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.

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.

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 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.

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.

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“心肠合治法”论乌梅丸

“心肠合治法”理论起源可追溯至《黄帝内经》,阐释了心与小肠在生理和病理上的相互影响,近年来,研究者多从“颅脑肠脑说”“心与肠道菌群说”“肠道菌群-脑-肠轴”等方面进行研究,证实了“心与小肠相表里”学说的科学性,从而也证明了“心肠合治法”在临床中的可行性、重要性。该文中“心”即心、脑、血脉,包括现代医学中的心血管系统、神经系统等,“肠”即小肠,包括消化系统中的十二指肠、空肠、回肠等。“心肠合治法”是一种很重要但未被重视起来的治疗思路,而乌梅丸即“心肠合治法”的代表方剂,在临床中常被用来治疗心系与肠系病。故该文就“心肠合治法”理论渊源、现代研究机制及其临床运用的研究概况进行探讨,以期从更多角度探究乌梅丸的配伍规律及临床应用。

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。

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。

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。

A Comparative Study of The Regular Pattern of Syndrome and Treatment of Lung-intestine Related Diseases in Ancient and Modern Medical Cases Based on Data Mining

Objective: To analyze the similarities and differences of the applications of "the lung and large intestine being interior-exteriorly related"between the ancient and modern clinical practices, and to reveal the theory meaning.Method: Based on the ancient and modern medical cases database, 245 ancient medical records and 373 modern medical records were studied with the general statistical description and analysis of association rules, and the results were compared to summarize the similarities and differences of the regular pattern of syndrome and treatment on lung-large intestine related diseases in ancient and modern medical records.Results: In modern medical cases, intestinal diseases appeared with the main symptom of constipation due to deficiency of lung qi and qi stagnation of large intestine were always treated by purgation together with replenishing and restoring lung qi. In ancient medical cases, large intestine heat was always caused by lung heat and a variety of diarrhea symptoms appeared. They were always treated by clearing heat and moistening lungs. In addition, the symptom of bound stool caused by qi stagnation of large intestine due to lung qi stagnation was always treated by lowering lung qi to regulate and smooth large intestine qi. And Armeniae Amarum Semen was used by both as a core medicinal herb.Conclusion: Ascending-descending of qi movement is the core of the lung and large intestine relationship. In other words, the lung and the large intestine communicate through qi.

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。

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。

基于“心与小肠相表里”论治双心疾病

深入剖析“心与小肠相表里”的学说内涵,揭示小肠与双心疾病的内在关系。认为心与小肠在生理上密切联系,病理上相互影响,并通过经络构成表里关系;现代研究进一步证实了二者存在缺血同步性、分泌相关性、环境平衡性;灵活运用化瘀通络、泌别清浊、益气温阳、养阴润肠等方法可以有效防治双心疾病。总之,从肠论治双心疾病不仅是中医整体观念的体现,同时也为双心疾病领域的研究提供思路。

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-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。

中医学对肠道菌群与非酒精性脂肪性肝病的理论认识

近年来,非酒精性脂肪性肝病全球流行率逐年升高,但发病机制至今尚未明确。中医学将非酒精性脂肪性肝病归属于“臌胀”“肝癖”“痰浊”“积聚”等,认为肝体用失调、脾肾亏虚是本病主要特点,痰、湿、浊、瘀、热为本病主要病理因素。随着对肠道菌群研究的不断深入,肠道菌群及其代谢产物有改善胰岛素抵抗、减少氧化应激、调节脂质代谢和调节免疫等多种作用,与肝脏功能及非酒精性脂肪性肝病之间的关系也受到广泛关注。许多研究揭示了肠-肝轴与非酒精性脂肪性肝病发生发展相关,饮食、抗生素、益生菌及益生元、粪菌移植、微生态制剂、噬菌体等干预措施均可以通过改变肠道菌群来缓解非酒精性脂肪性肝病。从现代医学对肠道菌群生理功能的研究中,我们发现现代医学“肠”的消化吸收、调节代谢、改善免疫等功能可属于中医“脾主运化”“脾主升清”功能的范畴。文章从中医“肝脾相关”“肝与大肠相通”“肝从左升,肺从右降,肺与大肠相表里”等理论视角出发,就中医学对肠道菌群与非酒精性脂肪性肝病关系的认识及相关治疗作一综述,阐述中医学治疗本病的理论基础,结合现代医学理念,以期为非酒精性脂肪性肝病的中医治疗提供新思路、新方法。

“肺与大肠相表里”物质相关性的研究进展

中医药文化历史源远流长,作为中医药藏象理论的重要组成部分,“肺与大肠相表里”阐述了肺-肠来源相同,生理上相互协作,病理上和治疗上相互影响。现基于“肺与大肠相表里”理论,分别从经络、津液代谢、黏膜免疫及肠道运动等方面探讨肺-肠物质相关性,为临床治疗肺肠相关疾病提供参考。

基于“心与小肠相表里”理论指导下的营养护理干预对慢性心力衰竭患者康复的影响

目的:探讨基于“心与小肠相表里”理论指导下的营养护理干预对慢性心力衰竭(CHF)患者康复的影响。方法:选取本院2019年8月~2021年8月期间于我院住院治疗的CHF患者84例,使用随机数字表法将患者分为研究组和对照组,每组42例。对照组予以常规饮食护理干预,研究组在对照组基础上予以基于“心与小肠相表里”理论指导下的营养护理干预。比较两组干预前后中医症候积分、脑钠肽(BNP)水平、营养状况、生活质量、住院时间及再住院率。结果:干预后,研究组气喘、乏力、心悸及自汗等症状评分及BNP水平显著低于对照组(P<0.05);研究组氯化三甲胺(TMAO)水平显著低于对照组,血红蛋白(Hb)、血清白蛋白(ALB)、血清前白蛋白(PA)水平显著高于对照组(P<0.05);研究组躯体状况、情绪变化及其他状况评分显著低于对照组(P<0.05);观察组住院天数、再住院率均显著低于对照组(P<0.05)。结论:基于“心与小肠相表里”理论指导下的营养护理干预可有效增强对CHF患者中医症候积分、营养状态、生活质量的改善作用,促进患者康复。

《黄帝内经》肺与大肠相表里理论临床体会

脏腑表里理论历史悠久,源远流长,是中医藏象学说的重要组成部分。此文通过医案举例,介绍肺与大肠相表里理论,强调该理论在临床中的治疗作用,得出应用此理论在辨证论治肺系、肠系相关疾病时,脏腑同治较脏病治脏、腑病治腑收效更佳。总之,运用肺与大肠相表里理论,为临床疾病治疗肺系、肠系疾病扩宽了思路,值得临床推广。