肠道、肺部菌群直接或通过肠—肺轴对 呼吸系统慢性疾病的影响

人体寄生的微生物与人体为共生关系,数量庞大,并形成不同的微生态系统,影响人体免疫、代谢、内分泌等生理过程。菌群失衡导致微生态紊乱,从而导致相关疾病的发生发展。呼吸系统慢性疾病患者常有肠道菌群和肺部菌群的改变,肠道菌群通过肠-肺轴影响呼吸系统免疫及呼吸系统慢性疾病,肺部菌群的改变导致肺部疾病的同时亦会通过血流引起肠道菌群的变化。近年来随着高通量测序及生物信息学技术的发展,相关研究也越发被重视,本文着重对肠道菌群、肺部菌群通过肠-肺轴或直接在肺部免疫及呼吸系统慢性疾病中所起的作用进行综述。     

Role of microbiota on lung homeostasis and diseases

The lungs, as a place of gas exchange, are continuously exposed to environmental stimuli, such as allergens, microbes, and pollutants. The development of the culture-independent technique for microbiological analysis, such as 16S rRNA sequencing, has uncovered that the lungs are not sterile and, in fact, colonized by diverse communities of microbiota. The function of intestinal microbiota in modulating mucosal homeostasis and defense has been widely studied; however, the potential function of lung microbiota in regulating immunity and homeostasis has just begun. Increasing evidence indicates the relevance of microbiota to lung homeostasis and disease. In this review, we describe the distribution and composition of microbiota in the respiratory system and discuss the potential function of lung microbiota in both health and acute/chronic lung disease. In addition, we also discuss the recent understanding of the gut-lung axis, because several studies have revealed that the immunological interaction among the gut, the lung, and the microbiota was involved in this issue.     

肠道菌群在肺纤维化疾病中的调节作用

肺纤维化是一种以成纤维细胞增殖及大量细胞外基质及胶原聚集,并伴随炎症损伤为特征的呼吸系统疾病终末期改变。该疾病以肺功能障碍和呼吸衰竭为主要病理基础,发病率逐年上升,目前治疗方法有限。在肠肺之间的功能调控研究中,肠道菌群构成变化引起的机体微生态失调能够通过多种方式影响呼吸系统疾病的进程。本文聚焦于肺纤维化等肺部疾病的肠肺调控研究前沿领域,综述了多种肺纤维化疾病的致病机制、肠道菌群的功能、肠肺双向调节和益生菌群干预治疗等方面的最新进展。此外,本文也提出了该领域目前存在的问题,以期为今后的调控机制探索和治疗药物研发提供有力的理论支持及策略支撑。     

消化系统类器官研究进展

类器官是一种近年来新发展的细胞三维培养系统。类器官与真实器官的三维结构相似,并具有自我更新和再现组织来源等特点,从而能够更好地模拟真实器官的功能。类器官为研究器官发生、再生、疾病发病机制以及药物筛选提供了一个崭新的研究和应用平台。消化系统在人体内发挥着重要功能,目前已成功建立多种消化器官的类器官模型。本文就近年来味蕾、食管、胃、肝和小肠类器官的研究进展及相关应用进行综述,并对这几种类器官的应用前景进行展望。     

肠段移植的研究进展

肠段移植作为外科手术一种替代治疗方式,目前已经广泛应用于临床多个学科,涉及消化系统、泌尿系统和生殖系统,主要包括食管、胃、胆道、膀胱、输尿管、阴道等的重建。现就肠段移植替代不同器官的功能重建做简要的综述。     

The COVID-19 epidemic and other notifiable infectious diseases in China

Many infection control measures have been implemented to prevent the spread of SARS-CoV-2 during COVID-19 pandemic. We aimed to investigate the impact of COVID-19 epidemic on the other notifiable infectious diseases in China, including respiratory infectious diseases, diseases transmitted through the digestive tract and animal-borne diseases. Compared with 2019, the overall decline rate of respiratory infectious diseases in 2020 is the highest (60–90%), and the diseases transmitted by the digestive tract and animal-borne diseases are similar at 20–30%. Both hepatitis and sexually transmitted diseases decreased significantly in February, and there were basically no significant changes in other months compared with previous years. The series of measures taken by China government to prevent the spread of SARS-CoV-2 are also very effective in preventing the spread of respiratory infectious diseases. But they also have a certain degree of prevention against notifiable infectious diseases spread by other routes.     

细胞药物的临床应用——细胞药物连载之五

近年来,细胞药物在基础研究领域的成果促进了临床应用。现在细胞药物治疗的疾病种类很多,包括神经系统疾病、自身免疫系统疾病、心血管系统疾病、血液系统疾病、消化系统疾病、下肢缺血、整形美容、抗衰老及抗肿瘤等,涉及的细胞主要有各种干细胞、软骨细胞、肝细胞、DC及CIK细胞等。国内外越来越多的机构和组织开展了细胞治疗的临床研究及应用。     

Alveolus formation: what have we learned from genetic studies?

The respiratory system has two basic functions: air exchange and pathogen clearance. The conducting airway and alveolar parenchyma are the basic structures to fulfill these functions during respiratory cycles. In humans, there are approximately 40 cell types in the lung that coordinately work together through various structural and signaling molecules. These molecules are vital for maintaining normal lung functions in response to environmental changes. Aberrant expression of these molecules can jeopardize human health and cause various pulmonary diseases. In this article, we will review some recent progress made in the pulmonary field, using genetic animal model systems to elucidate molecular mechanisms that are important for alveolar formation and lung diseases.     

FGF/FGFR signaling: From lung development to respiratory diseases

The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling system regulates a variety of biological processes, including embryogenesis, angiogenesis, wound repair, tissue homeostasis, and cancer. It exerts these regulatory functions by controlling proliferation, differentiation, migration, survival, and metabolism of target cells. The morphological structure of the lung is a complex tree-like network for effective oxygen exchange, and the airway terminates in the middle and distal ends of many alveoli. FGF/FGFR signaling plays an important role in the pathophysiology of lung development and pathogenesis of various human respiratory diseases. Here, we mainly review recent advances in FGF/FGFR signaling during human lung development and respiratory diseases, including lung cancer, acute lung injury (ALI), pulmonary arterial hypertension (PAH), chronic obstructive pulmonary disease (COPD), asthma, and pulmonary fibrosis.     

Nanotechnology in respiratory medicine

Like two sides of the same coin, nanotechnology can be both boon and bane for respiratory medicine. Nanomaterials open new ways in diagnostics and treatment of lung diseases. Nanoparticle based drug delivery systems can help against diseases such as lung cancer, tuberculosis, and pulmonary fibrosis. Moreover, nanoparticles can be loaded with DNA and act as vectors for gene therapy in diseases like cystic fibrosis. Even lung diagnostics with computer tomography (CT) or magnetic resonance imaging (MRI) profits from new nanoparticle based contrast agents. However, the risks of nanotechnology also have to be taken into consideration as engineered nanomaterials resemble natural fine dusts and fibers, which are known to be harmful for the respiratory system in many cases. Recent studies have shown that nanoparticles in the respiratory tract can influence the immune system, can create oxidative stress and even cause genotoxicity. Another important aspect to assess the safety of nanotechnology based products is the absorption of nanoparticles. It was demonstrated that the amount of pulmonary nanoparticle uptake not only depends on physical and chemical nanoparticle characteristics but also on the health status of the organism. The huge diversity in nanotechnology could revolutionize medicine but makes safety assessment a challenging task.     

虫草对肺部疾病治疗的研究进展

肺纤维化、慢性阻塞性肺病和哮喘是人类主要的呼吸系统疾病,它们均以肺部或呼吸道的慢性炎症为特征,当前的治疗方法尚不理想并伴随着很多的副作用,人们迫切需要一种更安全的替代疗法。冬虫夏草是我国传统的名贵药用真菌,被广泛用来治疗多种肺部疾病。近年来,冬虫夏草对肺部疾病治疗作用的研究取得了较大进展,本文综述了冬虫夏草、其无性型中国被毛孢(Hirsutella sinensis或Ophicordyceps sinensis)和其他相关虫草及其提取物对肺纤维化、慢性阻塞性肺病、哮喘等肺部疾病治疗作用的研究进展,并介绍了其作用机制的研究成果。     

Deriving respiratory cell types from stem cells

The reported pluripotential capabilities of many human stem cell types has made them an attractive area of research, given the belief they may hold considerable therapeutic potential for treating a wide range of human diseases and injuries. Although the bulk of stem cell based research has focused on developing procedures for the treatment of pancreatic, neural, cardiovascular and haematopoietic diseases, the potential for deriving respiratory cell types from stem cells for treatment of respiratory specific diseases has also been explored. It is suggested that stem cell derivatives may be used for lung replacement/regeneration therapeutics and high though-put pharmacological screening strategies for a variety of respiratory injuries and diseases including: cystic fibrosis, chronic obstructive pulmonary disease, respiratory distress syndrome, pulmonary fibrosis and pulmonary edema. This review will explore recent progress in characterizing adult respiratory and bone marrow derived stem cells with respiratory potential as well as the endogenous mechanisms directing the homing of these cells to the diseased and injured lung. In addition, the potential for embryonic stem cell based therapies in this domain as well as the histological, anatomical and molecular aspects of respiratory development will be summarized.     

Digestive proteases of blood-feeding nematodes

Blood-feeding parasites employ a battery of proteolytic enzymes to digest the contents of their bloodmeal. Host haemoglobin is a major substrate for these proteases and, therefore, a driving force in the evolution of parasite-derived proteolytic enzymes. This review will focus on the digestive proteases of the major blood-feeding nematodes - hookworms (Ancylostoma spp. and Necator americanus) and the ruminant parasite, Haemonchus contortus - but also compares and contrasts these proteases with recent findings from schistosomes and malaria parasites. Haematophagous nematodes express proteases of different mechanistic classes in their intestines, many of which have proven or putative roles in degradation of haemoglobin and other proteins involved in nutrition. Moreover, the fine specificity of the relationships between digestive proteases and their substrate proteins provides a new molecular paradigm for understanding host-parasite co-evolution. Numerous laboratories are actively investigating these molecules as antiparasite vaccine targets.     

Evaluation of the passage of Lactobacillus gasseri K7 and bifidobacteria from the stomach to intestines using a single reactor model

Background  

Probiotic bacteria are thought to play an important role in the digestive system and therefore have to survive the passage from stomach to intestines. Recently, a novel approach to simulate the passage from stomach to intestines in a single bioreactor was developed. The advantage of this automated one reactor system was the ability to test the influence of acid, bile salts and pancreatin.     

呼出气温度的研究现状

呼出气温度是一种新的呼吸系统疾病监测手段。从被发现开始,呼出气温度就引起了众多学者的兴趣。人们发现在哮喘等呼吸系统疾病患者身上测出的呼出气温度较正常健康人的呼出气温度要高。大量的研究结果表明呼出气温度的变化与患者肺部的炎症改变有关,学者们研究推断肺部的炎症改变使得肺部病变部位局部血管增生及血流量增加因而导致了肺部气道热量交换和损失的改变,最终导致患者呼出气温度的改变。这一发现在呼吸系统疾病中有着重要意义,科学家们认为呼出气温度可以作为一种非侵入性的新监测手段。     

黄连素及其衍生物抗呼吸系统肿瘤的作用及机制

近年来,呼吸系统肿瘤的发病人数和死亡人数均居世界前列且逐年上升,严重危害到人类的健康。目前,对于肿瘤的治疗多以手术切除和放化疗为主,容易出现扩散、转移和复发等现象,并且病人的身体要遭受巨大的病痛,同时也给病人及其家庭带来较大的经济负担。因此,对呼吸系统肿瘤的研究就变得十分重要。近年来,中医药发展迅速,越来越受到人们重视,以中草药中的天然化合物入药协助临床治疗已成为一种趋势。从药用植物黄连中提取的主要成分之一黄连素是一种异喹啉生物碱,对多种呼吸系统肿瘤都有特异性作用,能够通过mTOR、MAPK、CyclinB₁、TF、TGF、MMP-2、VEGF、HIF-1α、AMPK、PD-L1、γH2AX等靶点和信号通路共同作用于肺癌、喉癌、鼻咽癌等呼吸系统肿瘤细胞。诱导细胞凋亡,调节细胞自噬,抑制其增殖、迁移和侵袭,抑制肿瘤细胞血管新生,促进免疫治疗,降低肿瘤细胞的耐药性等。本文综述了近年来黄连素及其衍生物抗呼吸系统肿瘤肺癌、喉癌和鼻咽癌等的作用及机制,将近年来有关黄连素对抗呼吸系统肿瘤的研究进行了整理、归纳和总结,并对目前研究不足的地方作出了展望,希望能找出下一步研究的方向,也希望黄连素能在呼吸系统肿瘤的治疗中更好地发挥作用,同时促进中草药成分应用于临床。     

肺部微生态与肺癌的关系

近年来肿瘤相关微生物的研究已成为热点,主要涉及细菌、免疫细胞和肿瘤细胞之间的相互作用、细菌致癌途径及其在肿瘤诊断及治疗意义等方面。随着微生物检测手段的飞速发展,人们发现,肺部具有独特的微生态,越来越多的研究在求证肺部微生态与呼吸系统疾病之间的联系。肺癌目前仍然是威胁人类健康的最常见、预后极差的恶性肿瘤。寻求早期筛查、干预、诊治手段是目前攻克肺癌的重点和难点。肺癌患者的肺微生态有其特征性改变,微生物可能通过产生细菌毒素和其他炎性因子而影响肺癌的发生及发展。本文对肺微生态与肺癌相关性进行了综述,并对今后的研究提出了展望。     

超极化激活的环核苷酸门控性阳离子通道（HCN）与疾病的相关性

超极化激活的环核苷酸门控的阳离子通道(hyperpolarization-activated cyclic nucleotide-gate cation channel,HCN)是一种特殊的阳离子通道,存在于神经细胞、小肠间质细胞、窦房结细胞或心脏细胞等具有自律性的细胞膜上,是产生过度激活正离子电流的结构基础,被认为是起搏细胞的重要特征。HCN离子蛋白通道不但与细胞凋亡以及电流传导有着密切关系,而且还与多种生命活动过程密切相关,近年来,已涉及到疼痛、癫痫、心律失常、消化道系统等许多疾病,特别是有关神经系统方面的疾病,下面将超极化激活的环核苷酸门控性阳离子通道(HCN)与疾病的关系综述如下。