中国抗生素耐药性治理的政策演变及启示

目的:本研究系统梳理了我国在不同时期实施的抗生素耐药性治理,分析政策的演变历程和原因,旨在为下一步政策制定提供启示。方法:在国家卫生健康委员会等相关部委的官方网站上,系统检索有关抗生素耐药性问题的政策文件,提取关键信息并梳理政策内容与时间节点,归纳和总结中国为应对抗生素耐药性问题所采取的政策和行动。结果:中国抗生素耐药性治理的政策演变过程可划分为三个阶段:以药品管控为主要治理策略的第一阶段,以临床监测为主要治理手段的第二阶段,多领域参与的全面治理策略的第三阶段。结论:为进一步解决抗生素耐药性问题,中国应加强社区感染控制和抗生素合理使用,加强对农业和环境领域的耐药性治理,建立基于"One Health"框架下的跨部门、跨学科合作平台,并加大抗生素替代药品的研发力度。     

Idiopathic Intracranial Hypertension in a Mother and Pre-pubertal Twins

Idiopathic intracranial hypertension is a syndrome of elevated intracranial pressure without an identifiable cause. The majority of cases appear to be sporadic, and incidence is highest in obese women of childbearing age. The role of genetics in the pathophysiology of the disease is unclear, and familial cases are rare. We report a familial occurrence in a mother and her twin, 5-year-old sons.     

Encephalopathy related to status epilepticus during slow sleep (ESES) as atypical evolution of Panayiotopoulos syndrome: an EEG and neuropsychological study

Aim: We report two patients with Panayiotopoulos syndrome (PS) who developed encephalopathy related to status epilepticus during slow sleep (ESES) at the peak of their clinical course. Methods: Clinical charts and EEG data were reviewed. Results: The patients exhibited nocturnal autonomic seizures and occipital EEG foci, the latter of which later evolved into multifocal EEG foci with synchronous frontopolar and occipital spikes (Fp‐O EEG foci), and finally into continuous spikes‐waves during sleep (CSWS; spike‐wave index >85% based on whole‐night sleep recording) at eight years and seven years of age, respectively. The occipital spikes always preceded frontopolar spikes by 30～50 mseconds based on the analysis of CSWS. Neuropsychological ability, including IQ, deteriorated during the CSWS period in both patients. The autonomic seizures and focal to bilateral tonic‐clonic seizures were initially resistant to antiepileptic drugs (AEDs), and occurred more than 10 times in both patients. However, the seizures and EEG findings gradually resolved, and AEDs were successfully terminated in both patients. Conclusion: PS can progress to ESES if the clinical course exhibits atypical evolution. The initial autonomic symptom of the seizures and interictal Fp‐O EEG foci should be carefully monitored in patients with CSWS or ESES.     

Oxidative stress markers in seminal plasma of idiopathic infertile men may be associated with glutathione S-transferase M1 and T1 null genotypes

This study aimed to investigate the association between glutathione S-transferase (GST) M1 and T1 null genotypes and thiobarbituric acid reactive substances (TBARS), total antioxidant capacity (TAC) and nitric oxide (NO) levels in male infertility. For this purpose, semen samples were collected from fertile and infertile subjects, and then they were genotyped for GSTT1 and GSTM1 genes using multiplex-PCR. The TBARS, TAC and NO levels in seminal plasma were then measured via the ferric-reducing ability of plasma (FRAP). A significant association was observed between GSTT1 null genotype and oligozoospermia, asthenozoospermia and teratozoospermia. But, the GSTM1 null genotype was merely associated with teratozoospermia. Moreover, the GSTT1−/GSTM1+ combined genotype was associated with all subgroups of male infertility. Besides, an association was observed between GSTT1−/GSTM1− genotype and asthenozoospermia and teratozoospermia. Further analysis showed that the GSTT1 null genotype was associated with increased NO in asthenozoospermia. Also, the GSTT1 null genotype was associated with increased TBARS in oligozoospermia and asthenozoospermia. As well, GSTM1 null genotype was associated with decreased TAC and increased NO in asthenozoospermia respectively. As a preliminary conclusion, the GSTM1 and GSTT1 null genotypes could be considered as genetic risk factors for male infertility, interfering with some oxidative stress markers in infertile men.     

A multi-institutional experience in vascular Ehlers-Danlos syndrome diagnosis

ObjectiveVascular Ehlers-Danlos syndrome (vEDS) is a rare disorder and 1 of 13 types of EDS. The syndrome results in aortic and arterial aneurysms and dissections at a young age. Diagnosis is confirmed with molecular testing via skin biopsy or genetic testing for COL3A1 pathogenic variants. We describe a multi-institutional experience in the diagnosis of vEDS from 2000 to 2015.MethodsThis is a multi-institutional cross-sectional retrospective study of individuals with vEDS. The institutions were recruited through the Vascular Low Frequency Disease Consortium. Individuals were identified using the International Classification of Diseases-9 and 10-CM codes for EDS (756.83 and Q79.6). A review of records was then performed to select individuals with vEDS. Data abstraction included demographics, family history, clinical features, major and minor diagnostic criteria, and molecular testing results. Individuals were classified into two cohorts and then compared: those with pathogenic COL3A1 variants and those diagnosed by clinical criteria alone without molecular confirmation.ResultsEleven institutions identified 173 individuals (35.3% male, 56.6% Caucasian) with vEDS. Of those, 11 (9.8%) had nonpathogenic alterations in COL3A1 and were excluded from the analysis. Among the remaining individuals, 86 (47.7% male, 68% Caucasian, 48.8% positive family history) had pathogenic COL3A1 variants and 76 (19.7% male, 19.7% Caucasian, 43.4% positive family history) were diagnosed by clinical criteria alone without molecular confirmation. Compared with the cohort with pathogenic COL3A1 variants, the clinical diagnosis only cohort had a higher number of females (80.3% vs 52.3%; P < .001), mitral valve prolapse (10.5% vs 1.2%; P = .009), and joint hypermobility (68.4% vs 40.7%; P < .001). Additionally, they had a lower frequency of easy bruising (23.7% vs 64%; P < .001), thin translucent skin (17.1% vs 48.8%; P < .001), intestinal perforation (3.9% vs 16.3%; P = .01), spontaneous pneumothorax/hemothorax (3.9% vs 14%, P.03), and arterial rupture (9.2% vs 17.4%; P = .13). There were no differences in mortality or age of mortality between the two cohorts.ConclusionsThis study highlights the importance of confirming vEDS diagnosis by testing for pathogenic COL3A1 variants rather than relying on clinical diagnostic criteria alone given the high degree of overlap with other forms genetically triggered arteriopathies. Because not all COL3A1 variants are pathogenic, the interpretation of the genetic testing results by an individual trained in variant assessment is essential to confirm the diagnosis. An accurate diagnosis is critical and has serious implications for lifelong screening and treatment strategies for the affected individual and family members.     

《中国科技期刊研究》创刊30年文献统计分析

【目的】 探讨《中国科技期刊研究》(Chinese Journal of Scientific and Technical Periodicals,CJSTP)创刊30年来发表论文的文献计量学特征。【方法】 基于CNKI数据库检索CJSTP发表的全部论文,对简讯、更正等非论文条目进行手工清洗,导出每篇论文标题、作者(手工添加通信作者)、机构、基金项目、出版年、被引频次和下载量,对其进行统计分析。采用VOSviewer软件进行作者合作和关键词共现分析,采用CiteSpace软件进行突现词探测。【结果】 30年间CJSTP共发表学术论文6240篇,总被引频次为44627次,篇均被引频次为7.2次,总下载量为845562次,篇均下载量为135.5次,基金项目资助论文共1437篇,基金论文比为23.0%,年度发文量呈现近似M型分布,形成相对稳定的高影响力作者、团队和机构,研究主题的变化体现出从微观到宏观、从定性的思辨式研究到定量的实证研究的演进特征。【结论】 30年来,CJSTP的科学性、实用性不断增强,学术质量和影响力持续提升,为我国科技期刊人才队伍建设作出了重要贡献,为培育世界一流科技期刊提供了必要的人才保障。     

Inhibition of Intracellular Clusterin Attenuates Cell Death in Nephropathic Cystinosis

Nephropathic cystinosis, characterized by accumulation of cystine in the lysosomes, is caused by mutations in CTNS. The molecular and cellular mechanisms underlying proximal tubular dysfunction and progressive renal failure in nephropathic cystinosis are largely unclear, and increasing evidence supports the notion that cystine accumulation alone is not responsible for the end organ injury in cystinosis. We previously identified clusterin as potentially involved in nephropathic cystinosis. Here, we studied the expression of clusterin in renal proximal tubular epithelial cells obtained from patients with nephropathic cystinosis. The cytoprotective secretory form of clusterin, as evaluated by Western blot analysis, was low or absent in cystinosis cells compared with normal primary cells. Confocal microscopy revealed elevated levels of intracellular clusterin in cystinosis cells. Clusterin in cystinosis cells localized to the nucleus and cytoplasm and showed a filamentous and punctate aggresome-like pattern compared with diffuse cytoplasmic staining in normal cells. In kidney biopsy samples from patients with nephropathic cystinosis, clusterin protein expression was mainly limited to the proximal tubular cells. Furthermore, expression of clusterin overlapped with the expression of apoptotic proteins (apoptosis-inducing factor and cleaved caspase-3) and autophagy proteins (LC3 II and p62). Silencing of the clusterin gene resulted in a significant increase in cell viability and attenuation of apoptosis in cystinosis cells. Results of this study identify clusterin as a pivotal factor in the cell injury mechanism of nephropathic cystinosis and provide evidence linking cellular stress and injury to Fanconi syndrome and progressive renal injury in nephropathic cystinosis.