多中心、随机、双盲、安慰剂对照评价普瑞巴林添加治疗部分性癫癎发作的疗效和安全性

目的 评价普瑞巴林添加治疗部分性癫（癎）发作的疗效和安全性.方法采用随机、双盲、安慰剂对照、多中心平行设计添加治疗的方法,确诊为有部分性癫（癎）发作的225例癫（癎）患者,被随机分配入普瑞巴林治疗组（114例）与安慰剂组（111例）.在6周前瞻性基线期后,采用灵活剂量的普瑞巴林（150～600 mg·d-1）添加治疗成人部分性癫（癎）发作.主要疗效指标：部分性癫（癎）发作28 d-反应率.次要疗效指标：部分性癫（癎）发作28d-减少率、临床疗效评价、16周内癫（癎）无发作和发作减少率≥50％的病例比例、第13～16周癫（癎）无发作和发作减少率≥50％的病例比例以及临床疗效总评量表评分;并观察研究药物的安全性与不良反应情况.结果 普瑞巴林组部分性癫（癎）发作28 d-反应率（-40.24±37.88）％,显著高于安慰剂组（-22.84±37.61）％（F=15.063 9,P=0.000 l）.普瑞巴林组和安慰剂组的不良事件发生率分别为60.53％和47.75％,组间无显著差异;但普瑞巴林组的不良反应发生率较安慰剂组高（45.61％ vs 23.42％,P=0.000 7）,主要不良反应有头晕、嗜睡、视物模糊、乏力等.结论 普瑞巴林组的疗效显著优于安慰剂组.普瑞巴林作为部分性癫（痈）发作的添加药物有确定的疗效,安全耐受性较好,具有一定临床应用价值.     

Oxidative stress increased hepatotoxicity induced by nano‐titanium dioxide in BRL‐3A cells and Sprague–Dawley rats

Extensive studies have shown that titanium dioxide (TiO₂) nanomaterials (NMs) can cause toxicity in vitro and in vivo under normal conditions. However, an adverse effect induced by nano‐TiO₂ in many diseased conditions, typically characterized by oxidative stress (OS), remains unknown. We investigated the toxicity of nano‐TiO₂ in rat liver cells (BRL‐3A) and Sprague–Dawley (SD) rat livers under OS conditions, which were generated using hydrogen peroxide (H₂O₂) in vitro and alloxan in vivo, respectively. In vitro results showed that cell death ratios after nano‐TiO₂ exposure were significantly enhanced (up to 2.62‐fold) in BRL‐3A cells under OS conditions, compared with normal controls. Significant interactions between OS conditions and nano‐TiO₂ resulted in the rapid G0/G1 to S phase transition and G2/M arrest, which were opposite to G0/G1 phase arrest in cells after NMs exposure only. In vivo results showed that obvious pathological changes in rat livers and the increased activities of four enzymes (i.e. aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and alkaline phosphatase) owing to liver damage after nano‐TiO₂ exposure under OS conditions, compared with their healthy controls. In addition, compared with increased hepatotoxicity after nano‐TiO₂ exposure, micro‐TiO₂ showed no adverse effects to cells and rat livers under OS conditions. Our results suggested that OS conditions synergistically increase nano‐TiO₂ induced toxicity in vitro and in vivo, indicating that the evaluation of nanotoxicity under OS conditions is essentially needed prior to various applications of NMs in foods, cosmetics and potential treatment of diseases. Copyright © 2013 John Wiley & Sons, Ltd.     

直肠腺瘤合并原发性肝脏神经内分泌癌一例

原发性肝脏神经内分泌癌(PHNEC)较罕见,临床症状、体征、超声及影像学检查均不具特异性,病理表现和免疫表型是确诊的主要依据。本例患者因直肠和肝脏特殊的影像学表现,入院初考虑直肠癌伴肝转移,后经病理和免疫组化确诊PHNEC。该病例提示我们临床工作中应警惕因经验主义引起的误诊,应重视病理学诊断结果。     

几种特殊情况下先天性心脏病的封堵治疗

目的:探讨合并有其他疾病的特殊情况下,先天性心脏病介入封堵治疗的方法。方法:回顾分析17例先天性心脏病伴有各种其他疾病的患者行介入封堵治疗的术前处理、术中注意事项和手术时机及治疗结果。结果:17例先天性心脏病患者中合并脑梗死3例、心肌梗死1例、室上性心动过速2例、先天性Ⅲ度房室传导阻滞1例、肾移植术后1例、房颤6例、慢-快综合征1例、类风湿性关节炎1例、下腔静脉异位引流1例。所有病例全部封堵成功,技术成功率为100%。除1例患者术后第4天再发脑梗死而死亡外,随访6个月内患者均无不适症状,封堵器位置良好,未出现并发症。结论:对于合并有其他疾病的先天性心脏病患者,只要认真准备,掌握最佳手术时机,介入封堵治疗同样是安全的。     

球体形成实验联合药物筛选建立耐顺铂胰腺癌干细胞株

目的 探索建立顺铂耐药人胰腺癌干细胞株,并进行初步鉴定.方法 通过球体形成实验联合顺铂药物筛选建立耐顺铂胰腺癌干细胞株;MTT法计算耐药指数;免疫荧光半定量检测OCT-4、SOX-2表达水平,检测干细胞标记物;免疫荧光半定量检测MUC-1表达水平,检测细胞分化能力;通过流式细胞仪测量侧群细胞和表面特异抗原标记（CD44＋/CD24＋）检测肿瘤干细胞含量.结果 耐顺铂干细胞株的耐药指数是亲代株PANC-1的71.5倍;干细胞标记物的免疫荧光检测发现,耐药株中OCT-4、SOX-2、MUC-1均有不同程度的表达;耐药干细胞株及亲代株SP细胞比例分别为（25.1±1.1）％和（7.8士0.9）％,差异有统计学意义（t=6.89,P＜ 0.01）;耐药株及亲代株中CD44＋/CD24＋表型的细胞亚群分别占（20.8±1.3）％和（2.4±0.8）％,差异有统计学意义（t=16.13,P＜ 0.01）.结论 球体形成实验联合顺铂药物筛选能建立耐顺铂胰腺癌细胞株,该细胞株能高效富集胰腺癌肿瘤干细胞.     

急性中耳炎中IL-27通过信号通路PI3K对肺炎链球菌清除的影响

目的 探讨白细胞介素-27（IL-27）对急性中耳炎（AOM）中肺炎链球菌的清除作用以及其对磷脂酰肌醇-3-激酶（PI3K）信号的调节作用。方法 采用肺炎链球菌感染建立急性中耳炎小鼠模型。将实验小鼠随机分为正常组、模型组、实验组、对照组。实验组在感染肺炎链球菌前12 h耳后注射200 μL的浓度为5 μg/mL的IL-27;对照组在感染肺炎链球菌前12 h耳后注射200 μL的浓度为5 μg/mL的PI3K特异性抑制剂2-（4-吗啉基）-8-苯基-4H-1-苯并吡喃-4-酮[2-（4-morpholinyl）-8-phenyl-4H-1-benzopyran-4-on,LY294002],正常组、模型组注射等剂量的生理盐水。模型组、实验组、对照组小鼠每只耳鼓膜前下方注射5 μL肺炎链球菌,正常组注射等剂量的生理盐水。在感染注射5 d后,进行听性脑干反应（ABR）测试,检测中耳灌洗液（MELF）中炎性细胞和细菌数量,ELISA测定MELF中肿瘤坏死因子α（TNF-α）、IL-6的表达,苏木精-伊红染色（HE）检测各组小鼠中耳组织的病理变化,Western blot检测各组小鼠中耳组织中磷酸化磷脂酰肌醇-3激酶（p-PI3K）、磷酸化丝/苏氨酸蛋白激酶（p-AKT）的表达。结果 与正常组相比,模型组小鼠ABR阈值、炎性细胞以及细菌数、TNF-α、IL-6以及p-PI3K、p-AKT的表达明显升高;中耳组织AOM损伤病理明显;与模型组相比,实验组和对照组小鼠ABR阈值、炎性细胞以及细菌数、TNF-α、IL-6以及p-PI3K、p-AKT的表达明显降低,中耳组织AOM损伤病理明显减轻;差异均具有统计学意义（P<0.05）。结论 在肺炎链球菌感染的急性中耳炎中,IL-27能通过抑制PI3K信号的磷酸化来调节中性粒细胞对病菌的清除。     

The human δ2 glutamate receptor gene is not mutated in patients with spinocerebellar ataxia

The human glutamate receptor delta 2 gene （GRID2） shares 90%homology with the orthologous mouse gene. The mouse Grid2 gene is involved with functions of the cerebellum and sponta-neous mutation of Grid2 leads to a spinocerebellar ataxia-like phenotype. To investigate whether such mutations occur in humans, we screened for mutations in the coding sequence of GRID2 in 24 patients with familial or sporadic spinocerebellar ataxia and in 52 normal controls. We de-tected no point mutations or insertion/deletion mutations in the 16 exons of GRID2. However, a polymorphic 4 nucleotide deletion （IVS5-121_-118 GAGT） and two single nucleotide polymor-phisms （c.1251G〉T and IVS14-63C〉G） were identiifed. The frequency of these polymorphisms was similar between spinocerebellar ataxia patients and normal controls. These data indicate that spontaneous mutations do not occur in GRID2 and that the incidence of spinocerebellar ataxia in humans is not associated with GRID2 mutation or polymorphisms.     

Risk-based,response-adapted therapy for early-stage extranodal nasal-type NK/T-cell lymphoma in the modern chemotherapy era: A China Lymphoma Collaborative Group study

We aimed to determine the survival benefits of chemotherapy (CT) added to radiotherapy (RT) in different risk groups of patients with early-stage extranodal nasal-type NK/T-cell lymphoma (ENKTCL), and to investigate the risk of postponing RT based on induction CT responses. A total of 1360 patients who received RT with or without new-regimen CT from 20 institutions were retrospectively reviewed. The patients had received RT alone, RT followed by CT (RT + CT), or CT followed by RT (CT + RT). The patients were stratified into different risk groups using the nomogram-revised risk index (NRI). A comparative study was performed using propensity score-matched (PSM) analysis. Adding new-regimen CT to RT (vs RT alone) significantly improved overall survival (OS, 73.2% vs 60.9%, P < .001) and progression-free survival (PFS, 63.5% vs 54.2%, P < .001) for intermediate-risk/high-risk patients, but not for low-risk patients. For intermediate-risk/high-risk patients, RT + CT and CT + RT resulted in non-significantly different OS (77.7% vs 72.4%; P = .290) and PFS (67.1% vs 63.1%; P = .592). For patients with complete response (CR) after induction CT, initiation of RT within or beyond three cycles of CT resulted in similar OS (78.2% vs 81.7%, P = .915) and PFS (68.2% vs 69.9%, P = .519). For patients without CR, early RT resulted in better PFS (63.4% vs 47.6%, P = .019) than late RT. Risk-based, response-adapted therapy involving early RT combined with CT is a viable, effective strategy for intermediate-risk/high-risk early-stage patients with ENKTCL in the modern treatment era.     

Performance of the Steno type 1 risk engine for cardiovascular disease prediction in Italian patients with type 1 diabetes

Background and aimsPremature cardiovascular disease cause excess mortality in type 1 diabetes (T1D). The Steno T1D Risk Engine was developed and validated in northern European countries but its validity in other populations is unknown. We evaluated the performance of the Steno T1D Risk Engine in Italian patients with T1D.Materials and methodsWe included patients with T1D with a baseline visit between July 2013 and April 2014, who were free of cardiovascular disease and had complete information to estimate risk. The estimated cardiovascular risk score was compared with the 5-year rate of cardiovascular events by means of logistic regression.ResultsAmong 223 patients (mean age 43 ± 13 years, 34.5% male, mean duration of diabetes 22 ± 12 years) the mean estimated cardiovascular risk at 5 years was 5.9% (95% C.I. 5.2–6.5%). At baseline, high estimated risk discriminated the presence of asymptomatic atherosclerosis better than microangiopathy, and was not associated with markers of inflammation or endothelial activation. After a mean follow-up of 4.7 ± 0.5 years, only 3 cardiovascular events were observed and nonetheless the risk score was significantly associated with their incidence (OR 1.22; 95% C.I. 1.08–1.39, p = 0.001). However, the observed event rate was significantly lower than the estimated one (3 vs 13; 95% C.I. 12–14; p < 0.001).ConclusionThe Steno T1D Risk Score identified subjects with subclinical atherosclerosis and high cardiovascular risk in an Italian T1D population. However, the absolute risk was significantly overestimated. Further studies in larger population are needed to confirm these results.