太原市某医院孕妇尿中1-羟基芘水平与新生儿神经行为评分的关系

[目的]观察太原市某医院孕妇尿中1-羟基芘含量与新生儿神经行为评分的关系,探讨孕期多环芳烃（PAHs）暴露与新生儿神经系统发育的关系。[方法]高效液相色谱法（HPLC）测定2009年7月至2010年5月在太原市某医院生产并签署知情同意书的152名孕妇的尿中1-羟基芘含量,应用新生儿20项神经行为检查法（NBNA）测定新生儿神经行为发育情况,对NBNA得分与孕妇尿中1-羟基芘含量及孕妇一般情况进行多元线性回归分析,验证其相关性。[结果]152名新生儿神经行为得分中位数为38分,其中有4名新生儿神经行为能力未达正常标准（≤35分）,新生儿神经行为得分与孕妇尿中1-羟基芘含量、流产次数、孕妇和配偶年龄、居室外35m内有车流量大的干道呈负相关,与妊娠胎次和妊娠前有避孕措施呈正相关。[结论]孕期多环芳烃的暴露可能导致新生儿神经行为评分的降低。     

Assessment of Exposure to Polycyclic Aromatic Hydrocarbons in Police in Florence,Italy, through Personal Air Sampling and Biological Monitoring of the Urinary Metabolite 1-Hydroxypyrene

In this study, the authors evaluated exposure to airborne polycyclic aromatic hydrocarbons (PAHs) in workers exposed to exhaust gas from cars, and they assessed the efficiency of urinary 1-hydroxypyrene as an indicator of exposure to pyrene and PAHs. The authors selected 2 groups of police who worked in 2 areas in the city of Florence: 1 group was highly exposed to high-density traffic emissions during the winter and summer of 1997, and the 2nd group experienced low exposure to traffic emissions during the same period. Ambient monitoring was achieved with personal sampling of airborne PAHs during each workshift. Eight hydrocarbons were used as indicators of pollution caused by PAHs (e.g., pyrene, benzo[a]pyrene, benzo[a]anthracene, dibenzo[a,h]anthracene). Biological monitoring was performed through dosing of 1-hydroxypyrene (pyrene metabolite) in urine samples taken at the end of each workshift. The ambient monitoring revealed that PAH concentrations were influenced by both season of sampling and varying intensities of traffic in the different areas. The median concentration of benzo[a]pyrene in winter was twice as high in the high-density traffic area as in the low-density traffic area (i.e., 4.1 ng/m³ versus 1.8 ng/m³). In summer, the high-density traffic area experienced benzo[a]pyrene concentrations that were 6 times higher than in the low-density traffic area (i.e., 1.2 ng/m³ versus 0.2 ng/m³). Benzo[a]pyrene was also correlated highly (r _s = .92, p < .0001) with the mixture of total PAHs analyzed, thus confirming its function as a good indicator of exposure to PAHs in an urban environment. Levels of urinary 1-hydroxypyrene appeared to be generally influenced by the intensity of traffic, especially during the winter (i.e., median value in winter was 199.2 ng/gm creatinine in the high-density traffic area and 120.5 ng/gm creatinine in the low-density traffic area). An analysis of the general data revealed that 1-hydroxypyrene was, to some degree, related to pyrene, benzo[a]pyrene, and airborne total PAHs, whereas analysis of separate data for the area and the season revealed an emergence of a closer correlation during the winter in the high-traffic area. Therefore, 1-hydroxypyrene can be considered a good biological indicator of exposure to airborne PAHs in the urban environment, especially in winter and in high-density traffic areas.     

Urinary levels of 1-hydroxypyrene and health risk assessment in children living in Mexican communities with a high risk of contamination by polycyclic aromatic hydrocarbons (PAHs)

Health complications have been associated with polycyclic aromatic hydrocarbons (PAHs) exposure, a widespread environmental pollutants family. Therefore, the objective of this investigation was to develop a probabilistic health risk evaluation (using Monte-Carlo simulation) in an infantile population living in areas with a high risk of pollution by PAHs (indoor wood combustion, brick kiln industry, municipal landfill, and low and high vehicular traffic) in Mexico. Urine samples were obtained from Mexican children (n = 135) and urinary 1-OHP concentrations (used as a PAHs biomarker) were quantified. Highest urinary 1-OHP concentrations were detected in children living in areas that use wood combustion as the principal indoor fuel (3.50 ± 0.95 µg/L). Nevertheless, estimated hazard quotients (HQ) lower than 1 were found in all assessed sites after Monte-Carlo analysis. Although HQ <1.0 (a toxic effect is not expected), more data are necessary to determine the real impact of PAHs exposure on children health status.     

Laboratory investigations of herpes simplex virus-1 and -2 clinical samples in Korea

ObjectivesHerpes simplex virus (HSV) infections have been reported in 60% to 95% of the adult population worldwide, making them one of the most common infectious conditions globally. HSV-1 and HSV-2 cause severe disease in immunocompromised patients. Therefore, the aim of this study was to provide information that could be used to reduce the incidence of genital herpes caused by HSV-1 and HSV-2.MethodsFrom September 2018 to December 2020, 59,381 specimens were collected from outpatients across primary and secondary hospitals in Korea who requested U2Bio (Korea) to conduct molecular biological testing of their samples for sexually transmitted infections. In this study, the positivity rates of HSV-1 and HSV-2 were analyzed according to age, sex, and specimen type.ResultsIn the age-specific analysis of HSV-1, the highest positivity rate (0.58%) was observed in patients under 19 years of age, whereas the lowest positivity rate (0.08%) was observed in patients aged over 70 years. In the age-specific analysis of HSV-2, the highest positivity rate (2.53%) was likewise observed in patients under 19 years of age.ConclusionOur study identified differences in the infection rates of HSV-1 and HSV-2 depending on patients’ sex and age. These differences will be useful for improving disease prevention and control measures for HSV-1 and HSV-2.     

IGF-1和bcl-2在胃腺癌组织中的表达及其相关性

目的探讨胰岛素样生长因子-1(IGF-1)和B细胞淋巴瘤/白血病-2(bcl-2)在胃腺癌组织中的表达及其相关性。方法应用免疫组化SP技术,对56例胃腺癌组织、40例癌旁不典型增生组织和56例正常胃组织中IGF-1和bcl-2的表达情况进行检测分析。结果胃腺癌组织中IGF-1及bcl-2的阳性表达率分别为85.71%、55.36%,正常胃组织中IGF-1及bcl-2的阳性表达率分别为17.86%、10.71%,胃腺癌组织中IGF-1及bcl-2的阳性表达率显著高于正常胃组织(P<0.05);IGF-1的表达与胃癌的浸润深度、淋巴结转移、TNM分期及分化程度相关(P<0.05);bcl-2的表达与胃癌分化程度、TNM分期相关(P<0.05);IGF-1与bcl-2的表达呈正相关(P<0.01)。结论胃腺癌组织中IGF-1及bcl-2的过表达共同参与了肿瘤的发生、发展、浸润及转移,两者联合检测有更大的临床意义。     

CYP2E1和GST基因多态性对二甲基甲酰胺代谢及毒性的影响

二甲基甲酰胺（DMF）是一种广泛应用的工业原料。DMF的毒性与其在体内的代谢过程有关。CYP2E1是DMF的主要Ⅰ相代谢酶,Ⅱ相代谢酶谷胱甘肽-S-转移酶（glutathione S-transferase,GST）则可能在DMF的解毒过程中起重要作用。代谢酶的基因多态性对毒物的代谢及毒作用有较大的影响。本文就CYP2E1和GST基因多态性与DMF的代谢及毒性的关系进行综述。     

探讨HMGB2、CCL1及NO在骨关节炎发病中的相关性研究

目的：探讨HMGB2、CCL1与NO在骨关节炎发病中的相关性,以了解HMGB2及CCL1在骨关节炎发病中可能的生物学作用。方法：选取54例KOA患者作为试验组,24例正常人作为对照组,应用酶联免疫吸附测定HMGB2、CCL1,用硝酸还原法测定NO在关节滑液中的含量,分析HMGB2与CCL1、NO在膝骨关节炎关节滑液中的相关性。结果：试验组的HMGB2、CCL1和NO三个指标均明显高于对照组,差异均有统计学意义（P〈0.01）,表示HMGB2、CCL1和NO三个指标在骨关节炎关节滑液中的表达与正常人的关节滑液比较异常增高。HMGB2与CCL1和NO的水平作Spearman相关分析,相关系数分别为r=0.912、0.885（P〈0.01）,均呈正相关。结论：HMGB2可能是炎症因子CCL1和NO的趋化因子,可促进KOA的局部非感染性炎症形成。     

Antibody responses against NY-ESO-1 and HER2 antigens in patients vaccinated with combinations of cholesteryl pullulan (CHP)-NY-ESO-1 and CHP-HER2 with OK-432

Combination vaccines of the NY-ESO-1 protein complexed with cholesteryl pullulan (CHP), CHP-NY-ESO-1, and the truncated 146HER2 protein with CHP, CHP-HER2, were subcutaneously administered with the immuno-adjuvant OK-432 to eight esophageal cancer patients. Vaccination was well-tolerated. NY-ESO-1- and HER2-specific antibody responses were analyzed using the patients’ sera and samples from previous single CHP-NY-ESO-1 or CHP-HER2 vaccine trial. The responses to NY-ESO-1 in the combination vaccine study were comparable to the single vaccine. For responses to HER2, there were fewer antibody responses in the combination vaccines. Although there were marked individual variations in the antibody responses to the NY-ESO-1 and HER2 antigens, the reaction patterns to these antigens were comparable within each patient. Antibodies to OK-432 were not augmented. Protein cancer vaccines targeting multiple antigens are feasible.     

2型糖尿病并脑梗死患者血清MMP-2、TIMP-1水平变化

目的观察2型糖尿病并脑梗死患者血清基质金属蛋白酶-2（matrix metalloproteinase-2，MMP-2）及其抑制因子基质金属蛋白酶抑制因子-1（tissue inhibitors of matrix metalloproteinase-1，TIMP-1）的水平变化，探讨其在脑梗死发生发展过程中的作用和意义。方法用ELISA法检测48例2型糖尿病并脑梗死患者发病24h，以及35例2型糖尿病非脑梗死患者、29例非糖尿病脑梗死组、39例健康体检者血清MMP-2和TIMP-1的含量。结果2型糖尿病脑梗死患者血清MMP-2、TIMP-1水平显著高于2型糖尿病非脑梗死组、非糖尿病脑梗死组、对照组（P〈0．05）。2型糖尿病脑梗死发病24h的血清MMP-2水平与空腹血糖、糖化血红蛋白（HbAlc）正相关（r=0．296，r=0．339）；2型糖尿病脑梗死发病24h血清TIMP-1水平与空腹血糖呈正相关（r=0．293），与HbA1c呈正相关（r=0．391）。与神经功能缺损程度评分（脑卒中分值）、总胆固醇、甘油三脂均无明显相关性（P〉0．05）。结论2型糖尿病并脑梗死患者血清MMP-2和TIMP-1水平增高且与血糖水平呈正相关，MMP-2和TIMP-1在2型糖尿病脑梗死发病过程中起着重要的作用。     

Correlation of Anti-SARS-CoV-2 S1-specific IgG antibody levels and adverse events following vaccination with BNT162b2 mRNA COVID-19 vaccine in healthcare workers

Currently approved anti-COVID-19 vaccines have been found to be safe and effective and almost 60% of Israeli residents are already vaccinated with BNT162b2 vaccine.This observational study was designed to evaluate the adverse events of vaccine reported by 61 healthcare workers at least 7 days after the 2nd vaccination, and to investigate the correlation of adverse events and anti-SARS-CoV-2 IgG antibody levels.The median participant's age was 51.25 years, 16 men and 45 women; 77% (44% of male and 84.5% of female participants) reported adverse events. Injection site pain, fatigue and fever were the most common symptoms, and significantly higher antibody levels (average 19,387 AU/mL) were found in participants who had fever compared to those who did not experience fever (average antibody levels of 9,977 AU/mL, p < 0.001). This finding corresponds to previous observations of higher anti-SARS-CoV-2 IgG antibody levels in COVID-19 patients presented with fever.     

蜕膜Th1、Th2型细胞因子与妊娠及并发症

蜕膜组织是母胎界面间重要免疫微环境。正常妊娠是同种移植的成功典范,其取决于蜕膜组织中的辅助型T细胞1、辅助型T细胞2型细胞因子之间精确的动态平衡。蜕膜组织中的辅助型T细胞1/辅助型T细胞2系统平衡失调可能与妊娠失败及某些妊娠并发症有关,如流产、妊娠高血压疾病(包括子痫前期)及胎儿生长受限等。     

益生菌调节湿疹患儿Th1/Th2平衡及对肠道菌群的影响

【目的】研究应用益生菌治疗婴儿湿疹后,其外周血Th1/Th2细胞因子分泌细胞的变化及肠道菌群的改变,探讨益生菌作用的机理。【方法】60例重症湿疹患儿随机分成两组,益生菌组在对症治疗的同时服用双歧杆菌三联活菌,对照组仅对症治疗,不用任何微生态制剂。分别在益生菌治疗前及治疗后1月采指尖血,用ELISpot方法检测IFNγ,IL-4分泌细胞;同时采粪便标本,用荧光定量PCR的方法检测肠道菌群的变化。【结果】湿疹患儿在益生菌治疗30 d后,IL-4分泌细胞明显减少(P<0.05),IFNγ/IL-4比值明显升高(P<0.01),而IFNγ无明显变化。益生菌治疗前后,患儿肠道双歧杆菌,乳酸杆菌明显升高(P<0.01),而对照组无明显变化。【结论】益生菌能通过调节湿疹患儿肠道菌群,影响机体Th1/Th2平衡状态。     

乳腺癌患者血清转化生长因子β_1与白细胞介素6和白细胞介素2水平及临床意义

目的:探讨乳腺癌患者血清中转化生长因子β1(TGFβ1)、白细胞介素6(IL-6)和白细胞介素2(IL-2)的变化及其临床意义。方法:采用放射免疫分析(RIA)法测定28例乳腺癌患者、11例乳腺良性疾病患者和30例健康妇女血清TGFβ1、IL-6和IL-2的水平。结果:乳腺癌患者血清TGFβ1和IL-6活性水平均高于乳腺良性病变组及对照组(P<0.05),而IL-2活性水平则明显降低(P<0.05)。结论:乳腺癌患者血清中TGFβ1和IL-6活性水平升高及IL-2活性水平降低可能与乳腺癌发生、发展有关,测定其水平可作为临床病情观察和评估疗效的辅助手段。     

胰岛素受体底物和酪氨酸磷酸酶在 2 型糖尿病大鼠肌肉组织中的蛋白表达及其意义

目的研究2型糖尿病对胰岛素产生抵抗的分子机制。方法用Western杂交检测2型糖尿病模型(OLETF大鼠)肌肉组织内IRS-1及SH-PTP2的蛋白表达水平,并以同种属的Wistar大鼠做比较。结果OLETF糖尿病大鼠的空腹和餐后血糖水平较对照组明显增高(P<0.05);Western杂交显示OLETF大鼠肌肉组织内IRS-1蛋白表达较对照组减少(P<0.05);而SH-PTP2的蛋白表达则较对照组增加(P<0.05)。结论IRS-1及SH-PTP2蛋白表达的异常改变,可能是引起2型糖尿病产生胰岛素抵抗的分子机制之一。     

Effect of Inulin Intervention on Metabolic Control and Methylation of INS and IRS1 Genes in Patients with Type 2 Diabetes Mellitus

Background and Aims: Currently, treatments are being sought to improve the control of type II diabetes mellitus (T2DM), and inulin has been shown to be effective in reducing glucose levels and other metabolic control parameters. These effects on metabolic control may be associated with changes in the epigenetic modulation of genes of the insulin pathway. Therefore, our objective is to determine the effect of agave inulin in metabolic control parameters and in INS and IRS1 genes’ methylation in T2DM patients. Methods: This was a longitudinal experimental study with 67 Mexican participants who received an intervention of inulin agave (10 g daily) for 2 months. The methylation of the INS and IRS1 genes was determined by MSP. Results: For the INS gene, we found a significant decrease in the proportions of T2DM patients with methylated DNA after inulin intervention (p = 0.0001). In contrast, the difference in the proportions of the unmethylated IRS1 gene before and after the inulin intervention was not significant (p = 0.79). On the other hand, we observed changes in the number of T2DM patients’ recommended categories for metabolic control depending on the methylation of INS and IRS1 genes before and after treatment with inulin. Conclusion: For the first time, we report the modification in the methylation of two genes, INS and IRS1, of the insulin pathway and provide information on the possible relevant role of epigenetics as a key factor in positive changes in metabolic control parameters by inulin intake in T2DM patients.     

Beclin-1、Bcl-2、Bax在慢性氟中毒大鼠肾脏中表达

目的 观察自噬基因Beclin-1、凋亡基因Bcl-2、Bax在慢性氟中毒大鼠肾脏中的表达变化,探讨Beclin-1、Bcl-2、Bax在氟中毒肾脏损害过程中的作用。方法 将SD大鼠24只随机分为3组,每组8只,对照组(饮用含氟量 < 0.5 mg/L自来水),低、高氟组(自来水含氟量分别为50、100 mg/L);饲养9个月后,观察大鼠氟斑牙发生情况;氟离子电极法测定尿氟、骨氟含量;显微镜下观察大鼠肾组织病理形态学变化;采用免疫组织化学方法检测大鼠肾组织中Beclin-1、Bcl-2、Bax表达量;用原位杂交法测定大鼠肾脏Beclin-1 mRNA含量。结果 低氟组大鼠氟斑牙检出率为75%,高氟组为100%;与对照组比较,低、高氟组大鼠尿氟和骨氟含量分别为[(10.09±0.88)、(18.09±0.89)mg/L和(5 500.84±1 093.47)、(7 477.94±1 315.88)μg /g]明显升高,差异有统计学意义(P < 0.05);染氟大鼠肾脏肾小管上皮细胞水肿、间质血管扩张充血,且随染氟剂量增加损伤改变逐渐加重;与对照组比较,低、高氟组大鼠肾组织中Beclin-1、Bax表达[分别为(168.90±8.68)、(146.32±10.02)和(153.74±10.56)、(134.29±9.85)]明显降低(均P < 0.05);与对照组比较,低、高氟组大鼠肾组织中Bcl-2表达[分别为(167.64±7.51)、(185.32±8.55)]明显升高(P < 0.05);与对照组比较,低、高氟组大鼠肾组织中Beclin-1 mRNA表达[分别为(166.94±13.21)、(146.11±17.66)]明显降低(P < 0.05)。结论 慢性氟中毒可诱导肾小管上皮细胞自噬和凋亡相关分子的异常表达,自噬和凋亡可能共同参与慢性氟中毒肾脏损伤过程。     

缺血再灌注对大鼠腮腺导管细胞TGF-β1、Bcl-2表达的影响

目的探讨缺血再灌注损伤对大鼠腮腺导管细胞TGF-β₁、Bcl-2表达的影响。方法wistar大鼠经颈总动脉结扎造成腮腺缺血再灌注模型,应用免疫细胞化学及一般光镜技术,分别观察缺血0.5h和lh,再灌注6h（早期）、12h（中期）和24h（后期）腮腺导管上皮细胞的TGF-β₁和Bcl-2的动态表达情况及一般形态学变化。结果1.TGF-β₁：缺血再灌注组较对照组TGF-β₁表达明显提高（P<0.01）,且随缺血时间的延长,TGF-β_1、的表达呈逐渐增高趋势;组间比较,缺血lh比0.5h组表达提高（P<0.01）;再灌注各组间两两比较均无显著差异（P>0.05）。2.Bcl-2：再灌注6h组的表达较对照组明显增高（P<0.05）,而再灌注12h、24h较对照组无明显差异（P>0.05）;组间比较,缺血时间0.5h与lh组、再灌注各组间的两两比较均无显著差异（P>0.05）。3.形态学：与对照组正常形态比较,实验组在缺血再灌注早期开始出现腺泡细胞萎缩、坏死等形态学改变,中期明显,后期修复。导管上皮细胞变化较轻。结论缺血再灌注可明显提高大鼠腮腺导管细胞TGF-β₁的表达;缺血时间越长,TGF-β₁表达上调越明显;缺血再灌注使Bcl-2的表达在早期明显升高;而中晚期Bcl-2的表达无显著变化;缺血再灌注对TGF-β₁ 和Bcl-2表达的影响可能与形态学变化有关。     

未足月胎膜早破合并绒毛膜羊膜炎孕妇外周血miR-145表达及与Th1/Th2平衡的关系

目的探讨miR-145在未足月胎膜早破(preterm prelabor rupture of membranes,pPROM)合并绒毛膜羊膜炎(histological chorioamnionitis,HCA)孕妇外周血中表达情况,并分析其与Th1/Th2平衡的关系。方法选取2018年3月至2019年4月河北省儿童医院因胎膜早破入院的pPROM孕妇50例作为研究组,根据是否发生HCA分为HCA组(17例)与无HCA组(33例),另选取正常妊娠孕妇34例作为对照组,采集静脉血,分离血浆及外周血单个核细胞(peripheral blood mononuclear cells,PBMC),通过qRT-PCR法检测外周血血浆中miR-145的表达情况,利用流式细胞术检测PBMC中Th1细胞、Th2细胞占PBMC的比例,采用酶联免疫吸附法检测Th 1细胞分泌的细胞因子IL-2、IFN-γ、TNF-α以及Th 2细胞分泌的细胞因子IL-4、IL-6水平,Pearson法对miR-145与Th1、Th2细胞以及细胞分泌因子相关性进行分析,并通过ROC曲线分析外周血血浆miR-145对pPROM患者HCA发生的预测价值。结果与对照组、无HCA组相比,HCA组外周血血浆miR-145水平显著降低(P<0.05);与对照组、无HCA组相比,HCA组外周血Th1细胞比例、Th1/Th2比值显著升高(P<0.05),Th2细胞比例显著降低(P<0.05);与对照组、无HCA组相比,HCA组外周血血浆IL-2、IFN-γ、TNF-α水平显著升高(P<0.05),IL-4、IL-6水平显著下降(P<0.05);Pearson分析显示:外周血血浆miR-145表达与Th1细胞比例、Th1/Th2比值、IFN-γ、TNF-α、IL-2水平呈负相关(P<0.05),与Th2细胞比例、IL-4、IL-6水平呈正相关(P<0.05);ROC曲线分析显示miR-145水平预测pPROM患者HCA发生的截断值为0.56(曲线下面积0.859,敏感度89.3%,特异性68.2%)。结论pPROM合并HCA孕妇外周血血浆miR-145低表达,PBMC呈Th1优势,miR-145可能通过调控Th1/Th2平衡影响HCA的发生。