Scientific connotation of “treating different diseases with the same method” from the perspective of metabolic-immune dysregulation in inflammation-mediated carcinogenesis of digestive organs

Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system.In the chronic inflammation microenvironment,the metabolic activity of tissue cells undergoes extensive changes,which interfere with the normal function of immune cells.Dysregulation of cell metabolism and immune function has been identified as a key factor contributing to inflammation-mediated carcinogenesis within the major digestive organs,such as the stomach,liver,and colorectum.This metabolic-immune imbalance also corresponds to traditional Chinese medicine(TCM)theories of“yin-yang disharmony”and“disharmony between Ying-nutrients and Wei-defense.”The metabolic-immune imbalance has also been regarded as the key factor supporting“treatment of different diseases with the same method”,in which the same approach is adopted in the treatment of different conditions.In the TCM treatment process,it is necessary to first identify TCM patterns and then apply the corresponding TCM to correct the dysregulated metabolic and immune function,thereby blocking the progression from inflammation to malignancy.Our study findings deepen the TCM understanding of metabolic-immune dysregulation and the relationship between metabolic-immune dysregulation,pattern identification,and treatment method.They also provide new insights for the treatment of inflammation-mediated carcinogenesis in major digestive organs and help us further explore the scientific connotation of the TCM strategy of“treating different diseases with the same method”.

Network pharmacology unveils spleen-fortifying effect of Codonopsis Radix on different gastric diseases based on theory of “same treatment for different diseases” in traditional Chinese medicine

Objective: "Same treatment for different diseases" is a unique treatment strategy under the guidance of traditional Chinese medicine(TCM) theory.Codonopsis Radix(Codonopsis pilosula,Dangshen in Chinese)with spleen-fortifying effect was employed to understand the strategy of "Same treatment for different diseases",based on its common mechanism in the treatment of gastric diseases including gastric ulcer,gastritis and gastric cancer via network pharmacology research.Methods:Network pharmacology research methods were used to analyze the interaction network and potential mechanisms of Dangshen in treating gastric ulcer,gastritis and gastric cancer.The active components and their target proteins of Dangshen were integrated from TCMSP,BATMAN-TCM databases.The targets of gastric ulcer,gastritis and gastric cancer were collected through GeneCards,PubMed,TDD and DisGeNET Database.Through screening,the key components and the key targets of Dangshen in treating gastric ulcer,gastritis and gastric cancer were obtained.After KEGG pathway analysis and GO analysis,the important pathways and biological processes were analyzed.Results:Through data and literature mining,the common and specific pharmaceutical effects and mechanism of Dangshen were summarized in these three gastric lesions.It was shown that Dangshen mainly acted on gastric ulcer,gastritis and gastric cancer through the overall regulation of the PI3K-AkT signaling pathway.With the development of the disease,it will gradually increase the control of inflammation through TNF,NF-κB and other inflammation-related signaling pathways to reduce inflammatory damage.For tumorigenesis,it pays more attention to inhibiting the ErbB signaling pathways to reduce the proliferation and migration of tumor cells.In addition,Dangshen's regulation of HIF-1 signaling pathway may also be beneficial for the treatment of gastric ulcer,gastritis and gastric cancer.Conclusion:Dangshen achieves spleen-fortifying effect on gastric diseases including gastric ulcer,gastritis and gastric cancer through multiple targets in multiple pathways,especially PI3K-AKT pathway and HIF-1 pathway.It could provide a scientific basis for understanding the strategy of "Same treatment for different diseases" in traditional Chinese medicine.

Text Mining of Rheumatoid Arthritis and Diabetes Mellitus to Understand the Mechanisms of Chinese Medicine in Different Diseases with Same Treatment

Objective： To identify the commonalities between rheumatoid arthritis （RA） and diabetes mellitus （DM） to understand the mechanisms of Chinese medicine （CM） in different diseases with the same treatment. Methods： A text mining approach was adopted to analyze the commonalities between RA and DM according to CM and biological elements. The major commonalities were subsequently verified in RA and DM rat models, in which herbal formula for the treatment of both RA and DM identified via text mining was used as the intervention. Results： Similarities were identified between RA and DM regarding the CM approach used for diagnosis and treatment, as well as the networks of biological activities affected by each disease, including the involvement of adhesion molecules, oxidative stress, cytokines, T-lymphocytes, apoptosis, and inflammation. The Ramulus Cinnamomi-Radix Paeoniae Alba-Rhizoma Anemarrhenae is an herbal combination used to treat RA and DM. This formula demonstrated similar effects on oxidative stress and inflammation in rats with collagen-induced arthritis, which supports the text mining results regarding the commonalities between RA and DM. Conclusion： Commonalities between the biological activities involved in RA and DM were identified through text mining, and both RA and DM might be responsive to the same intervention at a specific stage.

The Characterization of Aortic Valve Calcification at Different Stage of Disease

Cardiac valve calcification is a common disease,especially among the elderly.Calcification can affect valve function and cause heart failure and sudden death(Adler et al.,2002).Aortic valve calcification is alsorelated to arteriosclerosis and coronary heart disease(Rashedi et al.,2015).However,the origin of valve calcification is still unclear.This study characterized the

Feasibility of establishing model of Parkinson disease by injecting 6-hydroxydopamine at different parts of the nigrostriatal pathway in the brain of rats

BACKGROUND： Previous researches found that animal models with Parkinson disease （PD） could be established by injecting 6-hydroxydopamine （6-OHDA） into medial forebrain bundle （MFB）, substantia nigra compacta （SNC） and caudate-putamen complex （CPU） of the nigrostriatal pathway. OBJECTIVE ： To compare behavioral, biochemica 6-OHDA injections in the areas of MFB, SNC and DESIGN： Controlled observational study and histological properties of these rats undergoing the CPU respectively. SEI-IING： Department of Neurology, First Affiliated Hospital of Guangxi Medical University MATERIALS： A total of 64 adult female SD rats weighing 180-230 g were provided by the Animal Experimental Center of Guangxi Medical University. 6-OHDA （Sigma Company, USA）; Brain solid positioner （Standard model 51600, Stoelting Co., IL, USA）; rotational monitoring of little animal （type QL-1, USA）; high liquid chromatography （HLC, Waters Company）. METHOOS： The experiment was carried out in the Medical Experimental Center of Guangxi Medical University from February to December 2005. ① According to digital table, 64 SD rats were divided into MFB group, SNC group, CPU group and control group with 16 in each group. On the basis of the brain atlas of Paxinos, rats in the first three groups were injected with 5 μL 6-OHDA into right MFB （0 mm of line of incisor tooth, A/P 4.4 mm, L/R 1.2 mm, ON -7.8 mm）, SNC （line of incisor tooth just equal to horizon, A/P -4.8 mm, L/R 1.6 mm, ON -7.8 mm） and CPU （0 mm of line of incisor tooth, A/P 1.2 mm, L/R 2.7 mm, ON -5.4 mm）, respectively. The rats in control group were injected with 5 μL ascorbic acid solution （2 g/L）. One week after operation, 0.1 g/L apomorphine （Apo, 0.05 mg/kg） was subcutaneously injected into neck and then rotational behavior induced by Apo was recorded once a week for 8 weeks. The PD models were considered successful only when rotational times more than or equal to 7 times per minute. Eight weeks after operation, micro-perfusion was used to obtain micro-perfusate in bilateral CPU and contents of 3,4-dihydroxyphenylacetic acid （3,4-DOPAC） and homovanillic acid （HVA） were also measured. In addition, amount of tyrosine hydroxylase positive cells （TH＊） in SNC was counted with immuno- histochemical staining. MAIN OUTCOME MEASURES ： ① Successful rate of PD models; ② contents of dopamine and its metabolite in MFB, SNC and CPU groups and TH＊ amount. RESULTS： All 64 SD rats were involved in the final analysis. ③ Successful rate and rotational behavior： One week after operation, there were 6 successful models both in SNC and MFB groups; in the 2^nd week, there were 6 both in SNC and MFB groups and 1 in CPU group; in the 3^nd week, there were 1 in MFB group and 3 in CPU group; in the 4^nd week, there were 3 in CPU group. Otherwise, no successful case was found out in the next 3 weeks. Abnormal rotational behavior was not observed in control group. Four weeks after operation, successful rates were 81% （13/16） in MFB group, 75% （12/16） in SNC group and 44% （7/16） in CPU group.② Contents of 3, 4-DOPAC and HVA： Eight weeks after operation, contents in the SNC area of the injured side were lower than those on non-lesion side （P 〈 0.01）.③Changes of TH＋ amount： Eight weeks after operation, TH＋ amount in the SNC area of the lesion side was lower than that on non-lesion side （P 〈 0.01 ）. CONCLUSION： Injecting 6-OHDA into MFB, SNC and CPU can damage dopaminergic cells and establish successful PD models.

不同症状类型苜蓿病毒病AMV病原检测及其寄主范围测定

为明确采自田间不同症状类型苜蓿病毒病病样中苜蓿花叶病毒(alfalfa mosaic virus,AMV)的带毒情况、症状表现与叶绿素含量的相关性及AMV的寄主范围,本试验通过田间调查采样、症状归类、丙酮乙醇混合液法和双抗体夹心酶联免疫吸附测定(DAS-ELISA)法对不同病样的叶绿素和AMV含量进行测定和检测,并对提纯至不同症状类型病样中AMV对9科32种植物的致病性进行测定。结果表明田间苜蓿病毒病病样有轻花叶、重花叶、叶片边缘褪绿黄化型和叶片畸形皱缩花叶矮化型4种症状类型,均带有AMV,且叶绿素含量、AMV含量与症状表现之间具有正相关性,症状表现最严重的叶片畸形皱缩花叶矮化型病样的叶绿素a、b、总叶绿素含量均比对照低58.00%以上,类胡萝卜素含量比对照高134.06%,AMV含量最高,为252.96 pg·mL^(-1);寄主范围测定表明AMV可侵染7科27种植物,对西葫芦致病性最强,症状表现为局部枯斑,30 d时AMV浓度为316.19 pg·mL^(-1)。

Mechanisms of Dihuang(Rehmanniae Radix)in treating diabetic nephropathy complicated with depression based on network pharmacology

Objective To predict the molecular mechanism of Dihuang(Rehmanniae Radix)in the treatment of diabetic nephropathy(DN)complicated with depression based on network pharmacology.Methods The components of Dihuang(Rehmanniae Radix)were identified from the Integrated Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP),Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and relevant literature.The component targets were detected by combining the SwissTargetPrediction and Pub Chem databases.Disease targets were collected from the Therapeutic Target Database(TTD),Dis Ge NET,and Ensembl databases with“diabetic nephropathy”and“depression”as keywords.The disease-component targets were mapped using Venny 2.1.0 to obtain potential targets.A protein-protein interaction(PPI)network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)database and Cytoscape 3.7.2.The co-expression genes of the key targets were collected based on the COXPRESdb 7.3.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed for potential targets using R language.Target-component docking was verified and evaluated using Discovery Studio 4.5.Results According to the databases and literature reports,Dihuang(Rehmanniae Radix)contained 65 active components,and had 155 related targets for the treatment of DN complicated with depression.PPI screening showed that the key targets included serine/threonine protein kinase 1(AKT1),signal transducer and activator transcription 3(STAT3),interleukin 6(IL-6),mitogen-activated protein kinase 1(MAPK1),and vascular endothelial growth factor A(VEGFA),etc.GO enrichment analysis mainly involved biological processes,such as lipid metabolism,protein secretion regulation,cell homeostasis,and phosphatidylinositol 3 kinase activity.KEGG pathway enrichment analysis included the role of the AGE-RAGE signaling pathway in diabetic complements,insulin resistance(IR),neurotrophin signal path,Toll-like receptor signaling pathway,relaxin signaling pathway,epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs),etc.Molecular docking showed that the target had high affinity for stachyose,manninotriose,verbascose,nigerose,etc.Conclusion Based on network parmacology,this study preliminarily predict the effects of Dihuang(Rehmanniae Radix)in treating DN complicated with depression by regulating inflammation,glucose metabolism,nution nerve,etc.

Mechanisms of Huanglian Jiedu Decoction in treating coronary heart disease and type 2 diabetes mellitus based on network pharmacology

Objective:To explore the common mechanism of Huanglian Jiedu Decoction in treating coronary heart disease and type 2 diabetes by network pharmacology.Methods:All chemical components and targets of the four drugs in Huanglian Jiedu Decoction were retrieved through TCMSP,and the genes were standardized through Uniprot database.Acquire disease targets related to coronary heart disease and diabetes in OMIM and GeneCards databases.The network diagram of"drug-component-target-disease"is constructed by using the software of cytopscape 3.7.2,the PPI network diagram of protein interaction is constructed by using STRING database,and the network diagram of"drug-disease"core target is constructed by using the software of cytopscape 3.7.2.DAVID's online database platform was used to analyze GO biological process and KEGG pathway enrichment of common targets of Huanglian Jiedu Decoction in treating coronary heart disease and type 2 diabetes.Results:103 active ingredients of Huanglian Jiedu Decoction were retrieved,including 140 acting targets,5342 coronary heart disease targets,114 diabetes targets,and 14 common intersection targets of drugs and diseases,involving AR,PPARG,TNF,IL6,CCL2,VEGFA,PON1,etc.The GO biological process analysis results in 98 biological processes,10 cell components and 10 molecular functions.Among them are positive regulation of gene expression,positive regulation of nitric oxide biosynthesis process,Extracellular space,cytokine activity,steroid hormone receptor activity and other biological processes;The enrichment analysis of KEGG pathway yielded 20 signal pathways(P≤0.05).It mainly involves Malaria,cancer in cancer,HIF-1 signaling pathway,TNF signaling pathway,NOD-like receptor signaling pathway,PI3K-Akt signaling pathway,etc.Conclusion:Huanglian Jiedu Decoction"treats different diseases at the same time"coronary heart disease and type 2 diabetes have the characteristics of multiple components,multiple targets and multiple pathways,which provide theoretical basis for Huanglian Jiedu Decoction to treat coronary heart disease and type 2 diabetes in clinic,but the key targets and pathways of Huanglian Jiedu Decoction to treat diseases still need further experimental verification.

Gender differences in adolescent dry eye disease:a health problem in girls

AIM： To evaluate the signs and symptoms of dry eye disease（DED） in adolescents. METHODS： This was a cross-sectional, case-control study and outpatients aged 10 to 19y were recruited from six eye clinics of various practices and locations in Japan, and 253 non-DED subjects and 70 DED patients were enrolled. Participants were examined for DED-related signs. Patients were also interviewed to ascertain the presence or absence of six common DED-related symptoms： dryness, irritation, pain, eye fatigue, blurring, and photophobia. Main outcome measures were differences in signs and symptoms of dry eye disease between boys and girls.RESULTS： Of the 323 adolescents recruited, 70（21.7%） were diagnosed with DED. Significant differences between the non-DED and DED groups were found for short tear break-up time（BUT; ≤5s; P=0.000） and superficial punctate keratopathy（SPK; staining score ≥3; P=0.000）. Late adolescent girls reported fewer symptoms than late adolescent boys, although their DED-related signs were worse compared to other groups. The prevalence and severity of DED were similar in the Tokyo area compared with suburban and local areas but myopic errors were worse. CONCLUSION： We find that adolescents reported symptoms of DED similar to those found in adults, and the majority have short BUT-type DED. The prevalence and severity of DED in late adolescent girls is comparable with adults. Adolescents with DED are underserved and we believe that DED is a hidden but potentially serious health problem for this age group.

Characteristics of Traditional Chinese Medicine Syndrome in Patients with Coronary Heart Disease at Different Disease Stages

Coronary atherosclerotic heart disease(CHD)has a high incidence,disability rate,and mortality rate,which severely affect people’s health,work,and life.Based on its clinical manifestations,traditional Chinese medicine(TCM)has classified CHD as“chest impediment”and“heart pain”for the treatment.The course of CHD is protracted,and the pathogenesis is complex and changeable.Moreover,different disease stages have different syndrome characteristics.Thus,this article aimed to summarize the classification and distribution characteristics of the TCM syndrome in various stages of CHD,such as before and after percutaneous coronary intervention therapy,disease progression,age,and complications,to provide references for the TCM clinical diagnosis and treatment of CHD.

An analysis of clinical features of celiac disease patients in different ethnic

Objective To summarize the clinical of different racial patients with celiac disease(CD)and analyze the disease prevalence,diagnosis and treatment in Chinese population.Methods All the patients were diagnosed as CD and enrolled in Beijing United Family Hospital between January 2005 and July 2015.Clinical data including nationality,age,symptoms,endoscopic and patho-

Clinical application and research of Shao's “three-acupoint and five-needling method”

Professor SHAO Jing-ming has obtained more significant effect during the clinical practice in treatment of wheezing diseases by adopting ＂three-acupoint and five-needling method＂ created by himself, and the effect has been widely recognized by doctors and patients. After decades of development, Shao＇s ＂three-acupoint and five-needling method＂ has become a therapy with complete theoretical system and a large number of clinical research achievements, and its application scope has been expanded. In this paper, the achievements of Shao＇s ＂three-acupoint and five-needling method＂ during clinical studies in the early, middle and current development stages and related problems were reviewed comprehensively.

Effect of Sancaijiangtang on plasma nitric oxide and endothelin-1 levels in patients with type 2 diabetes mellitus and vascular dementia:a single-blind randomized controlled trial

OBJECTIVE: To observe the effect of Sancaijiangtang powders on plasma nitric oxide and endothelin-1 levels. We sought to identify the common pathological link and mechanism of action for Traditional Chinese medicine in type 2 diabetes mellitus and vascular dementia,and to explicate the material basis for treating the different diseases with the same method in Traditional Chinese Medicine.METHODS: In total,168 patients with type 2 diabetes mellitus and vascular dementia were enrolled in the study,and randomly divided into two groups by simple randomization. Patients in the treatment group received oral Sancaijiangtang powders with pioglitazone hydrochloride three times daily,while patients in the control group received pioglitazone hydrochloride alone. The treatment course was for12 weeks. Mini-mental state examinations(Chinese version) and Montreal Cognitive Assessments(Beijing version) were performed,and fasting plasma glucose,fasting insulin,hemoglobin A1 c,homeostasis model assessment of insulin resistance,plasma nitric oxide and endothelin-1 levels were measured before and after the treatment.RESULTS: The post-treatment levels for all measurements in both groups were better than pre-treatment levels(P < 0.05). The post-treatment levels for all measurements in the treatment group were better than the levels measured in the control group(P < 0.05).CONCLUSION: Type 2 diabetes mellitus and vascular dementia have common pathological mechanisms for insulin resistance and endothelium dysfunction. Sancaijiangtang powders could improve the release of nitric oxide and inhibit the secretion of endothelin-1. Therefore,the material basis exists for treating the different diseases with the same method in Traditional Chinese Medicine.

Common mechanism of Citrus Grandis Exocarpium in treatment of chronic obstructive pulmonary disease and lung cancer

Objective:"Same treatment for different diseases"is a unique treatment strategy in traditional Chinese medicine.Two kinds of malignant respiratory diseases endanger human health-chronic obstructive pulmonary disease(COPD)and lung cancer.Citrus Grandis Exocarpium(Huajuhong in Chinese,HJH),a famous herbal,is always applied by Chinese medicine practitioners to dispersion the lung to resolve phlegm based on"syndrome differentiation and treatment"theory.However,the common mechanism for HJH’s treatment of COPD and lung cancer is not clear.Methods:In this study,based on network pharmacology and molecular docking technology,the common mechanism of HJH in the treatment of COPD and lung cancer was studied.The active ingredients and related targets of HJH were integrated from TCMSP,BATMAN-TAM,STP,and Pubchem databases.The standard names of these targets were united by Uni Prot database.Targets of COPD and lung cancer were enriched through Gene Cards,NCBI(Gene),Therapeutic Target Database,and Dis Ge NET(v7.0)databases.Then the intersection targets of HJH and diseases were obtained.The STRING network and the Cytoscape 3.7.2 were used to construct PPI network,the DAVID database was used to perform GO and KEGG analysis.Then Cytoscape 3.6.1 was used to build"ingredient-target-signal pathway"network.Finally,Auto Dock 1.5.6 software was used to perform molecular docking of key proteins and molecules.Results:Eleven active ingredients in HJH were obtained by searching the database,corresponding to 184 HJH-COPD-lung cancer targets intersection.The results of biological network analysis showed that naringenin,the active component in HJH,could mainly act on target proteins such as AKT1,EGFR.Then through positive regulation of vasoconstriction and other biological processes,naringenin could regulate estrogen signaling pathway,VEGF signaling pathway,HIF-1 signaling pathway,Erb B signaling pathway,PI3K-Akt signaling pathway to play an important role in the treatment of both COPD and lung cancer.Conclusion:Network pharmacology was employed to systematically investigate the active ingredients and targets of HJH in treatment of COPD and lung cancer.And then,the common pharmacodynamic network of HJH for the two malignant respiratory diseases was firstly described.Furthermore,naringenin was proved to strongly bind with AKT1 and EGFR.It may provide the scientific basis for understanding the"Same treatment for different diseases"strategy in traditional Chinese medicine and inspirit subsequent drug discovery for COPD,lung cancer and other malignant lung diseases.

Mechanism Exploration of the Classical Traditional Chinese Medicine Formula Huoluo Xiaoling Pill in Clinical Treatment and the Traditional Chinese Medicine Theory“Treating Different Diseases with the Same Method”:A Network Pharmacology Study and Molecula Docking Verification

Objective: To analyze the possible mechanism of the Huoluo Xiaoling Pill in the treatment of three diseases, hyperglycemia, hyperlipidemia, and metabolic syndrome, and to provide ideas for learning the mechanism of “Treating different diseases with the same method” in Traditional Chinese Medicine(TCM) theory. Materials and Methods: The Traditional Chinese Medicine System Pharmacology Database and Uni Prot databases were used to screen the main ingredients and targets of the Huoluo Xiaoling Pill. The Gene Cards database was used to screen the targets of the diseases, and Cytoscape 3.7.2 was used to construct a “Drug-Components-Targets-Disease” network to determine the core components. The STRING database was used to construct the protein-protein-interaction network, and gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomics enrichment analyses were carried out on the Metascape database. Auto Dock 1.5.6 was used for molecular docking. Results: A total of 118 active components and 208 targets were screened in the Huoluo Xiaoling Pill. Quercetin, tanshinone IIA, luteolin, and ellagic acid were potential core components of Huoluo Xiaoling Pill treating the three diseases, and interleukin 6, Tumor necrosis factor, and vascular endothelial growth factor were potential key targets. Co-occurring GO biological processes involved responses to the molecules of bacterial origin, and the AGE-RAGE signaling, fluid shear stress, and atherosclerosis pathways were the co-occurring pathways. Molecular docking revealed good docking conditions between screened targets and components. Conclusion: This study predicted the mechanism of the Huoluo Xiaoling Pill in treating the three diseases. At the same time, the co-occurring targets and pathways between the three diseases provided a material basis for the TCM theory, “Treating different diseases with the same method.”