胃泌素对大鼠胃粘膜环氧合酶及生长因子表达的影响

目的：探讨胃泌素对大鼠胃粘膜环氧合酶（COX）及生长因子表达的影响。方法：雄性SD大鼠皮下注射胃泌素1 μg/kg、10 μg/kg或100 μg/kg，Western blot和免疫组化检查胃粘膜COX-1、COX-2、肝细胞生长因子（HGF）和肝素结合表皮生长因子样生长因子（HB-EGF）表达。评价胃泌素受体拮抗剂YM022对COX-1、COX-2、HGF和HB-EGF表达的影响。结果：胃泌素剂量依赖性地增加大鼠胃粘膜COX-2和HB-EGF表达，而对COX-1和HGF表达无明显影响；YM022阻断胃泌素诱导的COX-2和HB-EGF表达。 结论： 胃泌素调节大鼠胃粘膜COX-2和HB-EGF蛋白表达，提示COX-2和HB-EGF参与与胃泌素相关联的胃粘膜增生和胃癌等的发病过程。     

miR-146a-5p regulates autophagy and NLRP3 inflammasome activation in epithelial barrier damage in the in vitro cell model of ulcerative colitis through the RNF8/Notch1/mTORC1 pathway

Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon that can be influenced by microRNAs (miRNAs). This study aims to investigate the impact of miR-146a-5p on lipopolysaccharide (LPS)-induced Caco-2/HT-29 cell autophagy and NLRP3 inflammasome activation and the underlying mechanism, with the aim of identifying potential therapeutic targets. We used LPS to establish Caco-2/HT-29 cell models and measured cell viability by CCK-8. The levels of miR-146a-5p, RNF8, markers of NLRP3 inflammasome activation and autophagy, proteins involved in the Notch1/mTORC1 pathway, and inflammatory factors were assessed by RT-qPCR, Western blot, and ELISA. Intestinal epithelial barrier function was evaluated by measuring transepithelial electrical resistance. Autophagic flux was measured using tandem fluorescent-labeled LC3. miR-146a-5p was highly-expressed in LPS-induced Caco-2/HT-29 cells, and autophagy flux was blocked at the autolysosomal stage after LPS induction. Inhibition of miR-146a-5p suppressed NLRP3 inflammasome activation, reduced intestinal epithelial barrier damage, and facilitated autophagy inhibition in LPS-induced Caco-2/HT-29 cells. The autophagy inhibitor NH4Cl partially nullified the inhibitory effects of miR-146a-5p inhibition on NLRP3 inflammation activation. miR-146a-5p targeted RNF8, and silencing RNF8 partly abrogated the action of miR-146a-5p inhibition on promoting autophagy and inhibiting NLRP3 inflammasome activation. miR-146a-5p inhibition suppressed the Notch1/mTORC1 pathway activation by upregulating RNF8. Inhibition of the Notch1/mTORC1 pathway partially nullified the function of silencing RNF8 on inhibiting autophagy and bolstering NLRP3 inflammasome activation. In conclusion, miR-146a-5p inhibition may be a potential therapeutic approach for UC, as it facilitates autophagy of LPS-stimulated Caco-2/HT-29 cells, inhibits NLRP3 inflammasome activation, and reduces intestinal epithelial barrier damage by upregulating RNF8 and suppressing the Notch1/mTORC1 pathway.     

Identification of peptides presented through the MHC-II of dendritic cells stimulated with Mycobacterium avium

Mycobacterium avium (M. avium) represents a species of concern, because of its ability to modulate the host’s innate immune response, and therefore influence trajectory of adaptative immunity. Since eradicative response against mycobacteria, and M. tuberculosis/M. avium, relies on peptides actively presented on a Major Histocompatibility complex-II (MHC-II) context, we assessed paradoxical stimulation of Dendritic Cell resulting on immature immunophenotype characterized by membrane minor increase of MHC-II and CD40 despite of high expression of the pro-inflammatory tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in supernatants. Identification of M. avium leucine rich peptides forming short α-helices shutting down Type 1T helper (Th1), contribute to the understanding of immune evasion of an increasingly prevalent pathogen, and may provide a basis for future immunotherapy to infectious and non-infectious disease.     

小陷胸汤合半夏泻心汤加减治疗痰湿壅盛型老年高血压病23例

目的 观察小陷胸汤合半夏泻心汤治疗痰湿壅盛型老年高血压病的临床疗效。 方法 将46例老年高血压病患者随机分为对照组和治疗组,每组各23例。对照组接受常规西药治疗,治疗组在常规西药治疗的基础上加用小陷胸汤合半夏泻心汤加减治疗,疗程6周。观察并比较两组临床疗效及中医症状积分;治疗前后分别测定两组患者尿微量白蛋白(urinary microalbuminuria, UmAlb)水平。结果 两组降压疗效的分布比较,差异无统计学意义（P＞0.05）。与治疗前比较,两组治疗后各症状积分、中医症状总积分及UmAlb水平显著降低（P<0.05）;治疗组治疗后头如裹、胸闷、呕吐痰涎评分,中医症状总积分及UmAlb下降值显著大于对照组（P<0.05）。结论 小陷胸汤合半夏泻心汤加减联合常规西药治疗痰湿壅盛型老年高血压病疗效较好,尤其在改善头如裹、胸闷、呕吐痰涎症状和UmAlb水平方面较常规西药具有明显优势。     

Graves病患者促甲状腺激素受体抗体与肝功能指标的关系

目的 探讨Graves病患者促甲状腺激素受体抗体（TRAb）与肝功能各指标间的关系。方法 选取 2014年1月—2018年6月南京中医药大学附属医院内分泌科收治的Graves病患者231例。其中,男性53例, 女性178例。检测所有患者TRAb、甲状腺功能及肝功能指标;通过非参数检验、Logistic回归模型分析及ROC曲线,分析Graves病患者肝功能异常指标与TRAb的关联性。结果 231例患者中,有58.4%患者存在不同程度的肝功能受损;TRAb水平四分位分组后发现,随着TRAb水升高,游离三碘甲腺原氨酸（FT3）和游离甲状腺素（FT4）上升（P?<0.05）,而肝功能指标中只有碱性磷酸酶（ALP）的组间比较,差异有统计学意义 （P?<0.05）;在控制性别、年龄、FT3、FT4和其他肝功能指标后,Logistic回归模型分析结果显示,随着TRAb水平升高,血清ALP升高的相对危险度增加（P?<0.05）,TRAb水平四分位的OlR值达3.284（95% CI：1.221, 8.832）;ROC曲线分析显示,当TRAb≥11.96?IU/L时,ALP升高的危险增加。结论 TRAb水平是Graves病 患者ALP升高的影响因素。     

从肾-脾轴论治强直性脊柱炎

强直性脊柱炎（AS）是一种慢性进展性自身免疫性疾病,传统中医临床一般多从肾论治,根据现代医学的最新研究及中医生克制化理论提出肾虚督亏是AS的致病之本,脾病湿盛是发病关键,提出从肾-脾轴论治AS的治疗思路,并以温肾强督、健脾祛湿为其治疗大法,自拟基础方温肾健脾定脊汤。      

槐耳颗粒逆转肝癌细胞对索拉非尼耐药的初步研究

目的 初步探讨槐耳颗粒对索拉非尼（Sorafenib）耐药肝癌细胞BEL-7402/S的作用及其相关机制。方法 CCK-8法测定槐耳颗粒对BEL-7402/S细胞的增殖-毒性作用以及对Sorafenib的耐药逆转倍数;qPCR及Western blot法检测槐耳颗粒对BEL-7402/S细胞的缺氧诱导因子-1α（HIF-1α）及血管内皮生长因子（VEGF） mRNA和蛋白表达水平的影响。结果 槐耳颗粒能够抑制BEL-7402/S细胞的活性;在无显著细胞毒性的剂量下,槐耳颗粒能够部分逆转BEL-7402/S细胞对Sorafenib的耐药,其耐药逆转倍数为2.08;qPCR结果显示槐耳颗粒可以下调BEL-7402/S细胞中HIF-1α的mRNA水平,但对VEGF的mRNA水平无显著性影响;Western blot结果显示槐耳颗粒可以降低HIF-1α、VEGF的蛋白表达水平。结论 槐耳颗粒可能具有部分逆转BEL-7402/S细胞对Sorafenib耐药的作用,其机制可能与降低HIF-1α以及VEGF的表达水平有关。      

任青玲运用滋阴补阳序贯法治疗多囊卵巢综合征伴胰岛素抵抗

肾为天癸之源、气血之根,女子以血为主,经、孕、产、乳皆以血为用。月经来潮及其周期性演变需在心肾交济、肝脾协调的整体配合下周而复始地完成。心肾燮理阴阳,肝脾协调气血,气血阴阳调摄有度,月经周期圆运动才能节律适常。故本病的治疗以心肾为核心,辨证论治兼调四脏,使得阴平阳秘,达到调经促孕的目的。任青玲教授在补养心肾调周法的基础上提出滋阴补阳序贯法,结合卵巢局部发生胰岛素抵抗的表现是卵巢局部“痰浊”的特点,对于多囊卵巢综合征伴胰岛素抵抗的治疗强调经前期以补阳为主,常用右归饮;经后期以滋阴为要,常用滋肾生肝饮;经间期温化痰湿以治标,常用苍附导痰汤。治疗上以补肾为主,兼以化痰、疏肝、活血等方法,配合周期不同阶段用药,使治疗更具有针对性。