222％)，组间比较差异均有统计学意义（P＜005）。2DTVU定性诊断CP和ITP的敏感性(8611％)、特异性(7714％)及准确性(8168％)均明显低于3DTVUOT（分别9444％、8571％、9014％），组间差异具有统计学意义（P＜005）。 结论 3DTVUOT对CP和ITP的早期定性诊断，具有较高的可靠性，优于2DTVU，可在临床推广应用。     

Association of heart rate and diabetes among 0.5 million adults in the China Kadoorie biobank: Results from observational and Mendelian randomization analyses

Background and aimsObservational studies have associated resting heart rate with incident diabetes. Whether the associations are causal remains unclear. We aimed to examine the shape and strength of the associations and assessed the causal relevance of such associations in Chinese adults.Methods and resultsThe China Kadoorie Biobank enrolled 512,891 adults in China. Cox proportional hazard regression models was conducted to estimate hazard ratios (HRs) for the associations of resting heart rate with type 2 diabetes and total diabetes. Among 92,724 participants, 36 single-nucleotide polymorphisms (SNPs) related to resting heart rate were used to construct genetic risk score. We used Mendelian randomization analyses to make the causal inferences. During a median follow-up of 9 years, 7872 incident type 2 diabetes and 13,349 incident total diabetes were documented. After regression dilution bias adjustment, each 10 bpm higher heart rate was associated with about a 26% higher risk of type 2 diabetes (HR, 1.26 [95% CI, 1.23, 1.29]) and 23% higher risk of total diabetes (HR, 1.23 [95% CI, 1.20, 1.26]). Instrumental variable analyses showed participants at top quintile compared with those at bottom quintile had 30% higher risk for type 2 diabetes (HR, 1.30 [95% CI, 1.17, 1.43]), and 10% higher risk for total diabetes (HR, 1.10 [95% CI, 1.02, 1.20]).ConclusionsThis study provides evidence that resting heart rate is an important risk factor for diabetes risk. The results suggest that novel treatment approaches targeting reduction of high heart rate for incidence of diabetes may be worth further investigation.     

成人1型糖尿病患者甲状腺功能与糖脂代谢的关系研究

探讨成人1型糖尿病(T1DM)患者甲状腺功能与糖脂代谢指标的关系。回顾性分析2008年1月至2020年1月在山东大学附属省立医院内分泌科住院的230例T1DM患者资料,结果显示,成人T1DM患者的促甲状腺激素(TSH)与总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白-胆固醇(LDL-C)水平呈正相关(r值分别为0.239、0.166、0.249,P值均<0.05)。游离三碘甲状腺原氨酸(FT 3)与空腹血糖(FPG)、糖化血红蛋白(HbA1c)、TC和LDL-C呈负相关(r值分别为-0.272、-0.240、-0.197、-0.220,P值均<0.005)。游离甲状腺素(FT₄)与TC、LDL-C呈负相关(r值分别为-0.171、-0.170,P值均<0.05)。TC是TSH、FT₃、FT₄的独立预测因子,FT₃、FT₄是HbA1c的独立预测因子,TSH是TC、TG、LDL-C的独立预测因子。成人T1DM患者甲状腺功能与糖脂代谢密切相关,有必要常规检测T1DM患者的甲状腺功能。     

细辛碎补汤联合米诺环素对慢性牙周炎患者牙周指标及 龈沟液炎症因子的影响

目的 探讨细辛碎补汤联合米诺环素对慢性牙周炎患者牙周指标及龈沟液炎症因子的影响。方法 选取 2019 年 1 月~2021 年 8 月杭州市萧山区中医院接诊的 96 例慢性牙周炎患者作为研究对象。以双色球法将患者 分为对照组和试验组，每组各 48 例。对照组患者在常规治疗基础上加用米诺环素，试验组患者在对照组治疗 基础上加用细辛碎补汤。比较两组患者的临床疗效、牙周指标、龈沟液炎症因子及不良反应发生情况。结果 试 验组患者总有效率显著高于对照组（P<0.05）。治疗后两组患者的探诊深度、菌斑指数、探诊出血指数、龈沟 液 C–反应蛋白、肿瘤坏死因子–α 及白介素–6 水平均显著低于本组治疗前（均 P<0.05），且试验组以上指标均 显著低于对照组（均 P<0.05）。两组患者不良反应发生率比较差异无统计学意义（χ2 =0.154，P=0.695）。结论 细 辛碎补汤联合米诺环素可有效提高慢性牙周炎患者疗效，改善牙周指标，其作用机制可能与降低龈沟液炎症 因子有关。     

Growth differentiation factor 9 inhibits vascular endothelial growth factor expression in human granulosa cells

Abstract

In aortic endothelial cells, the TGFβ signaling pathway is involved in the regulation of vascular endothelial growth factor (VEGF), which encodes a potent angiogenic factor crucial for the development of ovarian hyperstimulation syndrome. Growth differentiation factor 9 (GDF9) is a member of the TGFβ family and its effect on VEGF expression in human granulosa cells is unknown. In this study, human granulosa cells were collected from patients during the course of oocyte retrieval for in vitro fertilization and were cultured in vitro. After the first 48?h of culture, cells were treated with GDF9 with or without SB431542 (an ALK5 inhibitor) at various doses. The medium was then collected to determine the concentration of VEGF by ELISA. Cellular RNA was collected and extracted for quantification by real-time quantitative fluorescence PCR. Our study showed that GDF9 suppressed VEGF release from human granulosa cells in a dose-dependent manner and also downregulated VEGF mRNA levels in these cells. Furthermore, SB431542 antagonized the suppression of VEGF mRNA by GDF9 and diminished the inhibitory effect of GDF9 on VEGF release by human granulosa cells. Our results indicated that GDF9 can inhibit VEGF expression in human granulosa cells and ALK5 might mediate this process.