肿瘤坏死因子基因多态性与炎症性肠病的相关性分析

目的　明确我国汉族人群中炎症性肠病(IBD)患者肿瘤坏死因子(TNF)的基因多态性,探讨IBD的发病机制。方法　采用聚合酶链反应(PCR)、限制性片段长度多态性分析(RFLP)技术对131例IBD患者的TNFα和TNFβ基因多态性进行分析。结果　溃疡性结肠炎(UC)患者TNFα-308 位点基因型频率(15.5%)及等位基因频率(8.7%)显著高于正常人群的4.1%和2.0%(P<0.01),克罗恩病(CD)患者TNFα-308位点基因型频率及等位基因频率与正常人群比较差异无统计学意义(P>0.05);UC和CD患者TNFβ+252位点的基因型频率及等位基因频率与正常人群比较差异无统计学意义(P>0.05);TNFα-308与TNFβ+252位点基因多态性与IBD患者的年龄、性别、疾病的活动性及发病部位比较差异无统计学意义。结论　TNFα-308等位基因与UC发病的易感性相关,TNFα-308 的基因多态性与CD的发病无关;TNFβ+252的基因多态性与IBD的发病无关。     

慢性阻塞性肺病TNFA和LTA基因等位基因变异分析

目的中国北方汉族人群中研究TNF超家族基因等位基因变异是否与慢性阻塞性肺病(COPD)相关联.方法 以50例COPD患者为研究对象,应用聚合酶链反应-限制性片段长度多态性方法研究TNF超家族基因(TNFA和LTA)等位基因变异分布.结果 TNFA基因多态性位点-308G/A COPD组和对照组比较AA基因型频率分布差异显著(χ2=7.111,P＜0.01),OR值为10.756(95%CI为9.875～12.640).-308G/A多态性位点A等位基因频率差异显著(χ2=8.219,P＜0.01);LTA基因 252A/G多态性位点AG基因型频率分布COPD组与对照组比较差异显著(χ2=11.974,P＜0.01),OR值为4.373(95%CI为3.301～6.872).LTA基因 252 A/G多态性位点G等位基因频率差异不显著.在COPD患者组中TNFA基因GG正常基因型和LTA基因AG杂合基因型结合个体频率比对照组显著增高(χ2=4.10,P＜0.05).结论 中国北方汉族人群LTA基因等位基因变异、TNFA基因多态性变异组合与COPD相关联.     

中国华东地区多发性肌炎/皮肌炎患者肿瘤坏死因子-α基因多态性研究

目的 研究中国华东地区中多发性肌炎/皮肌炎(PM/DM)患者肿瘤坏死因子(TNF)-α基因多态性.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)测定69例PM/DM患者与57名健康对照TNF-α基因启动子区-238、-308、-1031位点的基因型,比较各位点的基因型、等位基因及单倍体型频率在2组中差异有无统计学意义.2组比较采用x2或者Fisher exact检验.结果 -238、-308、-1031位点基因型及等位基因频率在PM/DM组或DM组与健康对照组之间比较差异无统计学意义.单倍体型AGT在PM/DM组和DM组中的频率都为0,在健康对照组中的频率为5.6%,差异具有统计学意义(P值分别为0.01,0.02).单倍体型AGC在PM/DM组中的频率为4.3%,在DM组中的频率为5.80%,在健康对照组中的频率为0.6%,DM组与对照组相比,差异具有统计学意义(P=0.04,0R=9.84,95%CI 1.39～69.57),PM/DM组与对照组相比,差异无统计学意义(P=0.09,OR=7.22,95%CI 1.02～50.90).单倍体型GGC在PM/DM组中的频率为14.6%,在DM组中的频率为12.3%,在健康对照组中的频率为23.5%,DM组与健康对照组相比,差异有统计学意义(P=0.04,OR=0.47,95%CI 0.23～0.99).结论 TNF-α基因-238、-308、-1031位点单倍体型AGC是DM的易感因素.     

肺鳞癌患者TNF—β基因多态性及临床意义

目的了解TNF—β基因多态性与肺鳞癌的关系。方法选择肺鳞癌患者（鳞癌组）、肺良性病变患者（良性组）及健康对照者（正常对照组）各30例,提取其外周血DNA,采用PCR-限制性片段长度多态性的方法检测TNF—β基因多态性。结果TNF—β基因在＋252位点处存在两种等位基因鸟嘌呤、腺嘌呤,其分布频率在鳞癌组、良性组及正常对照组间无统计学差异;有3种不同的基因型,既TNF—β1纯合子、TNF-β1/2以杂合子和TNF—β2纯合子,各组间基因型频率的分布无统计学差异。结论TNF—β＋252位点等位基因的多态性可能与肺鳞癌无相关性。     

肿瘤坏死因子基因多态性在慢性乙型肝炎患者中的分布

目的探讨肿瘤坏死因子(TNF)基因多态性与慢性乙型肝炎病毒(HBV)感染者临床类型之间的关系。方法运用聚合酶链反应限制性片段长度多态性(PCRRFLP)分析的方法检测TNFα基因启动子区308位和TNFβ基因第一内含子252位的单个核苷酸多态性(SNPs)在不同临床类型的慢性HBV感染者及健康对照者中的分布频率,并用放射免疫法测定其血清TNFα浓度。结果56例慢性重型乙型肝炎患者(CSHB)中TNF1/2基因型频率及TNF2等位基因频率均显著高于健康对照组(90例)(25%vs11.1%,P=0.028;12.5%vs5.6%,P=0.036)和慢性轻度乙型肝炎及无症状携带者(AsC)组(71例)(25%vs8.5%,P=0.011;12.5%vs4.2%,P=0.015),且CSHB患者中,TNF1/2杂合子的血清TNFα及胆红素(TBiL)水平明显高于TNF1/1纯合子(P<0.05)。CSHB组与健康对照组的TNFβ2/2基因型及TNFβ2等位基因分布差异无统计学意义,而慢性轻度乙型肝炎患者及AsC组的TNFβ2/2基因型频率显著低于健康对照组(9.9%vs24.4%,P=0.043)和CSHB组(9.9%vs26.8%,P=0.043)。结论TNF基因多态性与HBV感染者的临床类型有关,可能为其宿主因素之一。     

肿瘤坏死因子β1069位点基因多态性与胃癌易感性的相关性研究

目的:探讨江苏汉族人群肿瘤坏死因子β(tumor necrosis fac-tor β,TNFβ)1069位点等位基因多态性与胃癌的关系.方法:采用聚合酶链反应-限制性片段长度多态性方法对168名健康人和45例胃癌患者TNFβ基因的单碱基突变多态性进行了分析.结果:胃癌患者的TNFβ1/2等位基因频率(66.7%)较正常人(47.0%)明显升高(P=0.019＜0.05).结论:TNFβ1/2等位基因频率与胃癌易患性相关.     

上海地区汉族人群维生素D受体基因多态性与1型糖尿病的相关性研究

目的 探讨上海地区汉族人群维生素D受体(VDR)基因多态性与1型糖尿病(T1DM)的关系. 方法 采用病例对照研究方法,运用PCR-RFLP方法测定80例T1DM患者(T1DM组)与80位正常对照者(NC组)的VDR-FoKΙ位点基因型. 结果 与NC组相比,T1DM组FF基因型频率(48.75%)、F等位基因频率(71.25%)明显增加;GAD65抗体阳性的T1DM组FF基因型频率(56%)、F等位基因频率(75%)也明显增加(P均<0.05). 结论 VDR-FoKΙ可能是上海地区汉族人群T1DM的易感基因,VDR-FoKΙ位点基因多态性也可能与GAD65抗体阳性的T1DM相关.     

原发性高血压患者载脂蛋白E基因多态性分析

应用聚合酶链反应-限制性片段长度多态性技术测定120例原发性高血压(EH组)和130例正常对照者(对照组)的载脂蛋白E(ApoE)基因多态性,并计算ApoE基因型及等位基因频率。结果中国北方汉族人群以ApoE3/3基因型为优势。与对照组相比,EH组的ApoE4/4基因型升高,差异有统计学意义(χ2=18.23,P<0.05)。两组均以ε3等位基因频率最高;EH组的ε4等位基因频率明显高于对照组,差异有统计学意义(χ2=70.83,P<0.01)。认为ApoEε4等位基因频率升高可能是中国北方汉族人群高血压发病的易感基因。     

肿瘤坏死因子基因多态性与溃疡性结肠炎相关性研究

目的 检测肿瘤坏死因子（TNF）α基因多态性是否与浙江地区汉族溃疡性结肠炎（UC）患者遗传易感相关.方法 血样来自浙江地区110例UC患者及292例健康对照者.通过特定引物的聚合酶链反应（PCR-SSP）方法直接检测野生型及TNF基因的6个多态性（TNF-1031T/C,-863C/A,-857C/T,-380G/A,-308G/A,-238G/A）.结果TNF-308A与汉族UC显著相关,等位基因频率在患者中为14.6%,在健康对照者中为8.9%,两者间差异有统计学意义（P=0.02）.TNF-857T的携带率在UC患者中为17.3%,健康对照者为12.2%,两者间差异无统计学意义（P=0.06）.单倍体分型显示,6种单倍体包括H5和H3,这两种单倍体都包含TNF-308A.H5单倍体频率在患者中为12.3%,在健康对照者为7.5%,两者间差异有统计学意义（P=0.03）.我们还发现了既往在白种人中较少见的单倍体H3.单倍体H4是由TNF基因启动子区域野生型等位基因组成,它的纯合子UC患者共有27例（24.5%）,在健康对照者中有102例（34.9%）,差异有统计学意义（P＜0.05）,说明野生型等位基因可能与疾病的发生无关.结论 TNF-308A可能与汉族UC患者遗传易感相关.进一步的功能研究有助于明确突变型TNFα在UC发病过程中的作用.     

TGF-β1-509C/T基因多态性与胃癌幽门螺杆菌感染的相关性

目的研究TGF-β1基因-509位点C/T多态性,探讨其与胃癌易感性及幽门螺杆菌感染的关系。方法采用聚合酶链反应-限制性片段长度多态性方法,检测80例胃癌患者与102例正常对照者TGF-β1基因-509位点C/T等位基因及基因型分布,并分析该基因多态性与胃癌幽门螺杆菌感染的相关性。结果胃癌组和正常对照组TGF-β1基因型频率无显著性差异;与正常对照组相比,胃癌组TGF-β1-509位点T等位基因频率显著增高(P=0.044,OR=1.550,95%C I=1.010~2.379)。胃癌患者TGF-β1基因型及等位基因频率与是否感染幽门螺杆菌无关。结论TGF-β1基因-509位点T等位基因可能是胃癌的遗传易感基因,而该位点基因多态性可能与是否感染幽门螺杆菌无关。     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

治疗高血压药物的经济学评价

重视高血压治疗中的经济学评价,对利用我国有限的卫生资源来遏制高血压对人民群众的危害有着重要的现实意义。药物经济学对于药物治疗的成本和治疗的结果给予同样的关注。因为治疗高血压的费用,不仅涉及药物价格,还包括患者的危险水平,降压疗效和对临床终点事件的影响,以及治疗的依从性和安全性。因此药物经济学更强调整体成本和价-效比。低危病人,若非药价低廉,治疗的价-效比不够理想。而在高危的患者,价-效比越小越经济而不是药费越便宜越好。