“Rule of Six”: How Does the Sendai Virus RNA Polymerase Keep Count?

The "rule of six" stipulates that the Paramyxovirus RNA polymerase efficiently replicates only viral genomes counting 6n + 0 nucleotides. Because the nucleocapsid proteins (N) interact with 6 nucleotides, an exact nucleotide-N match at the RNA 3'-OH end (3'-OH congruence) may be required for recognition of an active replication promoter. Alternatively, assuming that the six positions for the interaction of N with the nucleotides are not equivalent, the nucleotide position relative to N may be critical (N phase context). The replication abilities of various minireplicons, designed so that the 3'-OH congruence could be discriminated from the N phase context, were studied. The results strongly suggest that the application of the rule of six depends on the recognition of nucleotides positioned in the proper N phase context.     

“整合物种概念”和“分化路上的物种”

已有的各个物种概念对物种的认识类似盲人摸象, 只包含了物种的某一个方面; 而一个分化后期的成熟物种应涵盖了所有的物种概念。但是, 尚未到达分化后期的物种往往又已开始新一轮的物种分化; 自然中存在的多数“物种”处于分化路上。这种循环往复连续分化产生的物种, 存在种间生殖隔离不彻底、基因流频繁发生、网状进化突出等现象。此外, 对于不同的物种对, 最早开始分化的基因以及不同物种概念所要求的条件的分化顺序不是统一的, 而是随机的。定义一个适合所有“分化路上的物种”概念存在较大困难。但是, 应采用尽可能多的物种概念来界定分化路上的物种、发表新种和进行分类处理; 也应承认种间可能广泛存在不完全的生殖隔离和有限的基因流, 即有不属于两个物种群体的杂交或回交个体的存在。这样划分的物种比只依据一个物种概念认定的物种具有更高的客观性和科学性。     

Elacestrant in metastatic breast cancer: Is the “standard of care” meeting standard requirements?

The EMERALD trial was an open label phase 3 trial evaluating elacestrant, the first oral selective estrogen receptor degrader (SERD), as compared to “standard of care”, in ER+/HER2- (hormone receptor positive, no HER2 overexpression) advanced or metastatic breast cancer.The EMERALD trial restricted the “standard of care” control arm to limited options that may have led to a substandard control arm. We describe how the EMERALD trial protocol allowed different clinically inappropriate scenarios in the control arm, according to prior therapy. The main relevant question remains the potential advantage of elacestrant over fulvestrant in fulvestrant-naive patients.Analyzing outcomes in subgroups according to prior and per-protocol therapy would help analyzing trial results. However, these subgroup results may be non-significant, and another randomized trial will be needed. Trials should be designed to answer directly clinical questions that are relevant.     

“地衣”词考

本文考证了中国先秦时期到清末古籍中对“地衣”的解释;其中有共生学意义的“地衣”一词,是在清代李善兰的《植物学》一书中被提出的。     

而今迈步从头越: 马铃薯育种跨入“有种”时代

现代栽培马铃薯(Solanum tuberosum)是同源四倍体, 基因组高度杂合, 遗传组成复杂, 存在严重的自交衰退, 优异性状难以聚合, 使得育种周期漫长, 造成基于种子传代的马铃薯杂交育种难以突破。与此同时, 块茎无性繁殖导致马铃薯繁殖系数低、储运成本高和易携带病虫害等痼疾, 且种薯脱毒成本高, 限制其产业化发展。近期, 中国农业科学院深圳农业基因组研究所黄三文团队运用基因组设计理论和方法体系培育杂交马铃薯, 用二倍体育种替代四倍体育种, 实现了用杂交种子繁殖替代薯块繁殖, 创制了第1代高纯度的二倍体自交系和杂种优势明显的杂交马铃薯品系。该研究是马铃薯育种领域里程碑式的重大成果, 开启了基于基因组设计和种子迭代的马铃薯生物育种新纪元。     

Local Recurrence of Soft Tissue Sarcoma Revisited: Is there a Role for “Selective” Radiation?

BackgroundRadiation therapy (RT) is often utilized in cases of high-grade soft tissue sarcoma (STS), but there remain situations where treatment is with surgical excision alone. Our goals were to determine (1) the local recurrence (LR) rate with and without perioperative RT and (2) associations between local recurrence, patient, tumor, and treatment variables.MethodsWe performed a retrospective review of 165 consecutive STS patients. A Cox proportional hazards model was used to investigate variables associated with local recurrence.ResultsLR occurred in 15/78 (19%) without RT, 4/29 (14%) with postoperative RT, and 0/58 with preoperative RT (p=0.002). We found increased rates of local recurrence at 24 months for myxofibrosarcoma (p=0.001) and no-RT (p=0.003). Myxofibrosarcoma accounted for 33 (20%) of the study patients and 12 (63%) of the local recurrences.ConclusionThe LR rate in patients treated with surgery alone was disproportionately attributable to myxofibrosarcoma (11/23 cases, 48%). Other subtypes demonstrated a lower rate of LR in the absence of RT (4/55 cases, 7%), and no LR occurred when final margins were >2 mm. In certain circumstances treatment with a negative margin surgical resection followed by close observation is justifiable. RT is effective and should continue to be considered routinely in myxofibrosarcoma or when surgical margins are inadequate. Level of Evidence: III     

“瑞草”灵芝之现代研究

"灵芝"一词最早出现于东汉,人们"以为瑞草,服之神仙",称之为"灵芝"。现指隶属于真菌界Fungi、担子菌门Basidiomycota、伞菌纲Agaricomycetes、多孔菌目Polyporales、灵芝科Ganodermataceae的一类传统药用真菌的统称,具有免疫调节、抗肿瘤、抗氧化、抑菌、保肝护肝、止咳平喘等多种功效(林志彬2015;Gilletal.2016;Ahmad2018;Wuetal.     

“超级真菌”耳念珠菌研究进展

耳念珠菌Candida auris也被称为“超级真菌”,是近年来出现的一种人体病原真菌新物种,临床分离株通常具有多重耐药和高致死率等特征。2009年日本首次报道耳念珠菌之后,其感染病例在多个国家呈现出爆发式增长。目前已报道的病例分布在全球五大洲27个国家,包括中国。耳念珠菌感染给临床诊断和防控以及人类健康带来了巨大的挑战。本文从该菌临床分离菌株的生物学、遗传变异分化及耐药特征等方面入手,围绕分子流行病学、基因组特征、毒性因子和耐药性等方面系统地综述了近年来国内外取得的相关进展,并探讨了我国耳念珠菌感染的诊断、治疗和预防的措施。     

新医学是解决人类健康问题的真正钥匙——需“精准”理解奥巴马的“精准医学计划”

2015年年初,美国总统奥巴马在国情咨文中提出了一个预算2.15亿美元的“精准医学计划”,希望以此“引领一个医学时代”。新闻一经发布,“精准医学”立刻成为了媒体和百姓嘴边的热词,受此影响国内亦有不少人士纷纷为美国总统的这一计划点“赞”。有人用“医学革命”来形容它,有人用“开创性”来抬高它,还有一个传闻,受奥巴马“精准医学计划”的影响,中国将在15年内投入600亿元人民币启动并发展中国版的“精准医学计划”。对此,有人提出了质疑,美国版精准医学计划是否符合中国国情?是否存在“水土不服”的可能?直接套用美国总统的智慧能否解决具有中国特色的实际问题?争论由此引发一个让人思考的问题,究竟什么才是现代医学的核心?在盲目堆钱的行动前,我们确实有必要从科学和临床应用的角度来探讨和思考一下现代医学的发展方向。 为了能“精准”地看到问题的实质,我将从当下时髦并且相关的词汇谈起,通过梳理,期待找出解决人类健康问题的真正钥匙。