Myeloid neoplasms with germline predisposition: Practical considerations and complications in the search for new susceptibility loci

Genomic research in hematological malignancies has focused far more prominently on somatic mutations than on germline variants. Although increasing numbers of germline variants are being identified, a substantial proportion of familial myeloid malignancies have no causal allele pinpointed. Here we review the biological, technological, and clinical challenges that stand in the way of the goal of establishing, implementing, and interpreting a comprehensive panel of germline variants for testing. Achieving this goal would inform care for large numbers of myeloid malignancy patients. Furthermore, knowledge of germline susceptibility variants and their corresponding genes will shed light on disease processes, potentially suggesting therapeutic strategies tailored to specific variants.     

电设备应用策略管理对层流手术室PM2.5及切口感染的影响

目的探讨电设备应用策略管理对层流手术室PM2.5及切口感染的影响。方法将200例患者按是否实施层流手术室电设备应用策略管理分为两组,每组100例。对照组采用层流手术室电设备常规管理,管理组在对照组基础上采用层流手术室电设备应用策略管理,统计两组术中手术室内人员数、手术时间、术中出血量、术后切口感染发生情况,检测患者切口及口鼻周围PM2.5浓度。结果两组术中手术室内人员数、手术时间、术中出血量比较差异无统计学意义(P>0.05)。管理组距离切口1 cm、5 cm、10 cm、20 cm和距离患者口鼻5 cm处PM2.5浓度显著低于对照组(P<0.01),切口感染率显著低于对照组(P<0.05)。切口感染患者距离切口1 cm、5 cm、10 cm、20 cm和距离患者口鼻5 cm处PM2.5浓度显著高于无切口感染患者(P<0.05)。相关分析显示,层流手术室PM2.5浓度与切口感染率呈显著正相关(P<0.05)。结论电设备应用策略管理有助于降低层流手术室PM2.5浓度及切口感染发生率。     

Clonality and intracellular polyploidy in virus evolution and pathogenesis

In the present article we examine clonality in virus evolution. Most viruses retain an active recombination machinery as a potential means to initiate new levels of genetic exploration that go beyond those attainable solely by point mutations. However, despite abundant recombination that may be linked to molecular events essential for genome replication, herein we provide evidence that generation of recombinants with altered biological properties is not essential for the completion of the replication cycles of viruses, and that viral lineages (near-clades) can be defined. We distinguish mechanistically active but inconsequential recombination from evolutionarily relevant recombination, illustrated by episodes in the field and during experimental evolution. In the field, recombination has been at the origin of new viral pathogens, and has conferred fitness advantages to some viruses once the parental viruses have attained a sufficient degree of diversification by point mutations. In the laboratory, recombination mediated a salient genome segmentation of foot-and-mouth disease virus, an important animal pathogen whose genome in nature has always been characterized as unsegmented. We propose a model of continuous mutation and recombination, with punctuated, biologically relevant recombination events for the survival of viruses, both as disease agents and as promoters of cellular evolution. Thus, clonality is the standard evolutionary mode for viruses because recombination is largely inconsequential, since the decisive events for virus replication and survival are not dependent on the exchange of genetic material and formation of recombinant (mosaic) genomes.     

Mutational Signature Analysis Reveals NTHL1 Deficiency to Cause a Multi-tumor Phenotype

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Racial differences in characteristics and prognoses between Asian and white patients with nonsmall cell lung cancer receiving atezolizumab: An ancillary analysis of the POPLAR and OAK studies

This study aimed to compare the differences in characteristics and prognoses between Asian and white patients receiving immunotherapy for nonsmall cell lung cancer (NSCLC). We studied 390 patients who received atezolizumab as part of the POPLAR or OAK trial, and analyzed the differences in baseline characteristics, outcomes and genetic mutations in blood samples between Asian and white patients. Overall survival (OS) was longer in Asian compared to white patients (median OS: 18.7 vs. 11.1 months; p = 0.005). Race was identified as an independent prognostic factor for OS (Asian vs. white: hazard ratio 0.647, 95% confidence interval 0.447–0.936, p = 0.021), together with performance status, histology, baseline sum of the longest tumor diameters (BLSLD) and number of metastatic sites. The two groups also differed in terms of characteristics including smoking history, BLSLD, epidermal growth factor receptor (EGFR) mutation frequency, programmed death-ligand 1 expression and blood-based tumor-mutation burden. Blood mutations of STK11, EGFR, KEAP1, POLE, GRM3, ATM and STAG2 were associated with treatment response, and TP53, KEAP1, APC, RB1, CREBBP, EPHA5 and STAG2 mutations were associated with OS. The blood-based mutation profiles differentiated between Asian and white patients, especially in relation to EGFR (23.8 vs. 8.5%), TP53 (30.2 vs. 46.9%) and STK11 (1.6 vs. 12.3%) mutations (all p < 0.05). The different clinicopathological features and mutation profiles in Asian and white patients may explain the superior outcome following atezolizumab treatment in Asian patients with NSCLC. The results of this study have important implications for further studies on racial disparities in relation to immunotherapy.     

基于五运六气理论对新型冠状病毒感染肺炎的几点思考

基于五运六气理论,尤其是三年化疫理论,对当前正在流行的新型冠状病毒感染的肺炎进行病因病机分析及分期诊疗指导。     

How to implement guidelines and models of care

In subjects older than 50 years, the presence of clinical risk factors (CRFs) for fractures or a recent fracture is the cornerstone for case finding. In patients who are clinically at high short- and long-term risk of fractures (those with a recent clinical fracture or with multiple CRFs), further assessment with bone mineral density (BMD) measurement using dual-energy absorptiometry (DXA), imaging of the spine, fall risk evaluation and laboratory examination contributes to treatment decisions according to the height and modifiability of fracture risk. Treatment is available with anti-resorptive and anabolic drugs, and from the start of treatment a lifelong strategy is needed to decide about continuous, intermittent, and sequential therapy. Implementation of guidelines requires further initiatives for improving case finding, public awareness about osteoporosis and national policies on reimbursement of assessment and therapy.