线粒体DNA3537A→G、4824A→G、5351A→G突变与2型糖尿病的相关性研究

目的研究T2DM患者线粒体ND1基因3537A→G和ND2基因4824A→G、5351A→G突变与T2DM的相关性。方法应用PCR-RFLP技术检测145例T2DM和334例正常对照者（NC）线粒体DNA（mtDNA）3537A→G、4824A→G、5351A→G突变情况。结果NC组mtDNA4824A→G突变率高于T2DM组（P＜0．05）。3537A→G及5351A→G突变率在两组中无统计学差异（P〉0．05）。结论mtDNA4824A→G突变可能为T2DM患病的保护因素。3537A→G及5351A→G突变可能与T2DM不相关。     

线粒体DNA变异与老年2型糖尿病患者易感性的相关性

目的 研究湖北地区老年2型糖尿病(T2DM)患者中线粒体基因突变的发生率及其相关性.方法 采用PCR-RFLP、基因测序技术,对175例老年T2DM患者和200例糖耐量正常的健康老年对照组进行检测.结果 MIND1 3316(G→A)、MTTL1 3243(A→G)、MIND13394( T→C)、MIND14216(T→C) MIND14164(A→G)和MIND2 5178( T→C)变异率分别为3.26％、2.72％、1.71％、4％、34.9％;对照组检出3316(G→A)突变2例(0.99％)、4164 5例(0.99％)、5718(T→C)变异64例(32.3％),未检出3394、4216的点突变;两组间3394(T→C)变异率差别有统计学意义(P＜0.05);且T2DM组5178A基因型血清TC水平低于5178C基因型(P＜0.05),但TG、LDL-C、HDL-C、apoA、apoB、Lp(a)水平两组无统计学意义.结论 3394( T→C)与老年T2DM患者的易感性有一定关联,5178(T→C)变异与湖北地区老年汉族人T2DM的脂代谢相关.     

Angiopoietin-2基因多态性与2型糖尿病及糖尿病慢性肾脏疾病的相关性研究

目的研究血管生成素-2(Angiopoietin-2,Ang-2)基因多态性与T2DM及CKD的相关性。方法纳入525例T2DM患者(T2DM组)和255名健康人群(NC组),应用限制性片段长度多态性(RFLP-PCR)对Ang-2 759T→G→C及Ang-2 1087A→G进行基因检测;同时应用等位基因特异性聚合酶链式反应(ARMS-PCR)对Ang-2 1233A→G进行基因检测。根据UAER将T2DM组分为3个亚组:未合并CKD组(CKD0组)、合并微量蛋白尿组(CKD1组)和合并大量蛋白尿组(CKD2组),比较基因型、等位基因频率分布及临床变量间的差异。结果 Ang-2 1087A→G(AG+GG)、Ang-2 1233A→G(AG+GG)基因型频率和1087G、1233G等位基因频率在T2DM与NC组间比较,差异有统计学意义,在CKD0、CKD1、CKD2组间比较差异有统计学意义。多元回归分析显示,Ang-2 1078G、Ang-2 1233G等位基因、SBP、FPG、HbA1c、肾小球滤过率(eGFR)、单核细胞趋化蛋白(MCP-1)、Ang-2血清学水平、HOMA-β是糖尿病慢性肾脏疾病(CKD)的危险因素。Ang-2 1078G、Ang-2 1233G等位基因、MCP-1、Ang-2血清学水平与IR呈正相关。结论 Ang-2 1087G、Ang-2 1233G等位基因变异可能与CKD相关,同时Ang-21087A→G、Ang-2 1233A→G与T2DM相关。而Ang-2 759T→G→C与T2DM及CKD无相关性。Ang-2 1087G、Ang-2 1233G等位基因、SBP、FPG、HbA1c、HOMA-β是发生CKD的危险因素。     

解偶联蛋白3基因与肥胖或肥胖伴2型糖尿病的关系

目的探讨解偶联蛋白(UCP)3基因G304A多态性,外显子6剪接位点Ggt→Gat多态性和C427T突变与北方汉族人肥胖或肥胖伴2型糖尿病(T2DM)发病的关系。方法随机选择100例肥胖患者(BMI34.3±9.6kg/m2),其中60例伴有T2DM,另选40例健康人作为对照。运用聚合酶链反应和限制性片段长度多态性方法检测这3种基因变异。结果140例研究对象均不存在G304A多态性或外显子6剪接位点多态性,但发现1例肥胖伴T2DM患者存在C427T杂合突变。结论UCP3基因G304A或外显子6剪接位点GGT→GAT变异以及C427T突变可能不与我国北方汉族肥胖或肥胖伴T2DM的发病相关。     

广西壮族人Caveolin-3基因多态性与2型糖尿病的关系

目的探讨广西壮族人Caveolin-3基因外显子单核苷酸多态性（SNP）与2型糖尿病（T2DM）的关系。方法选择24例T2DM（T2DM组）患者及10例正常对照者（对照组）,应用PCR法对两组广西壮族人Caveolin-3基因外显子SNP进行PCR扩增后测序。结果 Caveolin-3基因第2外显子非编码区有2个位点发生突变,分别是12842 A→G和12715 A→T。2位点的等位基因频率在糖尿病组和正常对照组存在统计学差异（P〈0.05）。12842A→G和12715 A→T位点有三种联合基因型（AT、GT、GA）,其中AT、GA型的分布频率在两组中比较P〈0.05。结论 Caveolin-3基因12842 A→G和12715 A→T位点突变可能与T2DM的发病有关。     

中高海拔地区2型糖尿病患者抵抗素基因多态性与代谢相关脂肪性肝病相关性的研究

目的 探讨中高海拔地区T2DM患者抵抗素（RETN）基因多态性与代谢相关脂肪性肝病（MAFLD）的相关性。方法 选取青海地区T2DM患者400例,根据肝脏超声检查分为单纯T2DM组（n=200）及T2DM合并MAFLD组（T2DM+MAFLD,n=200）,同期选取我院体检健康者180名为正常对照（NC）组。采用ELISA法检测受试者RETN,PCR测序法检测RETN基因-420C/G及+299G/A位点多态性。结果 T2DM+MAFLD组G/G基因型频率和G等位基因频率高于NC、T2DM组（P<0.05）,C/C基因型频率和C等位基因频率低于NC、T2DM组（P<0.05）,C/G、G/G基因型及G等位基因可增加T2DM合并发生MAFLD风险的1.571、2.126和1.537倍。Logistic回归分析显示,-420C/G位点G/G基因型是T2DM合并MAFLD的危险因素。T2DM+MAFLD组A等位基因频率高于NC、T2DM组（P<0.05）,G等位基因频率低于NC、T2DM组（P<0.05）,等位基因A较G增加T2DM合并MAFLD风险的1.432倍。结...     

蛋白酪氨酸磷酸酶1B基因多态性与2型糖尿病和肥胖的相关性研究

目的 研究中国人群中蛋白酪氨酸磷酸酶1B（PTP-1B）基因的单核苷酸多态性（SNP）与2型糖尿病及肥胖的相关性。方法 采用直接测序法对PTP—1B基因作SNP筛查，并在夫妻配对样本中对所检出的SNP作基因分型。结果 共检出6个SNPs位点，其中内含子区3个（15／37C→A，16／82A→G，17／301C→T），外显子区3个（E8／45C→T，E9／35G→A，E10／372G→A），其中E9／35G→A为新发现的突变类型；在病例-配偶对照研究中发现，15／37C→A，16／82A→G和17／301C→T等位基因频率在糖尿病患者和正常人配偶中差异有统计学意义（均P〈0．05），其余位点的等位基因频率在两组间的分布则无明显差异。与肥胖的相关性研究中发现15／37C→A和17／301C→T位点与男性的腰臀比（WHR）相关（P〈0．05）。结论 PTP-1B基因的SNP位点15／37C→A，16／82A→G和17／301C→T多态性可能和2型糖尿病的发病相关，其中15／37C→A和17／301C→T与男性的WHR相关。     

线粒体DNA ND-1基因点突变与2型糖尿病的关系

2型糖尿病患者中线粒体DNA（mtDNA)3316G→A，3316G→A，3394T→C突变频率分别为3.9%(6/152)和5.3%(8/152)，显著高于正常对照者及冠心病患者，提示mtDNA3316G→A，3394T→G突变与2型糖尿病相关。     

微小核糖核酸miR-541在1型糖尿病中的遗传变异研究

目的 对1型糖尿病(T1DM)儿童微小RNA miR-541基因进行筛查,以了解T1DM儿童该基因变异情况.方法 选择2006年1月至2009年8月在南京医科大学附属南京儿童医院内分泌科确诊的T1DM患儿69例和46名健康对照儿,用PCR扩增结合直接测序方法,对miR-541基因-1084～+167区域的遗传变异进行筛选;用限制性片段长度多态性(RFLP)方法对筛选出的特定变异位点检测,并用RNA二级结构分析软件RNAfold分析.结果 发现1个单核苷酸多态性(SNP)数据库报道的SNP(rs12893725),以及新发现3个未报道的基因变异,其中-284杂合C→T、-569杂合G→A为SNP在健康对照和糖尿病儿童均存在,其发生率、发病年龄和发病时糖化血红蛋白在患者和对照组中无显著差异.因-404杂合G→T基因变异仅在3例糖尿病患者发现,随后采用RFLP对该位点变异在另外105名健康对照者进行筛查,发现健康对照者和T1DM儿童的-404杂合D→T基因变异发生率分别为1/(46+105)和3/69,是一种少见SNP,RNAfold分析发现-404G→T基因变异显著影响miR-541前体二级结构,可能导致其处理和表达差异.结论 发现miR-541基因在T1DM存在遗传变异,其中-404杂合G→T是可能的糖尿病相关变异.     

2型糖尿病患者载脂蛋白A5基因多态性与血脂异常的关联

应用PCR-RFLP研究载脂蛋白A5基因-1131T→C多态性位点各基因型及等位基因的分布频率及其与2型糖尿病(T2DM)的关系。T2DM组等位基因C携带者(CC TC)TG水平明显高于C非携带者(TT);T2DM组C等位基因的频率明显高于对照组,C等位基因与罹患T2DM有关,可能是湖北汉族人群T2DM的独立危险因子之一。     

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.     

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。     

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。     

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。