纳米颗粒和外泌体靶向载药系统诊治动脉粥样硬化的机遇与挑战

动脉粥样硬化是一种慢性炎症性疾病,粥样斑块慢性聚集并沉积于大中型动脉内膜,导致严重的狭窄和血运障碍,引发组织器官缺血缺氧。纳米药物相对于传统药物在动脉粥样硬化治疗中因其具有独特的优势而广泛受到关注。本文重点综述几种纳米靶向颗粒（系统）和外泌体靶向载药系统在抗动脉粥样硬化研究中的应用,简述代表性纳米材料的合成过程,对其靶向性进行分析,并概述纳米药物的益处和内在挑战。尽管面临着一些需要解决和完善的挑战,但是纳米颗粒和外泌体靶向载药治疗的前景广阔,并有望将其推广应用于临床实践中。     

Mutations in VMK1, a mitogen-activated protein kinase gene, affect microsclerotia formation and pathogenicity in Verticillium dahliae

Verticillium dahliae is an important soil-borne fungal pathogen that causes vascular wilt diseases in a large variety of important crop plants. Due to its persistence in the soil, control of Verticillium wilt relies heavily on soil fumigation. The global ban on methyl bromide, a highly effective soil fumigant, poses an urgent need to develop alternative control measures against Verticillium wilt; and these might be more forthcoming with a better understanding of the molecular and cellular mechanisms that underpin the pathogenicity of V. dahliae. In this study, we assessed the role in growth, development, and pathogenicity of VMK1, a gene encoding a mitogen-activated protein (MAP) kinase (hence, Verticillium MAP Kinase 1). Disruption of VMK1 via Agrobacterium tumefaciens-mediated transformation, in two V. dahliae isolates, one from lettuce and the other from tomato, resulted in severely reduced virulence in diverse host plants, suggesting that VMK1 is essential for pathogenicity and that the MAP kinase-mediated signaling pathway has a conserved role in fungal pathogenicity. The vmk1 mutants also exhibited reduced conidiation and microsclerotia formation, suggesting that the gene is important for multiple cellular processes. P.R. and R.G.B. equally contributed to the work     

Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes

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Allele-specific PCR and Next-generation sequencing based genetic screening for Congenital Adrenal Hyperplasia in India

Genetic screening of Congenital Adrenal Hyperplasia (CAH) is known to be challenging due to the complexities in CYP21A2 genotyping and has not been the first-tier diagnostic tool in routine clinical practice. Also, with the advent of massive parallel sequencing technology, there is a need for investigating its utility in screening extended panel of genes implicated in CAH. In this study, we have established and utilized an Allele-Specific Polymerase Chain Reaction (ASPCR) based approach for screening eight common mutations in CYP21A2 gene followed by targeted Next Generation Sequencing (NGS) of CYP21A2, CYP11B1, CYP17A1, POR, and CYP19A1 genes in 72 clinically diagnosed CAH subjects from India. Through these investigations, 88.7% of the subjects with 21 hydroxylase deficiency were positive for eight CYP21A2 mutations with ASPCR. The targeted NGS assay was sensitive to pick up all the mutations identified by ASPCR. Utilizing NGS in subjects negative for ASPCR, five study subjects were homozygous positive for other CYP21A2 variants: one with a novel c.1274G>T, three with c.1451G>C and one with c.143A>G variant. One subject was compound heterozygous for c.955C>T and c.1042G>A variants identified using ASPCR and NGS. One subject suspected for a Simple Virilizing (SV) 21 hydroxylase deficiency was positive for a CYP19A1:c.1142A>T variant. CYP11B1 variants (c.1201-1G>A, c.1200+1del, c.412C>T, c.1024C>T, c.1012dup, c.623G>A) were identified in all six subjects suspected for 11 beta-hydroxylase deficiency. The overall mutation positivity was 97.2%. Our results suggest that ASPCR followed by targeted NGS is a cost-effective and comprehensive strategy for screening common CYP21A2 mutations and the CAH panel of genes in a clinical setting.     

2017-2019年某医院综合ICU医院感染目标监测分析

目的分析某医院综合重症医学科(ICU)医院感染目标性监测情况。方法对2017-2019年宁夏回族自治区人民医院ICU目标性监测数据,包括医院感染发病率、医院感染部位分布、三管使用及其相关感染、医院感染病原菌分布等进行回顾性分析。结果共监测ICU患者4953例,医院感染发病率为6.42%,医院感染例次发病率为8.46%;感染部位以呼吸系统为主占73.03%;泌尿道插管相关泌尿道感染(CAUTI)、血管导管相关血流感染(CRBSI)、呼吸机相关肺炎(VAP)感染发病率分别为1.50‰、2.46‰和13.66‰;检出病原菌356株,前三位依次为鲍氏不动杆菌、肺炎克雷伯菌和金黄色葡萄球菌。结论医院ICU医院感染发病率较高,感染部位以呼吸系统为主,分离病原菌以革兰阴性菌为主,总器械使用率高,提示临床应严格留置导管指征,对VAP等医院感染高危因素及时采取有效地预防措施,降低感染风险,保障患者安全。     

Metastasectomy versus radiation of secondary sites in stage IV breast cancer: Analysis from a national cancer registry

PurposeLocoregional therapy at primary or secondary sites in breast cancer may be associated with improved survival as compared to systemic therapy alone. We explored the sociodemographic and clinicopathologic factors associated with the use of radiation versus surgical resection of metastatic sites (metastasectomy) in patients with de novo stage IV breast cancer, followed by the associated overall survival.MethodsWe sampled the National Cancer Database for patients with de novo stage IV breast cancer, (2010–2017) and described cohort's characteristics using univariate analyses. We identified 5 subgroups based on malignant site involvement: 1. Bone only, 2. Brain only, 3. Liver only, 4. Lung only, and 5. Metastasis involving >1 site. Kaplan-Meier modeling with log-rank testing and multivariate Cox Regression analysis were used to explore differences in overall survival between those that received radiation at secondary sites and those that underwent metastasectomy.ResultsN = 22,749patients were included in this analysis. Radiation (81.2%) was used more commonly than metastasectomy (28.8%). Metastasectomy was associated with better median overall survival across all 5 cohorts (p < .001), with the survival benefit being the most pronounced with lung only (OS: 56.9 months; HR 0.8, 95% CI 0.7–0.9, p = .032), or liver only (OS: 41.6 months; HR: 0.9; 95% CI: 0.7–1.1, p < .001) metastasis.ConclusionMetastasectomy in patients with de novo stage IV breast cancer may be associated with improved overall survival as compared to radiation of secondary lesions, particularly in those with only liver or lung involvement. Prospective randomized controlled trials investigating surgical resection of metastatic sites in patients with breast cancer are warranted.     

Selective transperineal prostate biopsy for fluoroquinolone-resistance patients reduces sepsis and cost

Background:Urosepsis is a recognized complication of transrectal ultrasound-guided prostate biopsy (TRUS-Bx). Pre-biopsy rectal swabs have been used to identify patients with microorganisms in the rectal flora resistant to the conventionally used empirical prophylaxis. The transperineal route of biopsy (TP-Bx) has a lower complication risk but comes at an increased cost.Materials and methods:Retrospective cohort study including patients undergoing prostate biopsies between October/2015 and April/2018. The intervention cohort, a rectal swab was performed, the result of which dictated the biopsy route; TRUS-Bx against TP-Bx. TP-Bx for patients with fluoroquinolone resistance or extended-spectrum β-lactamase. The control cohort underwent TRUS without a rectal swab receiving empirical antibiotics—oral ciprofloxacin and intravenous gentamicin.Results:Total 1000 patients were included in which 500 underwent a swab, 14 (2.8%) developed post-TRUS biopsy infective complications with 3 having positive bacteremia (0.6%); 500 had no swab, 47 (9.4%) developed post-TRUS biopsy infective complications with 22 (4.4%, p < 0.05) having positive bacteremia. Three patients (0.6%) of patients who underwent swab developed urinary tract infection symptoms whilst 12 (2.4%) had urinary tract infection in the control group. In those patients that underwent a swab, 14 required hospitalization with mean length of stay of 2.5 days versus 43 patients of the control with 3.6 days. Cost analysis concluded savings of this strategy was £18,711.Conclusions:We have demonstrated a protocol that reserves template biopsies for higher risk patients and can significantly reduce sepsis and other infectious complication rates whilst also proving to be a cost-efficient strategy. We recommend that units not utilizing rectal swabs to uncover the fluoroquinolone resistance rate by introducing them. We advocate units that already utilize rectal swabs, to introduce transperineal biopsy for their higher risk patients.     

靶向联合化疗与常规化疗治疗表皮生长因子受体基因突变肺腺癌患者的临床效果

目的探讨靶向联合化疗治疗表皮生长因子受体(EGFR)基因突变晚期肺腺癌患者的临床疗效及靶向联合化疗对EGFR基因不同突变位点患者的疗效差别。方法选择安徽省胸科医院2016年1～12月收治确诊的64例EGFR基因检测阳性的Ⅲb/Ⅳ期肺腺癌患者,使用随机数字表方法分为靶向联合化疗组(33例)与常规化疗组(31例),同时对靶向联合化疗组患者按照其基因突变位点不同分为3个亚组(19外显子突变组、21外显子突变组、20外显子突变组)。靶向联合化疗组患者采用EGFR受体酪氨酸抑制剂靶向治疗联合培美曲塞+卡铂/顺铂治疗,常规化疗组患者采用培美曲塞+卡铂/顺铂治疗。比较两治疗组患者的近期及远期疗效,并对靶向联合化疗组不同位点远期疗效进行数据分析。结果靶向联合化疗组的中位无进展生存期高于常规化疗组,两组差异有统计学意义(P <0. 05),两组患者总体疗效和不良反应总发生率相似,差异无统计学意义(P> 0. 05)。靶向联合化疗组中,不同外显子突变的肺腺癌患者之间靶向联合化疗的生存期相似,差异无统计学意义(P> 0. 05)。结论 EGFR基因突变晚期肺腺癌患者接受靶向联合化疗能延长无进展生存时间,且不良反应未见增加。不同位点基因突变患者接受靶向联合化疗的临床效果无明显差别。