自噬在槲皮素诱导人乳腺癌MCF-7细胞死亡中的作用

目的研究自噬在槲皮素诱导的人乳腺癌MCF-7细胞死亡中的作用。方法用不同浓度的槲皮素处理人乳腺癌MCF-7细胞,采用MTT法测定槲皮素对MCF-7细胞增殖的抑制作用;应用MDC荧光染色观察给药后MCF-7细胞的自噬征象;应用JC-1荧光染色观察给药后MCF-7细胞的线粒体变化;检测乳酸脱氢酶（LDH）漏出率以观察用自噬特异性抑制剂3-甲基腺嘌呤（3-MA）阻断自噬后槲皮素抑瘤作用的变化。结果槲皮素对MCF-7细胞增长有显著的抑制作用,且此作用呈明显的时间、剂量依赖性;槲皮素给药后早期可诱导MCF-7细胞发生自噬及线粒体变化;在槲皮素给药前和给药后阻断自噬,槲皮素对MCF-7细胞的细胞毒性作用均增强。结论槲皮素能明显抑制MCF-7细胞的生长,并诱导其发生自噬,伴随线粒体发生变化。由槲皮素引发的自噬能够明显保护MCF-7细胞,减少因槲皮素导致的细胞死亡。     

Macrolide resistance in group A beta haemolytic Streptococcus isolated from outpatient children in Latvia

Zavadska D, Bērzin¸a D, Drukal¸ska L, Puga?ova N¸, Mikla?evi?s E, Gardovska D. Macrolide resistance in group A beta haemolytic Streptococcus isolated from outpatient children in Latvia. APMIS 2010; 118: 366–70. Group A streptococci (GAS) are responsible for up to 30% of cases of pharyngitis in children, and such children do not benefit from treatment with antibiotics. During the last decade, increased resistance to macrolides has emerged as a critical issue in the treatment of GAS pharyngitis. The objective of this study was to determine the antimicrobial resistance of group A beta haemolytic Streptococcus isolated from outpatient children. From 2002 to 2006, 96 GAS strains were obtained from the pharynx of outpatients having symptoms of acute pharyngitis. Antibiotic resistance was determined by disc susceptibility tests according to CLSI standards. The presence of ermA, ermB and mefA was established by the amplification of streptococcal DNA with specific primers. Antimicrobial susceptibility tests revealed that all the strains tested were sensitive to vancomycin, linezolid, penicillin and ceftriaxone. Simultaneously, high levels of resistance to macrolides were evident; 78% of the isolates were resistant to clindamycin and erythromycin. No significant change in the yearly or seasonal incidence of resistance was observed. We describe high antimicrobial resistance of GAS to macrolides in outpatient children (78%), which can be explained by the frequent use of macrolides in the treatment of such individuals. Therefore, macrolides should not be the first drug of choice.     

The prevalence and patterns of substance use by birth cohort among HIV-positive adults in Florida

Objectives: Antiretroviral therapy is affording longer lifespans for people living with HIV (PLWH), yet factors such as substance use play an increasing role in morbidity and mortality in this population. Though previous studies have examined substance use differences between age cohorts of PLWH, no study has examined the influence of birth cohort on current substance use patterns. Thus, this study investigated the prevalence of past 12-month self-reported substance use between four birth cohorts, <1970 (M age = 54.1), 1970s (M age = 41.5), 1980s (M age = 31.3 years old), and 1990s (M age = 23.2 years old) of PLWH in Florida.

Methods: PLWH (N = 934) recruited from community health clinics in Florida completed a questionnaire assessing sociodemographics, health status, and substance use.

Multivariate logistic regressions utilizing the <1970 cohort as the referent group examined the relationship between birth cohort and substance use.

Results: The 1980s cohort had significantly greater odds of marijuana use compared to the oldest cohort (<1970s), while the three younger cohorts (1970s, 1980s, and 1990s) evidenced a significantly greater odds of ecstasy use compared to the oldest group. Contrastingly, the three younger birth cohorts reported significantly less crack use than the oldest cohort, while the youngest group (1990s) also demonstrated an 80% reduction in injection drug use compared to the oldest group.

Conclusion: The older cohort evidenced significantly greater crack and injection drug use, while the younger cohorts evidenced greater marijuana and ecstasy use. Therefore, it is important to develop age-specific substance use interventions among PLWH.     

Warifteine,a bisbenzylisoquinoline alkaloid,induces relaxation by activating potassium channels in vascular myocytes

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我国髌骨骨折经镍钛记忆合金聚髌器与AO张力带治疗的系统评价

目的：系统评价我国镍钛记忆合金聚髌器与AO张力带治疗髌骨骨折的疗效与安全性.方法：计算机检索中国知网（CNKI：2003～2013.6）、万方数据库（2003～2013.6）、维普数据库（2003～2013.6）,中国生物医学数据库及超星电子图书.手工检索国内近五年来发表于中国矫形外科杂志、临床骨科杂志、中国骨与关节杂志及当代医学等杂志上的文献.收集所有相关镍钛记忆合金聚髌器与AO张力带治疗髌骨骨折的随机对照试验及半随机对照试验,采用RevMan5.0软件进行系统评价.结果：共纳入11篇随机对照试验及半随机对照试验,共735例患者,纳入研究质量评价结果为B级9篇,C级2篇.系统评价结果显示,与AO张力带组相比,镍钛记忆合金聚髌器组手术时间短,[SMD=-1.91,95％CI（-3.23,-0.58）,P=0.005＜0.05];术后并发症少,[RR=0.20,95％CI（0.09,0.43）,P＜0.05];术后优良率高RR=1.11,95％CI（1.00,1.23）,P=0.05],但在术后骨折愈合时间方面差异无统计学意义.结论：镍钛记忆合金聚髌器在治疗髌骨骨折时优于AO张力带组,值得临床推广.但由于本文尚存在一定的局限性,故需要更严格的、大样本量的、多中心性的,并且采用正确的随机、盲法、分配隐藏等的文献研究来进一步论证.     

Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease

We sought to identify the molecular basis of the autosomal dominant form of Kufs disease, an adult onset form of neuronal ceroid lipofuscinosis. We used a combination of classic linkage analysis and Next Generation Sequencing to map and identify mutations in DNAJC5 in a total of three families. We analyzed the clinical manifestations in 20 individuals with mutation in DNAJC5. We report here the mapping and the identification of a p.L116del mutation in DNAJC5 segregating with the disease in two distinct American families, as well as a p.L115R mutation in an additional family. The age of onset and clinical manifestations were very homogeneous among mutation positive individuals, including generalized tonic–clonic seizures, myoclonus, ataxia, speech deterioration, dementia, and premature death. A few individuals also exhibited parkinsonism. DNAJC5, which encodes the cysteine string protein (CSPα), a presynaptic protein implicated in neurodegeneration, causes autosomal dominant Kufs disease. The leucine residues at positions 115 and 116 are hotspots for mutations and result in a homogeneous phenotype of progressive myoclonus epilepsy with onset around 30 years old.