Inhibition of endocan attenuates monocrotaline-induced connective tissue disease related pulmonary arterial hypertension

Connective tissue disease related pulmonary arterial hypertension (CTD-PAH) is characterized by vascular remodeling, endothelial dysfunction and inflammation. Endocan is a novel endothelial dysfunction marker. The aim of the present study was to investigate the role of endocan in CTD-PAH. Monocrotaline (MCT)-induced PAH rats were used as the CTD-PAH model. Short hairpin RNA packed in a lentiviral vector used to inhibit endocan expression was intratracheally instilled in rats prior to the MCT injection. Endocan was found to be increased in the serum and lung of MCT-induced PAH rats. Short hairpin RNA mediated knockdown of endocan significantly decreased right ventricular systolic pressure, attenuated pulmonary remodeling and inflammatory responses in the lung. In the in vitro study, tumor necrosis factor-α (TNF-α) exposure caused increased endocan expression in the primary cultured rat pulmonary microvascular endothelial cells (RPMECs). Endocan knockdown inhibited the permeability increase and adhesion molecules secretion in RPMECs induced by TNF-α. In addition, TNF-α induced MAPK activation was blocked when endocan gene was knocked down. These data demonstrate that endocan may play an important role in the development of CTD-PAH. This study provides novel evidence to better understand the pathogenesis of CTD-PAH, which may be beneficial for the treatment of this disease.     

生长激素与子宫内膜发育关系的研究进展

在体外受精-胚胎移植中用生长激素(GH)可促进子宫内膜发育,改善子宫内膜的功能,提高子宫内膜的容受状态,从而提高妊娠率。同时,GH刺激子宫内膜癌细胞基因的表达,使子宫内膜癌细胞总数增加,肿瘤体积增加,并且促进了癌细胞的迁移或浸润,提高了子宫内膜癌细胞的致癌性。GH拮抗剂可能会在子宫内膜癌晚期提供一个有用的治疗方案,以改善患者的预后,这将是一个新的研究课题。     

去整合素Kistrin对兔眼LECs增殖的抑制

目的 探讨不同浓度的去整合素Kistrin对兔眼后发性白内障(Posterior capsular opacification,PCO)发生过程中晶状体上皮细胞(lens epithelial cells,LECs)增殖的抑制作用,以明确Kistrin的眼内有效浓度.方法 制备兔眼PCO模型,行白内障摘除术,术毕3个实验组前房分别注入40 μg/L、80 μg/L、160 μg/L的Kistrin,对照组前房注入林格氏液.术后在裂隙灯显微镜下观察PCO发生情况及形态,于术后14 d及3个月时取材,分别检测晶状体囊膜上LECs增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的表达.结果 术后第14天实验组LECs的PCNA表达均较对照组降低(P<0.05);第3个月时仅80 μg/L组较对照组明显降低(P<0.05);两个时间点80 μg/L组LECs的PCNA表达均较其余实验组明显降低(P<0.05),40 μg/L组与160 μg/L组间无显著性差异(P>0.05).同一浓度术后第14天与3个月时LECs的PCNA表达比较,仅80 μg/L组差异无显著性,余三组比较差异有显著性.结论 80 μg/L Kistrin术后早期及3个月均可有效地抑制兔眼PCO的发生,可作为进一步研究去整合素抑制PCO形成研究的较适宜浓度.     

慢性肝炎基础上≤2cm肝局灶性病变的超声造影与增强CT特征比较

目的对比分析慢性肝炎或肝硬化基础上≤2 cm肝局灶性病变(FLLs)的超声造影与增强CT特征,探讨超声造影在CT诊断阴性或动脉期无强化且伴有慢性肝病的FLLs诊断中的价值。方法回顾性分析经穿刺病理证实的25例伴有肝硬化或者慢性肝病的FLLs的临床资料,所有患者均行超声造影及增强CT检查,病灶直径≤2.0 cm。结果所有病灶CT无阳性发现或动脉期无高增强。超声造影显示8例动脉期呈高增强的病灶病理结果提示高分化肝细胞癌(HCC)5例和中分化HCC 3例;13例动脉期呈等增强的病灶病理结果提示不典型增生3例、高分化HCC 5例及增生结节5例;4例动脉期呈低增强的病变病理提示高分化HCC 1例、增生结节3例。门脉期及延迟期22例等增强的病灶病理结果提示高分化HCC 11例、不典型增生3例及增生结节8例,3例低增强的病灶病理结果提示中分化HCC。结论 CT诊断阴性或动脉期无强化且伴有慢性肝病的FLLs,其超声造影结果表现不同,但绝对不能排除恶性病变,应结合超声引导穿刺活检进一步排除恶性病变,更利于为患者提供早期治疗。     

幼年特发性关节炎诊疗规范

幼年特发性关节炎(JIA)临床上常见亚型包括全身型JIA、少关节型/多关节型JIA和幼年脊柱关节炎。本病无特异性诊断指标, 需与感染性疾病和恶性病相鉴别。全身型JIA起病多急骤, 病情进展快, 易合并巨噬细胞活化综合征而危及生命。儿童风湿科医生对JIA的诊断及治疗经验仍不足, 规范化诊疗水平有待进一步提高。中华医学会风湿病学分会组织有关专家, 在借鉴国内外诊疗规范和分类标准的基础上, 制定本规范, 旨在规范JIA各亚型及全身型JIA合并巨噬细胞活化综合征的诊断和治疗方案, 以降低致死率和严重并发症的发生率, 从而改善患儿预后。     

CTLA-4Ig对B6.MRL-Faslpr/J狼疮小鼠脾脏Th17和Treg细胞表达的影响与其对小鼠狼疮样病征干预作用的相关性研究

目的:初步探讨B7阻断剂CD28与细胞毒T淋巴细胞相关抗原4免疫球蛋白(CTLA-4Ig)对B6.MRL-Faslpr/J狼疮小鼠脾脏Th17和调节性T细胞(Treg细胞)表达的影响与其对小鼠狼疮样病征干预作用之间的相关性。方法:将4个月龄大小雌性B6.MRL-Faslpr/J狼疮小鼠16只,随机分为观察组(Ⅰ组)和对照组(Ⅱ组),分别静脉注射CTLA-4Ig及等量PBS,检测小鼠干预前后24 h尿蛋白、ANA抗体、ds-DNA抗体及干预结束2周后血清IL-17A、脾脏中Th17细胞和Treg细胞百分比。结果:末次干预2周后Ⅰ组的24 h尿蛋白、血清ANA及ds-DNA较Ⅱ组下降均有统计学意义(均P0.05)。末次干预2周后Ⅰ组血清中IL-17A、脾脏Th17细胞比例均较Ⅱ组低,而脾脏的Treg细胞占CD4+T淋巴细胞的比例高于Ⅱ组,差异均有统计学意义(均P0.05)。结论:CTLA4-Ig具有减轻B6.MRL-Faslpr/J狼疮鼠狼疮样病征的作用;上调Treg细胞、下调Th17细胞可能是CTLA-4Ig减轻B6.MRL-Faslpr/J狼疮鼠狼疮样病征的重要机制之一。     

Expression of FK506-binding protein 52 (FKBP52) in chorionic villi with early recurrent spontaneous abortion

Objective: To investigate the mRNA and protein expression of FK506-binding protein 52 (FKBP52) in the chorionic villi of patients with recurrent spontaneous abortion (RSA) and normal women during early pregnancy.

Methods: Fresh chorionic villus tissues were collected from 60 subjects. A total of 30 patients with a history of RSA were enrolled into the RSA group and 30 normal pregnant women were enrolled into the control group. The FKBP52 mRNA expression levels in chorionic villi of the RSA patients and healthy controls were measured via semiquantitative RT-PCR. The protein distribution and expression levels of FKBP52 in chorionic villi were analyzed through immunohistochemistry (IHC). The correlation between FKBP52 expression and RSA was analyzed.

Results: We demonstrated that FKBP52 mRNA is expressed in chorionic villi samples of normal pregnancy and RSA. RSA patients exhibited significantly lower FKBP52 gene expression levels compared with those in normal pregnancies (p?<?0.05). FKBP52 immunoreactivity in chorionic villi was mainly observed in trophoblast cell cytoplasm. The FKBP52 protein expression levels in the chorionic villi of RSA patients was significantly lower than in normal women during pregnancy (p?<?0.05).

Conclusions: FKBP52 protein levels were decreased in the chorionic villi of RSA patients, which indicate that the decrease in FKBP52 may be associated with RSA. The low FKBP52 mRNA expression level, which is consistent with the IHC result, may affect embryonic development and even lead to abortion. FKBP52 may be involved in the pathogenesis of RSA and new therapies that increase the FKBP52 expression may help treat RSA.     

CTA及动态血清S-100B蛋白检测对SAH患者脑损害程度及脑血管痉挛的评价作用

目的：分析讨论多层螺旋CT血管成像（CTA）对原发性蛛网膜下腔出血（SAH）患者的诊断价值及动态血清S‐100B蛋白检测SAH患者脑损害程度及脑血管痉挛的评价作用。方法对166例SAH患者行CTA检查,抽取患者入院后1、2、3、7d时的肘静脉血检测血清S‐100B蛋白水平。结果166例SAH患者中,CTA共检出119处动脉瘤。Hunt‐HessⅠ～Ⅱ级患者入院后1dS‐100B蛋白水平为（0．71±0．11）μg／L,7d为（0．62±0．09）μg／L,Hunt‐HessⅣ级的患者入院后1dS‐100B蛋白水平为（2．12±0．23）μg／L,7d为（1．97±0．06）μg／L,S‐100B蛋白水平与Hunt‐Hess分级呈正比。格拉斯哥昏迷（GCS）评分3～8分的患者入院后1dS‐100B蛋白水平为（1．87±0．23）μg／L,7d为（1．87±0．23）μg／L。GCS评分13～15分的患者入院后1dS‐100B蛋白水平为（0．63±0．17）μg／L,7d为（0．44±0．15）μg／L,GCS评分越低,S‐100B蛋白水平越高。结论CTA可显示血管的空间立体结构及周边关系,有助于治疗方法的选择和难度的评估。检测血清中S‐100B蛋白浓度能评估继发性脑损害的严重情况和脑血管痉挛的可能性。     

Protective effect of gastrodin on bile duct ligation-induced hepatic fibrosis in rats

Gastrodin has been showed to possess many beneficial physiological functions, including protection against inflammation and oxidation and apoptosis. Studies showed inflammation and oxidation play important roles in producing liver damage and initiating hepatic fibrogenesis. However, it has not been reported whether gastrodin has a protective effect against hepatic fibrosis or not. This is first ever made attempts to test gastrodin against liver fibrosis in bile duct ligation (BDL) rats. The aim of the present study is to evaluate the effect of gastrodin on BDL-induced hepatic fibrosis in rats. BDL rats were divided into two groups, BDL alone group, and BDL-gastrodin group treated with gastrodin (5 mg/ml in drinking water). The effects of gastrodin on BDL-induced hepatic injury and fibrosis in rats were estimated by assessing serum, urine, bile and liver tissue biochemistry followed by liver histopathology (using hematoxylin & eosin and sirius red stain) and hydroxyproline content measurement. The results showed that gastrodin treatment significantly reduced collagen content, bile duct proliferation and parenchymal necrosis after BDL. The serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) decreased with gastrodin treatment by 15.1 and 23.6 percent respectively in comparison to BDL group did not receive gastrodin. Gastrodin also significantly increased the level of serum high density lipoprotein (HDL) by 62.5 percent and down-regulated the elevated urine total bilirubin (TBIL) by 56.5 percent, but had no effect on total bile acid (TBA) in serum, bile and liver tissues. The immunohistochemical assay showed gastrodin remarkably reduced the expressions of CD68 and NF-κB in BDL rats. Hepatic SOD levels, depressed by BDL, were also increased by gastrodin by 8.4 percent. In addition, the increases of hepatic MDA and NO levels in BDL rats were attenuated by gastrodin by 31.3 and 38.7 percent separately. Our results indicate that gastrodin significantly attenuated the severity of BDL-induced hepatic injury and fibrosis by attenuating oxidative stress and inflammation. Taken together, these findings suggest that gastrodin might be an effective antifibrotic drug in cholestatic liver disease.