IL-4/STAT6在变应性鼻炎豚鼠鼻黏膜的表达及鼻用糖皮质激素对其表达的影响

目的:研究IL-4/STAT-6在变应性鼻炎豚鼠鼻黏膜的表达和丙酸氟替卡松鼻喷雾剂对其表达的影响,进一步探讨变应性鼻炎的发病机制。方法:45只豚鼠随机分为对照组(NC组)、变应性鼻炎无干预组(AR组)和变应性鼻炎糖皮质激素干预组(Glu组),每组15只。其中AR、Glu组采用卵清白蛋白致敏法制备变应性鼻炎豚鼠模型;NC组用生理盐水替代卵清白蛋白进行同步处理。动物建模后用丙酸氟替卡松鼻喷雾剂(每次50μl/侧)治疗,每天2次,连续5d。观察各组大鼠行为学改变及鼻黏膜病理学改变,免疫组织化学法检测各组豚鼠鼻黏膜中IL-4、STAT6蛋白的表达并观察其变化情况及相关性。结果:与NC组比较,AR组豚鼠喷嚏及搔鼻次数明显增加,IL-4、STAT6表达增强;与AR组比较,Glu组激素干预后豚鼠喷嚏及搔鼻次数明显减少,IL-4、STAT6表达减弱,NC组与Glu组相比结果无明显差异。结论:IL-4/STAT6在Th2分化中起关键作用,丙酸氟替卡松鼻喷雾剂干预后可以通过影响IL-4/STAT6的表达发挥治疗作用。     

CDK4和p16在喉鳞状细胞癌中的表达

目的:探讨CDK4、p16在喉鳞状细胞癌中的表达。方法:采用免疫组织化学SP法检测30例喉鳞状细胞癌组织和20例癌旁组织中CDK4和p16的表达情况,并分析二者分别与喉鳞状细胞癌临床分期和病理分级的关系。结果:在喉鳞状细胞癌中CDK4、p16的表达率分别为63.3%、46.7%,在癌旁组织中CDK4、p16的表达率分别为25%、90%。CDK4在喉鳞状细胞癌中的表达高于癌旁组织(P<0.05),与病理分级、临床分期均无显著相关性(P>0.05);p16在喉鳞状细胞癌中的表达低于癌旁组织(P<0.05),与病理分级有相关性(P<0.05),与临床分期无显著相关性(P>0.05);CDK4与p16的表达呈负相关(rs=-0.786,P<0.05)。结论:p16的低表达和CDK4的高表达可能在喉鳞状细胞癌的发生发展中起重要作用,且p16的低表达可能作为判断肿瘤恶性程度的指标。     

Exosomes with FOXP3 from gene-modified dendritic cells ameliorate the development of EAE by regulating the balance of Th/Treg

Objective: To investigate the efficiency and potential mechanisms of exosomes from dendritic cells (DCs) transfected with Forkhead box protein P3 (FOXP3) in the development of experimental autoimmune encephalomyelitis (EAE).Method: Mouse bone marrow-derived immature DCs were loaded with adenovirus carrying FOXP3 gene, and exosomes were generated. Then the exosomes with FOXP3 (FOXP3-EXOs) were co-cultured with CD4+T cell in vitro to evaluate their potential on CD4+T cell proliferation and differentiation, and injected into EAE mice to assess their effects on the development of EAE.Result: FOXP3-EXOs were effective to inhibit the CD4⁺T cell proliferation and the production of Interferon gamma (IFN-γ), interleukin (IL)-6, and IL-17, while they promoted the production of IL-10 in vitro. Moreover, FOXP3-EXOs treatment significantly decreased the neurological scores, reduced the infiltration of inflammatory cells into the spinal cord, and decreased demyelination in comparison to saline and Con-EXOs treated EAE mice. Moreover, the FOXP3-EXOs treatment resulted in obvious increases in the levels of regulatory T (Treg) cells and IL-10, whereas levels of T helper 1 (Th1) cells, Th17 cells, IFN-γ, IL-6, and IL-17 decreased significantly in the splenocyte culture of EAE mice.Conclusion: The present study preliminarily investigated the effects and potential mechanisms of FOXP3-EXOs in EAE and revealed that the FOXP3-EXOs could inhibit the production of Th1 and Th17 cells and promote the production of Treg cells as well as ameliorate the development of EAE. The neuroprotective effects of FOXP3-EXOs on EAE are likely due to the regulation of Th/Treg balance.     

术后脑梗塞

术后脑梗塞并非罕见,一旦发生患者的预后严重恶化,还易引起医患纠纷.但重要的是至今我们对此没有规范的防治方法.此文回答了常见的有关问题:术后脑梗塞的危险因素、发病率、发病机制、既往有脑血管病患者行择期手术的推荐做法和脑梗塞的早期治疗.     

替吉奥单药治疗老年晚期乳腺癌的临床疗效与安全性

目的 观察替吉奥单药治疗老年晚期乳腺癌的疗效与安全性。方法 回顾性分析老年晚期乳腺癌患者65例,研究组32例(S组)：替吉奥 40～60 mg(＜1.25 m²,40 mg; 1.25～1．5 m²,50 mg;＞1.5 m²,60 mg),于早、晚饭后口服,连服14天,21天重复。对照组33例（X组）：卡培他滨每日2000 mg/m²,分2次,连服14天,21天重复,至少2周期后评价疗效。结果 65例患者均可评价疗效, S组、X组有效率（RR）分别为31.3％(10/32)、27.3％(9/33),疾病控制率（DCR）分别为78.1％（25/32）、69.7％(23/33）,中位疾病进展时间（TTP）分别为7.5、7.0月,中位总生存时间（OS）分别为17.3、15.2月,两组比较差异无统计学意义（P＞0.05）。研究组与对照组常见的不良反应为骨髓抑制、胃肠道反应、口角炎、乏力,多见Ⅰ～Ⅱ度,可耐受,两组差异无统计学意义;对照组手足综合征明显高于研究组,差异有统计学意义（P=0.000）。 结论 替吉奥单药治疗老年乳腺癌疗效肯定,耐受性好于卡培他滨,值得临床进一步研究、推广。     

肿瘤相关巨噬细胞表型逆转的研究进展

巨噬细胞是机体固有免疫反应的重要组成成份,在不同趋化因子的作用下极化为具有不同表面标志及功能的巨噬细胞。大量研究表明,肿瘤组织中的巨噬细胞为M2型,其能够促进肿瘤生长、侵袭和转移。M2型巨噬细胞在适当的诱导下可以转换为M1型。本文将近年来从HIV-1 Nef蛋白、CD40L、双磷酸盐及CpG-DNA联合IL-10R抗体等方面对巨噬细胞表型逆转的研究做一综述。巨噬细胞的表型逆转将可能为未来肿瘤治疗提供新的策略。     

Trends in the safety of inpatient hysterectomy for benign conditions in California, 1991-2004

OBJECTIVE: To assess the utilization rates of and complications associated with inpatient hysterectomy in California between 1991 and 2004. METHODS: We used the California Patient Discharge Database to analyze International Classification of Diseases, 9th Revision, Clinical Modification diagnostic and procedure codes for 649,758 women undergoing inpatient hysterectomy in California between 1991 and 2004 using multiple logistic regression models. RESULTS: Between 1991 and 2004, the incidence of any type of inpatient hysterectomy for benign gynecologic conditions declined 17.6%. The rates of laparoscopically assisted vaginal hysterectomy and subtotal hysterectomy increased substantially. The year of hysterectomy was a factor associated with both medical and surgical complications; the odds of inpatient complications between 1991 and 2004 steadily declined. CONCLUSION: In California between 1991 and 2004, the incidence of inpatient hysterectomy for benign gynecological conditions and the adjusted odds of complications declined substantially. Changes in practice and shorter hospital stays may have affected the changes in inpatient hysterectomy rates and associated inpatient complications.     

细胞周期调控基因p21和p27单核苷酸多态性与卵巢上皮性癌的关系

目的 探讨细胞周期调控基因p21和p27的单核苷酸多态性(SNP)与卵巢上皮性癌(卵巢癌)发病风险的关系.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测234例卵巢癌患者(卵巢癌组)和284例健康妇女(对照组)p21基因C/T和p27基因V/G SNP位点基因型和等位基因的频率分布.结果 (1)对照组妇女p21基因的C/C、C/T和T/T基因型频率分别为34.2%、49.6%和16.2%,C和T等位基因频率分别为59.0%和41.0%;卵巢癌组患者3种基因型频率分别为28.2%、53.0%和18.8%,C和T等位基因频率分别为54.7%和45.3%.两组基因型频率和等位基因频率分别比较,差异均无统计学意义(P＞0.05).3种基因型频率在4种病理类型的卵巢癌中的分布有明显差异(P=0.02),C/C基因型降低子宫内膜样癌的发病风险(OR为0.56,95%CI为0.32～0.98).(2)对照组妇女p27基因V/V、V/G和G/G基因型频率分别为88.4%、10.9%租0.7%,V和G等位基因频率分别为93.8%和6.2%;卵巢癌组患者的基因型频率分别为93.6%、5.1%和1.3%,V和G等位基因频率分别为96.2%和3.8%.两组基因型频率分布比较,差异有统计学意义(P=0.04),等位基因频率分布比较,差异则无统计学意义(P=0.09).与V/G和G/G基因型比较,V/V基因型增加卵巢癌的发病风险(OR为1.92,95%CI为1.02～3.63).结论 p21基因C/T多态性的C/C基因型可能降低子宫内膜样癌的发病风险,p27基因的V/V基因型可能是卵巢癌发病的潜在危险因素.     

Decrease and dysfunction of endothelial progenitor cells in umbilical cord blood with maternal pre-eclampsia

BACKGROUND: The pre-eclampsia is characterized by placental defective angiogenesis and maternal vascular/endothelial dysfunction. Recently, the decrease and senescence of endothelial progenitor cells (EPC) has been observed in maternal circulation with pre-eclampsia. Given the essential involvement of EPC in neovascularization and reendothelialization, we investigate whether or not the depletion of EPC is existent in placental/fetal circulation with maternal pre-eclampsia. METHODS: Samples of venous cord blood were collected during the labor of preeclamptic mothers (n = 14) and normotensive controls (n = 10). Circulating EPC were enumerated as AC133+/KDR+ cells via fluorescence-activated cell sorting (FACS) analysis. Additionally, EPC were expanded in vitro and identified by DiI-acLDL uptake and lectin staining by direct fluorescent staining under a laser scanning confocal microscope. EPC proliferation, migration and vasculogenesis activities were determined by MTT, modified Boyden chamber assay and in vitro vasculogenensis assay. RESULT: The placental/fetal circulating EPC numbers were significantly decreased in the pre-eclampsia group compared with the control (median, 200; range, 100-440 cells/mL vs 390; 270-440 cells/mL, P < 0.001), and after in vitro cultivation the numbers of EPC also decreased in pre-eclampsia group (19.5; 5.0-32.0 vs 39.5; 31.2-52.0 EPC/x200 field; P < 0.001). Both circulating EPC and cultivated EPC were inversely correlated with cord blood level of soluble fms-like tyrosine kinase 1 (sFlt-1). In addition, the EPC from patients with pre-eclampsia were significantly impaired in their proliferation, migration and vasculogenesis capacities. CONCLUSION: The present study documented the decrease and dysfunction of placental/fetal circulating EPC in patients with pre-eclampsia. The alteration is probably associated with the increased sFlt-1 levels in the umbilical cord blood.