结肠镜引导下腹腔镜治疗大肠疾病的动物试验及临床应用研究

目的探索在结肠镜引导下应用腹腔镜对某些大肠疾病进行手术的可行性。方法利用家猪实施结肠镜引导，定位后进行腹腔镜下大肠部分切除的操作训练。在此基础上于2002年10月-2003年12月对12例大肠良性肿瘤患者行大肠部分切除术。结果手术全部成功。手术时间在40—120分钟，平均80分钟。术中出血10-100毫升，平均55毫升。术后1—3天肠蠕动恢复，平均1．5天。术后无出血、吻合口漏、尿潴留等并发症。术后住院4—6天，平均5天，全部随访3—6个月。均无复发。结论在结肠镜引导、定位后行腹腔镜大肠部分切除安全可行。关键是要求手术者能熟练掌握腹腔镜手术技术和丰富的开腹大肠手术经验；同时需要内镜医生的大力配合。     

Efficient nuclear drug translocation and improved drug efficacy mediated by acidity-responsive boronate-linked dextran/cholesterol nanoassembly

The present study reported a lysosome-acidity-targeting bio-responsive nanovehicle self-assembled from dextran (Dex) and phenylboronic acid modified cholesterol (Chol-PBA), aiming at the nucleus-tropic drug delivery. The prominent advantage of this assembled nanoconstruction arose from its susceptibility to acidity-labile dissociation concurrently accompanied with the fast liberation of encapsulated drugs, leading to efficient nuclear drug translocation and consequently favorable drug efficacy. By elaborately exploiting NH₄Cl pretreatment to interfere with the cellular endosomal acidification progression, this study clearly evidenced at a cellular level the strong lysosomal-acidity dependency of nuclear drug uptake efficiency, which was shown to be the main factor influencing the drug efficacy. The boronate-linked nanoassembly displayed nearly no cytotoxicity and can remain structural stability under the simulated physiological conditions including 10% serum and the normal blood sugar concentration. The cellular exposure to cholesterol was found to bate the cellular uptake of nanoassembly in a dose-dependent manner, suggesting a cholesterol-associated mechanism of the intracellular internalization. The in vivo antitumor assessment in xenograft mouse models revealed the significant superiority of DOX-loaded Dex/Chol-PBA nanoassembly over the controls including free DOX and the DOX-loaded non-sensitive Dex-Chol, as reflected by the more effective tumor-growth inhibition and the better systematic safety. In terms of the convenient preparation, sensitive response to lysosomal acidity and efficient nuclear drug translocation, Dex/Chol-PBA nanoassembly derived from natural materials shows promising potentials as the nanovehicle for nucleus-tropic drug delivery especially for antitumor agents. More attractively, this study offers a deeper insight into the mechanism concerning the contribution of acidity-responsive delivery to the enhanced chemotherapy performance.     

Common Mechanism of Pathogenesis in Gastrointestinal Diseases Implied by Consistent Efficacy of Single Chinese Medicine Formula: A PRISMA-Compliant Systematic Review and Meta-Analysis

Gastrointestinal (GI) disorders often manifest similar symptoms with overlapping clinical diagnosis and unmet medical needs. Traditional Chinese medicine (TCM) has history-proven benefits for GI diseases; albeit language barrier prevents Western readers from accessing the original reports in Chinese. The TCM formula Si-Ni-San (SNS) consists of 4 herbs targeting on homeostatic disturbances characterized by “reflux” and “irritable” problems. Here we used SNS as a therapeutic tool to explore the common mechanisms of pathogenesis in non-neoplastic GI diseases.Data sources from PUBMED, Chinese National Knowledge Infrastructure, and Wanfang databases were searched for clinical trials. Comparisons were SNS as intervention and Western conventional medicine as control, which treat patients with upper GI disorders (gastroesophageal reflux disease, peptic ulcer, chronic gastritis, duodenogastric reflux), lower GI diseases (irritable bowel syndrome, ulcerative colitis), and functional dyspepsia. Participants and studies in accordance with the Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement were eligible. We used the Jadad scale to assess methodological qualities, the fixed or random-effect model to evaluate therapeutic efficacy, and the funnel plots to explore publication bias. Outcome was clinical efficacy defined by symptom relief with normal GI endoscopy, radiology, and pathology.We included 83 studies involving 7762 participants: 1708 versus 1397 of the upper GI disorders in 34 studies, 901 versus 768 of the lower GI diseases in 19 studies, 1641 versus 1348 of functional dyspepsia in 30 studies, and 328 versus 287 of relapse rate in 8 studies. Six studies had a Jadad score >2 points and the rest were <2 points. Pooled data showed significant efficacy of SNS for the upper GI disorders (odds ratio [OR] = 3.9, 95% confidence interval [CI] = 3.09–4.92), lower GI diseases (OR = 4.91, 95% CI = 3.71–6.51), and functional dyspepsia (N = 2989; OR = 3.94, 95% CI = 3.17–4.90). The relapse rate was 12.9% for SNS, significantly <46.5% for conventional therapies (OR = 0.16, 95% CI = 0.11–0.25).The consistent efficacy of the single TCM formula implicates common mechanisms of pathogenesis in GI disorders.     

金芪降糖片组分体外抗糖尿病的作用及机制

目的:探讨金芪降糖片各组分体外抗糖尿病的作用及机制。方法:采用DPPH自由基清除,活性氧自由基清除,AGEs形成抑制,α-糖苷酶抑制,醛糖还原酶抑制,脂肪酶抑制,脂多糖(LPS)诱发小鼠腹腔巨噬细胞活化一氧化氮(NO)释放抑制建立系统的体外抗糖尿病活性评价筛选模型,考察金芪降糖片的4个标准组分芪总黄酮、黄芪总皂苷、金银花总有机酸、黄连总生物碱对以上各模型的作用。结果:黄芪总黄酮、金银花总有机酸、黄连总生物碱具有清除DPPH自由基和活性氧自由基活性;各组分对AGEs形成无明显抑制活性;黄芪总黄酮、金银花总有机酸对糖苷酶有抑制活性;黄芪总黄酮、黄芪总皂苷、金银花总有机酸对醛糖还原酶有抑制活性;黄芪总黄酮、黄芪总皂苷、金银花总有机酸对胰脂肪酶具有抑制活性;黄芪总皂苷、黄连总生物碱对LPS诱导的小鼠腹腔巨噬细胞释放NO有抑制作用。结论:金芪降糖片具有多组分多靶点协同抗糖尿病的作用,机制涉及抑制α-糖苷酶、抑制脂肪酶、清除自由基、抑制醛糖还原酶、抑制NO释放。     

甲氨蝶呤联合来氟米特治疗中医不同证型类风湿关节炎疗效比较研究

【目的】观察甲氨蝶呤（methotrexate,MTX）联合来氟米特（1eflunomide,LEF）治疗中医不同证型类风湿关节炎（rheumatoidarthritis,RA）的疗效有无差异。【方法】选取175例中重度RA患者,按照中医辨证标准分为湿热痹阻证、寒湿痹阻证、寒热错杂证、痰瘀互结证、肝肾亏虚证5个证型组,采用MTX联合LEF口服治疗,疗程12周,观察基线时和治疗12周后肿胀关节数、压痛关节数、晨僵时间、患者疼痛评分（VAS）、红细胞沉降率（ESR）、类风湿因子（RF）、C反应蛋白（CRP）,计算DAS28评分,并观察ACR20、ACR50和ACR70的变化情况及不良反应,进行统计分析。【结果】与本组基线值比较,各组治疗12周后肿胀关节数、压痛关节数均减少,VAS、ESR、RF、CRP均降低,差异有统计学意义（P〈0．05）;除痰瘀互结证、肝肾亏虚证组外,其余各组关节晨僵时间均缩短,差异有统计学意义（P〈0．05）。湿热痹阻证、寒湿痹阻证、寒热错杂证组治疗后肿胀关节数、压痛关节数、晨僵时间、VAS、RF的改善情况及DAS28有效应答率、ACR20、ACR50、ACR70改善率均优于痰瘀互结证和肝。肾亏虚证组（P〈0．05）,各组不良反应比较无差异（P〉0．05）。【结论】MTX联合LEF治疗中重度RA疗效确切,无明显不良反应,湿热痹阻证、寒湿痹阻证、寒热错杂证疗效优于痰瘀互结证和肝’肾亏虚证。     

恩替卡韦联合扶正化瘀胶囊治疗慢性乙型肝炎肝纤维化临床观察

目的观察比较恩替卡韦分散片单用与联合扶正化瘀胶囊两种方法对乙型肝炎肝纤维化的疗效。方法60例乙型肝炎肝硬化患者随机分为两组,各30例,A组单独接受恩替卡韦分散片治疗,B组接受恩替卡韦分散片治疗的同时联合扶正化瘀胶囊抗病毒药物治疗,两组在护肝治疗上亦相同。结果 A组治疗前透明质酸（HA）、Ⅲ型前胶原（PCⅢ）、层粘连蛋白（LN）分别为（253.8±50.2）、（245.3±63.2）、（153.8±54.2）ng/L,B组治疗前HA、PCⅢ、LN分别为（248.8±47.2）、（257.3±74.2）、（154.3±53.2）ng/L,两组比较差异无统计学意义（P〉0.05）;A组治疗后HA、PCⅢ、LN分别为（136.8±41.2）、（146.5±44.2）、（123.4±23.4）ng/L,B组治疗后HA、PCⅢ、LN分别为（101.4±33.2）、（108.4±38.8）、（78.4±12.9）ng/L,两组比较差异有统计学意义（P〈0.05）;A组的HBV-DNA阴转率为90.0%,B组的HBV-DNA阴转率为93.0%,两组比较差异无统计学意义（P〉0.05）。结论恩替卡韦分散片联合扶正化瘀胶囊治疗肝纤维化疗效优于单药恩替卡韦分散片治疗。     

痹痛康丸对胶原性关节炎大鼠IL-1β的影响

【目的】观察痹痛康丸对胶原性关节炎(Collagen-induced Arthritis,CIA)大鼠踝关节滑膜白细胞介素1β(IL-1β)的影响,探讨其治疗作用机制。【方法】建立II型胶原加完全弗氏佐剂诱导的大鼠CIA模型,70只Wistar大鼠随机分为7组,分别为痹痛康丸低、中、高剂量组[0.3、3、30 g.(kg.d)-1],尪痹冲剂组3.g(kg.d)-1,甲氨蝶呤片组1.2 mg.(kg.w)-1,以上各组药物溶解于2 ml生理盐水中,1次/d,连续灌胃给药4周。空白对照组及模型组灌服生理盐水2 ml/只。8周后处死大鼠,观察右踝关节滑膜病理改变情况及关节滑膜中IL-1β蛋白表达量的变化。【结果】各用药组除痹痛康丸低剂量组外滑膜组织的病理改变均有不同程度的减轻,IL-1β蛋白的表达量较模型组降低(P<0.05)。【结论】痹痛康丸能有效降低CIA大鼠滑膜炎程度,防止骨破坏或关节重构,有免疫调节作用。