生存素蛋白在非小细胞肺癌中的表达及与MVD的关系

目的 探讨生存素蛋白在不同临床病理特征的非小细胞肺癌(NSCIC)组织中的表达情况及与肿瘤微血管密度(MVD)间的关系.方法 采用链霉素抗生物素过氧化酶(S-P)法检测66例 NSCLC组织和20例肺良性肿瘤组织中生存素及CD34表达情况.结果 NSCLC组织中生存素阳性表达率54.5%,显著高于肺良性肿瘤组织中的阳性表达率30%(P＜0.05);在腺癌组织中阳性表达率63.6%,在鳞癌组织中阳性表达率为54.5%,差异无统计学意义(P＞0.05);在中-高分化、低分化鳞癌组织中阳性表达率分别为44.0%、87.5%,在中-高分化、低分化腺癌组织中阳性表达率分别为41.2%、87.5%,差异均有统计学意义(P＜0.05);在淋巴结转移组的肺癌组织中阳性表达率为74.1%,显著高于无淋巴结转移组中的阳性表达率48.7%(P＜0.05);生存素阳性组MVD值(45.55±9.05)显著高于生存素阴性组MVD值(38.21±8.71)(P＜0.05).结论 生存素表达与肺癌分化程度密切相关,与有无淋巴结转移密切相关,揭示了生存素可以作为判断病情和评价预后的指标,生存素表达与MVD呈正相关,推测其可能具有促进肿瘤血管生成的作用.     

阿司匹林滴眼液防治糖尿病性白内障

目的:探讨阿司匹林滴眼液抑制糖尿病性白内障的作用效果及作用机制.方法:复制链脲佐菌素(streptozocin, STZ)糖尿病大鼠模型,成模后(血糖＞14 mmol/L)将动物分为低浓度阿司匹林治疗组(0.5 g/L)、高浓度阿司匹林治疗组(1 g/L)和未治疗组.治疗组每日给予2次阿司匹林滴眼液治疗左眼,采用裂隙显微镜观察并记录晶状体混浊的程度,使用分光光度计测定晶状体中谷胱甘肽、糖基化终末产物(advanced glycation end product, AGE)的含量以及谷胱甘肽还原酶、过氧化氢酶的活性.结果:建立糖尿病大鼠模型后6至9 wk,与糖尿病大鼠相比,治疗组大鼠晶状体混浊程度降低0.5～1个级别,谷胱甘肽的含量升高20%,过氧化氢酶的活性增强260%,而AGE的含量降低28%,它们之间差异均具有统计学意义(P＜0.05).结论:阿司匹林可能通过抑制晶状体蛋白质糖基化和氧化损伤的综合作用,延缓早期的糖尿病大鼠晶状体混浊.     

Characterization,quantification, and localization of passenger T lymphocytes and NK cells in human liver before transplantation

Quantification and localization of the main lymphocyte populations were studied in the livers of normal (n=8) and brain dead (n=8) subjects. Cytometric analysis performed on mononuclear cell suspensions obtained from liver biopsies was compared to an automatic image analysis of immunostained sections. The overall number of liver associated lymphocytes was in the usual range of peripheral blood content (2 to 9 · 10⁹ cells). Phenotypic analysis showed predominant NK and CD8+ cells that highly expressed class II antigen and CD25 and CD69 activation markers. Quantitative mapping of these activated lymphocytes revealed their preferential localization in the portal tract and the perisinusoidal area as compared to the pericentrolobular zone, especially in donor livers. This strategic localization could suggest a possible early cooperation between donor lymphocytes and initial infiltrating cells from the recipient and could explain the special immunological status of allografted livers.     

肝细胞生长因子基因转染骨髓间充质干细胞对脂肪颗粒移植存活率的影响

目的研究携带人肝细胞生长因子基因的重组腺病毒（Ad—HGF）修饰骨髓间充质干细胞（MSCs）对大鼠脂肪颗粒移植存活率的影响。方法用携带绿色荧光蛋白的重组腺病毒（Ad-GFP）、Ad—HGF转染雄性Wistar大鼠MSCs,测定转染效率与感染上清中肝细胞生长因子（HGF）的表达。用雌性Wistar大鼠150只,随机分为5组：空白对照组（A组）、Ad—HGF组（B组）、MSCs组（C组）、Ad—GFP感染MSCs组（D组）和Ad—HGF感染MSCs组（E组）,每组30只。各组均匀振动5分钟,将颗粒脂肪移植于自体背部皮下;移植后3、5、7、14、28、60d,每组各取5只大鼠脱颈处死,取出移植物;测体积、HE、Masson染色观察病理改变,免疫组织化学法测定组织中HGF表达和血管生成。结果积分吸光度＝100时,Ad—GFP转染MSCs效率可达89．6％;移植后3、5、7、14d,E组移植物中HGF的表达高于其他各组（P〈0．05）;移植后5、7、14、28、60d,E组血管数量也多于其他各组（P〈0．05）;28d和60d时,E组脂肪颗粒体积保持率明显好于其他4组（P〈0．05）。结论携带HGF基因的MSCs在移植物中能够持续表达HGF,有效地减少脂肪颗粒移植后的吸收,从而提高移植颗粒脂肪的存活率。     

Clinicopathological risk factors of Stage II colon cancer: results of a prospective study

Aim Adjuvant 5‐fluorouracil based chemotherapy has demonstrated benefit in Stage III colon cancer but still remains controversial in Stage II. The aim of this study was to analyse the prognostic impact of clinicopathological factors that may help guide treatment decisions in Stage II colon cancer. Method Between 1996 and 2006 data from patients diagnosed with colorectal cancer at Hospital Universitari Bellvitge and its referral comprehensive cancer centre Institut Català d′Oncologia/L’Hospitalet were prospectively included in a database. We identified 432 patients with Stage II colon cancer operated on at Hospital Universitari Bellvitge. The 5‐year relapse‐free survival (RFS) and colon‐cancer‐specific survival (CCSS) were determined. Results The 5‐year RFS and CCSS were 83% and 88%, respectively. Lymphovascular or perineural invasion was associated with RFS [hazard ratio (HR) 1.84; 95% CI 1.01–3.35]. Gender (women, HR 0.48; 95% CI 0.23–1) and lymphovascular or perineural invasion (HR 3.51; 95% CI 1.86–6.64) together with pT4 (HR 2.79; 95% CI 1.44–5.41) influenced CCSS. In multivariate analysis pT4 and lymphovascular or perineural invasion remained significantly associated with CCSS. We performed a risk index with these factors with prognostic impact. Patients with pT4 tumours and lymphovascular or perineural invasion had a 5‐year CCSS of 61%vs the 93% (HR 5.87; 95 CI 2.46–13.97) of those without any of these factors. Conclusion pT4 and lymphatic, venous or perineural invasion are confirmed as significant prognostic factors in Stage II colon cancer and should be taken into account in the clinical validation process of new molecular prognostic factors.     

强骨丹对去卵巢大鼠骨质疏松症防治作用的实验研究

[目的]探讨中药强骨丹对绝经后骨质疏松症的防治作用。[方法]运用切除大鼠卵巢方法建立去卵巢骨质疏松症模型,随机分为模型组、强骨丹高低剂量组、西药组,同时设假手术对照组。采用双能X线骨密度测定法、放射免疫分析法和ELISA法等检测各组实验鼠骨密度 (BMD)、骨矿含量 (BMC)、血清雌二醇 (E₂)、骨钙素 (BGP)、抗酒石酸酸性磷酸酶5b(TRACP5b)以及尿脱氧吡啶啉 (Dpol)。[结果]强骨丹可明显升高BMD、BMC,提高血清E₂ 水平,降低TRACP5b和Dpd水平,并降低BGP含量。[结论]强骨丹通过调节机体相关内分泌功能,抑制骨吸收,降低骨的转换率,减少骨丢失,增加骨密度,对绝经后骨质疏松症有防治作用。     

Pharmacometabonomic association of cyclophosphamide 4‐hydroxylation in hematopoietic cell transplant recipients

The widely used alkylating agent cyclophosphamide (CY) has substantive interpatient variability in the area under the curve (AUC) of it and its metabolites. Numerous factors may influence the drug‐metabolizing enzymes that metabolize CY to 4‐hydroxycyclophosphamide (4HCY), the principal precursor to CY’s cytotoxic metabolite. We sought to identify endogenous metabolomics compounds (EMCs) associated with 4HCY formation clearance (ratio of 4HCY/CY AUC) using global metabolomics. Patients who undergo hematopoietic cell transplantation receiving post‐transplant CY (PT‐CY) were enrolled, cohort 1 (n = 26) and cohort 2 (n = 25) donating longitudinal blood samples before they started HCT (pre‐HCT), before infusion of the donor allograft (pre‐graft), before the first dose of PT‐CY (pre‐CY), and 24 h after the first dose of PT‐CY (24‐h post‐CY), which is also immediately before the second dose of CY. A total of 512 and 498 EMCs were quantitated in two cohorts, respectively. Both univariate linear regression with false discovery rate (FDR), and pathway enrichment analyses using a global association test were performed. At the pre‐CY time point, no EMCs were associated at FDR less than 0.1. At pre‐HCT, cohort 1 had one EMC (levoglucosan) survive the FDR threshold. At pre‐graft, cohort 1 and cohort 2 had 20 and 13 EMCs, respectively, exhibiting unadjusted p values less than 0.05, with the only EMCs having an FDR less than 0.1 being two unknown EMCs. At 24‐h post‐CY, there were three EMCs, two ketones, and threitol, at FDR less than 0.1 in cohort 2. These results demonstrate the potential of pharmacometabonomics, but future studies in larger samples are needed to optimize CY.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

We report the first pharmacometabonomic study of the association of plasma EMCs with cyclophosphamide pharmacokinetics, specifically the ratio of 4HCY/CY AUC.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study addresses the question regarding if EMCs in the plasma before PT‐CY administration are associated with the ratio of 4HCY/CY AUC.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study adds to our knowledge that longitudinal collection of plasma EMC samples is feasible in HCT patients receiving PT‐CY. In addition, the plasma EMC changes over the ~21‐day time period that starts pre‐HCT to 24‐hr after the first PT‐CY dose.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

This study demonstrates the possibility of pharmacometabolomic research to evaluate the pharmacokinetics of a drug – in this case, cyclophosphamide – with a complex pharmacokinetic disposition.     

非酒精性脂肪性肝病合并多囊卵巢综合征的相关性研究

目的调查多囊卵巢综合征（PCOS）患者非酒精性脂肪性肝病（NAFLD）的发病情况,探讨NAFLD与PCOS患者代谢特征的相关性。方法选择PCOS组145例及对照组122例为研究对象,测定血清空腹血糖（FBG）、餐后2h血糖、空腹胰岛素（FINS）、餐后2h胰岛素、总甘油三酯（TG）、总胆固醇（Chol）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、谷丙转氨酶（ALT）、谷草转氨酶（AST）,以超声诊断脂肪肝。结果 PCOS组NAFLD的发生率明显高于对照组,差异有统计学意义（P〈0.01）;PCOS组的ALT、餐后2h INS、HOMA-IR高于对照组,差异有统计学意义（P〈0.01）。PCOS患者伴与不伴NAFLD组比较,NAFLD组的ALT、餐后2h INS、BMI、FINS、HO-MA-IR、TG明显高于非NAFLD组,差异有统计学意义（P〈0.05）;NAFLD的发生率与ALT、餐后2 h INS、BMI、FINS、HOMA-IR呈正相关。结论 PCOS患者易患NAFLD,对肥胖及胰岛素抵抗的PCOS患者应常规进行转氨酶及肝脏超声检查。     

Efectividad y seguridad de la terapia de rescate en pacientes VIH

IntroductionThe treatment used after failure of at least two lines of antiretroviral treatment in HIV patients is called salvage therapy. The study aims to describe the characteristics of HIV patients subjected to such a regimen, and determine the safety and effectiveness of treatment with tipranavir (TPV), darunavir (DRV), enfuvirtide (ENF) and etravirine (ETR) combined with an optimised antiretroviral regimen.Patients and methodsHIV patients treated with ENF, TPV, DRV or ETR in a tertiary hospital infectious diseases department subjected to at least 12 weeks treatment. The patient characteristics are described and the effectiveness, durability and adherence to the treatment analysed.ResultsThere were 28 patients studied, with an average of 10 treatment regimens prior to starting salvage therapy (SD = 3.5; 95 % CI, 8.9-11.1). A total of 85.7 % patients had treatment adherence > 90 %. For ENF, 70.8 % of the treatment lines were suspended during follow-up. After salvage therapy, the percentage of patients with viral load (VL) < 400 copies/ml doubled, and cases with undetectable CV (< 50 copies/ml) almost tripled. The treatments used did not change the liver or kidney profiles; however, they changed the lipid profile and increased the percentage of patients with hyperglycaemia.ConclusionsThe salvage therapy studied was effective. Good adherence to the therapy is critical for its effectiveness.