颈动脉内膜剥脱术后即期脑中风的病因、影响因素及治疗

对２９１例颈动脉内膜剥脱术后患者进行随访研究，１例术后即期死亡；２２例（６．３％）在术后发生脑中风，１７例为中度中风，５例为严重中风，即期中风的病因包括：１４例手术部位颈动脉血栓形成（１４／２２，６４％），４例术中或术后即期脑栓塞，２例阻断颈动脉所致脑缺血，１例脑出血，１例原因不明。此外讨论了术后中风的危险因素和处理方法。     

In vitro generation of tumor-specific cytotoxic lymphocytes. Secondary allogeneic mixed tumor lymphocyte culture of normal murine spleen cells

In vivo or in vitro immunity to murine leukemia virus (MuLV)-induced leukemia cells which do not effectively produce virus, has been difficult to demonstrate. Because immunizations with allogeneic murine leukemia cells have been used to confer syngeneic tumor immunity to virus- producing cells, we attempted to generate lymphocytes, cytotoxic to syngeneic nonproducer leukemia cells, by stimulating normal murine spleen cells with allogeneic nonproducer leukemia cells in mixed tumor lymphocyte culture (MTLC) reactions in vitro. Secondary allogeneic MTLC of normal C57BL/6 or DBA/2 spleen cells effectively produced syngeneic tumor-specific cytotoxic lymphocytes. Target cells lysed in lymphocyte- mediated cytolysis (LMC) assays, included both Friend and Rauscher virus- induced syngeneic murine leukemia cells and chemically-induced hematopoietic tumor cells. Syngeneic tumor cells were lysed regardless of whether they produced infectious MuLV or expressed viral antigens gp-71, p-30, or p-12 at the cell surface. Syngeneic normal cells (thymus, lymph node, or Concanavalin A-stimulated spleen cells) used as targets in LMC assays were uneffected by lymphocytes harvested from secondary allogeneic MTLC. Several other in vitro culture treatments including secondary syngeneic MTLC and repetitive mixed lymphocyte culture stimulations were incapable of generating tumor-specific cytotoxic lymphocytes. Based upon these results, we propose that secondary MTLC stimulation of normal spleen cells with allogeneic nonproducer leukemia cells selects for the proliferation of two subpopulations of antigen-specific cytotoxic lymphocytes. The population capable of effecting syngeneic tumor cell lysis is directed against tumor-associated cell surface antigens which may be distinct from viral structural proteins or glycoproteins. The growth of these tumor-specific cytotoxic lymphocytes may be enhanced by a soluble allogeneic effect factor produced by the proliferation of the second subpopulation of lymphocytes generated in repetitive allogeneic MTLC, namely those lymphocytes with specificities directed against differing histocompatibility antigens.     

Development of a stratum corneum and barrier function in an organotypic skin culture

The stratum corneum of human skin is responsible for maintaining the epidermal permeability barrier. We have developed a bilayered skin culture (SC) which forms a corneum 35 ± 1 cell layers thick 21 days after being raised to the air-liquid (A/L) interface. By the 7th day after raising to the A/L interface the corneocytes were irregularly shaped and had cross-sectional areas (CSA) of 300 m². By the 21st day the corneocytes had assumed polygonal shapes and had a CSA (100–250 m²) similar to that of human foreskin. The total lipid (TL) content of the corneum averaged 5–7% of the lyophilized weight. Ceramide content increased from 20% of TL at day 7 of A/L interface culture to 30% at day 21. Triglycerides decreased from 43% to 17% of TL during the same period. Free fatty acids comprised 5.5% of TL at day 21 of A/L interface culture. The intercorneocyte spaces contained stacks of lipid lamellae. However, the stacks lacked the Landmann unit repeat. Abnormal lamellar structures were observed in both the intra- and extracorneocyte spaces. Transepidermal water loss (TEWL) was >4 mg/cm² per h throughout the culture period. Lipid supplementation of the culture medium and culturing in a low humidity environment improved barrier function by 50%. However, the effects were not additive. The SC developed a near-normal corneum, but did not achieve barrier competence, due at least partially to abnormalities in lipid composition and organization. Improvement of barrier function with lipid supplementation or low humidity indicates that modifications of the culture environment may facilitate the SC in assembling a permeability barrier equivalent to human skin.     

白芍总苷治疗干燥综合征的研究进展

干燥综合征（SS）是一种慢性自身免疫性疾病,常侵犯泪腺、唾液腺等外分泌腺,同时还会造成肺、肾、消化和神经系统损害甚至累及全身器官。其病因复杂,发病机制目前尚未完全阐明。本病临床治疗为对症治疗,常用药物为免疫抑制剂,糖皮质激素等。白芍总苷辅助治疗本病可改善患者的外分泌腺功能,具有较好的临床疗效和安全性。本文从白芍总苷治疗SS的相关机制进行综述,以期为相关实验研究及临床提供更多的理论依据。     

金藤清痹颗粒治疗急性痛风性关节炎的作用机制研究

目的 应用网络药理学分析金藤清痹颗粒治疗急性痛风性关节炎（acute gouty arthritis，AGA）的作用机制，并建立AGA大鼠模型进行验证。方法 在清热解毒、活血止痛治法指导下，通过TCMSP数据库搜集金藤清痹颗粒的活性成分及靶点，利用GeneCards、NCBI数据库等搜集AGA相关靶点，与金藤清痹颗粒作用靶点整合后，构建共有靶点蛋白质-蛋白质相互作用（protein-protein interaction，PPI）网络和“金藤清痹颗粒-中药-活性成分-靶点-AGA”网络，并进行基因本体（gene ontology，GO）功能及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析。雄性SD大鼠随机分为空白组、模型组、秋水仙碱（0.3 mg/kg）组和金藤清痹颗粒低、中、高剂量（1.05、2.10、4.20 g/kg）组，每组6只，踝关节注射单钠尿酸盐（monosodium urate，MSU）晶体建立AGA大鼠模型。采用游标卡尺测量大鼠踝关节直径，计算踝关节肿胀度；采用全自动生化仪检测血清尿酸（serum uric acid，SUA）、C反应蛋白（C-reactive protein，CRP）水平；采用苏木素-伊红（HE）染色观察踝关节组织病理变化；采用qRT-PCR、ELISA和Western blotting检测踝关节组织及血清中关键靶点和信号通路的表达。结果 共检索到金藤清痹颗粒110种活性成分、212个作用靶点，272个AGA治疗靶点，共有靶点29个，关键靶点有白细胞介素-1β（interleukin-1β，IL-1β）、肿瘤坏死因子（tumor necrosis factor，TNF）及IL-6，涉及TNF信号通路、IL-17信号通路和NOD样受体信号通路等。大鼠踝关节注射MSU晶体后明显肿胀（P<0.01），SUA及CRP显著升高（P<0.05、0.01），滑膜组织增生明显、结构紊乱，有大量炎症细胞浸润，NOD样受体热蛋白结构域相关蛋白3（NOD-like receptor thermal protein domain associated protein 3，NLRP3）、NIMA相关蛋白激酶7（NIMA-related kinases 7，NEK7）、凋亡相关斑点样蛋白（apoptosis-associated speck-like protein containing a CARD，ASC）、半胱氨酸天冬氨酸蛋白酶-1（cystein-asparate protease-1，Caspase-1）、消皮素D（gasdermin D，GSDMD）、IL-18、IL-1β、IL-6及TNF-α表达水平明显升高（P<0.01）；秋水仙碱或金藤清痹颗粒治疗后，有效缓解踝关节肿胀（P<0.05、0.01），SUA及CRP均显著降低（P<0.05、0.01），关节滑膜增生、炎症细胞浸润均得到改善，同时显著抑制IL-1β、TNF-α及IL-6等靶点和NOD样受体信号通路的表达（P<0.05、0.01）。结论 金藤清痹颗粒对AGA大鼠具有明显的保护作用，其机制可能与抑制NOD样受体信号通路的异常激活，降低炎症因子水平，改善关节滑膜增生、炎症细胞浸润有关。     

The erroneous perception of a clinical sign: Cholestasis preceding sepsis mimicking hepatitis in an adolescent patient

Jaundice should be considered as a first clinical sign preceding severe invasive bacterial infection or sepsis in patients of all ages including childhood and adolescence. Early laboratory investigations and MR imaging studies for osteomyelitis or myositis are paramount to avoid progression to life‐threatening sepsis and significant morbidity and mortality.     

生物碱类天然药物抗痛风作用及作用机制的研究进展

痛风是由于机体嘌呤代谢异常和(或)尿酸排泄障碍所致的一组异质性疾病。生物碱是一类含有氮的有机化合物,广泛存在于植物中,用于痛风等多种疾病引起的炎症反应。通过查阅国内外最新相关文献报道,对生物碱抗痛风作用及作用机制的研究进展进行综述,以期为生物碱的进一步研究和临床应用提供科学依据和理论指导。