老年骨关节炎患者关节软骨和滑膜中转化生长因子β及受体和金属蛋白酶组织抑制物的研究

目的 探讨骨关节炎（OA）患者关节软骨和滑膜中转化生长因子β（TGFβ1）、转化生长因子β受体（TGFβR）和金属蛋白酶组织抑制物－1（TIMP－1）变化及其与OA发病的关系。方法 采用免疫组化方法检测23例老年OA患者及3例外伤患者正常关节软骨和滑膜TGFβ1、转化生长因子βI类受体（TGFβRI）、转化生长因子βⅡ类受体（TGFβRⅡ）和TIMP－1的分布和阳性程度。结果 OA患者中14例关节软骨和16例滑膜TGFβ1染色呈阳性或弱阳性,14例关节软骨和15例滑膜TIMP－1染色呈弱阳性,全部OA患者关节软骨和滑膜TGFβRI和TGFβRⅡ染色呈强阳性。阳性细胞包括软骨细胞、滑膜衬里细胞、滑膜下层的血管内皮细胞和间质巨噬细胞等。结论 老年OA患者关节软骨和滑膜中TGFβ1、TGFβ及TIMP－1的变化可能与OA发病有一定的关系。     

类风湿关节炎滑膜组织人糖皮质激素诱导型肿瘤坏死因子受体表达的免疫组织化学研究

目的 观察研究人糖皮质激素诱导型肿瘤坏死因子受体(hGITR)在类风湿关节炎(RA)滑膜组织和软骨组织中的表达及其与滑膜炎性病变程度的相关性.方法 用免疫组织化学的方法对16例RA患者、9例骨关节炎(OA)患者及4例无关节病变的截肢患者滑膜组织和软骨组织中hGITR的表达进行描述分析,并对hGITR表达情况与RA患者滑膜炎性病变程度相关性进行分析.结果 hGITR在RA滑膜组织主要分布于血管翳周围,如血管内皮细胞和炎性细胞等,hGITR阳性细胞数约为69%.而该受体在RA患者软骨组织细胞中的表达率与对照组比较差异无统计学意义.OA滑膜组织和软骨组织细胞中hGITR也呈现不同程度的阳性表达,但与RA比较阳性程度较弱,阳性细胞数量较少;对hGITR表达与RA滑膜炎性程度的相关性分析发现,hGITR与RA滑膜炎性程度呈正相关(r=0.895,P<0.01).结论 hGITR在RA滑膜组织炎性细胞及血管内皮细胞上的异常表达可能是其参与RA血管翳的形成及滑膜组织的侵袭等病理过程导致RA患者滑膜损伤的一个重要机制.     

骨关节炎关节软骨及游离体中胶原ⅠⅡⅢ型的表达

目的 进一步了解与骨关节炎相关的关节软骨及游离体软骨细胞表型改变。方法 通过组化和免疫组化方法,观察纤维性胶原Ⅰ、Ⅱ、Ⅲ型在人正常和骨关节炎关节软骨及游离体中的表达。结果 在１０例骨关节炎关节软骨标本中,有９例可在关节软骨的中层和深层的软骨细胞中显示强烈的Ⅱ、Ⅲ型胶原蛋白 阳性表达信号,而Ⅰ型胶原表达蛋白只在中下层及深层观察到,表达强度较Ⅲ型弱,表达区域部分与Ⅲ型重叠。在１０例骨关节炎游离体标本中     

骨关节炎关节软骨及游离体中胶原Ⅰ Ⅱ Ⅲ型的表达

目的　进一步了解与骨关节炎相关的关节软骨及游离体软骨细胞表型改变。方法　通过组化和免疫组化方法,观察纤维性胶原Ⅰ、Ⅱ、Ⅲ型在人正常和骨关节炎关节软骨及游离体中的表达。结果　在10例骨关节炎关节软骨标本中,有9例可在关节软骨的中层和深层的软骨细胞中显示强烈的Ⅱ、Ⅲ型胶原蛋白的阳性表达信号,而Ⅰ型胶原表达蛋白只在中下层及深层观察到,表达强度较Ⅲ型弱,表达区域部分与Ⅲ型重叠。在10例骨关节炎游离体标本中,均可在游离体内部软骨细胞及基质中显示强烈的Ⅲ型胶原蛋白阳性表达信号。相同标本中Ⅰ型胶原蛋白仅在游离体内部软骨细胞中有表达,表达的阳性信号相对较低,未见明显的Ⅱ型胶原表达。在正常关节软骨中,Ⅱ型胶原的表达的信号较弱,未见Ⅰ、Ⅲ型胶原蛋白表达信号。结论　在骨关节炎关节软骨及游离体中,一定区域内的软骨细胞表型发生了改变,表达合成了Ⅲ型胶原和Ⅰ型胶原,可能在骨关节炎发病机制中发挥重要作用。     

类风湿关节炎滑膜组织PDGF与TGF-β1的表达与意义

应用免疫组织华沙SABC对24列类风湿关节炎（RA）及4例正常滑膜组织中血小板源性生长因子（PDGF），转化生长因子β1（TGF－β1）的表达分布情况进行观察分析，结果发现20例RA滑膜组织衬里层的巨噬细胞样细胞，浸润的炎性细胞与血管内皮细胞，成纤维细胞可见PGDF的表达分析，且巨噬细胞样细胞，浸润的炎症细胞的阳性程度强于血管内皮细胞，成纤维细胞。22例RA滑膜组织衬里层与衬里下层的成纤维细胞，巨噬细胞样细胞，血管内皮细胞均见TGF－β1的阳性表达分布。两者比较，阳性细胞的染色程度，染色细胞数与分布范围大致相等。4例正常滑膜组织中PDGF，TGF－β1的表达分布均为阴性。认为RA滑膜组织中PDEFTGF－β1的表达分布较正常多且表达程度大致相等，两者协同作用，参与了RA病理过程的滑膜衬里层增生，炎性细胞浸润，血管增殖与滑膜血管翳的形成。     

Smad4和TGF-βRⅡ在肝细胞癌中的表达及意义

目的探讨转化生长因子β(TGF-β)通路中Smad4蛋白与转化生长因子βⅡ型受体(TGF-β RⅡ)蛋白的变化及其在肝细胞癌中可能的作用机制.方法用免疫组化SABC法检测45例石蜡包埋人肝细胞癌标本及36例癌旁组织中Smad4、TGF-β RⅡ蛋白表达情况.结果 45例肝癌组织中,Smad4、TGF-βRⅡ阳性表达率分别为51.5%和42.2%.肝细胞癌组织中Smad4、TGF-β RⅡ阳性表达与癌旁组织比较均明显降低(P＜0.05),且与包膜是否完整和有无癌栓有关(P＜0.05),TGF-βRⅡ与肝细胞癌组织分化程度有相关性(P＜0.05).结论肝细胞癌组织中Smad4、TGF-β RⅡ阳性表达均降低,Smad4及TGF-β RⅡ的丢失、功能失活对诱发肝细胞癌及肝细胞转移都起到一定作用.     

骨关节炎患者软骨及滑膜高迁移率族蛋白1的表达

目的探讨高迁移率族蛋白1(HMGB1)与骨关节炎(OA)发生和发展的关系。方法采用免疫组织化学方法观察42例老年 OA 患者关节软骨、滑膜和3例未累及关节的创伤患者正常关节软骨和滑膜 HMGB1的表达规律与分布特点及其与 C 反应蛋白(CRP)的关系。结果 42例OA 中,35例软骨 HMGB1染色阳性,占83.3%;30例滑膜 HMGB1染色阳性.占71.4%,其表达以胞浆分布为主,胞核中较少,3例正常关节软骨和滑膜 HMGB1标记均为阳性。其表达以胞核分布为主,胞浆中极少分布。OA 患者关节软骨和滑膜 HMGB1细胞内分布与关节正常者有明显的不同。OA 患者 HMGB1阳性的软骨细胞数占软骨细胞总数的70.2%,HMGB1阳性的滑膜上皮细胞数占滑膜上皮细胞总数的60.5%,与关节正常者比较,差异无统计学意义(P>0.05)。OA 患者外周血CRP 含量[(20.4±16.7)ng/L]明显升高(P<0.01)。结论 OA 患者关节软骨及滑膜中核外HMGB1可能在 OA 组织损伤的病理过程中发挥作用,OA 患者关节软骨及滑膜上皮细胞中核外HMGB1作为晚期炎症因子参与了 OA 的疾病过程。     

类风湿关节炎中尿激酶型纤溶酶原激活物及其受体蛋白和基因的表达

目的　检测尿激酶型纤溶酶原激活物 (uPA)及其受体 (uPAR)蛋白和mRNA在类风湿关节炎 (RA)的表达 ,探讨uPA、uPAR基因在RA细胞外基质降解中的作用。方法　采用免疫组化和cDNA mRNA原位分子杂交技术分别检测了 2 4例RA、18例骨关节炎 (OA)和 6例正常滑膜组织中uPA、uPAR蛋白和mRNA的分布及表达情况。结果　 2 4例RA滑膜组织均呈uPA、uPAR蛋白和mRNA的阳性表达 ,uPA、uPAR蛋白的强阳性率高于mRNA。uPA、uPAR蛋白和mRNA阳性信号主要分布在RA滑膜衬里细胞、滑膜下层单核细胞、巨噬细胞样细胞及血管内皮细胞 ;18例OA滑膜组织中 ,uPA、uPAR蛋白和mRNA的表达部位类似于RA ,但阳性率、阳性程度及分布范围均明显低于RA滑膜组织 ,两组之间蛋白和mRNA表达的差异均有显著性 (P <0 0 1或P <0 0 0 1)。 6例正常滑膜组织呈阴性反应。结论　RA滑膜组织存在高水平uPA、uPAR蛋白和mRNA的表达 ,提示在RA的发生发展过程中 ,uPA和uPAR基因起着重要作用 ;RA和OA中uPA、uPAR基因表达水平的差异 ,可能与这两种疾病软骨和骨基质降解的程度及进程等临床表现密切相关     

骨关节炎软骨细胞和滑膜细胞金属蛋白酶活性的影响因素

目的 探讨几种细胞因子、生长因子和药物等刺激物对骨关节炎软骨细胞及滑膜细胞金属蛋白酶活性的影响。方法 骨关节炎患者的单层软骨细胞和膜细胞均以白细胞介素-1β、转化生长因子-β1、肿瘤坏死因子-α、双氯芬酸钠、多西环素和地塞松分别处理72h。应用酶谱分析细胞培养上清液中酶活性。结果 单层软骨细胞产生金属蛋白酶-9和-2,而滑膜细胞仅产生金属蛋白酶-2。白细胞介素-1β,肿瘤坏死因子-α和双氯芬酸钠均能显著增强金属蛋白酶-9活性,其中以白细胞介素-1β作用最强,与肿瘤坏死因子-α或双氯芬酸钠有协同作用。多西环素、转化生长因子-β1和地塞米松均能抑制金属蛋白酶-9和-2活性,并与白细胞介素-1β、肿瘤坏死因子-α和地塞米松均能抑制金属蛋白酶-9和-2活性,并与白细胞介素-1β、肿瘤坏死因子-α和双氯芬酸钠起拮抗作用。多西环素为最强的抑制物。结论 白细胞介素-1β和肿瘤坏死因子-α可能为破坏关节软骨的重要细胞因子,转化生长因子-β1则为保护因子,多西环素则可能成为骨关节炎的有效治疗药物。     

脱氢表雄酮对兔骨关节炎影响的实验研究

目的观察关节腔内注射脱氢表雄酮(DHEA)对兔骨关节炎的影响,并探讨其作用机制。方法40只新西兰大白兔行单侧前交叉韧带切除术,术后4周随机分为实验组和对照组。实验组关节腔内注射100μmol/L DHEA(DHEA溶于二甲基亚砜),每周1次,连续5周；对照组注射同剂量的二甲基亚砜。术后9周处死兔子,取膝关节行大体和组织病理学检查,用反转录聚合酶链反应(RT-PCR)方法检测关节软骨及滑膜中基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶组织抑制因子-1(TIMP-1)和白细胞介素-1β(IL-1β)mRNA的表达。结果大体和组织病理学检查显示实验组软骨和滑膜病变程度轻于对照组。实验组软骨和滑膜中MMP-3 mRNA的表达水平显著低于对照组(均P＜0．05),而TIMP-1 mRNA的表达显著高于对照组(均P＜0．05)。实验组软骨IL-IβmRNA的表达与对照组表达差异无统计学意义(P＞0．05),而滑膜IL-1βmRNA的表达显著低于对照组(P＜0．01)。结论DHEA对兔软骨有修复和保护的作用,减轻滑膜的炎症,能够延缓骨关节炎的进展。下调软骨、滑膜MMP-3和上调软骨、滑膜TIMP-1的表达及下调滑膜IL-1β的表达可能是DHEA对骨关节炎的作用机制。     

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。     

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。     

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.     

Angiographic diagnosis of the degree of serosal invasion of carcinoma of the colon

Angiography using Prostaglandin El^® was performed on 38 patients with carcinoma of the colon in order to diagnose the degree of serosal cancer invasion. The findings at angiography were classified into four groups:1) AG-S3, abnormal change (irregularity and/or encasement) up to marginal vessels; 2) AG-S2, abnormality up to vasa recta; 3) AG-S1, abnormality of penetrating branches of vasa recta within the wall of the colon; and 4) AG-S0, no distinct findings of abovementioned vessels. These angiographic findings were compared with both macroscopic and microscopic serosal cancer invasion. Angiographic diagnosis is in accord with the macroscopic findings in 84.2 percent of cases. Angiographic diagnosis is in accord with the microscopic findings in 32.4 percent of cases. Macroscopic findings confirm the angiographic diagnosis precisely but the conflict with microscopic findings should not be overlooked. This may be the result of inflammatory change, adhesion, and fibrosis around carcinoma of the colon.