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中华预防医学杂志
中华医学会杂志社
中华预防医学杂志

中华医学会杂志社

陈君石

月刊

0253-9624

cjpm@cma.org.cn

010-85158377

100710

北京市东城区东四西大街42号

中华预防医学杂志/Journal Chinese Journal of Preventive MedicineCSCD北大核心CSTPCD
查看更多>>1953年10月创刊,中华医学会主办。本刊是学界中历史最悠久的公认的核心期刊。刊登内容涵盖流行病学、环境卫生、营养与食品卫生、劳动卫生、儿童少年卫生学、卫生毒理、疾病检测与计划免疫、疾病预防与健康促进等所有预防医学与公共卫生类学科。多年来一直被美国医学索引(Medline)、化学文摘(CA)、生物学文摘(BA)等国内外20余种重要数据库收录。2006—2009年连续4年被评为“精品科技期刊(C类)”,在2007年被评为中国百种杰出学术期刊。
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    2019—2021年四川省某儿童医院急性呼吸道感染的非细菌性病原学特点与临床特征分析

    常莉刘芳车光璐杨秋霞...
    219-226页
    查看更多>>摘要:目的 探讨四川地区儿童急性呼吸道感染的非细菌性病原体分布、流行病学特点及临床特征。 方法 采用回顾性队列研究方法,选取2019年2月至2021年1月期间在四川大学华西第二医院诊断为急性呼吸道感染,并通过聚合酶链反应(PCR)-片段分析法进行13种病原体检测的住院患儿为研究对象,按照年龄分为婴儿组(<1岁)、幼儿组(1岁≤年龄<3岁)、学龄前期儿童组(3岁≤年龄<6岁)和学龄期儿童组(6岁≤年龄<18岁),分析不同患儿的病原体阳性分布及季节流行特点、临床特征、部分实验室检测指标等。采用SPSS 22.0软件进行统计学分析,计数资料以百分比表示,组间比较采用χ2检验。 结果 本研究共纳入2 922例患儿,检出病原体阳性1 748例(59.8%),其中1 391例(79.6%)为单一病原体检出,357例(20.4%)为2种及2种以上病原体混合检出,病原体检出率排名前三的依次为鼻病毒(HRV)(39.7%)、合胞病毒(RSV)(22.8%)及副流感病毒(PIV)(12.5%)。病原体阳性患儿以<6岁龄多见(1 563例,χ2=146.59,P<0.001),男性患儿阳性率(61.3%,1 047/1 707)略高于女性患儿(57.7%,701/1 215)(χ2=3.91,P=0.048),且与病原体阴性患儿相比,阳性患儿更易出现咳嗽、喘息和气促等症状(χ2=259.15,366.06,12.48,P<0.001)。不同病原体在各年龄组儿童中的分布存在差异,HRV多见于幼儿组和学龄前期儿童组(χ2=9.74,P<0.001),而RSV多见于婴儿组(χ2=178.63,P<0.001),而肺炎支原体(MP)和流感病毒(InfA/B)则少见于<1岁患儿(χ2=92.54,12.90,22.21,P<0.01)。多种病原体流行呈现季节性变化,HRV在春季和秋季呈现较高的流行趋势,而RSV感染流行性主要见于秋、冬季节,多种呼吸道病原体在新型冠状病毒肺炎疫情发生后的阳性率较疫情前明显降低(χ2=252.68,P<0.001)。 结论 2019—2021年四川地区儿童呼吸道非细菌性病原体检出率高,易引起咳嗽、喘息、气促等症状,其中以HRV和RSV为主,且呼吸道病原体阳性率在不同年龄阶段、性别和季节间存在一定差异。 Objective To explore the non-bacterial pathogen distribution, epidemiological characteristics, and clinical features of acute respiratory infections in children in Sichuan Province. Methods Using a retrospective cohort study method, this study selected hospitalized children diagnosed with acute respiratory infections at West China Second Hospital of Sichuan University from February 2019 to January 2021, and tested 13 pathogens using polymerase chain reaction (PCR)-fragment analysis. The children were divided into infant group (<1 year old), toddler group (1 year old ≤ age <3 years old), preschool group (3 years old ≤ age <6 years old) and school-age group (6 years old ≤ age <18 years old). The distribution of pathogen positive rates, seasonal epidemic characteristics, clinical characteristics, and some laboratory test indicators were analyzed in children. Statistical analysis was performed on the results using SPSS 22.0 software, with count data expressed as percentages and inter group comparisons using SPSS 22.0 softwareχ2 Inspection. Results A total of 2 922 pediatric patients were included in this study, with 1 748 (59.8%) positive for pathogens detected. Among them, 1 391 (79.6%) were detected as a single pathogen, and 357 (20.4%) were detected as a mixture of two or more pathogens. The most commonly detected pathogens were rhinovirus (HRV) (39.7%), syncytial virus (RSV) (22.8%), and parainfluenza virus (PIV) (12.5%). Pathogen positivity is more common in children under 6 years old (χ2=146.59, P<0.001), with a slightly higher positivity rate in male children (61.3%, 1 047/1 707) than in female children (57.7%, 701/1 215) (χ2=3.91, P=0.048), and compared with pathogen negative children, positive children are more prone to symptoms such as cough, wheezing, and shortness of breath (χ2=259.15, 366.06, 12.48, P<0.001). The distribution of different pathogens varies among children of different age groups, and HRV is more common in children aged 1-3 and 3-6 years old (χ2=9.74, P<0.001), while RSV is more common in children under 1 year old (χ2=178.63, P<0.001), while mycoplasma pneumoniae (MP) and influenza virus (InfA/B) are less common in children under 1 year old (χ2=92.54, 12.90,22.21, P<0.01). The prevalence of multiple pathogens showed seasonal changes. HRV showed a high prevalence trend in spring and autumn, while the prevalence of RSV infection was mainly seen in autumn and winter festivals. The positive rate of different pathogens after the outbreak of novel coronavirus pneumonia was significantly lower than that before the outbreak (χ2=252.68, P<0.001). Conclusion The detection rate of non-bacterial respiratory pathogens in children in Sichuan Province from 2019 to 2021 is high, which is prone to symptoms such as cough, wheezing, and shortness of breath, with HRV and RSV being the main types. The positive rate of respiratory pathogens varies among different age groups, genders, and seasons.

    儿童呼吸道感染流行病学临床特征病原体

    中国9个长寿地区65岁及以上老年人尿镉水平与体重指数及身体围度的关联研究

    章正吴兵曲英莉李阳...
    227-234页
    查看更多>>摘要:目的 研究我国9个长寿地区65岁及以上老年人尿镉与体重指数(BMI)及身体围度的关联。 方法 研究对象来自2017—2018年在我国9个长寿地区开展的“中国老年健康生物标志物队列研究”,共计1 968名65岁及以上老年人被纳入本研究。通过问卷调查和体格检查,收集调查对象的社会人口学特征、生活方式、膳食摄入和健康状态等信息,采集调查对象晨尿以检测尿镉和尿肌酐水平;身体围度包括腰围、臀围和小腿围。根据尿肌酐校正后尿镉水平三分位数将调查对象分为低水平组(<0.77 μg/g·肌酐)、中水平组(0.77~1.69 μg/g·肌酐)和高水平组(≥1.69 μg/g·肌酐),采用多重线性回归模型分析尿肌酐校正后尿镉不同水平与BMI及身体围度的关联,采用限制性立方样条拟合多重线性回归模型分析尿肌酐校正后尿镉水平与BMI及身体围度的剂量-反应关系。 结果 1 968名研究对象年龄为(83.34±11.14)岁,尿肌酐校正后尿镉水平的M(Q1,Q3)为1.13(0.63,2.09)μg/g·肌酐,BMI为(22.70±3.82)kg/m2,腰围为(85.42±10.68)cm,臀围为(92.67±8.90)cm,小腿围为(31.08±4.76)cm。多重线性回归模型分析结果显示,调整相关混杂因素后,尿肌酐校正后尿镉每增加1 μg/g·肌酐,BMI、腰围、臀围和小腿围的变化水平β(95%CI)值分别为-0.28(-0.37,-0.19)kg/m2、-0.74(-0.96,-0.52)cm、-0.78(-0.96,-0.61)cm和-0.20(-0.30,-0.11)cm;限制性立方样条模型结果显示,尿肌酐校正后尿镉水平与BMI呈负向非线性关联(P非线性<0.001),与腰围、臀围和小腿围呈负向线性关联(均P线性<0.001)。 结论 中国9个长寿地区65岁及以上老年人尿肌酐校正后尿镉水平与BMI、腰围、臀围和小腿围呈负向关联。 Objective To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China. Methods Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model. Results The mean age of subjects was (83.34±11.14) years old. The median(Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI (Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference (Plinear<0.001), hip circumference (Plinear<0.001), and calf circumference (Plinear<0.001). Conclusion Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

    体重指数老年人横断面研究尿镉身体围度

    CD4 +T淋巴细胞及身体成分与重庆市老年HIV感染者生理衰弱的关联分析

    陈晨徐杰江震吴国辉...
    235-240页
    查看更多>>摘要:目的 探索CD4+T淋巴细胞(CD4细胞)计数水平与老年HIV感染者生理衰弱患病的关联关系及体成分指标对二者的修饰作用。 方法 2022年5—10月于重庆市江津区疾病预防控制中心辖区内7家抗病毒治疗点招募485例接受抗反转录病毒治疗(ART)的老年HIV感染者。采用自制问卷通过面对面调查收集对象基本特征(年龄和性别)、生活习惯(吸烟和饮酒情况)和疾病史情况(包括代谢性疾病、心脑血管疾病、呼吸系统疾病和恶性肿瘤)等资料。采用Fried量表评估研究对象的生理衰弱情况。进行体质(步速、握力、身高和体重)和体成分(骨骼肌量、体脂肪量和基础代谢率)测量。由中国艾滋病综合防治数据信息管理系统获取对象抗反转录病毒治疗资料。计算老年感染者生理衰弱现患率,采用多因素logistic回归探索不同CD4水平对老年HIV感染者生理衰弱的影响,并对体成分指标进行亚组分析探索是否存在交互作用。 结果 485例对象年龄为(72±5)岁,其中>70岁者占48.2%(234例),男性占70.9%(344例),且已全部启动抗病毒治疗。老年HIV感染者生理衰弱率为7.4%(36/485)。多因素logistic回归模型分析显示:调整年龄、性别、吸烟、饮酒、体成分指标、ART时长、病毒载量和合并症数量等因素后,CD4细胞水平增加与老年HIV感染者生理衰弱患病风险下降相关;CD4细胞每增加5.0×107个/L,老年感染者生理衰弱患病风险下降12%[OR(95%CI):0.88(0.76~1.01)];与CD4细胞低水平组相比,CD4细胞正常水平组生理衰弱风险下降69%[OR(95%CI):0.31(0.10~0.92)]。体成分指标亚组分析显示:CD4细胞水平与生理衰弱的关联在高骨骼肌量和高基础代谢率感染者中更强(P交互值<0.05)。 结论 重庆市老年HIV感染者生理衰弱率相对较低;CD4细胞水平、骨骼肌量和基础代谢率与生理衰弱有关联。 Objective To identify the association between CD4+T lymphocyte (CD4) counts and physical frailty among HIV-infected people aged 65 years and older, and evaluate whether this association will be modified by the indicators of body composition. Methods From May to October 2022, 485 elderly HIV-infected patients receiving antiretroviral therapy (ART) were recruited from 7 antiviral treatment sites in Jiangjin District Center for Disease Control and Prevention, Chongqing. The data of basic characteristics (age and gender), living habits (smoking and drinking) and disease history (metabolic diseases, cardiovascular and cerebrovascular diseases, respiratory disease and malignant tumors) were collected through the face-to-face investigation with self-made questionnaires. Fried Frailty Scale was used to evaluate the status of physical frailty. Physical fitness (walking speed, grip strength, height, and weight) and body composition (skeletal muscle mass, body fat mass, and basal metabolic rate) were measured. The antiretroviral treatment data were obtained from the China AIDS Integrated Prevention and Treatment Data information management system. The prevalence of physical frailty was calculated among the HIV-infected patients. The potential effects of CD4 counts on physical frailty were explored by using multivariate logistic regression. Subgroup analyses were repeated in the logistic regression with muscle mass, body fat mass, and other indicators of body composition as subgroup variables to determine whether the association might be modified by body composition. Results The age of 485 patients were (72±5) years old, of which 48.2% (234 cases) were>70 years old and 70.9% (344 cases) were male, and all of whom had initiated the ART treatment. The prevalence of physical frailty among these patients was 7.4% (36/485). Multivariate logistic regression showed that after adjusting for age, sex, smoking, drinking, body composition index, ART duration, viral load and the number of comorbidities, increased CD4 cell level was associated with decreased prevalent risk of physical frailty among elderly HIV-infected patients. For every increase of 5.0×107 CD4 cells/L, the prevalent risk of physical frailty decreased by 12% [OR (95%CI): 0.88 (0.76-1.01)]. Compared with the low CD4 cell level group, the risk of physical frailty in those with normal CD4 cell level decreased by 69% [OR (95%CI): 0.31 (0.10-0.92)]. Subgroup analysis of body composition indicators showed that the protective effect of normal CD4 cell level on physical frailty was more pronounced in the high skeletal muscle mass and high basal metabolic rate group (Pinteraction<0.05). Conclusion The prevalence of physical frailty among elderly HIV-infected patients is relatively lower in Chongqing, and the CD4 cell level, skeletal muscle mass and basal metabolic rate are related to physical frailty.

    HIV老年人身体成分生理衰弱

    医院污水中噬菌体的分布研究

    鲁鉴英潘宏伟孙恩华李伟...
    241-247页
    查看更多>>摘要:噬菌体疗法是治疗多重耐药菌感染的重要手段之一。这类噬菌体通常从医院污水中分离得到,然而迄今为止对医院污水中噬菌体的分布情况尚无系统研究。本研究旨在以临床分离的常见病原菌为宿主,分离其对应的噬菌体,以此评估医院污水中噬菌体的生态分布情况,并为临床耐药菌噬菌体的分离和应用提供参考。本研究采用横断面研究设计,选择2023年5—6月山东大学齐鲁医院临床微生物实验室分离得到的125株病原菌(分属于16个不同的菌种)作为目标菌株,利用双层平板夹心法从医院污水中分离纯化这些菌株对应的噬菌体。同时,借助宏基因组二代测序技术(mNGS)分析同批次污水中病原菌的分布情况,初步探究污水中病原菌与噬菌体之间的丰度对应关系。结果显示,以125株临床病原菌为宿主,共分离获得56株噬菌体,分别对应鲍曼不动杆菌、肺炎克雷伯菌、大肠埃希菌、金黄色葡萄球菌、铜绿假单胞菌、嗜麦芽窄食单胞菌等6种病原菌。这6种病原菌均包含了不同耐药程度的菌株,其中鲍曼不动杆菌、大肠埃希菌和铜绿假单胞菌中多重耐药菌株占比较高。这6种病原菌的噬菌体获得率由高到低依次为:大肠埃希菌(80%)、嗜麦芽窄食单胞菌(75%)、铜绿假单胞菌(70%)、肺炎克雷伯菌(66.67%)、鲍曼不动杆菌(36.36%)和金黄色葡萄球菌(12.5%)。初步的mNGS测序结果显示,在该批次污水中,丰度较高的病原菌分别为屎肠球菌、肺炎克雷伯菌、大肠埃希菌、粪肠球菌、鲍曼不动杆菌、产气克雷伯菌、密歇根克雷伯菌和铜绿假单胞菌。综上,医院污水中可分离到大多数临床常见革兰阴性病原菌的噬菌体,且分离率较高;然而革兰阳性病原菌的噬菌体分离率较低,在本研究中仅分离到与金黄色葡萄球菌对应的噬菌体。对应的mNGS测序结果表明革兰阴性病原菌在污水中的分布与噬菌体的生态分布可能具有一定的正相关关系。 Phage therapy is one of the most important tools for the treatment of infections with multi-drug resistant bacteria. Such phages are usually isolated from hospital effluents, however, no systematic study on the distribution of phages in hospital effluents has been conducted so far. The aim of this study was to isolate the corresponding phages of common pathogenic bacteria isolated in the clinic as hosts, so as to assess the ecological distribution of phages in hospital wastewater and to provide a reference for the isolation and application of phages of drug-resistant bacteria in the clinic. A cross-sectional study design was used in this study. The 125 pathogenic bacteria (belonging to 16 different strains) isolated from the clinical microbiology laboratory of Qilu Hospital of Shandong University from May to June 2023 were selected as the target strains, and the phages corresponding to these strains were isolated and purified from the hospital wastewater by using the double-layer plate sandwich method. At the same time, the distribution of pathogenic bacteria in the same batch of wastewater was analyzed with the help of mNGS sequencing technology, so as to preliminarily investigate the abundance correspondence between pathogenic bacteria and phages in wastewater. The results showed that a total of 56 phage strains were isolated from 125 clinical pathogens as hosts, corresponding to six pathogens, including Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. All six pathogenic bacteria contained strains with different degrees of drug resistance, with a higher percentage of multi-drug resistant strains in A. baumannii, Escherichia coli and P. aeruginosa. The phage acquisition rates of these six pathogens were, in descending order, Escherichia coli (80%), Stenotrophomonas maltophilia (75%), Pseudomonas aeruginosa (70%), Klebsiella pneumoniae (66.67%), Acinetobacter baumannii (36.36%) and Staphylococcus aureus (12.5%). Preliminary mNGS sequencing results showed that the pathogenic bacteria with higher abundance in the batch of effluent were Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Acinetobacter baumannii, Klebsiella aerogenes, Klebsiella michiganensis and Pseudomonas aeruginosa. In conclusion, phages of most common clinical Gram-negative pathogens were isolated from hospital wastewater with high isolation rates however, phages of Gram-positive pathogens were isolated at lower rates, and only phages corresponding to Staphylococcus aureus were isolated in this study. The corresponding mNGS sequencing results showed that the distribution of Gram-negative pathogens in sewage may had a positive correlation with the ecological distribution of phages.

    多重耐药菌医院污水噬菌体

    非伤寒沙门菌对喹诺酮类药物的耐药分子机制研究

    罗嘉俊曾诗寒黄玉兰冯玉连...
    248-253页
    查看更多>>摘要:通过回顾性研究分析,探究非伤寒沙门菌(NTS)对喹诺酮类药物的耐药性及耐药机制。以南方医科大学第五附属医院2020年5月至2021年2月临床标本中分离的105株NTS为研究对象,采用VITEK2 Compact全自动鉴定药敏分析系统和血清学实验对菌株进行鉴定;用琼脂稀释法检测菌株对环丙沙星、左氧氟沙星和萘啶酸的敏感性;对105株NTS 进行全基因组测序,采用Abricate等软件分析菌株的耐药相关基因,包括质粒介导的喹诺酮耐药基因(PMQR)和喹诺酮耐药决定区(QRDR);采用SISTR和MLST分析血清型和ST型,并构建系统发育树。结果显示,分离的NTS主要为ST34鼠伤寒沙门菌(53.3%)。药敏结果显示NTS对环丙沙星、左氧氟沙星和萘啶酸的耐药率分别为30.4%、1.9%和22.0%,对环丙沙星、左氧氟沙星的中介率为27.6%、54.2%;62株喹诺酮类非敏感株中共有46株(74.2%)携带PMQR基因,主要为qnrS1(80.4%),其次为aac(6′)-Ib-cr(15.2%);QRDR突变分析共有14株和8株NTS分别存在gyrA和parC基因突变,gyrA均为第87位氨基酸位点突变,分别为Asp87Tyr、Asp87Asn、Asp87Gly,parC检出Thr57Ser突变。综上,本研究发现,NTS对喹诺酮类药物耐药性相对较高,携带qnrS1基因主要导致NTS对环丙沙星和左氧氟沙星的敏感性下降,发生gyrA:87位点突变主要导致NTS对萘啶酸耐药;同时携带多种PMQR和存在QRDR突变,可导致NTS对3种喹诺酮类药物耐药。鼠伤寒沙门菌在临床分离株中存在克隆传播现象,需进一步加强流行病学的监测。 By conducting retrospective analysis, this study aim to investigate the resistance mechanism of quinolones in non-typhoidal Salmonella (NTS). A total of 105 strains of NTS isolated from clinical specimens from the Fifth Affiliated Hospital of Southern Medical University from May 2020 to February 2021 were used as research objects. VITEK2 Compact automatic identification drug sensitivity analysis system and serological test were used to identify the strains. The sensitivity of the strains to ciprofloxacin, levofloxacin and nalidixic acid was detected by AGAR dilution method. The whole genome of 105 strains of NTS was sequenced. Abricate and other softwares were used to analyze drug-resistant genes, including plasmid-mediated quinolone resistance gene (PMQR) and Quinolone resistance determination region (QRDR). Serotypes and ST types were analyzed using SISTR and MLST, and phylogenetic trees were constructed. The results showed that the NTS isolated in this region were mainly ST34 Salmonella typhimurium (53.3%). The drug sensitivity results showed that the drug resistance rates of NTS to ciprofloxacin, levofloxacin and nalidixic acid were 30.4%, 1.9% and 22.0%, respectively, and the intermediate rates of ciprofloxacin and levofloxacin were 27.6% and 54.2%.A total of 46 (74.2%) of the 62 quinolone non-susceptible strains carried the PMQR gene, mainly qnrS1 (80.4%), followed by aac(6′)-Ib-cr(15.2%) there were 14 NTS and 8 NTS had gyrA and parC gene mutations, respectively. The gyrA was mutations at the amino acid position 87, Asp87Tyr, Asp87Asn, Asp87Gly, and Thr57Ser mutations were detected in parC. In conclusion, this study found that NTS had relatively high resistance to quinolones, carrying qnrS1 gene mainly resulted in decreased sensitivity of NTS to ciprofloxacin and levofloxacin, and gyrA:87 mutation mainly resulted in NTS resistance to Nalidixic acid Salmonella typhimurium in clinical isolates showed clonal transmission and required further epidemiological surveillance.

    沙门菌属喹诺酮耐药基因耐药机制

    抗Ⅹa因子活性评估血液透析低分子肝素抗凝的效果

    王振兴毛永辉王源付沛颉...
    254-260页
    查看更多>>摘要:本研究使用抗Ⅹa因子活性探讨低分子肝素(LMWH)在血液透析(hemodialysis,HD)时的合理剂量及防止体外滤器凝血(ECC)的策略。回顾性病例对照研究纳入2020年12月至2021年1月期间在北京医院血液净化中心使用LMWH抗凝的维持性血液透析(MHD)的患者,收集患者体重、身高、基础肾脏病、透析龄等基础数据以及透析前、透析中及透析后的抗Ⅹa因子活性等实验室检查结果。共入组46例患者,其中凝血组5例(10.9%)、非凝血组41例(89.1%),HD开始后0.5 h抗Ⅹa因子活性达峰值,将4 h抗Ⅹa因子水平纳入受试者工作特征曲线(ROC曲线),分析结果显示ROC曲线下面积(AUC)为0.802(95%置信区间:0.651~0.954,P=0.029),截点值为0.31 IU/ml(敏感性1,特异性0.683)。建议以体表面积作为基准估算血液透析LMWH抗凝剂量,HD 4 h抗Ⅹa因子活性≤0.31 IU/ml,对ECC具有较高的诊断价值。此外,二分类logistic回归分析结果显示,透析龄是ECC的独立危险因素(OR值1.319,95%CI 1.052~1.654,P=0.017)。综上,本研究揭示了透析龄可能是HD患者ECC的危险因素以及HD 4 h 抗Ⅹa因子活性≤0.31 IU/ml可作为潜在的ECC的诊断截点,为预防血液透析滤器凝血的监测提供参考依据。 The purpose of this study was to explore the reasonable dose of low molecular weight heparin (LMWH) in hemodialysis (HD) and the strategy of preventing extracorporeal circuit coagulation (ECC). A retrospective case-control study included patients who used LMWH for anticoagulation during maintenance hemodialysis (MHD) in the Hemodialysis Center of Beijing Hospital from December 2020 to January 2021. Basic data such as weight, height, basic kidney disease, dialysis age and anti-Ⅹa factor activity before, during and after dialysis were collected. A total of 46 patients were enrolled in this study, including 5 patients in coagulation group (10.9%) and 41 patients in non-coagulation group (89.1%). The anti-Ⅹa factor activity reached its peak at 0.5 h after the start of HD. The level of anti-Ⅹa factor was incorporated into the receiver operating characteristic curve (ROC curve). The results showed that the area under the ROC curve (AUC) was 0.802 (95% confidence interval: 0.651-0.54, P=0.029), and the cutoff was 0.31 IU/ml (sensitivity 1, specificity 0.683). It is suggested that the body surface area should be used as the basis to estimate the anticoagulant dose of LMWH in HD, and the activity of HD 4 h anti-Ⅹa factor ≤0.31 IU/ml, which is of diagnostic value for ECC. In addition, the results of binary logistic regression analysis showed that dialysis age was an independent risk factor for ECC (OR value 1.319, 95%CI 1.052-1.654, P=0.017). In summary, this study reveals that dialysis age may be a risk factor for ECC and that the activity of HD 4 h anti-Ⅹa factor ≤0.31 IU/ml can be used as a potential diagnostic cut-off point for ECC in HD patients, which provides a scientific basis for monitoring strategies to prevent blood coagulation in HD filters.

    血液透析低分子肝素抗凝抗Ⅹa因子活性

    NRF2通过抑制ROS诱导的自噬减轻卵巢颗粒细胞损伤

    周晓花梁莹贺曙光田仕芸...
    261-267页
    查看更多>>摘要:通过研究核因子E2相关因子2(nuclear factor erythroid-2 related factor 2,NRF2)对卵巢颗粒细胞的作用及可能机制,为预防卵巢早衰提供依据。本文为细胞实验研究设计,于2022年1—12月在湖南师范大学附属长沙市妇幼保健院的医学实验中心完成。通过4-乙烯基环己烯二环氧(VCD)处理人卵巢颗粒细胞KGN细胞构建颗粒细胞损伤模型。先以不同浓度的VCD处理KGN细胞,采用细胞计数试剂(CCK-8)检测卵巢细胞增殖情况。CCK8确定半抑制(IC50)后,采用酶联免疫吸附试验(ELISA)检测细胞上清中雌二醇和孕酮的含量,活性氧(ROS)检测试剂盒检测卵巢细胞中ROS的含量,实时荧光定量聚合酶链式反应(qRT-PCR)检测NRF2的mRNA表达水平,免疫印迹检测NRF2的蛋白表达水平。进一步通过慢病毒转染构建NRF2干扰(siNRF2)和过表达(NRF2-OE)细胞模型,通过检测激素水平、氧化应激指标(ROS、SOD、GSH-Px)和自噬情况(LC3B水平)以分析调控NRF2对VCD处理细胞模型的影响。结果显示,VCD干预后以时间依赖性和剂量依赖性方式抑制卵巢颗粒细胞的增殖(F>100,P<0.05),24 h的IC50为1.2 mmol/L。VCD处理后细胞上清中雌二醇由(56.32±10.18)ng/ml降低至(24.59±8.75)ng/ml(t=5.78,P<0.05);孕酮由(50.25±7.03)ng/ml降低至(25.13±6.67)ng/ml(t=6.54,P<0.05)。VCD处理后细胞的SOD由(44.47±7.71)ng/ml降低至(30.92±4.97)ng/ml(t=3.61,P<0.05);GSH-Px由(68.51±10.17)ng/ml降低至(35.19±6.59)ng/ml(t=5.73,P<0.05)。同时伴随自噬的增加和NRF2的下降。成功构建沉默NRF2和过表达NRF2的KGN细胞模型,随后采用VCD处理各组细胞,发现siNRF2组的细胞增殖活性明显减弱(t=8.37,P<0.05),而NRF2-OE能逆转VCD造成的细胞活性损伤(t=3.37,P<0.05)。siNRF2组的雌二醇水平最低(t=5.78,P<0.05),而NRF2-OE能逆转VCD造成的细胞雌二醇水平降低(t=5.58,P<0.05)。siNRF2组的孕酮水平最低(t=3.02,P<0.05),而NRF2-OE能逆转VCD造成的细胞孕酮水平降低(t=2.41,P<0.05)。siNRF2组的ROS水平最高(t=2.86,P<0.05),NRF2-OE能逆转VCD引起的ROS增加(t=3.14,P<0.05),siNRF2组的SOD酶含量最低(t=2.98,P<0.05),NRF2-OE能逆转VCD引起的SOD酶含量降低(t=4.72,P<0.05)。siNRF2组的GSH-Px酶含量最低(t=3.67,P<0.05),NRF2-OE能逆转VCD引起的抗氧化酶含量降低(t=2.71,P<0.05)。siNRF2组的LC3B水平最高(t=2.45,P<0.05),NRF2-OE能逆转VCD引起的LC3B升高(t=9.64,P<0.05)。综上,NRF2抑制ROS诱导的自噬性,从而发挥减少卵巢颗粒细胞损伤的作用。 This study explores the effects and possible mechanisms of nuclear factor E2 related factor 2 (NRF2) on ovarian granulosa cells, providing a scientific basis to prevent premature ovarian failure. An ovarian cell injury model was constructed by treating human ovarian granulosa cell (KGN cell) with 4-Vinylcyclohexene dioxide (VCD). Firstly, KGN cells were treated with different concentrations of VCD, and cell counting kit 8 (CCK-8) was used to detect ovarian cell proliferation. After determining IC50 by CCK8, the levels of estradiol and progesterone in the cell supernatant were detected using enzyme-linked immunosorbent assay (ELISA), reactive oxygen species (ROS) assay kit was used to detect the content of ROS in ovarian cells, real-time fluorescence quantitative polymerase chain reaction (qRT PCR) was used to detect the mRNA expression level of NRF2, and Western blot was used to detect the protein expression level of NRF2. Further, NRF2 silence (siNRF2) and overexpression (NRF2-OE) cell models were constructed through lentivirus transfection, and the effects of regulating NRF2 on VCD treated cell models were investigated by detecting hormone levels, oxidative stress indicators (ROS, SOD, GSH-Px), and autophagy (LC3B level). The results showed that VCD intervention inhibited the proliferation of ovarian granulosa cells in a time-dependent and dose-dependent manner (F>100,P<0.05), with an IC50 of 1.2 mmol/L at 24 hours. After VCD treatment, the level of estradiol in the cell supernatant decreased from (56.32±10.18) ng/ml to (24.59±8.75) ng/ml (t=5.78, P<0.05). Progesterone decreased from (50.25±7.03) ng/ml to (25.13±6.67) ng/ml (t=6.54, P<0.05). After VCD treatment, the SOD of cells decreased from (44.47±7.71) ng/ml to (30.92±4.97) ng/ml (t=3.61, P<0.05). GSH-Px decreased from (68.51±10.17) ng/ml to (35.19±6.59) ng/ml (t=5.73, P<0.05). Simultaneously accompanied by an increase in autophagy and a decrease in NRF2. This study successfully constructed KGN cell models that silenced NRF2 and overexpressed NRF2. Subsequently, this study treated each group of cells with VCD and found that the cell proliferation activity of the siNRF2 group was significantly reduced (t=8.37, P<0.05), while NRF2-OE could reverse the cell activity damage caused by VCD (t=3.37, P<0.05). The siNRF2 group had the lowest level of estradiol (t=5.78, P<0.05), while NRF2-OE could reverse the decrease in cellular estradiol levels caused by VCD (t=5.58, P<0.05). The siNRF2 group had the lowest progesterone levels (t=3.02, P<0.05), while NRF2-OE could reverse the decrease in cellular progesterone levels caused by VCD (t=2.41, P<0.05). The ROS level in the siNRF2 group was the highest (t=2.86, P<0.05), NRF2-OE could reverse the increase in ROS caused by VCD (t=3.14, P<0.05), the SOD enzyme content in the siNRF2 group was the lowest (t=2.98, P<0.05), and NRF2-OE could reverse the decrease in SOD enzyme content caused by VCD (t=4.72, P<0.05). The GSH-Px enzyme content in the siNRF2 group was the lowest (t=3.67, P<0.05), and NRF2-OE could reverse the decrease in antioxidant enzyme content caused by VCD (t=2.71, P<0.05). The LC3B level was highest in the siNRF2 group (t=2.45, P<0.05), and NRF2-OE was able to reverse the LC3B elevation caused by VCD (t=9.64, P<0.05). In conclusion, NRF2 inhibits ROS induced autophagy, thereby playing a role in reducing ovarian granulosa cell damage, which may be a potential target for premature ovarian failure.

    卵巢早衰活性氧自噬核因子E2相关因子2

    树花粉过敏原组分诊断策略:识别关键过敏原以制定治疗方案

    罗文婷郑贤惠张嘉乐孙宝清...
    268-274页
    查看更多>>摘要:全球树花粉致敏阳性率逐年增加,严重影响过敏性疾病患者的生活质量。在华北和华中地区,桦木花粉、柏树花粉和梧桐树花粉是春季花粉症患者中最为常见的过敏原。不同地理区域的植物分布和花粉传播规律导致了不同的花粉暴露结果,从而进一步加大了对诊断和治疗个体化需求的挑战。本文通过深入解读欧洲过敏和临床免疫学会(EAACI)发布的《过敏原组分诊断指导建议2.0》中关于树花粉过敏的研究进展和临床应用,探讨了PR-10蛋白、Profilins、Polcalin等树花粉的主要过敏原家族和组分蛋白,以及可能导致花粉食物过敏综合征的交叉反应组分。通过过敏原组分诊断可以区分真正过敏患者和对多重过敏原的反应,从而更有针对性地选择过敏原进行特异性免疫治疗,提高治疗效果,如Bet v 1和Cup a 1为桦树和柏树过敏患者免疫治疗的特异性指标。本文对该指南解读,为树花粉过敏领域的专业人员提供前沿信息,深入分析树花粉过敏原组分蛋白、临床表现和治疗的相关研究,有助于更好地理解和应对树花粉过敏的挑战。 With the increasing global prevalence of tree pollen allergies, there has been a significant impact on the quality of life for populations. In North and Central China, birch pollen, cypress pollen, and plane tree pollen are the most common allergens for springtime pollen allergy sufferers. The distribution of plants and patterns of pollen transmission in different geographical areas result in varying pollen exposure outcomes, further complicating the challenges in diagnosis and individualized treatment. This article delves into the research progress and clinical application of tree pollen allergies based on the "Molecular Allergology User′s Guide 2.0 (MAUG 2.0) " published by the European Academy of Allergy and Clinical Immunology (EAACI). It discusses major allergen families and component proteins of tree pollen such as PR-10 proteins, profilins, polcalcins, as well as cross-reactive components that may cause pollen-food allergy syndrome. Allergen component diagnostics can distinguish true allergy sufferers from those with multiple allergen reactions, enabling more targeted selection of allergens for specific immunotherapy, thus enhancing treatment effectiveness. Bet v 1 and Cup a 1, for instance, are specific indicators for immunotherapy in birch and cypress allergy patients. Overall, this article provides cutting-edge information for professionals in the field of tree pollen allergies, offering in-depth exploration of tree pollen allergen component proteins, clinical manifestations, and treatment-related research, aiding in better understanding and addressing the challenges of tree pollen allergies.

    树花粉过敏原过敏过敏原组分诊断