基于伏邪理论从“寒热-痰瘀-虚劳”角度分期辨治肺痿

肺痿是以肺叶痿弱为特征的慢性肺脏虚损性疾病,以咳唾涎沫、气短为主症,与现代医学特发性肺纤维化（IPF）相类似。临床以咳嗽、进行性呼吸困难、喘促胸闷为主要表现,甚则呼吸衰竭危及生命。肺痿属于古代疑难杂症,现代医学治疗亦十分棘手。汉代张机从“寒热-痰瘀-虚劳”的角度阐述了肺痿的主要病机,开创了治疗肺痿之先河。肺痿的病因病机复杂多样,病情迁延难愈,与伏邪理论“伏而不发”的特点不谋而合。因此,基于伏邪理论,结合中西医病机特点,进一步探讨肺痿早期、进展期、终末期3个阶段的分期论治思路,以期为肺痿不同阶段论治提供新的辨证论治思路。     

正气辨析

正气属中医学的气学范围,是一身之气或人气相对邪气时的称谓,是指人体内具有抗病、祛邪、调节、修复等作用的一类细微物质;正气以其运动而发挥防御、调节、修复等作用,具有物质运动的自然科学属性。正气分布到腑腑经络,则为脏腑经络之气;分布到脉之内外,则为营气和卫气。脏腑经络之气和营卫之气的防御、修复和调节作用,可因其构成成分和所在部位的不同而有所区别,但都是正气的功能体现。     

Aggregatibacter actinomycetemcomitans–Induced Bone Loss and Antibody Response in Three Rat Strains

Background: The aim of this study is to compare the colonization, immunoglobulin (Ig) G response, and alveolar bone loss in Aggregatibacter actinomycetemcomitans (Aa)–inoculated Fawn Hooded Hypertensive (FHH), Dahl Salt‐Sensitive (DSS), and Brown Norway (BN) rats. Methods: Each rat strain was divided into wild‐type Aa‐inoculated and non‐inoculated control groups. Blood taken at 12 weeks after inoculation was assessed for Aa‐specific IgG antibodies by an enzyme‐linked immunosorbent assay. Colonization was assessed 12 weeks postinoculation. Bone loss was estimated by measuring the distance from the cemento‐enamel junction (CEJ) to the alveolar bone crest (ABC) at 20 molar sites. Colonization and antibody levels were compared by using the Student t test. Diseased rats were defined as having two sites per quadrant with CEJ–ABC distances that were significantly greater than the control CEJ–ABC distances. Results: The Aa colonization of FHH rats was significantly higher than in other strains (P <0.05). The Aa‐specific IgG levels in the DSS Aa‐inoculated group were significantly higher than in its control group (P <0.05). Only FHH rats showed Aa disease‐associated bone loss (P = 0.0021). Conclusions: Aa colonized and caused more disease in FHH rats than in the other rat strains. The rat strains each responded differently to the same Aa strain.     

Gene evolutionary trajectories in Mycobacterium tuberculosis reveal temporal signs of selection

Genetic differences between different Mycobacterium tuberculosis complex (MTBC) strains determine their ability to transmit within different host populations, their latency times, and their drug resistance profiles. Said differences usually emerge through de novo mutations and are maintained or discarded by the balance of evolutionary forces. Using a dataset of ∼5,000 strains representing global MTBC diversity, we determined the past and present selective forces that have shaped the current variability observed in the pathogen population. We identified regions that have evolved under changing types of selection since the time of the MTBC common ancestor. Our approach highlighted striking differences in the genome regions relevant for host–pathogen interaction and, in particular, suggested an adaptive role for the sensor protein of two-component systems. In addition, we applied our approach to successfully identify potential determinants of resistance to drugs administered as second-line tuberculosis treatments.

The Mycobacterium tuberculosis complex (MTBC) is a genetically monomorphic group of bacteria (1, 2) whose members cause tuberculosis in humans and animals. The MTBC comprises both human-associated (L1, L2, L3, L4, L5, L6, L7, L8, and L9) and animal-associated (A1, A2, A3, and A4) clades (3–7). Due to the absence of horizontal gene transfer, plasmids, and measurable recombination among strains and other species (8–10), chromosomal mutations represent the source of MTBC genetic diversity. The maximum genetic distance between any two MTBC strains is around 2,500 single-nucleotide polymorphisms (SNPs). Strikingly, studies have highlighted large phenotypic differences between strains involving traits like gene expression, drug resistance, transmissibility, and immune response, despite this limited variation. In some cases, the mutations driving phenotypic differences have been identified—for example, nonsynonymous variants in genes, such as rpoB, katG, or gyrA, cause drug-resistant phenotypes (11–13). Furthermore, single mutations in regulatory elements can induce alterations to downstream gene expression, which can foster differential virulence characteristics (14, 15). Finally, specific gene mutations may affect transmission (9), host tropism within the complex (16), and the host immune response (17). However, many of the genomic determinants of these phenotypes remain elusive, despite robust evidence that they are driven by genetic differences between strains (18, 19).Several types of evolutionary forces play crucial roles in the fixation of mutations in bacterial populations. Previous research has provided evidence for the ongoing positive selection of specific genes and regions (9, 20–23), while other studies have reported ongoing purifying selection of specific genomic regions, especially in epitopes and essential genes (24). Additionally, there exists some evidence that genetic drift may have significant functional and evolutionary consequences (25).Detecting selection in MTBC at the genome-wide level remains a challenging task due to limited genetic diversity. The significant accumulation of nonsynonymous substitutions has been previously used to characterize patterns of mutation accumulation in large categories of genes (24, 26); however, these studies employed a limited number of strains. Of note, the number of MTBC sequences has undergone a recent and rapid expansion, with studies involving hundreds to thousands of strains. The large number of available sequences has allowed, for example, the estimation of the ratio of nonsynonymous to synonymous substitutions (dN/dS) signatures in more than 10,000 strains (27), thereby allowing the identification of targets of selection with some probably related to host–pathogen interactions. Host–pathogen interaction signals are specially challenging as they are likely obscured by the force exerted by antimicrobial therapies. Weaker signals are also expected in genes related to second-line drugs related to the relative underuse of related treatments and the low abundance of associated resistant strains in genome databases (28).We reasoned that to detect signs of selection, we should focus on when and/or where they occurred in the phylogenetic tree instead of averaging signs across the phylogeny. In this study, we developed a methodology to study temporal signs of selection in MTBC genes and identified positive selection in a larger number of genes than previously described. This allowed the identification of past and currently unknown players in the MTBC evolution, particularly two-component systems (2CSs), related to host adaptation and second-line drug resistance. This methodology can be applied to other tuberculosis settings to explore signs of selection associated with changing selective pressures and could be extremely useful to unravel hidden details in the evolution of other human pathogens.     

论络病与温病营血证

就温病营血证与络病关系进行探讨,认为络脉是外感温热之邪深入营血的主要途径,络脉病变是温病营血证的病理基础,“通”络的治则贯穿于温病营血证的治疗中,营血证即是温病后期极期外感温热之邪深入脏腑阴终的一种病理状态,其物质基础是络脉及络脉的病变。     

Gastric alpha-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology

The progressive degenerative process associated with sporadic Parkinson's disease (sPD) is characterized by formation of alpha-synuclein-containing inclusion bodies in a few types of projection neurons in both the enteric and central nervous systems (ENS and CNS). In the brain, the process apparently begins in the brainstem (dorsal motor nucleus of the vagal nerve) and advances through susceptible regions of the basal mid-and forebrain until it reaches the cerebral cortex. Anatomically, all of the vulnerable brain regions are closely interconnected. Whether the pathological process begins in the brain or elsewhere in the nervous system, however, is still unknown. We therefore used immunocytochemisty to investigate the gastric myenteric and submucosal plexuses in 150 microm cryosections and 8 microm paraffin sections from five autopsy individuals, whose brains were also staged for Parkinson-associated synucleinopathy. alpha-synuclein immunoreactive inclusions were found in neurons of the submucosal Meissner plexus, whose axons project into the gastric mucosa and terminate in direct proximity to fundic glands. These elements could provide the first link in an uninterrupted series of susceptible neurons that extend from the enteric to the central nervous system. The existence of such an unbroken neuronal chain lends support to the hypothesis that a putative environmental pathogen capable of passing the gastric epithelial lining might induce alpha-synuclein misfolding and aggregation in specific cell types of the submucosal plexus and reach the brain via a consecutive series of projection neurons.     

Diabetes and immunity to tuberculosis

The dual burden of tuberculosis (TB) and diabetes has attracted much attention in the past decade as diabetes prevalence has increased dramatically in countries already afflicted with a high burden of TB. The confluence of these two major diseases presents a serious threat to global public health; at the same time it also presents an opportunity to learn more about the key elements of human immunity to TB that may be relevant to the general population. Some effects of diabetes on innate and adaptive immunity that are potentially relevant to TB defense have been identified, but have yet to be verified in humans and are unlikely to fully explain the interaction of these two disease states. This review provides an update on the clinical and epidemiological features of TB in the diabetic population and relates them to recent advances in understanding the mechanistic basis of TB susceptibility and other complications of diabetes. Issues that merit further investigation — such as geographic host and pathogen differences in the diabetes/TB interaction, the role of hyperglycemia‐induced epigenetic reprogramming in immune dysfunction, and the impact of diabetes on lung injury and fibrosis caused by TB — are highlighted in this review.     

2012—2013年北京市流感样病例监测与流感病原学监测结果的相关性分析

目的通过分析2012—2013年北京市流感流行季（2012年9月--2013年4月）流感样病例监测与流感病原学监测结果的相关性,评价北京市一级以上医疗机构和二级以上医疗机构流感样病例监测工作的适用性和有效性。方法分析北京市421家一级以上医疗机构和144家二级以上医疗机构的流感样病例监测数据,按周次分别与北京市14家医疗机构开展的流感病原学监测数据进行相关性分析和回归检验。结果一级以上和二级以上医疗机构门急诊流感样病例百分比（ILI％）与流感病毒病原学监测中病毒分离阳性率成正相关（一级医院r=0．794,P〈0．001;二级医院r=0．787,P〈0．001）。一级以上和二级以上医疗机构ILI％与流感病毒分离阳性率的回归确定系数r2分别为0．630（P〈0．001）和0．620（P〈0．001）。结论一级以上和二级以上医疗机构流感样病例中归因为流感病毒感染的比例基本一致,从成本效益分析角度考虑,北京市利用144家二级以上医疗机构开展流感样病例监测已经可以满足对疾病监测的需要,比扩展到421家一级以上医疗机构具有更好的成本效益比。     

重症感染性疾病患儿病原菌检测及耐药性观察

目的调查近年因感染性疾病住院患儿的病原菌菌株、细菌的药物敏感性及耐药性检测情况。方法采用回顾性调查方法,收集2000年10月～2005年10月,0～16岁因急危重症感染性疾病住院患儿的血液、尿液、痰液及鼻咽分泌物、粪便、胸腔积液、脑脊液以及皮肤感染灶的浓汁为标本,对细菌培养中病原学菌株类型、抗生素的耐药性和药物敏感性检查结果进行分析。结果256份标本培养中,检出99种细菌菌株,阳性率为38．7％;其中肺炎克雷伯菌为35.4％,金黄色葡萄球菌28.3％,大肠埃希菌22．2％,其他病菌为15．1％。肺炎克雷伯菌对药物敏感性依次为亚胺培南、哌拉西林／他唑巴坦、丁胺卡那、环丙沙星;耐药性依次为替卡西林、庆大霉素、氨曲南、头孢吡肟。金黄色葡萄球菌对万古霉素、复方新诺明、庆大霉素、环丙沙星敏感;对青霉素G、红霉素、苯唑西林、阿莫西林／棒酸耐药。大肠埃希菌对亚胺培南、丁胺卡那、哌拉西林／他唑巴坦敏感;对哌拉西林、环丙沙星耐药。结论急危重症感染性疾病患儿感染病原菌中以肺炎克雷伯菌、金黄色葡萄球菌、大肠埃希菌感染为主,依据药敏实验选择抗生素具有重要的临床指导意义。