Bench to bedside: recent advances in lung cancer pathological research with implications for diagnostic clinical practice

After decades of relative stagnation lung cancer is emerging as a disease type where rapid progress is being made in diagnosis and therapy, as well as in our understanding of disease biology. Much of this progress is of immediate impact to diagnosticians, and more is likely to affect diagnostic practice in the near future. In this review we seek to briefly summarize several key areas of active research of immediate or probable imminent value to trainee and consultant pulmonary pathologists alike. We cover some major changes in tumour classification, grading, and patient stratification, as well as considering the state of the art in machine-assisted interpretation of lung cancer histology, and the use of genetically modified lung cancer models.     

《针灸大成》关于气海穴临床应用的文献研究

目的:通过检索《针灸大成》中与气海穴治疗作用相关的文献条文,总结气海穴在治疗各系统疾病中运用频次较高的疾病及其配穴规律,为临床针灸对气海穴的使用提供理论支持。方法:以《中华医典》(第五版)中《针灸大成》作为文献检索来源,将气海穴及气海穴的别称“脖胦”“下肓”“丹田”“肓之原”“肓原”“下言”和“气泽”为检索词,用计算机检索工具及人工检索相结合的方法检索符合要求的文献条文,通过建立本研究的数据库,频次分析、条形统计图比较分析等方法,总结出气海穴在治疗各系统疾病中的运用频次及其配穴规律。结果:在《针灸大成》所涉及的条文中,气海穴尤善治疗内科疾病,在治疗内科疾病中排名前3位的是脾胃系病症、气血津液疾病、肾系病症和妇科疾病,气海穴配穴习惯为上下配穴法,同名经配穴法,以及前后配穴法,其中主要为前后配穴法和同名经配穴法。结论:气海穴《针灸大成》中单穴应用占比最高,而在气海穴众多配穴中,运用了本经配穴法、上下配穴法、前后配穴法,配穴归经主要来自任脉和足太阳膀胱经。同名经配穴法,同气相求,可增加疗效;与气海穴配伍较多的足太阳膀胱经以背腧穴为主,此为前后配穴法,亦称腹背阴阳配穴法,腹部为阴,腰背为阳,前后配穴法可起到“从阳引阴”亦可“从阴引阳”的作用,以达到调节阴阳,调和脏法,调畅经络的目的。     

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”。     

清代名医陈念祖“重视气血”治疗月经病用药规律及特点研究

[目的] 探讨研究陈念祖治疗月经病的用药规律及特点。[方法] 收集陈氏《女科要旨》《南雅堂医案》《医学从众录》中治疗月经病的处方81首，构建处方数据库。运用Excel 2010与SPSS Statistics 26.0软件对高频药物进行频数和聚类分析，并结合理论分析，提炼出陈氏治疗月经病的用药规律及特点。[结果] 收集的81首处方中，涉及药物共121味。≥6次的高频药物共32味，使用频数排前3位的是当归、白芍、茯苓。高频药物种类以补血药、补气药为主；四气以温性为首；五味以甘、苦、辛为主；归经以脾经为首，肝经次之，心经再次。聚类分析得出5组核心药组，涉及归脾汤、六君子汤、越鞠丸等方剂。用药特点:使气血化生而调和脾胃，畅气血运行而疏理心肝，守气血循经而调理冲任。[结论] 陈氏治疗月经病以气血为核心，调和脾胃气血、调畅心肝气机、调理冲任气血，多运用补血药、补气药、理气药。     

新型冠状病毒肺炎危重症中医药干预的必要性思考

新型冠状病毒肺炎(NCP)是一种具有广泛传染、较强致病性的外感疫病,对公众健康造成极大威胁[1-2]。由于病邪侵入人体后传变迅速,疫毒易于弥漫三焦、充斥表里转为危重症,处于危重症时现代医学目前只能对症支持治疗,为恢复危重症患者脏器机能、改善危重症状,配合中医药辨证施治值得深入思考。现以中医整体辨证的视角对新型冠状病毒肺炎所致危重病症辨证梳理,为临床提供一定的借鉴。     

Benzophenone-3 promotion of mammary tumorigenesis is diet-dependent

Benzophenone-3 is a putative endocrine disrupting chemical and common ingredient in sunscreens. The potential of endocrine disrupting chemicals to act as agonists or antagonists in critical hormonally regulated processes, such as mammary gland development and mammary tumorigenesis, demands evaluation of its potential in promoting breast cancer. This study identifies the effects of BP-3 on mammary tumorigenesis with high-fat diet during puberty versus adulthood in Trp53-null transplant BALB/c mice. Benzophenone-3 exposure yielded levels in urine similar to humans subjected to heavy topical sunscreen exposure. Benzophenone-3 was protective for epithelial tumorigenesis in mice fed lifelong low-fat diet, while promotional for epithelial tumorigenesis in mice fed adult high-fat diet. Benzophenone-3 increased tumor cell proliferation, decreased tumor cell apoptosis, and increased tumor vascularity dependent on specific dietary regimen and tumor histopathology. Even in instances of an ostensibly protective effect, other parameters suggest greater risk. Although benzophenone-3 seemed protective on low-fat diet, spindle cell tumors arising in these mice showed increased proliferation and decreased apoptosis. This points to a need for further studies of benzophenone-3 in both animal models and humans as a potential breast cancer risk factor, as well as a more general need to evaluate endocrine disrupting chemicals in varying dietary contexts.     

Avian mud nest architecture by self-secreted saliva

Mud nests built by swallows (Hirundinidae) and phoebes (Sayornis) are stable granular piles attached to cliffs, walls, or ceilings. Although these birds have been observed to mix saliva with incohesive mud granules, how such biopolymer solutions provide the nest with sufficient strength to support the weight of the residents as well as its own remains elusive. Here, we elucidate the mechanism of strong granular cohesion by the viscoelastic paste of bird saliva through a combination of theoretical analysis and experimental measurements in both natural and artificial nests. Our mathematical model considering the mechanics of mud nest construction allows us to explain the biological observation that all mud-nesting bird species should be lightweight.

Bird nests come in a variety of forms made from diverse building materials (1, 2). Each type of bird nest is subjected to mechanical constraints imposed by material characteristics. To overcome these constraints, birds have devised brilliant architectural technologies, which provide inspiration for a novel materials processing scheme and help us to better understand animal behavior.For instance, some birds including storks (Cicioniidae) and eagles (Accipitidae) build nests by piling up hard filamentary materials such as twigs, harnessing their friction as the cohesion mechanism (3). Weaverbirds (Ploceidae) weave soft filamentary materials such as grass and fine leaves into a woven nest tied to a tree branch. Some bird species use their own saliva in nest building, which Darwin considered an example of natural selection (4). An extreme case is the Edible-nest Swiftlets, which build their nest purely of self-secreted saliva so that it can be attached to cliff walls and cave ceilings where the above twig piles and tied leaves are not allowed (5).Swallows (Hirundinidae), phoebes (Sayornis), and other mud nesters have developed a unique building material, a mixture of mud and their own saliva, in contrast to those made of purely collected or self-secreted materials (6) (Fig. 1). During construction, mud nesters repeatedly pile a beakful of wet mud on the nest, and liquid bridges are formed in the nest due to evaporation. While building a nest usually takes several weeks, a transition from wet to dry structures can occur within a few hours. Hence, the capillary forces of liquid bridges temporarily provide cohesion such as those in sandcastles. However, unlike sandcastles, dehydrated saliva comes into play for permanent cohesion after complete evaporation (SI Appendix, Supplementary Note 1).Open in a separate windowFig. 1.A nest of the barn swallow (H. rustica). (A) Photograph of a barn swallow nest, taken from under the ceiling of a house in Suwon-si, Gyunggi-do, South Korea (37°16′13.5″N 126°59′01.0″E). (B) SEM image of the nest surface. (C) Chemical composition analysis of the surface shown in B by EDS. The red area indicates a region containing mostly carbon atoms, which may originate from bird saliva. The green area indicates a region containing mostly the silicon atoms of clay particles.Mud itself cannot confer sufficient cohesion and adhesion in mud nests. The ability of mud nests to bear tensile loads originates from the gluing agent in the bird''s saliva, which permeates into granules as a liquid and binds them as a solid after solvent evaporation (6–8) (SI Appendix, Supplementary Note 2). The gluing agent is called mucin, a family of large glycoproteins that are ubiquitous in animal organs and form a mucus gel with versatile functionality (9). Fig. 1B shows the scanning electron microscopy (SEM) image of a barn swallow’s mud nest consisting of platelet clay particles and larger grains. Energy-dispersive spectroscopy (EDS) mapping image of Fig. 1C clearly shows regions corresponding to organic material which is presumed to be from bird’s saliva.Of particular interest and worth biophysical investigation are the tensile strength of the mud nest with hardened saliva, design principles associated with the saliva-originated strength, and the resulting effects on the evolution of these mud-nesting birds. Principles behind cohesion in granular materials, such as wet sands (10), cemented powder aggregates (11), construction materials (12), and pharmaceutical tablets (13), have been studied to date, exploring the stress transmission, elasticity, and failure (14–18), and the formation of solidified bridges (19–21). However, little attention has been paid to the cohesion effects of self-secreted polymer materials upon evaporation and the biologically constructed granular architecture like birds’ mud nests. Here we devised experimental techniques to measure the strength of the relatively small and fragile nest specimens in order to mechanically characterize birds’ mud nests. We elucidate how solutes from bird saliva generate solid bridges that give rise to macroscopic tensile strength, which has long awaited physicochemical explanation since its first observation (4). To characterize the design principle of bird''s mud nests, we investigated natural and three-dimensional (3D)-printed artificial nests with various tools for visualization and mechanical testing. Along with the experimental studies, we theoretically investigated the effects of biopolymer concentration on nest strength. This combination of theory and experiment suggests that there is a size limit for mud-nesting birds, which is supported by biological data.     

Using cortical non-invasive neuromodulation as a potential preventive treatment in schizophrenia - A review

BackgroundEvidence suggests that schizophrenia constitutes a neurodevelopmental disorder, characterized by a gradual emergence of behavioral and neurobiological abnormalities over time. Therefore, applying early interventions to prevent later manifestation of symptoms is appealing.ObjectiveThis review focuses on the use of cortical neuromodulation in schizophrenia and its potential as a preventive treatment approach. We present clinical and preclinical findings investigating the use of neuromodulation in schizophrenia, including the current research focusing on cortical non-invasive stimulation and its possibility as a future preventive treatment.MethodsWe performed a search in Medline (PubMed) in September 2020 using a combination of relevant medical subject headings (MeSH) and text words. The search included human and preclinical trials as well as existing systematic reviews and meta-analysis. There were no restrictions on language or the date of publication.ResultsNeurodevelopmental animal models may be used to investigate how the disease progresses and thus which brain areas ideally should be targeted at a given time point. Here, abnormalities of the prefrontal cortex have been often identified as an early and persistent impairment in schizophrenia. Currently there is insufficient evidence to either support or refute the use of neuromodulation to the cortex in adult patients with already manifested symptoms. However, preclinical results show that early non-invasive neuromodulation to the prefrontal cortex of adolescent animals, sufficiently prevents later psychosis-relevant abnormalities in adulthood. This points to the promising potential of cortical non-invasive neuromodulation as a preventive treatment when applied early in the course of the disease.ConclusionPreclinical translational-oriented findings indicate, that neuromodulation to cortical areas offers the possibility of targeting early neuropathology and through this diminish the progression of a later schizophrenic profile. Further studies are needed to investigate whether such early cortical stimulation may serve as a future preventive treatment in schizophrenia.     

Modelling human pathology of traumatic brain injury in animal models

Traumatic brain injury (TBI) is caused by a head impact with a force exceeding regular exposure from normal body movement which the brain normally can accommodate. People affected include, but are not restricted to, sport athletes in American football, ice hockey, boxing as well as military personnel. Both single and repetitive exposures may affect the brain acutely and can lead to chronic neurodegenerative changes including chronic traumatic encephalopathy associated with the development of dementia. The changes in the brain following TBI include neuroinflammation, white matter lesions, and axonal damage as well as hyperphosphorylation and aggregation of tau protein. Even though the human brain gross anatomy is different from rodents implicating different energy transfer upon impact, especially rotational forces, animal models of TBI are important tools to investigate the changes that occur upon TBI at molecular and cellular levels. Importantly, such models may help to increase the knowledge of how the pathologies develop, including the spreading of tau pathologies, and how to diagnose the severity of the TBI in the clinic. In addition, animal models are helpful in the development of novel biomarkers and can also be used to test potential disease‐modifying compounds in a preclinical setting.