病毒性心肌炎中树突状细胞的体内迁移及机制

目的观察树突状细胞（DCs）在小鼠急性病毒性心肌炎（VMC）中的迁移途径及趋化因子的作用。方法雄性Balb／c小鼠随机分为正常对照组60只和VMC组80只。VMC组腹腔注射柯萨奇B组病毒（CVB3）,正常组腹腔注射等容积不含病毒的EMEM液。趋化实验分析DCs对CCL4、CCL19的趋化反应;检测心肌组织中DCs相应的趋化因子CCL4、CCL19及其受体CCR5、CCR7的表达变化以及脾脏中CCL19和CCR7的表达情况。DCs体外感染CVB3后检测CCR5和CCR7表达。结果VMC组DCs对趋化因子CCL4、CCL19的趋化反应能力增强（P〈0．05）;VMC组心肌组织中CCR5和CCR7及CCL4和CCL19表达增加（P〈0．05）,脾脏中CCR7和CCL19表达均增加（P〈0．05）。DCs体外感染CVB324小时后CCR5和CCR7表达明显上升。结论DCs在急性病毒性心肌炎小鼠体内发生定向迁移,和趋化因子与趋化因子受体相互作用有关。     

黄芪总黄酮对柯萨奇B3病毒性心肌炎小鼠急性期心肌组织连接蛋白43表达的影响

目的探讨黄芪总黄酮（TFA）对柯萨奇B3病毒性心肌炎（VMC）小鼠急性期心肌组织连接蛋白43（Cx43）表达的影响。方法Balb／c小鼠腹腔注射柯萨奇B3病毒感染建立VMC小鼠模型,给予TFA40mg／L灌胃治疗,第14天无痛苦处死全部小鼠并留取心脏。免疫组织化学法检测Cx43蛋白水平表达,并进行定量分析。结果①VMC组小鼠心室肌组织炎症病灶中变性、坏死周围心肌细胞Cx43表达明显减弱,甚至阴性,分布不规则,Cx43蛋白表达明显低于对照组,差异有统计学意义（P〈0．01）。@TFA组Cx43蛋白表达明显高于模型组,差异有统计学意义（P〈0．01）。结论VMC心肌炎小鼠急性期心肌组织Cx43蛋白表达下降。TFA能明显提高CVB心肌炎小鼠急性期心肌组织Cx43蛋白表达。     

黄芪、红景天、FTY720对柯萨奇病毒CVB3诱导小鼠病毒性心肌炎的药效学研究

目的：观察黄芪、红景天、FTY720作为单味药物对小鼠柯萨奇B3（CVB3）所致病毒性心肌炎（VMC）的治疗作用。方法：腹腔接种CVB3病毒液以建立VMC模型。随机分为空白组、VMC对照组、黄芪组、红景天组、FTY720组，观察五组动物在心肌重／体重比值；心肌组织切片（HE染色）；心肌酶（LDH．CK-MB）活力改变差异。结果：在心肌重／体重上，给药组与VMC对照组间无显著性差异（P〉0．05）；显微镜下观察心肌组织切片，VMC对照组局部可见广泛增生纤维组织，小鼠淋巴单核细胞浸润严重。药物干预组仅有淋巴单核细胞浸润，无纤维组织增生，空白对照组无病理性组织变化；LDH的活性测定显示黄芪组、红景天、FTY720组酶活性明显降低与VMC对照组有显著性差异（P〈0．01、P〈0．05）。CK-MB测定结果表明黄芪、红景天、FTY720组与VMC对照组有显著性差异（P〈0．01、P〈0．05）。结论：黄芪、红景天、FTY720对CVB，诱导小鼠急性病毒性心肌炎有一定治疗作用。     

哮喘小鼠骨髓树突状细胞的表型及共刺激分子研究

目的 探讨哮喘小鼠骨髓来源树突状细胞（DCs）的表型及共刺激分子在哮喘发病中的影响。方法 用卵清蛋白建立哮喘模型，利用rmGM-CSF和rmIL-4体外诱导骨髓细胞分化为DCs，流式细胞仪检测DCs表面共刺激分子的表达，混合淋巴细胞反应检测DCs刺激同种异体的T淋巴细胞增殖的能力。结果 在两种细胞因子的作用下，从骨髓中可以诱导出大量的DCs；且均表达DCs的表面标志（33D1）。哮喘组DCs表达CD86分子的水平高于对照组。而CD40、CD80在两组之间没有差异；哮喘组与对照组DCs均能强烈刺激同种异体T淋巴细胞的增殖，哮喘组DCs的刺激能力明显强于对照组。结论 哮喘组DCs的抗原递呈能力增强，表明DCs在哮喘的发病中可能起着重要作用。     

妊娠滋养细胞疾病患者病变组织中CD146的表达及意义

目的探讨妊娠滋养细胞疾病（包括完全性葡萄胎、侵蚀性葡萄胎及绒毛膜癌）病变组织中细胞黏附分子CD146的表达变化及意义。方法采用免疫组化二步法检测80例完全性葡萄胎、37例侵蚀性葡萄胎、39例绒毛膜癌患者病变组织中CD146的表达，与30例正常胎盘绒毛中CD146的表达作比较。结果完全性葡萄胎恶变者CD146的表达较正常胎盘绒毛和完全性葡萄胎未恶变者显著增强（P均〈0．01）；CD146预测完全性葡萄胎恶变的敏感度和特异性分别为71．05％和78．57％。侵蚀性葡萄胎和绒毛膜癌组织中CD146的表达较完全性葡萄胎显著增强（P均〈0．01）。CD146在滋养细胞肿瘤（包括侵蚀性葡萄胎及绒毛膜癌）晚期的表达显著强于早期（P〈0．01），且预后高危者CD146表达显著强于低危者（P〈0．01）。结论CD146对完全性葡萄胎恶变有一定的预测价值，其表达与滋养细胞肿瘤的临床分期及预后有关。     

Flt3L刺激体外培养小鼠骨髓源CD8α＋树突状细胞及其成熟状态分析

目的建立体外快速制备大量具有免疫活性的小鼠骨髓来源不成熟CD8α＋DCs方法。方法实验分2组。Fh3L组：将小鼠骨髓前体细胞用含终浓度为100ng／mlFlt3L的BMDC培养基混悬后接种于细胞培养皿中,每平皿10ml,37C培养至第7d收集细胞;GM-CSF＋IL4组：将骨髓前体细胞用含终浓度为20ng／mlGM-CSF、5ng／mlIL-4的BMDC培养基混悬后接种于细胞培养皿中,每平皿10ml,分别于37℃培养第3d和第5d半量换液,培养第7d收集细胞,采用磁选法分离CD11c＋ BMDCs,用流式细胞仪检测。结果Flt3L刺激组CD11c＋ BMDCs得率为（95．07±0．09）％,GM-CSF＋IL-4刺激组为（83．97±0．43）％,差异有统计学意义（P〈0．01）。Flt3L刺激组CD11c＋ CD8α＋BMDCs得率为（9．83±0．33）％,GM-CSF＋IL-4刺激组刺激组为（4．06±0．17）％,差异有统计学意义（P〈0．01）。Flt3L刺激组CD11c＋ CD8α＋ BMDCs表面几乎不表达CD40、CD80、CD86,仅低表达MHCI、MHCII,处于未成熟阶段。结论采用Fh3L刺激小鼠骨髓前体细胞的方法可获得大量未成熟的CD11c＋ CD8α＋ BMDCs,方法简单,得率较高,为开展CD8α＋DCs相关基础和临床研究奠定了基础。     

HEC-1-B细胞培养上清液对子宫内膜癌树突状细胞成熟的影响

目的探讨子宫内膜癌细胞株HEC-1-B培养上清液对子宫内膜癌患者外周血单核细胞源性树突状细胞（DCs）成熟的影响。方法梯度离心法分离子宫内膜癌患者外周血单核细胞,在含重组人粒细胞一巨噬细胞集落刺激因子和重组人自介素4的DCs培养液中培养,使其分化为DCs。实验组将收集的子宫内膜癌细胞株HEC-1-B培养上清液过滤后与DCs共同孵育48h,对照组不给予任何干预措施。镜下观察DCs形态变化,采用流式细胞术检测DCs表型（CD1α、CD83、CD86）表达,ELISA法检测细胞上清液中自细胞介素10（IL-10）、IL-12含量。结果实验组细胞生长状态较好,具有典型的树枝状突起,数量不等、形态不一;实验组DCs表型CD1α、CD83、CD86分子的表达分别较对照组升高（P〈0．01）;实验组OCs分泌的细胞因子IL-10水平较对照组降低（P〈0．01）,IL-12水平较对照组升高（P〈0．01）。结论子宫内膜癌细胞株HEC-1-B培养上清液能够在体外诱导子宫内膜癌患者外周血单核细胞源性DCs成熟。     

骨髓增生异常综合征骨髓细胞免疫表型的探讨

用流式细胞术分析45例原发性骨髓增生异常综合征（MDS）患者和10例良性血液病病人的骨髓细胞免疫表型。结果：88．9％MDS表现二系或二系以上免疫标志异常，基中CD2、CD71、CD13、CD33、HLA－DR、CD34免疫标志变化最大，明显高于对照组（P＜0．01）。RA组：CD2、CD71（P＜0．05）、HLA－DR（P＜0．01）明显高于对照组；RAEB：除上述标志同RA外，髓系相关标志CD13、CD33（P＜0．01）和干／祖细胞标志CD34明显增高（P＜0．05）；RAEB－t组：髓系相关标志CD13（P＜0．05）、CD33（P＜0．01）和干／祖细胞标志CD34、HLA-DR（P＜0．01）表达率增高。CD15：HLADR与CD15：CD34比值在RAEB－t最低。     

60Coγ射线左半身照射对小鼠非照射区域骨髓造血组织VEGF表达的影响

目的探讨局部电离辐射对小鼠非照射区域骨髓造血组织血管内皮生长因子（VEGF）表达的影响。方法将6—8周龄雄性昆明小鼠随机分为正常对照组、全身照射组、全身屏蔽照射组以及左半身照射组，用铅屏蔽建立半身照射模型，以8．0Gy^60Coγ射线照射，观察小鼠外周血白细胞和骨髓有核细胞计数，检测血清SOD、MDA变化，用Western blotting和免疫组织化学结合激光共聚焦显微镜观察骨髓造血组织VEGF表达的改变。结果在半身照射条件下，小鼠外周血白细胞降低，未照射侧骨髓有核细胞计数减少，血清MDA升高，SOD降低（与正常对照组比，P〈0．01）；非照射区域骨髓造血组织VEGF表达明显减少，VEGF阳性细胞显著下降（与正常对照组比，P〈0．01）。结论局部电离辐射作用后，可导致非照射区域骨髓造血组织增殖抑制，VEGF表达显著减少，氧自由基激活可能参与了该损伤过程。     

多参数流式细胞术分析难治性贫血伴原始细胞增多患者骨髓细胞的免疫表型特点

目的探讨骨髓增生异常综合征（MDS）亚型中难治性贫血伴原始细胞增多（RAEB）患者骨髓细胞免疫表型特点及其在诊断、鉴别诊断及预后中的临床意义。方法应用多参数流式细胞术,对35例RAEB患者和20例非MDS患者骨髓细胞表面抗原表达进行检测。结果RAEB组与非MDS组相比,原始细胞比例明显升高（P〈0．01）,成熟粒细胞比例显著下降（P〈0．01）,而淋巴、单核及有核红细胞比例无显著差异（P〉0．05）;RAEB组CD34、CD7和CD56在原始细胞表达明显增高（P〈0．01）;CD19在淋巴细胞亚群表达降低（P〈0．05）,而CD,。表达升高（P〈0．05）,CD,表达无差异;HLA—DR、CD56及CD15^＋ CD11b^-在粒-单核细胞亚群表达明显升高（P〈0．01）,而CD10、CD15^＋ CD11b^-表达明显下降（P〈0．01）,CD13和CD33表达无差异;RAEB组CD34及CD7高表达者的生存期短于低表达者。结论多参数流式细胞术可用于检测RAEB骨髓细胞异常免疫表型特点,为临床对三系减少或者贫血患者的诊断、鉴别诊断及预后评价提供新方法。     

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.     

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.     

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.     

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     

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。     

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。