重型甲型H1N1流感患者外周血免疫细胞变化及其临床意义

目的 通过动态观察重型甲型H1N1流感(重症及危重症)患者外周血淋巴细胞的数量变化,探讨患者的免疫病理机制及淋巴细胞亚群检测在甲型H1N1流感诊断中的临床意义.方法 采用流式细胞技术检测2009年10-12月在我院住院治疗的41例重症、危重症甲型H1N1流感患者和同期41例轻症患者的外周血T、B和NK细胞数量.结果 在发病初期,重症及危重症患者外周血总T细胞、CD8+T细胞、NK细胞较轻症甲型H1N1流感患者显著降低(P＜0.01),CD4+T细胞较轻症患者降低(P＜0.05);危重症患者总T细胞、CD4+T细胞、CD8+T细胞、NK细胞低于重症患者(P＜0.01).恢复期重症及危重症甲型H1N1流感患者总T细胞、CD8+T细胞低于轻症患者(P＜0.05),NK细胞低于轻症患者(P＜0.01),B细胞高于轻症患者(P＜0.05).结论 重症及危重症甲型H1N1流感患者存在明显的细胞免疫损伤.     

32例甲型H1N1流感危重症患者心肌酶谱结果分析

目的探讨危重症甲型H1N1流感心肌酶谱各项指标在不同时间动态变化的意义。方法应用OLYMPUS AU 5400全自动生化分析仪检测32例甲型H1N1流感危重症患者100份外周血样品心肌酶谱指标并进行分析比较。结果将甲型H1N1流感危重症患者的在不同病程期间的心肌酶相互比较：肌酸激酶（CK）在病程的4-6 d明显升高（P〈0.05）,10-14 d降至正常范围（P〈0.05）,大于14 d时较正常值再次升高;乳酸脱氢酶（LDH）、天冬氨酸氨基转移酶（AST）在整个病程中均有不同程度升高,以14 d以后尤为明显,但是无统计学意义;肌酸激酶同工酶（CK-MB）、α-羟丁酸脱氢酶（HBDH）变化不大。结论甲型H1N1流感危重症患者各病程期间心肌酶谱呈失衡状态,动态检测各期心肌酶有助于鉴别病情变化。     

新生儿肺炎患儿血清心肌酶、C-反应蛋白及基质金属蛋白酶9的变化与病情、感染类型的关系

目的探讨新生儿肺炎患儿血清心肌酶学指标、C-反应蛋白(CRP)及基质金属蛋白酶9 (MMP9)的变化与患儿病情、感染类型的关系。方法选取2016年1月-2019年10月该院新生儿科收治的140例新生儿肺炎患儿作为肺炎组,另选取同期于该院出生的健康新生儿60例作为对照组;检测两组血清肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、CRP及MMP9水平,并按照病情程度、病原感染类型将肺炎组进行分组对比。结果肺炎组患儿血清CK、CK-MB、LDH、CRP及MMP9水平均高于对照组(P0. 05);重症肺炎组患儿血清CK、CK-MB、LDH、CRP及MMP9水平均高于轻症肺炎组(P0. 05);病毒感染组患儿血清CK、CK-MB、LDH、MMP9水平均高于细菌感染组和支原体感染组(P0. 05),支原体感染组患儿血清CK、LDH水平均高于细菌感染组(P0. 05);细菌感染组患儿血清CRP显著高于病毒感染组和支原体感染组(P0. 05)。结论检测血清CK、CK-MB、LDH、CRP及MMP9水平对于新生儿肺炎的病情判断、感染病原的鉴别均具有一定的辅助作用。     

早期抗病毒治疗对妊娠合并重症甲型H1N1流感患者围产预后的影响

目的:研究早期及时抗病毒治疗妊娠合并重症甲型H1N1流感患者对母儿围产预后的影响。方法:回顾性分析2009年11月7日～2010年1月30日于中国医科大学附属盛京医院就诊的妊娠合并重症甲型H1N1流感患者18例,比较48h内用药(早期用药组,n=6)与48h后用药(晚期用药组,n=12)患者的妊娠结局及预后相关指标,包括住院时间、进行机械通气时间、术前氧合指数、肌酸激酶(CK)、乳酸脱氢酶(LDH)水平和新生儿预后情况。结果:早期用药组均痊愈,晚期用药组2例死亡。与早期用药组相比,晚期用药组平均住院时间长(P=0.009),进行机械通气时间多(P=0.028),CK水平高(P=0.018);而两组间术前氧合指数、LDH水平则无统计学差异(P>0.05)。早期用药组新生儿出生后均无窒息症状,晚期用药组胎死宫内3例,1例死亡和1例轻度窒息,7例Apgar评分10分。所有存活新生儿生后3天进行咽拭子检查均为阴性,且无流感表现,6例继续妊娠至足月后分娩的新生儿均未发现畸形。随访2～9个月,婴儿体格发育和智力发育同正常同龄儿。结论:发病48h内及时应用药物治疗的重症患者预后明显优于发病48h后应用药物治疗的患者,且前者新生儿的预后亦明显优于后者。采用奥司他韦抗病毒治疗妊娠中期和晚期的甲型H1N1流感患者对母儿均是安全的,未见致畸作用。若疑似为妊娠合并甲型H1N1的患者应及时尽早给予抗病毒治疗,可以获得较好的母儿预后。     

甲型H1N1流感重症肺炎临床分析

目的分析医院甲型H1N1流感重症肺炎的临床资料,总结防治措施,积累临床救治经验。方法对2009年11月28日-12月5日医院收治的甲型H1N1流感重症肺炎5例临床资料进行回顾性分析。结果 5例甲型H1N1流感患者均系咽拭子标本检测病毒核酸阳性的确诊病例;均表现为Ⅰ型呼吸衰竭,符合重症肺炎诊断标准;伴随症状可表现为胸痛(2例)、乏力(3例)、肌肉酸痛(3例),ALT、AST、LDH、CK、CK-MB增高(5例),CRP明显升高(5例),血小板正常(5例),白细胞减少(3例),白细胞正常(2例);胸部影像学表现为斑片、片状、毛玻璃影及间质性改变,以两侧肺底为主(5例),病灶可以快速进展;5例患者均接受奥司他韦抗病毒、β-内酰胺类联合新喹诺酮类抗感染及氧疗,症状明显好转,咽拭子甲型H1N1流感病毒核酸检测结果转阴性,复查胸部X线及CT病灶好转,康复出院。结论急性起病,发热、咳嗽、咯血、呼吸困难,血常规检查WBC低或不高,胸部影像学显示两下肺为主的斑片、片状及间质性改变,病灶快速进展,伴血LDH、CK、CK-MB、ALT、AST升高者,要高度警惕甲型H1N1流感,尽早检测呼吸道标本甲型H1N1流感病毒核酸,早诊断、早治疗、预后相对较好。     

支气管肺炎患儿血清AST、LDH、CK、CK—MB的检测及其临床意义

目的探讨支气管肺炎患儿血清天冬氨酸氨基转移酶（AST）、乳酸脱氢酶（LDH）、肌酸激酶（cK）,肌酸激酶同工酶（CK-MB）等心肌酶水平变化及临床意义。方法采用酶法及速率法对76例支气管肺炎患儿和40名健康儿童血清AST、LDH、CK、CK--MB水平进行检测。结果支气管肺炎患儿组血清AST,LDH、CK、CK-MB等指标水平均明显高于正常对照组（P〈0．05）。结论检测支气管肺炎惠儿血清AST、LDH,CK、CK-MB活性对其心肌损害及病情变化的检测具有重要临床价值。     

支气管肺炎患儿血清AST、LDH、CK、CK-MB的检测及其临床意义

目的 探讨支气管肺炎患儿血清天冬氨酸氨基转移酶(AST)、乳酸脱氩酶(LDH)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)等心肌酶水平变化及临床意义.方法 采用酶法及速率法对76例支气管肺炎患儿和40名健康儿童血清AST、LDH、CK、CK-MB水平进行检测.结果 支气管肺炎患儿组血清AST、LDH、CK、CK-MB等指标水平均明显高于正常对照组(P＜0.05).结论 检测支气管肺炎患儿血清AST、LDH、CK、CK-MB活性对其心肌损害及病情变化的检测具有重要临床价值.     

重症甲型H1N1流感患者治疗前后心肌酶谱水平变化探讨

目的 探讨重症甲型H1N1流感患者抗病毒治疗后心肌酶谱水平变化的临床意义.方法 对38例住院重症甲型H1 N1流感患者尽早给予奥司他韦抗病毒治疗,应用日立7060型生化分析仪检测治疗前后心肌酶谱的变化,并进行比较.结果 与治疗前比较,治疗后患者血清肌酸激酶显著下降[(130±186)U/L比(69±119)U/L](P<0.01),血清天冬氨酸氨基转移酶、乳酸脱氢酶L、肌酸激酶同工酶MB、羟丁酸脱氢酶均有下降,但差异无统计学意义(P>0.05).结论 重症甲型H1N1流感患者尽早应用奥司他韦抗病毒治疗,治疗后短期内心肌得到了明显修复,其他脏器短期内无明显改变.     

新生儿肺炎免疫功能及心肌酶谱变化的临床意义

目的探讨新生肺炎患儿免疫功能及心肌酶谱的变化。方法选取2016年1月-2017年6月本院收治的90例感染肺炎的新生儿作为观察组对象,其中轻症患儿50例(轻症组),重症患儿40例(重症组),另选取同期50例健康新生儿作为对照组对象,检测并比较各组CD3~+、CD4~+、CD8~+、CD4~+/CD8~+比值以及肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、谷草转氨酶(AST)及乳酸脱氢酶(LDH)水平。结果重症组与轻症组的CD3~+、CD4~+、CD4~+/CD8~+均低于对照组,而CD8~+明显高于对照组,差异均有统计学意义(P0.05);重症组的CD3~+、CD4~+、CD4~+/CD8~+均低于轻症组,而CD8~+明显高于轻症组,差异均有统计学意义(P0.05)。重症组与轻症组的CK、CK-MB、AST、LDH均高于对照组,差异均有统计学意义(P0.05);重症组的CK、CK-MB、AST、LDH均高于轻症组,差异均有统计学意义(P0.05)。结论新生儿肺炎患儿的免疫功能相对低下,血清心肌酶水平异常升高,特别是重症患儿的免疫与心肌损伤更严重,监测新生儿肺炎患儿免疫功能及心肌酶谱的变化对判断病情具有重要参考价值。     

北京市2009年甲型H1N1流感疫情分析

目的 分析北京市2009年甲型H1N1流感流行病学特征.方法 采用SPSS11.0软件,对北京市2009年甲型H1N1流感确诊病例的流行病学特征进行描述与分析.结果 2009年北京市共确诊甲型H1N1流感10 802例,重症、危重症病例621例,死亡73例,病死率为0.7%(73/10 802);北京市甲型H1N1流感流行过程可分为输入期、传播期、扩散期、稳中有降期等4个阶段;感染者以青少年为主,占47.9%(5169/10 802),男女性别比为1.3:1;职业分布以学生最多,占52.2%(5 639/10 802),重症、危重症病例及死亡病例均以离退人员为多,分别为15.9%(99/621)及23.3%(17/73);10月份达到流行高峰.结论 北京市2009年甲型H1N1流感病例以青少年学生为主,重症、危重症病例及死亡病例均以离退人员为多.     

Polymorphisms in GSTT1, GSTZ1, and CYP2E1, Disinfection By-products,and Risk of Bladder Cancer in Spain

Background

Bladder cancer has been linked with long-term exposure to disinfection by-products (DBPs) in drinking water.

Objectives

In this study we investigated the combined influence of DBP exposure and polymorphisms in glutathione S-transferase (GSTT1, GSTZ1) and cytochrome P450 (CYP2E1) genes in the metabolic pathways of selected by-products on bladder cancer in a hospital-based case–control study in Spain.

Methods

Average exposures to trihalomethanes (THMs; a surrogate for DBPs) from 15 years of age were estimated for each subject based on residential history and information on municipal water sources among 680 cases and 714 controls. We estimated effects of THMs and GSTT1, GSTZ1, and CYP2E1 polymorphisms on bladder cancer using adjusted logistic regression models with and without interaction terms.

Results

THM exposure was positively associated with bladder cancer: adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.2 (0.8–1.8), 1.8 (1.1–2.9), and 1.8 (0.9–3.5) for THM quartiles 2, 3, and 4, respectively, relative to quartile 1. Associations between THMs and bladder cancer were stronger among subjects who were GSTT1 +/+ or +/− versus GSTT1 null (p_interaction = 0.021), GSTZ1 rs1046428 CT/TT versus CC (p_interaction = 0.018), or CYP2E1 rs2031920 CC versus CT/TT (p_interaction = 0.035). Among the 195 cases and 192 controls with high-risk forms of GSTT1 and GSTZ1, the ORs for quartiles 2, 3, and 4 of THMs were 1.5 (0.7–3.5), 3.4 (1.4–8.2), and 5.9 (1.8–19.0), respectively.

Conclusions

Polymorphisms in key metabolizing enzymes modified DBP-associated bladder cancer risk. The consistency of these findings with experimental observations of GSTT1, GSTZ1, and CYP2E1 activity strengthens the hypothesis that DBPs cause bladder cancer and suggests possible mechanisms as well as the classes of compounds likely to be implicated.     

Genetic polymorphisms of MnSOD, GSTM1, GSTT1, and OGG1 in coal workers' pneumoconiosis

Little is known about the genetic susceptibility to coal workers' pneumoconiosis (CWP). We investigated the association between genetic polymorphisms of MnSOD, GSTM1, GSTT1, or OGG1 and susceptibility to CWP. The study population was composed of 259 Chinese retired coal miners who had similar dust exposure histories. Of these, there were 99 cases with International Labor Organization chest radiologic criteria for CWP and 160 controls (with no radiologic criteria for CWP). Individual dust exposure variables were estimated from work histories, and smoking information was obtained from interviews. Polymerase chain reaction-based techniques evaluated the genotypes of all study subjects. There were no differences in genotype frequency of MnSOD, GSTM1, GSTT1, and OGG1 between miners with CWP and miners without CWP, by logistic regression analysis. Cumulative dust exposures, but not genetic polymorphisms, were associated significantly with the presence of CWP. This study illustrates the complexity of factors that may contribute to the development of CWP.     

GSTM1, GSTT1, GSTP1, and GSTA1 polymorphisms and urinary isothiocyanate metabolites following broccoli consumption in humans

Isothiocyanates (ITC) are potentially anticarcinogenic phytochemicals formed from the metabolism of glucosinolates and are found in cruciferous vegetables as well as a select number of other foods. ITC are both substrates for and inducers of glutathione S-transferase (GST) phase II metabolizing enzymes involved in carcinogen detoxification as well as effectors of phase I pathways. Previous studies report mixed results on the interaction between cruciferous vegetable intake, GST polymorphisms, and risk of cancer. We conducted a study of 114 healthy human subjects between 18 and 50 y of age to examine the biologic mechanism underlying the associations, specifically, to assess whether GST genotype is associated with urinary ITC metabolites following a known dose of broccoli. After 48 h of abstaining from all sources of glucosinolates, participants provided a blood sample, consumed 1 meal containing 2.5 g broccoli/kg body weight, and collected urine for 24 h. ITC metabolites were measured in the urine using a HPLC cyclocondensation assay. DNA was extracted from blood samples, and GSTM1 deletion, GSTT1 deletion, GSTP1 Ile105Val, and GSTA1*A/*B were genotyped by matrix-assisted laser desorption/ionization time-of-flight. A chi-square test was used to compare high and low ITC excretion levels across genotypes. ITC levels were regressed on genotype, adjusting for gender. There were no substantial differences in ITC levels among genotypes, either individually or in combination. Contrary to our hypothesis, a higher proportion of GSTM1 null individuals had high ITC excretion (62%) compared with the proportion of GSTM1 present with high ITC excretion (39%) (P = 0.03). These results are in agreement with another feeding study, and lend support to the idea of alternative routes of ITC metabolism.     

Association of genetic polymorphisms in CYP2E1, MPO,NQO1, GSTM1, and GSTT1 genes with benzene poisoning

Metabolic enzymes involved in benzene activation or detoxification, including NAD(P)H, quinone oxidoreductase 1 (NQO1), cytochrome P450 2E1 (CYP2E1), myeloperoxidase (MPO), glutathione-S-transferase mu-1 (GSTM1), and glutathione-S-transferase theta-1 (GSTT1), were studied for their roles in human susceptibility to benzene poisoning. The potential interactions of these metabolic enzymes with lifestyle factors such as cigarette smoking and alcohol consumption were also explored. We studied 156 benzene-poisoning patients and 152 workers occupationally exposed to benzene in South China. Sequencing, denaturing HPLC, restriction fragment-length polymorphism, and polymerase chain reaction were used to detect polymorphisms on the promoters and complete coding regions of NQO1, CYP2E1, MPO, and the null genotypes of GSTM1 and GSTT1. Seventeen single nucleotide polymorphisms (SNPs) were identified in NQO1, CYP2E1, and MPO genes, including 6 novel SNPs in CYP2E1 and MPO. Of the subjects who smoked and drank alcohol, an 8.15-fold [95% confidence interval (CI), 1.43-46.50] and a 21.50-fold (95% CI, 2.79-165.79) increased risk of benzene poisoning, respectively, were observed among the subjects with two copies of NQO1 with a C-to-T substitution in cDNA at nucleotide 609 (c.609 C>T variation; i.e., NQO1 c.609 T/T) compared to those with the heterozygous or wild (NQO1 c.609 C/T and c.609 C/C) genotypes. Our data also indicated that individuals with CYP2E1 c.-1293 C/C and c.-1293 G/C, and NQO1 c.609 T/T, and GSTT1 null genotypes tended to be more susceptible to benzene toxicity. Our results suggest that the combined effect of polymorphisms in NQO1, CYP2E1, and GSTT1 genes and lifestyle factors might contribute to benzene poisoning.     

Arsenic methylation, GSTT1, GSTM1, GSTP1 polymorphisms, and skin lesions

OBJECTIVE: We investigated whether primary and secondary arsenic methylation ratios were associated with skin lesions and whether GSTT1, GSTP1, and GSTM1 polymorphisms modify these relationships. METHODS: A case-control study of 600 cases and 600 controls that were frequency matched on age and sex was conducted in Pabna, Bangladesh, in 2001-2002. Individual well water, urine, and blood samples were collected. Water arsenic concentration was determined using inductively coupled plasma mass spectrometry (ICP-MS). Urinary arsenic speciation was determined using high performance liquid chromatography hydride with generator atomic absorption spectrometry and ICP-MS. Genotyping was conducted using multiplex polymerase chain reaction and TaqMan. RESULTS: A 10-fold increase in primary methylation ratio [monomethylarsonic acid (MMA)/(arsenite + arsenate] was associated with a 1.50-fold increased risk of skin lesions (multivariate odds ratio = 1.50; 95% confidence interval, 1.00-2.26). We observed significant interaction on the multiplicative scale between GSTT1 wildtype and secondary methylation ratio [dimethylarsinic acid/MMA; likelihood ratio test (LRT), p = 0.01]. No significant interactions were observed for GSTM1 or GSTP1 or for primary methylation ratios. CONCLUSION: Our findings suggest that increasing primary methylation ratios are associated with an increase in risk of arsenic-related skin lesions. The interaction between GSTT1 wildtype and secondary methylation ratio modifies risk of skin lesions among arsenic-exposed individuals.     

Polymorphisms in CYP1A1, GSTM1, GSTT1 and lung cancer below the age of 45 years

BACKGROUND: A genetic component of early-onset lung cancer has been suggested. The role of metabolic gene polymorphisms has never been studied in young lung cancer cases. Phase 1 and Phase 2 gene polymorphisms are involved in tobacco carcinogens' metabolism and therefore in lung cancer risk. METHODS: The effect of metabolic gene polymorphisms on lung cancer at young ages was studied by pooling data from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database. All primary lung cancer cases of both sexes who were Caucasian and 相似文献   

HES1与ICN1、Notch1在胃癌组织中的表达及其意义

目的:探讨Notch1信号通路主要分子在人胃癌组织中的表达及意义。方法:免疫组化SP法观察HES1、ICN1、Notch1在胃癌组织、癌旁萎缩性胃炎、癌旁浅表性胃炎、胃镜浅表性胃炎中的表达,分析三者表达与胃癌临床病理特征的关系以及胃癌组织中三者表达的相关性。结果:(1)HES1在胃癌组织的表达高于癌旁浅表性胃炎和胃镜浅表性胃炎(P<0.05);HES1表达与胃癌浸润深度、淋巴转移和肿瘤分期相关(P<0.01)。(2)Notch1、ICN1在胃癌组织的表达低于癌旁萎缩性胃炎(P<0.001);Notch1、ICN1的表达与胃癌分化程度相关(P<0.05)。(3)胃癌组织中Notch1、ICN1的表达呈正相关(P<0.01),HES1与Notch1、ICN1的表达无显著相关性。结论:HES1促进胃癌的发生发展并可能主要由其他通路调控;Notch1与胃癌的分化有关。     

The role of polymorphisms of glutathione S-transferases GSTM1, M3, P1, T1 and A1 in susceptibility to alcoholic liver disease

AIMS AND METHODS: Oxidant stress is proposed to be an important pathogenic factor in liver damage related to alcohol. The glutathione S-transferases (GSTs) are a group of polymorphic enzymes that are important in protection against oxidant stress. As there is evidence for genetic susceptibility to alcohol-related liver disease we have compared the frequency of polymorphisms of GSTM1, M3, P1, T1 and A1 by polymerase chain reaction (PCR) on leucocyte DNA in patients from North Staffordshire, Birmingham and Liverpool with alcohol-related chronic liver disease heavy drinking and normal local controls. RESULTS: There were no significant differences in GSTM1, GSTM3 or GSTP1 genotype frequencies among patients, drinking and non-drinking controls from the three centres. There was a significant increase in the GSTT1 null Liverpool alcoholic liver disease (ALD) patients compared with corresponding non-drinking controls (26.3 and 14.6%, respectively; P = 0.044, odds ratio (OR) = 2.1, 95% CI = 1.1-4.7) though this was not repeated in the Birmingham and North Staffordshire cohorts. For GSTA1, the -69 CC genotype was associated with increased risk of ALD in the Liverpool group, but a reduced risk in the North Staffordshire group. CONCLUSIONS: We have failed to demonstrate within the limitation of a case-control study a reproducible significant association of GST polymorphisms with susceptibility to ALD but there are suggestions that GSTA1 and GSTT1 warrant further study.     

GSTM1, GSTT1, and GSTP1 Polymorphisms and Associations between Air Pollutants and Markers of Insulin Resistance in Elderly Koreans

Background: Previous studies have suggested that diabetes mellitus (DM) is an outcome of exposure to air pollution, and metabolic detoxification genes affect air pollution–related outcomes.Objectives: We evaluated associations between air pollutants and markers of insulin resistance (IR), an underlying mechanism of type 2 DM, and effect modification by GSTM1, GSTT1, and GSTP1 genotypes among elderly participants in the Korean Elderly Environmental Panel (KEEP) study.Methods: We recruited 560 people ≥ 60 years of age and obtained blood samples from them up to three times between 2008 and 2010. For air pollution exposure, we used ambient air pollutant [i.e., particulate matter ≤ 10 µm in diameter (PM₁₀), sulfur dioxide (SO₂), ozone (O₃), and nitrogen dioxide (NO₂)] monitoring data. We measured levels of fasting glucose and insulin and derived the homeostatic model assessment (HOMA) index to assess IR. Mixed-effect models were used to estimate associations between air pollutants and IR indices on the same day or lagged up to 10 days prior, and effect modification by GSTM1, GSTT1, and GSTP1 genotypes.Results: Interquartile range increases in PM₁₀, O₃, and NO₂ were significantly associated with IR indices, depending on the lag period. Associations were stronger among participants with a history of DM and among those with GSTM1-null, GSTT1-null, and GSTP1 AG or GG genotypes.Conclusions: Our results suggest that PM₁₀, O₃, and NO₂ may increase IR in the elderly, and that GSTM1-null, GSTT1-null, and GSTP1 AG or GG genotypes may increase susceptibility to potential effects of ambient air pollutants on IR.