Network Biological Modeling:A Novel Approach to Interpret the Traditional Chinese Medicine Theory of Exterior-Interior Correlation Between the Lung and Large Intestine

Objective To study the common pathogenesis of pneumonia and colitis using modern biological network analysis tools,and to explore the theory that the lung and large intestine are exteriorly and interiorly related.Methods The relevant target genes(hereinafter,“targets”)of pneumonia and colitis were separately queried on the GeneCards database.The main targets of the two diseases were then screened out according to their correlation scores and intersected to obtain those common to the two diseases.Metascape was used to analyze the main and common targets identified,and the Database for Annotation,Visualization and Integrated Discovery(DAVID)was used to enrich and analyze the common targets.Cytoscape 3.7.2 software was used to build the network diagram.Results In total,54 targets,such as TNF,IL-10,IL-6,IL-2,IL-4,TLR4,TLR2,CXCL8,IL-17A and IFNG,etc.,are common to pneumonia and colitis,which are mainly enriched in these processes such as cytokine–cytokine receptor interaction,the Tcell receptor signaling pathway,the Toll-like receptor signaling pathway and the Jak-STAT signaling pathway.The Metascape modular analysis identified 11 modules for pneumonia,six modules for colitis,and two modules for the common targets.Conclusions Pneumonia and colitis have the same pathogenic targets and mechanisms of action and finally interact with each other through inflammatory reactions and immune responses.This provides a probable molecular mechanism that explains the theory that the lung and large intestine are exteriorly and interiorly related.

A Novel Apprehension of the Primary Lung Meridian, Sinew Channel, Divergent Channel, Luo-Connecting Channel Acting as a Single Unit System to Serve Respiration Function Based on Modern Neurophysiology and Kinesiology

The TCM philosophy of a meridian and associated channels pertains to the specific function of one or more organs. We define the Lung Primary Meridian (LUM) together with the Lung Sinew (LUSC), Divergent (LUDC), Luo-connecting (LULCC) Channels as a system of routes plus some parts of the body (such as muscles) to fulfil respiration, as a main function under different situations. There is very limited information about the Lung associated channels in classical literature of TCM. With a clear focus on the function of respiration, we have carried out a detailed analysis of the biomedical consequence of stimulating the LUM, analysed the roles played by LUSC, LUDC, and LULCC. The updated LUM and LUDC include acupoints of other meridians, serving the same purpose of performing satisfactory respiration starting from checking the quality of the inflow through the nose. The LUSC includes the respiratory muscles (plus the associated connective tissues) extending to various parts of the body. The muscles of the limb (as part of the LUSC) embrace the nerves that provide routes for somatosensory reflexes and play the role of locomotion, providing voluntary respiration via the pectoralis muscles. The muscles of LUSC are bounded by stiff connective tissue layers, forming compartments, and are part of the pulley system for various body locomotions. Within a compartment, the interstitial fluid, blood, lymph flows must be potent to protect the associated nerves related to LUM;the healthy state of the LUSC also provides freedom of various types of locomotion. The LULCC exists because the vagus nerve has a part of it passing through the spinal cords all the way down to the sacrum domain, with exiting nerve innervating two-third of the large intestine. The crucial steps of our deductions are supported by experimental evidence based on modern neurophysiology and kinesiology. We discover that all the four channels stated above work as a unit system to allow respiration to be possible under various postures/conditions. The complexity of structures and processes is eased off by providing 29 figures and 13 tables for the relevant muscles and nerves. In addition to respiration, the Lung system in TCM context includes interaction of this system with the sweat gland and neuroendocrine system;such aspects will be left to another study.

Experimental Study on the Mechanism of Protective Effect of Free Fu on Gut-derived Endotoxin-Mediated Lung Damage

The effect of tumor necrosis factor-α (TNF-α) on endotoxin (ET)-mediated lung damage caused by incomplete ligation of large intestine and the influence of free Fu on the expression of TNF-α mRNA were explored. Forty SD rats were randomly divided into 4 groups: normal control group, model group, ligation group and treatment group (n=10 in each group). The models were made by the method of partly ligating the rectum outside the body. The plasma level of lipopolysaccaride was measured by dynamic nephelo metric method and the serum level of TNF-α was detected by the method of radioactive immunity. The expression of TNF-α mRNA in lung tissue was detected by RT-PCR method. The results were compared among the 4 groups. The results showed the plasma levels of ET and serum TNF-α in the model group and the expression of TNF-α mRNA in the lung tissues were remarkably higher than those in the normal control group (P<0.01). After the treatment of free Fu, all of the above indexes in the treatment group were all decreased as compared with model group (all P<0.01), and the damage to lung was alleviated. It was concluded that TNF-α might play a very important role in the ET-mediated lung damage caused by incomplete ligation of large intestine, free Fu could protect the lung from damage.

The Association between Pulmonary Function Impairment and Colon Inflammation in Ulcerative Colitis Patients： A Scientific Basis for Exterior-Interior Correlation between Lung and Large Intestine

Objective： To investigate the involvement of pulmonary function impairment in ulcerative colitis（UC）, and explore a scientific basis for the Chinese medicine（CM） theory of exterior-interior correlation between Lung（Fei） and Large intestine（Dachang）. Methods： Totally 120 patients with a diagnosis of UC were recruited and the demographics, clinical data, and blood samples were collected. C-reactive protein（CRP） and erythrocyte sedimentation rate（ESR） concentrations were measured. Every patient accepted pulmonary function test and took chest radiograph（CXR）. Results： Pulmonary function abnormalities were present in 72 of 120 patients. The median（interquartile range） vital capacity（VC）, forced vital capacity（FVC）, forced expiratory volume in 1 s（FEV_1）, carbon monoxide diffusion capacity（DL_∞） of lung, total lung capacity（TLC） and functional residual volume（FRV） were decreased in distal UC and pancolitis compared with ulcerative prochitis（P〈0.0005）. Male patients had increased VC, FEV_1/FVC, and residual volume（RV）/TLC compared with female（P〈0.0005）, but decreased DLCO and carbon monoxide iffusion capacity（KCO） of lung/alveolar ventilation（P〈0.0005）. Age was strongly correlated with RV（Spearman rank correlation coefficient（rs）=–0.57, P〈0.0001）, and RV/TLC（rs=0.48, P〈0.0001）. Age was also correlated with FEV_1/FVC（rs=–0.29, P=0.001）, forced expiratory flow in 75% vital capacity（FEF75%, rs=–0.20, P=0.03）, DLCO（rs=–0.21, P=0.02）, TLC（rs=–0.25, P=0.006）, and FRV（rs=–0.28, P=0.002）. The course of disease was correlated with FEF75%（rs=–0.18, P=0.049） and KCO（rs=–0.19, P=0.036）. Chest radiograph abnormalities were presented in 38 of 120. Pulmonary symptoms were presented in 10 of 120. Other extraintestinal complications were presented in 21 of 120. Conclusions： Pulmonary function impairment was more frequently than other extraintestinal complications in UC patients, which may be affected by sex, age, extent and course of disease. These results may be a scientific basis for the theory of exterior-interior correlation between Lung and Large intestine.

The influence of intestine-based treatment using Xuan Bai Cheng Qi Tang on the concentration of trace elements in the main organs of COPD rats

Objective:To test two theories from traditional Chinese medicine:'exterior -interior relationship between the lung and large intestine' and 'treating from the intestine principle for lung disorders'.The influence of intestine-based treatment using Xuan Bai Cheng Qi Tang (XBCQT) on the concentration of three trace elements-copper (Cu),zinc (Zn),and manganese (Mn)-was observed in the tissues of the lung,small intestine,large intestine,and stomach of rats suffering from chronic obstructive pulmonary disease (COPD).Methods:Thirty-five male Wistar rats were divided randomly and equally into five groups:control;model;Fei treatment (A);Chang treatment (B);and Fei-Chang treatment (C).A rat model of COPD was prepared by tracheal injection of lipopolysaccharide plus exposure to cigarette smoke.Treatments with medicinal herbs started day-22 of administration and exposure to cigarette smoke for 7 days.The control group and model group were administered physiologic (0.9%) saline solution via the stomach.After 7 days of intervention,the tissues of the lung,small intestine,large intestine,and stomach were removed.Inductively coupled plasma-atomic emission spectroscopy was used to detect the levels of Cu,Zn,and Mn in those tissues.Results:Compared with the control group,the Cu concentration in the tissues of the small intestine,large intestine,and stomach increased significantly in the model group (P <.05);the Mn concentration in the tissues of the lung,large intestine,and stomach increased significantly in the model group (P <.05);the Zn concentration in the tissues of the lung and large intestine decreased significantly in the model group (P <.05).In comparison of the model group:the Cu concentration in the tissues of the lung and large intestine decreased significantly in the B group (P <.05);the Mn concentration in the tissues of the lung,small intestine,and large intestine decreased significantly in the B group (P <.05);the Zn concentration in the tissues of the lung,small intestine,and large intestine increased significantly in the B group (P <.05).For the A group versus C group comparison,the Zn concentration in the tissues of the small intestine and stomach increased significantly in the latter (P <.05).Conclusion:This study showed that 'treating from the intestine' using Xuan Bai Cheng Qi Tang and its modified formulae can regulate the concentration of trace elements in the main organs of COPD rats.This may be one of the mechanisms for intestine-based treatment for COPD.

杨燕教授从肺论治儿童功能性便秘的临床经验

儿童功能性便秘约占小儿便秘的95%以上,是小儿消化系统的常见病,病程迁延易对儿童的身心健康产生严重影响。文章总结杨燕教授治疗儿童功能性便秘的临床经验。杨燕教授认为便秘的病机主要是大肠的传导功能失常,但与肺脏密切相关。肺与大肠相表里,肺气亏虚或肺气郁闭,宣肃失职,气机不畅,津液疏布失常,肺热移于大肠,肠失濡润,均可导致便秘发生。从肺论治,临证采用塞因塞用之法补气启闭治虚秘,提壶揭盖之法理肺通腑治实秘,同时重视良好的饮食结构及日常护理,临床疗效显著。附验案1则以佐证。

基于“肺与大肠相表里”探析血管内皮细胞与肠道菌群的关联

肠道菌群及其代谢物失调对内皮细胞损伤和功能障碍具有重要影响。中医“肺”与血管内皮细胞在结构、生理及病理方面具有相关性。中医学“肺与大肠相表里”理论是肺与肠在结构、生理及病理方面相关性的高度概括,可作为血管内皮细胞与肠道菌群相关联的理论基础。本文可为以肠道菌群为切入点、修复血管内皮细胞损伤干预心血管疾病的实验研究提供理论依据,并为中医药临床治疗相关疾病提供参考。

健脾祛湿和络方治疗特发性膜性肾病内涵探讨

从多维论治角度结合部分健脾祛湿和络方的研究进展,阐释健脾祛湿和络方有效治疗特发性膜性肾病(IMN)的中医学内涵。IMN以脾虚证、肾虚证为核心证候,健脾祛湿和络方立方以调理脾胃为基础,脾肾同治。从肺肾相关、肠肾相关、肺与大肠相表里等理论看,健脾祛湿和络方亦体现出了脾肺同治、肠肾同治、肠肺同治的中医学内涵,脾、肺、肠、肾相结合的多维论治是健脾祛湿和络方取效之根本。

Infrared Thermal Imaging-Based Research on the Intermediate Structures of the Lung and Large Intestine Exterior-Interior Relationship in Asthma Patients

Objective: By observing body surface temperature variation of the intermediate structures of the Lung(Fei) and Large Intestine(Dachang) exterior-interior relationship in asthmatic patients, to investigate the pathological response on the pathway of channels and to substantiate the objective existence of the intermediary structures. Methods: The study included 60 subjects meeting the bronchial asthma inclusion criteria(experimental group) and 60 healthy subjects(normal control group). ATIR-M301 infrared thermal imaging device was used for detecting body surface temperature of the subjects and collecting the infrared thermal images. The temperature values of the intermediate structures of Lung and Large Intestine exterior-interior relationship [throat, Quepen, elbow, nose, Lieque(LU 7), Pianli(LI 6)], control areas(0.2 cm lateral to the above structures) and Yintang(EX-HN 3) were measured on the infrared thermal image by infrared imaging system. Then, the above temperature values were compared and analyzed within and between two groups. Results: There were insignificant differences between the temperature on the left and right sides of the intermediate structures(Quepen, elbow, LU 7, LI 6) in normal control group(P>0.05). Except for that of Quepen, there were insignificant differences between the temperature of the intermediate structures and their corresponding control areas in normal control group(P>0.05). In the experimental group, the temperature on the left and right sides of the intermediate structures(Quepen, elbow, LU 7, LI 6) showed statistically significant differences(P<0.05 or P<0.01); the temperature difference between intermediate structure(throat, Quepen, elbow, nose, LI 6) and their respective control areas were also significant(P<0.05 or P<0.01). The temperature of the intermediate structures(throat, Quepen, elbow, LU7, LI 6) between the experimental group and normal control group showed significant differences(P<0.05 or P<0.01). Conclusions: This study is an initial step to validate the objective existence of Lung and Large Intestine exterior-interior relationship intermediate structures, as described in the Chinese classical medical literatures, through the functional imaging angle. The intermediate structures are the pathological reaction areas of the bronchial asthmatic patients.

从“金郁泄之”论治溃疡性结肠炎

“金郁泄之”理论出自《黄帝内经》,“金”是肺与肠的基本属性,“郁”指郁滞,壅塞不通的异常状态,故“金郁”可理解为属金脏腑如肺、大肠所发壅滞、阻塞之证。“泄之”是五行属金脏腑郁滞的治疗方法,其具体含义应随“金郁”的病理产物、病位的不同而不同。溃疡性结肠炎多由邪蕴肠腑,气血瘀滞,肠道传导失司,湿、热、瘀于大肠相互搏结成郁,改变肠道属金肃降之性所致,其核心病机为湿热内蕴,气血瘀滞,属于“金郁”的范畴,病位虽在大肠,可波及于肺。故治疗应顺应“泄之”的法则,以祛除肺肠之郁为主,包括清泄与宣泄两种方法,同时补益肺、脾、肾三脏之气,以恢复肺肠之功能,达到扶正祛邪,标本兼顾的目的,促进溃疡性结肠炎的愈合。

Understanding the viscera-related theory that the lung and large intestine are exterior-interiorly related

Pairing of the viscera and bowels is an important theory,which provides guidance to traditional Chinese medicine(TCM) clinical practice.Investigating this theory has been the focus of research on the basic theory of TCM.Recently,researchers have performed many studies on the theory that the lung and large intestine are exterior-interiorly related,which is a different point of view to that of previous literature,recent clinical studies and experimental studies,and these recent studies have enforced the theoretical connotation of the statement.However,there are problems in some of these studies including recent clinical studies and experimental studies.In the current article,literature on the viscera-related theory of the lung and large intestine are exterior-interiorly related is reviewed from physiological,pathological,and clinical views,and some opinions on the current research status are discussed.

从“肺与大肠相表里”阐释针灸治疗哮喘的理论内涵

针灸治疗肺系疾病有深厚的理论根源和得天独厚的优势,并有丰富的临床应用经验。“肺与大肠相表里”理论指导下针灸“肺肠同治”对改善哮喘症状及气道炎症反应具有重要意义。基于“肺与大肠相表里”理论,主要从肺与大肠组织相连、经络相通、功能上相互为用以及病理上的相互影响等方面,系统阐释肺与大肠的特殊关系,进而阐释“肺肠同治”针灸治疗哮喘的理论内涵和意义,为临床“肺肠同治”针灸治疗哮喘的推广和应用提供理论基础,更好地指导临床实践。

基于“肺与大肠相表里”理论和“整体观念”探讨慢性肺系病合并功能性便秘的诊治思路

慢性肺系病和功能性便秘均是临床常见的难治性疾病,且易合并出现。对二者分别进行干预是现代医学的常规治疗模式,但疗效及安全性均不能令人满意。课题组在临床实践中发现,中医药治疗慢性肺系病合并功能性便秘具有独特的优势。笔者在中医“肺与大肠相表里”理论和“整体观念”指导下,提出慢性肺系疾病合并功能性便秘的病机涉及肺失宣肃致腑气不通、大肠传导失司致肺气上逆、脾失健运、肾精亏损、气血两虚、久病瘀滞等方面,治疗当以“肺肠合治”为总则,辅以健脾益肾、补气养血以扶本虚,行气化瘀以祛实邪,并据此整理临床常用方药,系统总结了本病的中医诊治思路。

基于“肺合大肠”理论探讨肺纤维化中医病机

肺纤维化是一种以肺泡上皮细胞损伤、成纤维细胞病理性增殖转型、细胞外基质过度沉积导致肺组织结构破坏及功能丧失的呼吸系统疾病,病死率高且尚无较好治疗方法。本文以“肺合大肠”的中医认识即“肺与大肠相表里”理论为基础,以“肺合大肠”的现代医学认识即“肠-肺轴”理论为关键点,结合二者探讨相关机制,初步阐述中医药调控“肠-肺轴”治疗肺纤维化的内涵,为临床通过“肠-肺轴”治疗肺纤维化提供新思路。

针刺治疗重症急性胰腺炎大鼠早期肺损伤组织中iNOS及eNOS mRNA表达影响的初步研究

目的:通过观察在"肺与大肠相表里"理论指导下,针刺对急性重症胰腺炎(SAP)大鼠肺组织中诱导型一氧化氮合酶(iNOS)和内皮型一氧化氮合酶(eNOS)mRNA表达的影响,探讨针刺在SAP早期肺损伤(ALI)发病过程中的作用及其机制。方法:40只雄性Wistar大鼠随机分为sham组、SAP组、针刺治疗组和针刺对照组(n=10)。以3.5%牛黄胆酸钠逆行注射胰胆管的方法制作SAP模型,针刺治疗组在"肺与大肠相表里"的理论指导下,于SAP造模0.5h后行针刺肺、大肠、脾经穴位及其背腧穴;针刺对照组在造模0.5h后行针刺肺、脾经穴位及其背腧穴。光镜下观察SAP造模6h后各组大鼠肺组织病理变化,对肺脏进行病理学评分及检测肺组织湿/干重比,应用RT-PCR法检测肺组织中诱导型iNOS、eNOS mRNA的表达水平。结果:针刺治疗组6h后肺损伤评分、肺组织湿/干重比、肺组织iNOS及eNOS mRNA的表达水平均低于SAP组和针刺对照组(均P<0.05)。结论:"肺与大肠相表里"理论指导下的针刺对SAP大鼠早期肺损伤保护作用明显,其作用机制可能为通过抑制肺组织iNOS及eNOS mRNA的过度表达来发挥。

基于宣补通降法论治便秘型肠易激综合征

肠易激综合征是一种与胃肠功能改变相关的功能性疾病,其作为消化科常见疾病之一,发病机制目前尚未被阐明,临床上主要表现为慢性或复发性腹胀、腹痛、排便习惯改变及大便性状的异常,可分为腹泻型、便秘型、混合型和未定型。便秘型肠易激综合征作为肠易激综合征的亚型之一,在全球的发病率为22%。由于现代生活的快节奏化,目前,该病发病率呈现出逐年上升趋势。便秘型肠易激综合征作为现代的常见疾病,往往易因情志异常被诱发或加重。中医学多将其归属于“便秘”“腹痛”等范畴,其病位在大肠。西医治疗以对症为主,疗效欠佳,且疾病往往易反复发作,而中医强调辨证施治,讲究个体化治疗,对该病的治疗有独特优势。对此,文章依据肺与大肠相表里等相关脏腑理论,认为便秘型肠易激综合征发病核心为肠腑气壅,并提出相应的治疗大法——宣补通降法,从宣肺揭盖、培土生金、清肺通腑三方面具体论治便秘型肠易激综合征,从而使得肠腑气机条畅,便秘得消。并结合典型医案分析宣补通降法治疗该病的成功经验,为临床治疗便秘型肠易激综合征提供参考。

基于“肺-肠轴”交互作用探讨宣白承气汤在肺系疫病治疗中的意义

肺系疫病是由外感疫毒引起的急性呼吸道传染病,消化道症状为其常见兼证被视为疾病的传变。“肺-肠轴”交互作用与中医“肺与大肠相表里”理论具有一致性,均阐释了肺与大肠的协调与统一。医家多认为肺系疫病的治疗应从肺肠同治的角度出发,宣肺以畅达气机,泻下以通调水道。本文通过分析古代与现代医家对肺系疫病的研究以及患者的症状,基于“肺与大肠相表里”理论,从宣肺通腑的角度出发,探讨宣白承气汤肺肠同治原则在肺系疫病治疗中的意义,给肺系疫病以新的诊疗思路,提供新的治疗途径。

从肠论治脓毒症所致ALI/ARDS有效性的Meta分析

目的系统评价在中医“肺与大肠相表里”理论下指导下,从肠论治脓毒症所致急性肺损伤/急性呼吸迫综合征(ALI/ARDS)的临床疗效,为临床提供循证参考。方法通过计算机检索中国知网(CNKI)、万方数据库、维普中文期刊数据库、中国生物医学文献数据库(CBMdisc)荷兰医学文摘Embase数据库、美国国立医学图书馆PubMed数据库、Cochrane图书馆数据库中,从建库至2020年10月8日发表的将通腑法作为干预措施治疗脓毒症所致ALI/ARDS的随机对照试验(RCT)。对照组采用常规西医治疗,试验组在常规西医治疗基础上联合通腑法治疗。由2名研究者筛选文献并对符合纳入标准的文献进行数据提取,运用改良Jadad量表进行质量评价,采用RevMan5.4和Stata16.0软件对数据进行Meta分析。结果最终纳入13篇文献,均为单中心RCT,其中≥4分的文献7篇,<4分的文献6篇。共纳入579例患者,其中试验组290例,对照组289例。Meta分析显示,与对照组比较,联合通腑法治疗能明显提高脓毒症所致ALI/ARDS患者氧合指数[PaO_(2)/FiO_(2),均数差(MD)=62.55,95%可信区间(95%CI)为55.74~69.37,P<0.05],降低白细胞介素-6(IL-6,MD=-29.70,95%CI为-48.34~-11.06,P<0.05)、肿瘤坏死因子-α(TNF-α,MD=-2.94,95%CI为-5.28~-0.59,P<0.05)降钙素原(PCT,MD=-1.34,95%CI为-2.17~-0.51,P<0.05)和C-反应蛋白(CRP,MD=-22.41,95%CI为-36.52~-8.29,P<0.05)水平,缩短机械通气时间(MD=-2.26,95%CI为-2.86~-1.66,P<0.05)和重症监护病房(ICU)住院时间(MD=-4.15,95%CI为-7.47~-0.84,P<0.05),降低28d病死率[相对危险度(RR)=0.43,95%CI为0.24~0.76,P<0.05]和急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ,MD=-3.53,95%CI为-5.41~-1.64,P<0.05)。结论从肠论治对减轻脓毒症所致ALI/ARDS患者病情及改善预后有一定价值,但仍需进一步开展高质量的RCT以验证其疗效,为临床治疗提供更准确的循证医学证据。

从“肺-肠”轴角度探讨肠道菌群与过敏性鼻炎的关系

过敏性鼻炎属于全球高发的气道变应性疾病,较多人群深受其影响,关于其更安全有效的治疗方式仍不断被探寻与挖掘。近年来关于肠道微生态与肺部疾病的相互关系被深入研究,文章基于肺肠关系,结合中医“肺与大肠相表里”理论,并从西医胚胎发育、菌群微环境、内分泌代谢、黏膜免疫等角度探讨肺-肠关系,在此基础上,认为肠道菌群可从细胞因子免疫平衡、机体黏膜等方面影响过敏性鼻炎的发生发展,以期为临床治疗过敏性鼻炎提供更多思路。

基于“肺与大肠相表里”综述中药干预肺系疾病对肺、肠组织炎性因子及菌群变化

肺是维系呼吸道健康的重要门户,各种原因如感染细菌或病毒、接触过敏原、吸烟、遗传因素等均可引起肺部疾病,引发不同程度的炎症反应。呼吸道感染可伴随不同程度的肠道症状,即“肺病及肠”,故“肺与大肠相表里”这一中医理论在临床对此类症状疾病的治疗中应用广泛,且疗效显著。文章通过对近年来相关文献的研究,试从肺、肠道组织炎症因子、菌群变化等角度出发,综述中医药治疗肺系疾病的作用机制及疗效,以期为日后的研究开展新方向。