国产恩替卡韦治疗乙型肝炎肝硬化患者52周疗效分析

目的 探讨恩替卡韦联合胸腺素治疗代偿期乙型肝炎肝硬化患者的临床疗效。方法 选取本院收治的代偿期乙型肝炎肝硬化患者84例,随机分为恩替卡韦治疗37例和恩替卡韦联合胸腺素治疗47例。比较两组患者治疗前后ALT、INR、TBIL、ALB、肝弹性值、HBV DNA水平变化。结果 恩替卡韦组治疗前和52周末血清ALT分别为（86.5±66.7）IU/L和（27.1±12.2）IU/L（P<0.05）;联合用药组治疗前和52周ALT分别为（87.3±66.9）IU/L和（33.1±11.8）IU/L（P<0.05）;恩替卡韦组治疗前和52周ALB分别为（42.5±5.6）g/L和（45.6±4.2）g/L（P<0.05）;两组治疗后肝弹性值均显著下降,但两组无显著性相差（P>0.05）;在治疗52周末,在37例恩替卡韦治疗患者中,17例（45.9%）出现HBV DNA低于检测下限,而47例联合用药组患者中有32例（68.1%）出现HBV DNA低于检测下限,两组有统计学差异（P<0.05）。结论 恩替卡韦联合胸腺素治疗能有效地抑制HBV DNA复制,改善肝纤维化程度。结论 恩替卡韦联合胸腺素治疗乙型肝炎肝硬化有效。     

恩替卡韦联合自拟中药治疗失代偿期乙型肝炎肝硬化患者疗效初步研究

目的研究恩替卡韦联合自拟中药方剂治疗失代偿期乙型肝炎肝硬化患者的疗效。方法2015年12月~2016年12月我院住院的失代偿期乙型肝炎肝硬化患者60例,被分为两组,每组30例。给予对照组常规护肝和恩替卡韦抗病毒治疗,联合组在此基础上,给予太子参20 g、炒白术15 g、褚实子12 g、茯苓15 g、桃仁10 g、丹参10 g、延胡索10 g、香附12 g、制鳖甲20 g、土鳖虫3 g以及炙甘草6 g,辨证加减,治疗12 w。结果在治疗24 w末,联合组患者血清肝功能指标和Child-Pugh评分改善显著优于对照组（P<0.05）;血清HBV DNA水平为 （2.94±1.19） lg copies/ml,与对照组的 （2.86±1.43） lg copies/ml比,无显著性相差（P>0.05】。结论恩替卡韦联合中药方剂治疗失代偿期乙型肝炎肝硬化患者临床有效,在快速抑制乙型肝炎病毒复制的同时,能改善肝功能。     

恩替卡韦与阿德福韦酯治疗慢性乙型肝炎患者近期疗效和不良反应比较研究

目的 比较恩替卡韦（ETV）与阿德福韦酯（ADV）治疗慢性乙型肝炎（CHB）患者的近期疗效与安全性。方法 2014年3月~2016年3月我院收治的CHB患者80例,接受ETV治疗40例,接受ADV治疗40例。观察72 w疗效。结果 在治疗4 w、12 w、48 w和72 w末,ETV组患者血清HBV DNA水平分别为（5.02±0.62） lg copies/ml、（4.10±0.45） lg copies/ml、（3.20±0.34） lg copies/ml和（1.45±0.32） lg copies/ml,均显著低于ADV组【（5.98±0.75） lg copies/ml、（5.08±0.54） lg copies/ml、（4.02±0.41） lg copies/ml和（2.76±0.43） lg copies/ml,P<0.05】;在治疗12 w、48 w和72 w末,ETV组血清ALT水平分别为（71.3±30.4） U/L、（45.2±23.4） U/L和（40.4±17.2） U/L,均显著低于ADV组【（101.7±34.2） U/L、（65.7±30.4） U/L和（61.2±22.3）U/L,P<0.05】;两组均未发生严重的不良反应。结论 在治疗CHB患者过程中,ETV和ADV均具有一定的效果,但在降低血清HBV DNA和ALT水平方面,ETV更具优势。     

恩替卡韦治疗失代偿期乙型肝炎肝硬化3年疗效观察

目的 探讨恩替卡韦治疗失代偿期乙型肝炎肝硬化患者的疗效及其对血清肝纤维化指标的影响。方法 按照住院时间顺序编号,将190例失代偿期乙型肝炎肝硬化患者随机分为观察组95例和对照组95例,给予观察组口服恩替卡韦治疗,给予对照组水飞蓟等综合治疗。应用SPSS 17.0统计软件进行分析。结果 在治疗3年末,观察组血清HBV DNA载量为（2.01±1.1） lg copies/ml,显著低于对照组的（5.93±1.3） lg copies/ml（P<0.05）;观察组ALT为32.3±4.6 U/L、TBIL为13.2±3.3 μmol/L、ALB为35.1±4.6 g/L和INR为0.9±0.1,与对照组的（262.5±25.5 U/L、29.5±4.1 μmol/L、28.5±4.1 g/L和1.6±0.1）比,差异显著（P<0.05）;观察组血清HA、LN、IV-C和PCⅢ分别为180.7±20.6 ng/ml、190.8±23.4 ng/ml、153.7±19.3 ng/mL和31.21±5.62 ng/ml,显著低于对照组的（310.7±20.8 ng/ml、410.5±20.9 ng/ml、214.7±20.2 ng/ml和79.56±8.23 ng/ml,P<0.05）。结论 恩替卡韦治疗失代偿期乙型肝炎肝硬化可以显著降低血清HBV DNA水平,改善肝功能和阻断肝纤维化进展,且安全性高,延长了生存期。     

恩替卡韦联合复方鳖甲软肝片治疗早期乙型肝炎肝硬化临床观察

目的探索恩替卡韦联合复方鳖甲软肝片治疗早期乙型肝炎肝硬化的疗效。方法 43例乙型肝炎肝硬化患者接受恩替卡韦和复方鳖甲软肝片联合治疗,40例患者只给予恩替卡韦组治疗,观察1年。结果 12个月后联合治疗组及恩替卡韦组肝功能均明显恢复,两组比较差异无统计学意义;两组HBeAg阴转、HBeAg/HBeAb血清转换和HBV DNA阴转率无显著性相差（P〉0.05）;联合治疗组肝组织炎性活动度和纤维化程度改善更明显（t值分别为3.30和2.75,P均〈0.05）。结论恩替卡韦与复方鳖甲软肝片联合治疗早期乙型肝炎肝硬化有效。     

恩替卡韦联合扶正化瘀胶囊治疗64例乙型肝炎肝硬化超声表现及临床疗效分析

目的观察恩替卡韦（ETV）联合扶正化瘀胶囊治疗乙型肝炎肝硬化的疗效。方法将122例乙型肝炎肝硬化患者随机分为治疗组64例和对照组58例。治疗组应用恩替卡韦0.5mg/d联合扶正化瘀胶囊1.5g/d治疗12个月;对照组应用恩替卡韦0.5g/d治疗12个月。结果治疗12个月时,治疗组与对照组血清HBV DNA阴转率分别为96.8%（62/64）和96.5%（56/58）;治疗组26例血清HBeAg阳性患者中8例阴转,对照组18例HBeAg阳性患者中6例转阴,两组之间无显著性差异;治疗组与对照组Child-Pugh评分分别由治疗前的8.9±4.7和9.0±2.8降至治疗后的5.0±0.2和7.4±1.4（P≤0.01）;治疗后治疗组门静脉内径和脾厚度缩小均较对照组明显（P〈0.05）;治疗组血清HA、LN、PC-Ⅲ和IV-C下降与对照组比有非常显著性差异（P〈0.01）。结论恩替卡韦联合扶正化瘀胶囊治疗乙型肝炎肝硬化疗效优于单独应用恩替卡韦治疗者。     

恩替卡韦治疗46例失代偿期乙型肝炎肝硬化患者临床效果观察

目的分析失代偿期乙型肝炎肝硬化患者应用恩替卡韦治疗的效果。方法选取我院2012年5月~2014年6月期间收治的92例失代偿期乙型肝炎肝硬化患者作为临床研究对象,随机均分为恩替卡韦治疗组和阿德福韦治疗组,每组46例。采用荧光定量聚合酶链反应法检测HBV DNA 定量。结果在治疗48 w末,恩替卡韦治疗组患者血清HBV DNA转阴率达到82.61%,显著高于阿德福韦治疗组的63.05%（P<0.01）;恩替卡韦治疗组患者Child- Pugh评分为（6.1±1.4）分,相比阿德福韦治疗组Child- Pugh评分（7.4±1.5）分,明显降低（P<0.05）。结论应用恩替卡韦治疗失代偿期乙型肝炎肝硬化患者,临床效果较好。     

抗病毒治疗对HBV DNA阳性乙型肝炎肝硬化门脉高压症患者术后临床转归的影响*

目的 探讨抗病毒治疗对血清HBV DNA阳性的门脉高压症患者术后临床转归的影响。方法 将89例HBV DNA阳性乙型肝炎肝硬化伴门静脉高压症患者随机分成治疗组48例,采用选择性断流联合恩替卡韦治疗和对照组41例,采用单纯手术治疗。常规检测肝功能、HBV DNA定量、Child-Pugh评分和肝纤维化指标。结果 在术后1 m和3 m时,治疗组患者血清HBV DNA水平分别为（5.79±1.78） lgcopies/L和（4.24±1.61） lgcopies/L,显著低于对照组[分别为（7.90±1.83） lgcopies/L和（6.46±1.43）lgcopies/L,P<0.05];治疗组患者血清ALT和总胆红素较对照组降低,白蛋白升高;治疗组1 a生存率为93.75%,3 a生存率为75%,对照组患者1 a生存率为87.92%,3 a生存率为68.30%,治疗组显著高于对照组（P＜0.05）。结论 抗病毒治疗可以促进HBV DNA阳性的门脉高压症患者术后肝功能恢复,改善患者预后。     

国产恩替卡韦治疗慢性乙型肝炎患者早期抗病毒疗效观察*

目的 比较国产恩替卡韦与合资恩替卡韦治疗不同病毒载量的慢性乙型肝炎（CHB）患者24周的疗效。方法 57例CHB患者接受国产恩替卡韦治疗,40例接受合资产恩替卡韦治疗。国产药物治疗患者中血清HBeAg阳性39例,血清HBV DNA水平≥1×106 IU/m1者38例,合资产药物治疗患者HBeAg阳性26例,高病毒载量者27例。采用实时荧光定量PCR法检测血清HBV DNA水平,采用微粒子发光法检测血清HBsAg和HBeAg水平。结果 治疗前两组间各指标比较无显著性差异。在治疗24 w末,国产和合资产恩替卡韦治疗患者血清HBsAg水平分别为（3651.7±1403.2）IU/ml和（3713.9±1117.5） IU/ml（P＞0.05）;血清HBeAg阴转率分别为17.9%和19.2%（P＞0.05）;在高病毒载量患者,24 w末血清HBV DNA水平分别为[lg （3.0±0.5）和lg （2.9±0.4）,P＞0.05];在低病毒载量患者,则分别为【lg （2.6±0.3）和lg （2.5±0.5）,P＞0.05】。结论 两种恩替卡韦在降低血清HBsAg水平、促进血清HBeAg阴转和抗病毒疗效等方面疗效确切,无显著性差异。     

恩替卡韦对慢性乙型肝炎患者HBV cccDNA的影响

目的评价恩替卡韦治疗2年对慢性乙型肝炎（慢乙肝）患者血清及肝细胞内HBV共价闭合环状DNA（cccDNA）水平的影响。方法选择112例恩替卡韦治疗2年的慢乙肝患者,比较治疗前后血清HBV DNA、HBV cccDNA的变化。同时比较其中12例具备治疗前后肝活检标本患者的肝细胞内HBV cccDNA水平的变化。结果治疗2年后,112例患者中有96例（85．71％）血清HBV DNA低于500 copies／ml,所有患者血清中均检测不到HBV cccDNA。12例患者肝细胞内均可检测到HBV cccDNA,且与治疗前相比元明显下降。结论恩替卡韦治疗可有效抑制HBV复制,但不能清除肝细胞内的HBV cccDNA,停药后仍有病毒反弹的可能。     

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。