S1PR4-dependent CCL2 production promotes macrophage recruitment in a murine psoriasis model

The sphingolipid sphingosine-1-phosphate (S1P) fulfills distinct functions in immune cell biology via binding to five G protein-coupled receptors. The immune cell-specific sphingosine-1-phosphate receptor 4 (S1pr4) was connected to the generation of IL-17-producing T cells through regulation of cytokine production in innate immune cells. Therefore, we explored whether S1pr4 affected imiquimod-induced murine psoriasis via regulation of IL-17 production. We did not observe altered IL-17 production, although psoriasis severity was reduced in S1pr4-deficient mice. Instead, ablation of S1pr4 attenuated the production of CCL2, IL-6, and CXCL1 and subsequently reduced the number of infiltrating monocytes and granulocytes. A connection between S1pr4, CCL2, and Mϕ infiltration was also observed in Zymosan-A induced peritonitis. Boyden chamber migration assays functionally linked reduced CCL2 production in murine skin and attenuated monocyte migration when S1pr4 was lacking. Mechanistically, S1pr4 signaling synergized with TLR signaling in resident Mϕs to produce CCL2, likely via the NF-κB pathway. We propose that S1pr4 activation enhances TLR response of resident Mϕs to increase CCL2 production, which attracts further Mϕs. Thus, S1pr4 may be a target to reduce perpetuating inflammatory responses.     

乳腺浸润性导管癌中ER、PR、Her-2、Ki-67表达与病理特征及预后的相关性

目的 探究Ki-67、ER、PR、Her-2等基因在乳腺浸润性导管癌（IDC）组织中的表达,分析其与患者临床病理特征及预后的相关性。方法 收集2013年1月~2014年12月广东医科大学附属医院病理科乳腺包埋石蜡块IDC组织74例。采用免疫组织化学法检测ER、PR、Her-2、Ki-67在IDC组织中的表达,分析其与患者年龄、组织学分级、TNM分期、淋巴结转移及预后的相关性。结果 ①不同年龄、组织学分级、淋巴结转移及TNM分期的IDC患者ER、PR表达情况比较,差异均无统计学意义（P＞0.05）;未发生淋巴结转移的IDC患者Her-2表达低于转移患者,差异有统计学意义（P＜0.05）;不同年龄、组织学分级、TNM分期的IDC患者Her-2表达比较,差异无统计学意义（P＞0.05）;不同TNM分期的IDC患者Ki-67表达情况比较,差异有统计学意义（P＜0.05）,不同年龄、组织学分级、淋巴结转移的IDC患者Ki-67表达比较,差异均无统计学意义（P＞0.05）。 ②Spearman相关性分析显示,ER与PR正相关,ER与Her-2、PR与Her-2负相关,ER、Ki-67和PR、Ki-67负相关,Her-2与Ki-67正相关。③Ki-67阳性表达的IDC患者病死率高于Ki-67阴性表达的患者,差异有统计学意义（P＜0.05）;不同ER、PR、Her-2表达情况的IDC患者病死率比较,差异无统计学意义（P＞0.05）;Ki-67阴性表达患者的总生存时间（OS）高于阳性表达患者,COX多因素分析显示,Ki-67阳性表达是影响IDC患者OS的独立因素（95%CI:0.212~0.865,P=0.018）。结论 Ki-67可作为乳腺浸润性导管癌危险评估的分子标志物,其阳性表达可影响乳腺癌患者的预后。ER、PR、Her-2的表达对乳腺浸润性导管癌患者的预后没有明显影响。     

Autoimmune associated congenital heart block: integration of clinical and research clues in the management of the maternal / foetal dyad at risk

One of the strongest associations with autoantibodies directed to components of the SSA/Ro‐SSB/La ribonucleoprotein complex is the development of congenital heart block (CHB) in an offspring, an alarming prospect facing 2% of primigravid mothers with these reactivities. This risk is 10‐fold higher in women who have had a previously affected child with CHB. Anti‐Ro/La antibodies are necessary but insufficient to cause disease. In vitro and in vivo experiments suggest that the pathogenesis involves exaggerated apoptosis, macrophage/myfibroblast crosstalk, TGFβ expression and extensive fibrosis in the conducting system and in some cases surrounding myocardium. A disturbing observation is the rapidity of disease progression, with advanced heart block and life‐threatening cardiomyopathy observed <2 weeks from normal sinus rhythm. Once 3rd degree (complete) block is identified, reversal has never been achieved, despite dexamethasone. Current strategies include the evaluation of an early echocardiographic marker of injury, such as a prolonged PR interval and the use of IVIG as a preventative measure for pregnancies of mothers with previously affected children.     

Hepatoprotective effects of Artemisiae Capillaris Herba and Picrorrhiza Rhizoma combinations on carbon tetrachloride–induced subacute liver damage in rats

The hepatoprotective properties of Artemisiae Capillaris Herba (AC) and Picrorrhiza Rhizoma (PR) are well known. The aim of this study was to determine the optimal composition of AC and PR mixtures for better complimentary or alternative regimens in reducing the level of hepatic fibrosis. Ten weeks of carbon tetrachloride injections caused subacute hepatic damage, manifested as significantly less body weight gain and hepatic protein content, and a higher liver weight, serum aspartate aminotransferase and alanine aminotransferase levels, hepatic malondialdehyde (an index for lipid peroxidation), and hydroxyproline (an index for collagen synthesis) concentrations. The carbon tetrachloride–induced toxic effects were inhibited by 11 different AC/PR mixtures as well as the single AC or PR treatment. More favorable effects were detected in all mixed-formulation groups compared with the AC or PR single formulations. Moreover, the AC/PR 2:1 formulation showed the most favorable hepatoprotective activity. The AC and PR mixtures showed good synergic hepatoprotective activity that was attributed to increasing free-radical scavenging ability. Among the 11 types of mixed formula tested in this study, the AC/PR 2:1 formulation had the most impressive synergic effects on inhibiting the subacute hepatic damage induced by carbon tetrachloride in rats and showed more favorable effects than with an equal dose of silymarin.     

乳结平胶囊对乳腺增生大鼠乳腺组织ER、PR表达的影响

目的:探讨乳结平胶囊对乳腺增生大鼠病理组织雌激素受体(ER)和孕酮受体(PR)表达的影响。方法:先采用苯甲酸雌二醇注射液连续im25d,后改用黄体酮注射液连续im5d,从而建立大鼠乳腺增生模型,以三苯氧胺为阳性对照药物,用乳结平胶囊高、低剂量治疗30d。结果:三苯氧胺组及乳结平胶囊高、低剂量组均能减轻大鼠乳头红肿或增生症状,降低大鼠血清雌二醇(E2)、催乳素(PRL)水平及升高孕酮(P)水平,降低子宫指数,明显减少导管上皮细胞层数和腺泡数,同时减少乳腺组织ER、PR的含量,抑制乳腺组织增生。结论:乳结平胶囊可通过调节雌激素水平,改善增生乳腺的病理形态变化,从而有效治疗大鼠乳腺增生。     

卵巢上皮性癌ER、PR和Ki67表达及其临床意义分析

[目的]研究ER、PR和Ki67在卵巢上皮性癌中的表达及其临床意义。[方法]用单克隆抗体、免疫组化技术测定74例原发性卵巢上皮性癌患者中ER、PR和Ki67的表达。[结果]ER、PR、Ki67的阳性表达率分别是59．5％、60．8％、74_3％，PR表达与临床分期相关。多因素分析显示PR表达、临床分期是独立的预后因素。[结论]在卵巢上皮性癌中，PR表达、临床分期具有独立的判断患者预后的价值。     

ER PR和p16联合检测在子宫内膜腺癌和宫颈腺癌鉴别诊断中的应用

目的:探讨ER,PR和p16联合免疫组化染色在子宫内膜腺癌和宫颈腺癌鉴别诊断中的价值.方法:采用免疫组化SP法染色,观察ER,PR,p16在子宫内膜腺癌和宫颈腺癌中的表达情况.结果:子宫内膜腺癌中ER,PR和p16的阳性率分别为85.29%、76.47%、23.52%;宫颈腺癌为33.33%、42.86%、80.95%,子宫内膜腺癌ER,PR的阳性率明显高于宫颈腺癌,宫颈腺癌p16的阳性率明显高于子宫内膜腺癌.在子宫内膜腺癌和宫颈腺癌中3种标记差异均有显著性(ER:x2=20.78 P＜0.005;PR:x2=8.32 P＜0.01;p16 x2=17.24 P＜0.005).结论:ER,PR,p16联合检测对鉴别子宫内膜腺癌和宫颈腺癌有一定实用价值.