环境内分泌干扰物广泛存在于人们的生产生活环境中,其种类繁多,不仅干扰人体的生殖、神经、免疫等系统,更是对体内最大的内分泌器官——甲状腺产生不可忽视的影响.然而,以往研究多从甲状腺激素和甲状腺的组织病理学入手,很少从自身免疫性甲状腺疾病和甲状腺癌的角度切入.本文通过系统回顾,阐述了几种常见的环境内分泌干扰物在自身免疫性甲状腺疾病和甲状腺癌发生发展过程中的作用,包括诱导抗甲状腺自身抗体产生和影响T细胞分化等,为研究自身免疫性甲状腺疾病和甲状腺癌的潜在环境暴露危险因素提供依据,对该类疾病的防治有积极意义.

1 临床资料 患者男性,26岁,因"体检心电图异常1个月余",于2021年4月7日就诊. 患者1个月前在当地就业体检时心电图示异常:V1～V4导联异常Q波伴ST段抬高0.10～0.35 mV.之后在当地住院查肝肾功能、血电解质、血细胞分析、弥散性血管内凝血(DIC) 检查、甲状腺功能全套、血脂、血糖、B 型利钠肽(BNP)、心肌损伤标志物、输血前检查(输血传播疾病+血型血清学)均未见明显异常,冠状动脉造影检查正常(图1),超声心动图正常;否认有胸闷、胸痛、气短、心悸等症状;精神、饮食、睡眠及大小便正常.既往体健,否认晕厥、黑矇、高血压及糖尿病等病史.既往通过大学、研究生入学体检,但未做心电图.否认毒物、化学品接触史,否认烟酒史.否认猝死家族史.

目的:探究维持性血液透析(maintenance hemodialysis,MHD)患者冠状动脉钙化的相关危险因素.方法:纳入2018年3月-2020年3月在南京医科大学第一附属医院血液净化中心规律血液透析,且透析龄≥3个月的MHD患者188例,收集患者临床资料和实验室指标,冠状动脉多层螺旋CT测定冠状动脉钙化积分(coronary artery calcification score,CACS),分析冠状动脉钙化的相关危险因素.结果:冠状动脉钙化(CACS＞ 100分)的发生率为54.8％(103/188),CACS中位数为143(0,728)分.与CACS＜ 100分组相比,CACS≥400分组患者年龄、透析龄、血清钙、甲状旁腺激素(intact parathyroid hormone,iPTH)、碱性磷酸酶(alkaline phosphatase,ALP)等指标显著增高(P＜0.05).Spearman相关分析显示,CACS与年龄(r=0.292,P＜0.001)、透析龄(r=0.242,P＜0.001)、收缩压(r=0.167,P=0.024)、血钙(r=0.263,P＜0.001)、iPTH(r=0.191,P=0.009)及ALP(r=0.171,P=0.019)呈正相关(P＜0.05);多因素线性回归显示ALP与CACS显著相关(P=0.012).受试者工作特征曲线分析示ALP预测重度冠状动脉钙化的曲线下面积是0.615(P=0.009),最佳临界值为226.5 U/L.多因素Logistic回归分析显示经过多因素校正后ALP≥226.5 U/L组患者重度冠脉钙化风险显著升高(OR=3.05,95％可信区间:1.30～7.18,P=0.011).结论:血清ALP水平是MHD患者冠状动脉钙化的独立预测因子,ALP有望成为MHD患者心血管钙化的预测指标和干预靶点.

泛素蛋白酶体途径介导的蛋白质降解途径是机体调节细胞内蛋白水平与功能的一个重要方式.鉴于E3泛素连接酶可以特异性识别靶蛋白,在泛素蛋白酶体中发挥着关键作用.减轻缺血再灌注损伤一直是临床工作的重点与难点,近年来越来越多的研究发现E3泛素连接酶在缺血再灌注损伤性疾病的发生和发展过程中有重要的作用.针对E3泛素连接酶进行深入研究,帮助人们更好地认识缺血再灌注损伤性疾病,有助于为临床治疗缺血再灌注损伤性疾病提供新的思路和潜在的治疗靶点.

目的 分析职业性铬暴露的工人尿铬水平与血清素、五羟基吲哚乙酸、褪黑素水平的相关性.方法 选取市郊某电镀铬企业85名电镀工人作为暴露组,选取不接触铬生产线的工人120人为对照组,采集电感耦合等离子体质谱仪测定尿中铬水平,超高液相色谱串联质谱测定尿中血清素、五羟基吲哚乙酸、褪黑素水平,分析各组间指标的差异及尿铬水平与其的相关性.结果 暴露组的尿铬水平(0.32±0.18)[log(μg/g肌酐)]高于对照组(0.23±0.11)[10g(μg/g肌酐)],暴露组尿液中血清素和褪黑素水平高于对照组(P值均＜0.05).对照组、低暴露组、中暴露组、高暴露组之间血清素和褪黑素水平差异具有统计学意义(P值均＜0.05),五羟基吲哚乙酸的差异无统计学意义(P＞0.05).尿铬水平与尿液中血清素、褪黑素水平呈正相关关系(β=0.152,95％CI:0.036～0.926;β=0.229,95％CI:0.269～1.065).结论 尿铬水平与尿液中血清素和褪黑素水平的增高呈正相关关系,未观察到与五羟基吲哚乙酸有关.

Objective:To investigate the Alzheimer disease (AD)-like changes caused by methamphetamine (METH) exposure, and to elucidate the role of L-type calcium channels in this pathological change. Methods:After primary cultured neurons were exposed to METH (0, 30, 100, 300, and 1 000 μmol/L), Western blotting assay was performed to investigate the expression of AD-like pathological protein amyloid precursor protein (APP) and p-Tau with or without the treatment of nifedipine. Results:After METH treatment, APP and p-Tau increased in a dose-dependent manner. Meanwhile, with a certain concentration of METH cultured with the neurons, the level of APP and p-Tau was increased in a time-dependent manner. After pre-incubation with the calcium channel inhibitor nifedipine (NIF), the METH-induced AD-like changes were significantly improved. Conclusion:METH exposure can cause AD pathological protein changes and L-type calcium channel ihhibitor can partially reverse the adverse changes, therefore, L-type calcium channel may be a potential intervention target for METH with the potential intervention value.

目的:应用心脏CT评估房颤患者左心房、左心耳结构以及功能状况,探讨其与房颤患者卒中发生的关系.方法:回顾性分析221例房颤患者心脏CT资料,根据病程中患者有无发生卒中分成卒中组和非卒中组.以图像后处理软件测量左心房和左心耳最大、最小容积,计算左心房及心耳的射血分数.根据心耳形态将其分成鸡翅型和非鸡翅型,并观察心耳内是否存在血栓或血栓前状态.对左房各项参数进行单因素及多因素统计学分析.结果:221例中47例发生了卒中事件.卒中组患者的左心房最大容积、最小容积均较非卒中组增大(P＜0.05),卒中组左心房射血分数较非卒中组下降(P＜0.05).卒中组左心耳非鸡翅型的比例更高(P=0.006);卒中组左房内存在血栓或血栓前状态的比例高于非卒中组(P=0.01).左心房容积、左心耳分叶结构及左心耳血流动力学状态是房颤患者卒中发生的独立危险因素.结论:心脏CT获得的左房参数对房颤患者卒中发生具有一定预测价值.

Objective To investigate the effects of selective serotonin reuptake inhibitors(SSRIs) on social cognition in patients with major depressive disorders (MDD). Methods A total of 60 patients who met the Diagnostic and Statistical Manual of Mental Disorders-5 diagnostic criteria for MDD were allocated to a SSRI treatment group (SSRITG, n=30) and a TCA treatment group (TCATG, n=30). The emotion intensity recognition task (EIRT) and the interpersonal perception task-15 (IPT-15) were measured at baseline and then after 4 and 12 weeks of treatment with SSRIs or TCAs. The differences of IPT-15 scores and EIRT scores between research groups and control group were compared. Results Both SSRIs and TCAs decreased the Hamilton Depression Scale (HAMD) scores. At baseline, the total scores and factor scores of the IPT-15 and EIRT were significantly lower in the SSRITG and TCATG than those of the controls. A repeated measures analysis of variance revealed a significant main effect of time period (baseline, 4 weeks, and 12 weeks) and significant interactions for time period × group (SSRITG and TCATG). A multivariate analysis of variance showed no significant differences between the SSRITG and TCATG on IPT-15 scores and EIRT scores at the end of the 4th week, but there were significant differences between these two groups at the end of the 12th week. The score of the SSRIs was significantly higher than the TCAs group. Conclusions MDD patients have impairments in social cognitive function, which might be improved by SSRIs.

目的 探讨抑郁症患者的情感强度识别能力及氟西汀对其的影响,为改善抑郁症患者的情感强度识别能力提供参考.方法 于2015年12月-2017年5月在无锡精神卫生中心选取符合《精神障碍诊断与统计手册(第5版)》(DSM-5)诊断标准的抑郁症住院患者56例,采用随机数字表法分为氟西汀组和阿米替林组各28例,分别给予氟西汀和阿米替林治疗,均治疗12周.分别于基线期及治疗4、12周后采用汉密顿抑郁量表17项版(HAMD-17)评定患者抑郁症状,用情感强度识别任务(EIRT)评定患者情感强度识别能力.同期招募28名健康者作为对照组,采用EIRT评定其情感强度识别能力.结果 治疗12周后,氟西汀组和阿米替林组HAMD-17评分均低于基线期,差异均有统计学意义(P均＜0.01);但两组HAMD-17评分差异无统计学意义(P＞0.05).在基线期,氟西汀组和阿米替林组EIRT总评分及6个因子评分差异均无统计学意义(P均＞0.05),但均低于对照组(P＜0.05或0.01);治疗12周后,两患者组EIRT总评分及6个因子评分均高于基线期,氟西汀组EIRT评分高于阿米替林组,差异均有统计学意义(P均＜0.05).结论 抑郁症患者可能存在情感强度识别能力受损,氟西汀和阿米替林均能改善抑郁症患者的情感强度识别能力,但氟西汀效果更佳.

目的 了解电镀工人六价铬低水平接触情况及其接触途径.方法 采用判断抽样法,以某电镀企业95名电镀工人为研究对象,对其进行现场职业卫生学调查.采集工作场所空气样品测定铬和六价铬水平时间加权平均浓度(CTWA),检测研究对象六价铬个人接触水平和血铬水平,测定其工作场所桌面、工作服等表面六价铬污染量.结果 该电镀企业非镀铬组工作场所空气中铬的CTWA均<0.010,六价铬CTWA的M为0.001 mg/m3;镀铬组工作场所空气中铬、六价铬CTWA的M分别为0.013和0.019 mg/m3.7名镀铬工人六价铬个体接触CTWA的M为0.017 mg/m3.工作场所工作面六价铬污染量为1.6～7860.2μg/m2.电镀工人血铬水平M为1.29μg/L.镀铬组工人血铬水平高于非镀铬组(M:3.73 vs 0.87 g/L,P<0.01).非镀铬组工人中,工龄>10年组工人血铬水平分别高于其他3个工龄组(P<0.05).结论 电镀作业存在六价铬的低水平污染.直接镀铬作业和工龄是影响电镀工人血铬水平的主要因素.

目的 探讨药物治疗基础上联合重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)对抑郁症患者负性认知及情绪的影响.方法 将抑郁症患者60例随机分为研究组(n=30,在氟西汀治疗的基础上联合rTMS)及对照组(n=30,单用氟西汀治疗),在治疗前、治疗2周、4周、6周末,采用汉密尔顿抑郁量表24项版本(Hamilton rating scale for depression,HAMD-24)评估患者抑郁程度,采用自动思维量表(automatic thoughts questionnaire,ATQ)评估患者负性认知情况.结果 重复测量方差分析显示,HAMD-24评分的组别×时间交互作用无统计学意义(F=0.455,P=0.586),组别主效应(F=11.754,P=0.001)与时间主效应(F=787.600,P＜0.001)均有统计学意义,随时间推移,两组HAMD评分降低均有统计学意义(P＜0.001).治疗6周末研究组的HAMD减分率高于对照组(77.1％±6.8％ vs.72.4％±9.7％,t=2.152,P=0.036).ATQ评分的组别×时间交互作用有统计学意义(F=6.512,P=0.004),治疗后两组ATQ评分降低均有统计学意义(P＜0.001),且研究组在治疗2周末、4周末、6周末的评分均低于对照组(P＜0.05).结论 药物联合rTMS不仅有助于改善抑郁症患者的抑郁情绪,也有利于改善其负性认知.

目的 观察链脲佐霉素(STZ)诱导的糖尿病模型小鼠脑胰岛素信号的改变.方法 20只SPF级C57BL/6J小鼠随机分为两组,每组10只.STZ处理组采用STZ腹腔注射连续7d,建立小鼠糖尿病模型;对照组注射同等体积生理盐水.采用实时定量PCR检测两组小鼠大脑皮层胰岛素及其受体、胰岛素受体底物1(IRS-1)、IRS-2、胰岛素样生长因子1(IGF-1)、IGF-2、胰岛素样生长因子受体1 (IGF-1R)、IGF-2R、葡萄糖转运体1(GLUT-1)、GLUT-3和GLUT-4 mRNA的表达.结果 与对照组比较,STZ处理组小鼠FBG升高(P＜0.01),成功建立糖尿病模型.与对照组比较,STZ处理组小鼠大脑皮层胰岛素及其受体、IRS-1、IRS-2、IGF-1、IGF-2、IGF-1R、IGF-2R、GLUT-1、GLUT-3和GLUT-4 mRNA的表达均下降(P＜0.05).结论 STZ诱导的糖尿病模型小鼠脑胰岛素信号明显减弱,表现为胰岛素抵抗样改变,提示外周的高血糖可能会引起脑胰岛素信号紊乱,进而导致渐进性脑损伤.

采用电感耦合等离子体质谱分析法(ICP-MS)测定血浆中钒(v)、铬(Cr)、锰(Mn)、铁(Fe)、钻(Co)、镍(Ni)、铜(Cu)、锌(Zn)、砷(As)、硒(Se)、铷(Rb)等34种元素.探索简便、实用、高效的检测血液样品的前处理技术.采用直接稀释法对待测样本进行前处理,稀释液(0.5％ HNO3+0.005％ Triton X-100)稀释倍数为20倍.对ICP-MS测定血浆微量元素进行方法学验证,算出该检测方法的线性范围、检出限、加标回收率、日间精密度与日内精密度等.各元素的相关系数均优于0.999,元素的低、中、高加标回收率为70.0％ ～ 115.0％,各元素的日内精密度优于10％,日间精密度均优于20％.提示,采用ICP-MS法测定血浆中多种元素含量,此法实用高效,精密度、准确度、线性范围和最低检测限都达到了满意结果,可在科研及检验工作中加以应用.

Objective:To explore the antidepressant effect and its influence on cognitive function of modi-fied electroconvulsive therapy(MECT)combined with repetitive transcranial magnetic stimulation(rTMS)in patients with major depressive disorder(MDD). Method:Fifty-four MDD patients were randomly divided in-to two groups. Based on MECT,the study group(26 cases)and the control group(28 cases)combined with rTMS or sham rTMS treatment,respectively. The Hamilton dcpression rating scale for depression 17-item version (HAMD),Wisconsin card sorting test(WCST)and the event related potential P300 were assessed and tested at the baseline and the day after the sixth MECT,respectively. Results:At the baseline,there were no signifi-cant differences between groups within HAMD score,WCST indicators including the perseverative errors(PE) and trials to compete first category(TFC),as well as the amplitude and latency of P300. After 6 times of MECT,the average HAMD score was significantly lower,and its reduction rate was significantly higher in the study group than that in the control group. Covariance analysis showed that the increases of PE,P300 latency and the decrease of P300 amplitude in the study group were significantly lower than those in the control group (F=6.155,6.761,7.138;all P<0.05). Conclusion:The antidepressant effect of MECT combine with rT-MS in MDD patients can be increased,and the cognitive impairment caused by MECT can be reduced.

糖尿病是一种严重危害人类健康的慢性代谢性疾病,是由遗传、环境、行为等多种危险因素共同参与和相互作用而引起的,其中环境因素的影响至关重要,包括饮食、体力活动、经济状况等,而环境内分泌干扰物(environmental endocrine disruptors,EEDs)也被认为是其不可忽视的环境危险因素.笔者综述了与糖尿病发病密切相关的EEDs的种类、来源、接触途径等,分析EEDs致糖尿病发病的生物学机制,为进一步探索糖尿病病因及有效预防糖尿病发病提供科学依据.

目的:探讨缓解期抑郁障碍患者面孔情绪识别的特点及与正常人的异同. 方法:采用改编的情绪启动范式对缓解期抑郁障碍患者30例(研究组)和与其性别、年龄及文化程度相匹配的健康人30名(正常对照组)进行测试,分别对两组的反应时、错误率及判断一致程度进行分析并比较两组之间差异. 结果:研究组靶刺激与线索词的9种组合平均反应时长于正常对照组(P均＜0.01);研究组对中性面孔情绪图片-悲伤(x2=14.652)、平淡(x2=4.837)和正性面孔情绪图片-快乐(x2=8.251)的错误率显著高于正常对照组(P＜0.05或P＜0.01);对正性面孔情绪图片-快乐(F=28.680)和中性面孔情绪图片-平淡(F=35.342)这两个组合一致性的判断程度低于正常对照组(P均＜0.001). 结论:缓解期抑郁障碍患者对正性和中性面孔情绪识别性低,且存在中性面孔情绪识别悲观偏倚的特点,但对负性面孔情绪的识别正常.

目的 观察甲基苯丙胺(Methamphetamine,METH)处理后瞬时外向钾通道Kv4.2的表达,阐述Kv4.2在METH引起神经元损伤中的作用.方法 利用全细胞膜片钳的实验方法观察METH处理后瞬时外向钾电流的改变,采用Western blot法观察Kv4.2的蛋白表达及膜转移情况,并观察主导Kv4.2膜转移蛋白KChIP2(Kv channel interacting protein 2),KChIP3/4(Kv channel interacting protein 3/4)的改变,通过慢病毒上调Kv4.2,观察METH作用后,细胞凋亡标志性蛋白cleaved-caspase 3的表达.结果 不同浓度METH处理神经元细胞后,瞬时外向钾电流显著增大;在蛋白水平,METH处理后Kv4.2表达显著增高,且具剂量依赖性,此外在METH作用下,Kv4.2发生向细胞膜的转移,该过程可能与支配Kv4.2膜转移的KChIP2,KChIP3/4蛋白显著上调相关;Kv4.2高表达后,METH作用引起的神经元损伤比Kv4.2一般表达的神经元损伤更加严重,差异具有统计学意义(P＜0.05).结论 Kv4.2参与了METH引起的神经元损伤,因而该研究可为METH引起神经元损伤的干预提供潜在干预靶点.

Objective:To investigate the response of human pulmonary artery smooth muscle cells (PASMCs)to hypoxia with or without Xinmailong injection (XML),and explore the mechanism for XML to remit pulmonary artery hypertension (PAH).Methods:Na2S2O4 was used for building the hypoxic pulmonary artery smooth muscle cell model.The changes of apoptosis rate and apoptosis associated genes were detected by flow cytometry and realtime PCR,respectively,and membrane potentials and cytoplasmic Ca2+ under hypoxic stimulation were investigated by a laser scanning confocal microscope.Results:Under hypoxia condition,the proliferation of PASMCs was significant compared with that of the control group (P ＜ 0.05),however,this effects can be markedly retarded by the treatment of XML (P ＜ 0.05).Moreover,under hypoxia condition,Bcl-2 expression in PASMCs was obviously increased,while Bax expression was decreased when compared with those of the control group (P ＜ 0.05).Noteworthily,XML can reverse both Bcl-2 and Bax expression induced by hypoxia (P ＜ 0.05).In addition,XML stabilized the membrane potential and reduced the cytoplasmic Ca2+ under the hypoxic condition.Conclusion:Hypoxia leads to the proliferation of PASMCs,depolarization of membrane and increase of cytoplasmic Ca2+.The Chinese medicine XML can reduce all the effects induced by hypoxia,thereby our work might provide the experimental evidence for therapeutic strategy for pulmonary artery hypertension.

Objective:To explore the effects of cell injury and the expression of inflammation related genes in rat microglial cells induced by methamphetamine(Meth).Methods:Cell viability and apoptosis induced by Meth were detected by MTF and in situ end labeling(TUNEL) after primary culture of SD fetal rat microglial cells.The effect of Meth on the expression of inflammatory cytokines mRNA in the microglial cells was evaluated by real time fluorescence quantitative polymerase chain reaction(real-time PCR).The secretion of interleukin(IL)-6,tumor necrosis factor(TNF)-α and inducible nitric oxide synthase(iNOS)in microglia cells induced by Meth were detected by ELISA method.Results:MTIT showed that Meth reduced microglia viability in a concentration dependent manner (25,50,100,and 200 μ mol/L) with statistically significant at a concentration of 200 μmol/L (P＜0.05).TUNEL results showed that 200 μ mol/L Meth significantly contributed to cell apoptosis compared with the control group(P＜0.05).Q-PCR results showed that Meth reduced the expression levels of IL-24 and nitric oxide synthase 3(NOS3) in microglial cells for 24 hours.However,the expression levels of Peli3,Sigma receptor 1(sigl)-R,IL-1,IL-6 and Toll like receptor 4(TLR4) were up-regulated.In addition,protein levels were also confirmed that Meth promoted the secretion of IL-6 and TNF-α.Conclusion:Meth exposure obviously contributes to microglial damage.Moreover,it causes IL-1 β,IL-1 R,IL-6,TLR4 and other inflammatory factors mRNA expression changes,and promotes the secretion of IL-6 and TNF-α,which may damage the central nervous system,resulting in neurotoxicity.