Autophagy inhibition sensitizes WYE-354-induced anti-colon cancer activity in vitro and in vivo

Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and mTORC2 are frequently dysregulated in human colon cancers. In the present study, we evaluated the potential anti-colon cancer cell activity by a novel mTORC1/2 dual inhibitor WYE-354. We showed that WYE-354 was anti-survival and anti-proliferative when adding to primary (patient-derived) and established (HCT-116, HT-29, Caco-2, LoVo, and DLD-1 lines) colon cancer cells. In addition, WYE-354 treatment activated caspase-dependent apoptosis in the colon cancer cells. Mechanistically, WYE-354 blocked mTORC1 and mTORC2 activation. Meanwhile, it also induced autophagy activation in the colon cancer cells. Autophagy inhibitors (bafilomycin A1 and 3-methyladenine), or shRNA-mediated knockdown of autophagy elements (Beclin-1 and ATG-5), remarkably sensitized WYE-354-mediated anti-colon cancer cell activity in vitro. Further studies showed that WYE-354 administration inhibited HT-29 xenograft growth in severe combined immunodeficient (SCID) mice. Importantly, its activity in vivo was further potentiated with co-administration of the autophagy inhibitor 3-MA. Phosphorylations of Akt (Ser-473) and S6 were also decreased in WYE-354-treated HT-29 xenografts. Together, these pre-clinical results demonstrate the potent anti-colon cancer cell activity by WYE-354, and its activity may be further augmented with autophagy inhibition.     

Right Ventricular Remodeling after Transcatheter Closure of Atrial Septal Defect

Background: Right ventricular (RV) volume overload is a well‐known cardiac consequence of atrial septal defect (ASD) shunt, accounting for most of its long‐term complications. Thus cardiac volumetric unloading is a major aim of transcatheter ASD closure. We set to study the right ventricular remodeling after transcatheter ASD closure in patients with secundum ASD. Methods: We enrolled 46 patients who underwent successful transcatheter closure of ASD. We performed routine transthoracic echocardiographic studies, including three‐dimensional echocardiography and right ventricular myocardial performance index (RVMPI), before transcatheter ASD closure, and 3 days, 1 month after transcatheter ASD closure. Results: We found that: (1) the right ventricular end‐diastolic volume (RVEDV) and right ventricular end‐systolic volume (RVESV) (respectively 106.54±25.97 vs 69.78±10.46 mL, P < 0.05; 59.73±17.59 vs 33.84±7.18 mL, P < 0.05) were enlarged in patients with ASD compared with those in control subjects, resulting in a marked decrease of the right ventricular ejection fraction (RVEF) (44.82%±4.51% vs 54.11%±5.89%, P < 0.05) from normal values; (2) the isovolumic relaxation and isovolumic contraction times (respectively [77.61±16.49] ms vs (64.09±11.82) ms, P < 0.05; [28.04±9.57] ms vs [20.45±6.53] ms, P < 0.05) were prolonged and ejection time ([250.02±24.21] ms vs [272.73±20.51] ms, P < 0.05) was shortened in patients with ASD compared with that in control subjects, resulting in a marked increase of the MPI (0.41±0.07 vs 0.31±0.05, P < 0.05) from normal values; and (3) after transcatheter closure, the RVEDV and RVESV decreased and the RVEF increased markedly and RVMPI decreased markedly. Conclusions: Transcatheter closure of ASD results in rapid normalization of RV volume overload and improvement of RV function. (ECHOCARDIOGRAPHY, Volume 26, November 2009)     

慢性阻塞性肺疾病社区综合管理研究进展

慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）是一种以不完全可逆的气流受限为特征的疾病，本病具有明显的肺外效应，在不同的患者影响其疾病严重程度。COPD是全球范围内慢性病发病和死亡的重要原因，社会经济负担重。由于其患病率高，知晓率、治疗率、控制率低，已成为一个重要的公共卫生问题。近年来，COPD的社区治疗越来越受关注。研究表明，系统的社区综合管理对COPD患者非常有益。本文就COPD社区综合管理进展进行综述。     

三株大肠杆菌在低营养水中菌密度变化的比较

目的：探讨3株大肠杆菌在4种温度下于低营养水体中菌密度随保存时间变化的规律性及其对实际工作的意义。方法：选用大肠杆菌标准株ATCC25922、8099及从人类粪便分离的野生型大肠杆菌，分别配制成一定菌密度的模拟水样，置于恒温水浴箱中，控温在5，15，25，35℃4个水平，以滤膜荧光法定量检测其菌密度的变化。结果：大肠杆菌在低营养水中不繁殖，菌密度随时间的变化在不同温度下均呈负指数函数关系，y=ae^-bt，在相同温度条件下，ATCC25922菌密度下降最快，野生株次之，8099株最慢，不同温度下其规律为35℃下降最快，25℃次之，15℃最慢。结论：不同菌株大肠杆菌在低营养水体中的菌密度变化各不相同，与菌体、环境温度以及保存时间关系密切。     

煤烟对大鼠肺细胞氧化性损伤作用途径的探讨

目的：探讨煤烟导致肺Ⅱ型细胞氧化性损伤的途径，方法：通过对加入抗氧化剂N－乙酰半胱氨酸、维生素E、维生素C和甘露醇作为实验干预手段，采用MTT法观察其对煤烟所致大鼠肺Ⅱ型细胞毒性的影响，结果：与对照组相比，加入10mmol/L N-乙酰半胱氨酸，维生素E，维生素C后的实验组细胞毒性有所下降，而甘露醇没有观察到类似的作用。结论：煤烟可以通过产生氧自由基或脂质过氧化物等多种途径对机体造成氧化性损伤。     

口服果汁后MRCP评价胰管形态学的临床研究

目的　评价口服果汁后MRCP对胰管成像的价值。 资料与方法　31例受试者口服果汁前后分别行MR-CP检查,评价胰管各部分显示情况和直径,胰管最佳显示时间,以及胃肠道重叠干扰情况。 结果　所有受试者口服果汁后胰管各部分显示情况及平均直径均比口服前显著提高,口服后胰管最佳显示时间为(55.75±15.65) min,胃肠道内液体重叠干扰最明显的时间是(43.88±17.12) min。 结论　口服果汁后MRCP可显著提高胰管显示情况,胰管显示最佳时间为口服后60 min。     

Perfluorononanoic acid-induced apoptosis in rat spleen involves oxidative stress and the activation of caspase-independent death pathway

Perfluoroalkyl acid (PFAA)-induced apoptosis has been reported in many cell types. However, minimal information on its mode of action is available. This study explored the possible involvement of apoptotic signaling pathways in a nine-carbon-chain length PFAA–perfluorononanoic acid (PFNA)-induced splenocyte apoptosis. After a 14-day exposure to PFNA, rat spleens showed dose-dependent levels of apoptosis. The production of pro-inflammatory and anti-inflammatory cytokines was significantly increased and decreased, respectively. However, protein levels of tumor necrosis factor receptor 1 (TNFR1), fas-associated protein with death domain (FADD), caspase 8 and caspase 3, which are involved in inflammation-related and caspase-dependent apoptosis, were discordant. Peroxisome proliferator-activated receptors alpha (PPARα) and PPARγ genes expression was up-regulated in rats treated with 3 or 5 mg/kg/day of PFNA, and the level of hydrogen peroxide (H₂O₂) increased concurrently in rats treated with the highest dose. Moreover, superoxide dismutase (SOD) activity and Bcl-2 protein levels were dramatically decreased in spleens after treatment with 3 and 5 mg/kg/day of PFNA. However, protein levels of Bax were unchanged. Apoptosis-inducing factor (AIF), an initiator of caspase-independent apoptosis, was significantly increased in all PFNA-dosed rats. Thus, oxidative stress and the activation of a caspase-independent apoptotic signaling pathway contributed to PFNA-induced apoptosis in rat splenocytes.     

Filling paste extruded from primary root canal remains for extended period: Two case reports

We examined 2 patients with filling material extruded from root canals of their primary teeth that remained for a long time. In Case 1, 3 separate small radiopaque masses were initially identified below the mandibular right second primary molar at the age of 7 years 6 months old and the patient was followed for approximately 7 years. The permanent successor was congenitally absent and the radiodensity of the masses decreased as the patient matured, though they were still apparent 7 years later. In Case 2, a large radiopaque mass was detected in the crown region of the permanent central incisor of a patient aged 5 years 2 months old, which had come from the root canal of the corresponding primary tooth that had been filled with iodoform calcium hydroxide paste. The radiopaque filling material in the root canal and the large mass seen superimposed on the crown of the permanent successor had apparently become separated. The mass became smaller and nearly disappeared 1 year 6 months later. In both cases, the root canal filling materials were speculated to have been extruded from the root apex. Differences in features of the radiopaque masses are discussed in this report.     

胆管癌围手术期死亡因素分析

目的探讨影响胆管癌围手术期死亡的危险因素。方法对62例胆管癌手术患者的临床资料进行回顾性研究。用Logistic回归法分析影响围手术期死亡的危险因素。对每一指标行单因素分析，筛选出P〈0．1的自变量方可进入多因素分析。结果单因素分析显示影响围手术期死亡的可能因素有7个，即年龄、术前总胆红素、γ-GT、白（清）蛋白、肝功能分级、肿瘤分期、术前合并症；多因素分析显示显著影响围手术期死亡的危险因素有3个，按影响大小依次为年龄、肿瘤分期和γ-GT。结论高龄、高1-GT水平和肿瘤分期晚增加胆管癌围手术期死亡的风险。