刺果甘草全基因组Survey及叶绿体基因组特征分析＊

目的 基于基因组Survey分析对刺果甘草Glycyrrhiza pallidiflora Maxim.基因组大小和杂合率进行估计，并通过叶绿体基因组序列特征对其在甘草属Glycyrrhiza L.中的系统发育位置进行研究。方法 使用二代测序技术对刺果甘草进行测序，采用K-mer方法对测序reads进行分析，估算刺果甘草基因组大小和杂合率，使用生物信息学方法进行叶绿体基因组组装、注释和系统发育分析。结果 Survey分析结果显示其基因组大小约为577.82 Mb，杂合度约为0.31%，重复序列比例约为53.72%。叶绿体基因组长度为127，267 bp，不具有典型的四分体结构，总GC含量为34.32%，包含110个基因，其中76个蛋白质编码基因，30个tRNA基因和4个rRNA基因。系统发育分析表明，刺果甘草与圆果甘草G. squamulosa Franch.亲缘较接近。结论 刺果甘草存在低杂合和重复序列较多的特点，为了更好地对全基因组进行序列拼接和组装，可尝试采用三代测序结合二代测序的分析策略进行基因组组装；刺果甘草叶绿体全基因组比对和系统发育分析，为后续开展甘草属遗传多样性研究和分子鉴定标记筛选提供了重要依据。     

基于Oncomine数据库分析分泌性磷蛋白1在肝细胞癌中的表达及临床意义

目的分析分泌性磷蛋白1(SPP1)在肝细胞癌中的表达,探索其对肝癌患者预后的影响。方法基于Oncomine数据库,对肝细胞癌中的SPP1差异表达情况进行分析,探讨其意义;利用Kaplan Meier-Plotter在线分析工具,对患者生存情况进行分析;基于String数据库在线构建蛋白互作网络。结果在筛选到的4项研究中,肝癌组SPP1基因的表达分别为4.92±0.24,0.35±0.30,-0.92±0.29和5.12±0.50,与相应正常组表达量1.96±0.28,-1.23±0.06,-2.93±0.13和1.89±0.31相比较均显著增高,差异均有统计学意义(均P <0.001);SPP1高表达组患者诊断后总体中位生存期为37.8个月,较SPP1低表达组(84.4个月)明显降低,差异有统计学意义(P <0.001);在男性(41.0个月vs 84.7个月)、亚洲人群(7.2个月vs 56.2个月)、GradeⅢ级(5.7个月vs23.7个月)或未感染肝炎病毒患者(25.2个月vs 70.5个月)亚组中的总体生存期均显著下降(错误发现率<5%,P <0.001)。透明质酸受体、整合素β1、基质金属蛋白酶7、金属蛋白酶组织抑制因子1、白细胞介素6和纤维连接蛋白1等是显著的节点基因。结论 SPP1与肝细胞癌进展显著相关,高SPP1表达与HCC患者的不良存活密切相关。     

Four cases of sodium nitrite suicidal ingestion: A new trend and a relevant Forensic Pathology and Toxicology challenge

Sodium nitrite (NaNO₂) is an inorganic compound commonly used as a food additive, antifreeze admixture, and fertilizer. Its toxicity mechanism is mainly represented by the oxidation of ferrous iron to ferric iron of one of the four heme structures in haemoglobin with the onset of methaemoglobin. The mechanism of death by sodium nitrite toxicity is severe hypoxia. We present four cases of suicidal sodium nitrite ingestion that closely occurred within a two months-period. Self-poisoning with sodium nitrite actually represents an increasing trend in nitrates’ related deaths. In order to reach a precise diagnosis of NaNO₂ intoxication, a complete toxicological analysis should be carried out including not only MetHb blood levels but also nitrites and nitrites in standard or alternative matrices as a routine procedure. Autopsy should be carefully performed to detect common indicators of hypoxia or more rarely evident typical by themselves-non specific signs of sodium nitrite toxicity. Suicidal manner of death should be carefully considered when circumstantial data support that ingestion of large amounts of NaNO₂ occurred as a consequence of a self-injurious behaviour. Relevant informations include victim’s previous Internet or book researches about paths to follow to commit suicide with sodium nitrate, employment and past medical history, with strong regard to psychiatric diseases as well as eventual taking psycotropic drugs.Finally, an accurate integration of autoptic and toxicological results with circumstantial data is necessary to make correct diagnosis of death due to acute respiratory failure secondary to suicidal sodium nitrite ingestion.     

黄花蒿Dof基因家族鉴定及在GA-UV处理下对青蒿素生物合成的影响＊

目的 Dof（DNA binding with one finger）家族是高等植物中特有的一类转录因子家族，参与植物中光、激素、非生物胁迫等多种胁迫响应调控。本研究基于全基因组数据对黄花蒿Dof（AaDof）转录因子家族进行鉴定及表达模式分析，探究Dof家族基因在青蒿素合成调控中的作用。方法 经PFAM数据库鉴定获得AaDof序列，通过生物信息学软件分析其理化性质、亚细胞定位、基因结构、蛋白保守结构以及启动子序列结合元件等，并基于赤霉素（Gibberellic acid， GA）、紫外线B（UV-B）及二者协同胁迫下黄花蒿转录组数据对其表达模式进行分析。结果 本研究从全基因组水平共鉴定出51个AaDof基因，均含有保守的C₂-C₂单锌指结构，依据系统发育分析分为8个亚族，同一亚族内基因结构与蛋白保守结构域相对保守。亚细胞定位预测显示12个AaDof蛋白定位在细胞外，其余均定位在细胞核。启动子元件分析发现AaDof家族基因启动子区富含光、激素等多种响应元件。对AaDof在GA、UV-B和GA+UV-B处理下的表达模式分析发现，AaDof基因对GA胁迫处理响应较弱，仅有少量基因敏感，其表达主要受到UV-B胁迫影响。C1及C2.1亚族大部分基因在UV-B胁迫下上调表达，而A亚族大部分基因在UV-B胁迫下下调表达。qRT-PCR验证表明AaDof1、AaDof17和AaDof44在GA和UV-B处理下表达量显著上调，推测其可能通过参与GA和UV-B调控网络，正向调控青蒿素生物合成。结论 本研究系统鉴定了黄花蒿AaDof家族基因并筛选了3个可能正向调控青蒿素生物合成的候选AaDof基因，为黄花蒿Dof家族基因功能研究及其在青蒿素生物合成中的调控机制解析奠定基础。     

Cost-effectiveness frameworks for comparing genome and exome sequencing versus conventional diagnostic pathways: A scoping review and recommended methods

PurposeMethodological challenges have limited economic evaluations of genome sequencing (GS) and exome sequencing (ES). Our objective was to develop conceptual frameworks for model-based cost-effectiveness analyses (CEAs) of diagnostic GS/ES.MethodsWe conducted a scoping review of economic analyses to develop and iterate with experts a set of conceptual CEA frameworks for GS/ES for prenatal testing, early diagnosis in pediatrics, diagnosis of delayed-onset disorders in pediatrics, genetic testing in cancer, screening of newborns, and general population screening.ResultsReflecting on 57 studies meeting inclusion criteria, we recommend the following considerations for each clinical scenario. For prenatal testing, performing comparative analyses of costs of ES strategies and postpartum care, as well as genetic diagnoses and pregnancy outcomes. For early diagnosis in pediatrics, modeling quality-adjusted life years (QALYs) and costs over ≥20 years for rapid turnaround GS/ES. For hereditary cancer syndrome testing, modeling cumulative costs and QALYs for the individual tested and first/second/third-degree relatives. For tumor profiling, not restricting to treatment uptake or response and including QALYs and costs of downstream outcomes. For screening, modeling lifetime costs and QALYs and considering consequences of low penetrance and GS/ES reanalysis.ConclusionOur frameworks can guide the design of model-based CEAs and ultimately foster robust evidence for the economic value of GS/ES.     

Effect of orbital wall resection areas in the treatment of patients with endocrine orbitopathy

In patients treated by orbital wall decompression for endocrine orbitopathy (EO) there is limited evidence on the effect of orbital wall resections. Thus, the aim of this study was to evaluate the effect of one, two, and three-wall resections on orbital parameters to determine if any such correlations exist. Preoperative and postoperative data from all patients at a tertiary care centre who underwent decompression surgery from 2010 - 2020 were digitally analysed. The effect of the number and area of resected walls on orbital area, orbital volume, and Hertel value, and the effect of lateral rim advancement (LARA) were determined. A total of 131 orbital areas showed an increase from a mean (SD) preoperative area of 42.0 (4.6) cm² to 47.3 (6.1) cm² postoperatively (p<0.001). In total, the mean (SD) area of osseous wall removed in all patients was 6.2 (1.7) cm² at the lateral orbit (n = 129), 6.7 (2.3) cm² at the orbital floor (n = 123), and 5.8 (1.8) cm² at the medial orbital wall (n =30). The mean (SD) orbital volume increased by 6.0 (3.0) cm³ after decompression. There was also a significant reduction in exophthalmos of 7.3 (3.2) mm (from 25.2 (3.9) to 17.9 (3.5), p<0.001). LARA was performed in 50 patients. Changes in volume and area, and reduction in exophthalmos were not significantly different with or without LARA. The postoperative effects of orbital wall resection are predictable and exhibit a relation with six units of change. Two-wall resection is the most common intervention.     

Dietary patterns and the risk of abnormal blood lipids among young adults: A prospective cohort study

Background and aimsThe extent to which dietary patterns influence the risk of abnormal blood lipids throughout young adulthood remains unclear. The aim was to investigate whether early young adulthood dietary patterns predict the risk of abnormal blood lipids during later young adulthood.Methods and resultsWe used data from a long running birth cohort study in Australia. Western dietary pattern rich in meats, processed foods and high-fat dairy products and prudent pattern rich in fruit, vegetables, fish, nuts, whole grains and low-fat dairy products were derived using principal component analysis at the 21-year follow-up from dietary data obtained using a food frequency questionnaire. After 9-years, fasting blood samples of all participants were collected and their total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterols and triglyceride (TG) levels were measured. Abnormal blood lipids were based on clinical cut-offs for total, LDL and HDL cholesterols, and TG and relative distributions for total:HDL and TG:HDL cholesterols ratios. Log-binomial models were used to estimate risk of each outcome in relation to dietary patterns. Greater adherence to the Western pattern predicted increased risks of high LDL (RR: 1.47; 95%CI: 1.06, 2.03) and TG (1.90; 1.25, 2.86), and high ratios of total:HDL (1.48; 1.00, 2.19) and TG:HDL (1.78; 1.18, 2.70) cholesterols in fully adjusted models. Conversely, a prudent pattern predicted reduced risks of low HDL (0.58; 0.42, 0.78) and high TG (0.66; 0.47, 0.92) and high total:HDL (0.71; 0.51, 0.98) and TG:HDL (0.61; 0.45, 0.84) cholesterols ratios.ConclusionThis is the first prospective study to show greater adherence to unhealthy Western diet predicted increased risks of abnormal blood lipids, whereas healthy prudent diet predicted lower such risks in young adults. Addressing diets in early course may improve cardiovascular health of young adults.     

基于临床观察文本解析痛经辨治规律研究

目的:研究痛经的中医药辨治规律。方法:检索国家知识基础设施数据库(CNKI)1988—2019年应用中药治疗痛经的相关文献,采用Medcase Ver38诊籍中医师工作室-名老中医经验传承辅助平台,运用文本解析对临床医案进行研究。结果:研究文献131篇,医案104则,涉及病例128次,332诊次,涉及症状92条,病机33条,舌象27条,脉象17条,药物249种。结论:中医药治疗痛经的特异症状为“经行腹痛”,可见症为“夹血块、月经色暗、手足冰冷、经期腰酸”,相关舌脉为“舌质暗红,苔薄白”“脉沉细弦”,核心病机为“瘀血阻滞”,常用治法为“行气化瘀,活血止痛”,常用药物为“当归、白芍、甘草、延胡索、川芎”。