RETRACTED: Resibufogenin suppresses growth and metastasis through inducing caspase-1-dependent pyroptosis via ROS-mediated NF-κB suppression in non-small cell lung cancer

The purpose of this study is to explore the antitumor properties of resibufogenin (RB) in non-small cell lung cancer (NSCLC) and elucidate its underlying mechanism. A549 and H520 cells were treated with various concentrations of RB with or without NLRP3 inhibitor (MCC950), caspase-1 inhibitor (VX765), or N-acetyl-l -cysteine (an ROS scavenger). Cell counting kit-8 and colony formation assays were conducted to determine cell viability. Cell invasion was detected by using the transwell assay. The release of lactate dehydrogenase (LDH) was determined by the LDH detection assay. The protein expression levels of related genes were measured by western blotting and immunohistochemistry. The reactive oxygen species (ROS) level was detected by using a 2,7-dichlorodihydrofluorescein diacetate ROS Assay Kit. The in vivo effects of RB were evaluated in a xenograft mouse model. RB treatment reduced cell viability and invasion in a dose-dependent manner. Furthermore, RB also enhanced pyroptosis levels in A549 and H520 cells, as indicated by the increased release of LDH and pyroptosis-related proteins. Interestingly, we also found that the antiproliferative and antimetastatic effects of RB were alleviated by the blockade of pyroptosis using NLRP3 inhibitor MCC950. Further study demonstrated that RB induced pyroptosis in a caspase-1-dependent manner, as evidenced by the finding that VX765 effectively reversed the effects of RB on A549 and H520 cells. We also found that RB could trigger caspase-1-dependent pyroptosis through ROS-mediated NF-κB suppression. In summary, our findings provide a potential antitumor agent and a novel insight into the mechanism of RB treatment of NSCLC.     

A mitochondrial-targetable dual functional near-infrared fluorescent probe to monitor pH and H2O2 in living cells and mice

A lower pH level and high hydrogen peroxide (H₂O₂) concentration in mitochondria is closely associated with a variety of diseases including cancer and inflammation. Thus, determination of changes in the level of acidic pH and H₂O₂ is of great importance and could provide new insights into the key functions under both physiological and pathological conditions. Herein, we present a novel mitochondria-targetable probe NIR-pH-H₂O₂, as the first near infrared (NIR) fluorescent small molecule, to monitor changes of endogenous pH (pk_a = 6.17) and H₂O₂ with high sensitivity, good compatibility and low cytotoxicity. Futhermore, it was successfully employed to monitor pH and H₂O₂ in a mouse acute inflammation model. These results demonstrate that NIR-pH-H₂O₂ is a novel bifunctional mitochondrial-targeted NIR probe to sense acidic pH and H₂O₂in vitro and in vivo, indicating its huge potential for the diagnosis of pH and H₂O₂-related diseases.

A lower pH level and high hydrogen peroxide (H₂O₂) concentration in mitochondria is closely associated with a variety of diseases including cancer and inflammation.     

创伤后肘关节僵硬553例回顾性分析

目的 研究创伤后肘关节僵硬的发病情况.方法 收集1997年1月至2013年12月北京积水潭医院收治的553例创伤后肘关节僵硬患者的病历资料进行回顾性研究.记录患者的临床资料和影像学资料.结果 553例中男性366例,女性187例;平均年龄为35岁(12 ～ 76岁),以＞30 ～40岁年龄组的患者最多(166例,占30.8％).中低能量损伤301例(54.4％),高能量损伤227例(41.1％);关节外骨折、损伤60例(10.8％),平均固定时间6.1周,关节内骨折、脱位493例(89.2％),平均固定时间4.9周;肘关节活动范围平均30°(0°～110°);肘部有异位骨化者457例(82.6％),无异位骨化96例(17.4％).结论 创伤后肘关节僵硬通常累及年轻、活跃人群,在临床工作中应重视低能量损伤、关节外骨折和简单关节内骨折的治疗,避免超过3周的制动,采取适当的手术固定方式,早期进行以主动功能锻炼为主,辅以轻柔的被动练习,另外需积极应对异位骨化的发生.     

Dissecting the hypothalamic pathways that underlie innate behaviors

Many complex behaviors that do not require learning are displayed and are termed innate. Although traditionally the subject matter of ethology,innate behaviors offer a unique entry point for neuroscientists to dissect the physiological mechanisms governing complex behaviors. Since the last century,converging evidence has implicated the hypothalamus as the central brain area that controls innate behaviors. Recent studies using cutting-edge tools have revealed that genetically-defined populations of neurons residing in distinct hypothalamic nuclei and their associated neural pathways regulate the initiation and maintenance of diverse behaviors including feeding,sleep,aggression,and parental care. Here,we review the newly-defi ned hypothalamic pathways that regulate each innate behavior. In addition,emerging general principles of the neural control of complex behaviors are discussed.     

Complementary functions of ATM and H2AX in development and suppression of genomic instability

Upon DNA damage, histone H2AX is phosphorylated by ataxia-telangiectasia mutated (ATM) and other phosphoinositide 3-kinase-related protein kinases. To elucidate further the potential overlapping and unique functions of ATM and H2AX, we asked whether they have synergistic functions in the development and maintenance of genomic stability by inactivating both genes in mouse germ line. Combined ATM/H2AX deficiency caused embryonic lethality and dramatic cellular genomic instability. Mechanistically, severe genomic instability in the double-deficient cells is associated with a requirement for H2AX to repair oxidative DNA damage resulting from ATM deficiency. We discuss these findings in the context of synergies between ATM and other repair factors.     

儿童泪囊炎致病菌分布及耐药性分析

目的了解儿童泪囊炎感染致病菌分布及其耐药情况。方法采集泪囊炎患儿泪囊分泌物标本,常规方法培养、分离致病菌,采用VITEK2全自动细菌鉴定仪、API鉴定条及纸片扩散法进行致病菌鉴定和耐药性检测。结果共检出致病菌800株,革兰阳性菌502株,占62.75%,以肺炎链球菌、草绿色链球菌、金黄色葡萄球菌为主;革兰阴性菌295株,占36.88%,以肺炎克雷伯菌、铜绿假单胞菌为主;白色念珠菌3株,占0.37%。肺炎链球菌和草绿色链球菌对妥布霉素、红霉素和克林霉素的耐药率高达53.8%~91.9%,金黄色葡萄球菌对青霉素的耐药率高达99.3%;肺炎克雷伯菌对氨苄西林的耐药率高达98.6%,对三代头孢类和妥布霉素较为敏感,对亚胺培南完全敏感。泪囊炎患儿以大于1个月至1岁年龄段儿童为主。结论儿童泪囊炎好发于小年龄段婴幼儿,致病菌对常用抗菌药物耐药率较高。     

吻合器痔上黏膜环切术(PPH)治疗重度痔术后并发症分析(附384例报告)

目的探讨PPH术后并发症的原因及防治体会。方法回顾性分析2011-01—2013-12间实施PPH术治疗的384例重度痔患者术后并发症的情况。结果尿潴留81例(21.1%),肛门疼痛需用止痛剂165例(42.9%),术后原发性出血4例(1.1%),术后继发性出血7例(1.8%),肛门残留皮赘或仍有轻度痔核脱垂18例(4.7%),肛门狭窄2例(0.5%),直肠阴道瘘1例。随访10~30个月,有2例再次入院行痔切除术。结论 PPH术虽具有操作简便,创伤小、恢复快等优点,但仍需进一步规范手术操作及围手术期处理,减少并发症发生。     

腹腔镜超声引导下微波消融治疗肝细胞性肝癌合并肝硬化的价值

目的评价肝硬化背景下经腹腔镜超声引导微波消融治疗肝细胞性肝癌的安全性和有效性。方法选取经腹腔镜超声引导下微波消融治疗伴有肝硬化的肝细胞性肝癌患者71例,定期对患者行血清甲胎蛋白(AFP)及影像学检查以评估治疗效果。结果术中腹腔镜超声检查,发现7个术前影像学未检出的肝内病灶(6.9%)。共计101个肝肿瘤病灶,均在腹腔镜超声引导下成功完成肿瘤微波消融治疗,患者血清AFP水平明显降低,与术前比较差异有统计学意义(P0.01)。术后仅1例患者出现术后严重并发症(1.4%),无死亡情况。术后1个月后复查,超声造影及增强CT均显示肝病灶完全消融,未见残留。术后随访(11.5±10.1)个月,4个病灶发现局部复发,6个病灶出现远处转移,3个病灶同时发生局部复发和远处转移。结论腹腔镜超声引导下的肝癌微波消融治疗具有安全、有效、恢复期短及并发症发生率低等优点。