Construction of a clinical prediction model for the impact of acupuncture on pregnancy outcomes in poor ovarian response (POR) patients based on a patient registry research platform. / åŸºäºŽç— ä¾‹æ³¨å†Œç™»è®°ç ”ç©¶å¹³å°æž„å»ºé’ˆç¸å¯¹åµå·¢ä½Žååº”æ‚£è€ å¦Šå¨ ç»“å±€çš„ä¸´åºŠé¢„æµ‹æ¨¡åž‹.

OBJECTIVES: To construct a clinical prediction model for the impact of acupuncture on pregnancy outcomes in poor ovarian response (POR) patients, providing insights and methods for predicting pregnancy outcomes in POR patients undergoing acupuncture treatment. METHODS: Clinical data of 268 POR patients (2 cases were eliminated) primarily treated with "thirteen needle acupuncture for Tiaojing Cuyun (regulating menstruation and promoting pregnancy)" was collected from the international patient registry platform of acupuncture moxibustion (IPRPAM) from September 19, 2017 to April 30, 2023, involving 24 clinical centers including Acupuncture-Moxibustion Hospital of China Academy of Chinese Medical Sciences. LASSO and univariate Cox regression were used to screen factors influencing pregnancy outcomes, and a multivariate Cox regression model was established based on the screening results. The best model was selected using the Akaike information criterion (AIC), and a nomogram for clinical pregnancy prediction was constructed. The prediction model was evaluated using receiver operating characteristic (ROC) curves and calibration curves, and internal validation was performed using the Bootstrap method. RESULTS: (1) Age, level of anti-Müllerian hormone (AMH), and total treatment numbers of acupuncture were independent predictors of pregnancy outcomes in POR patients receiving acupuncture (P<0.05). (2) The AIC value of the best subset-Cox multivariate model (560.6) was the smallest, indicating it as the optimal model. (3) The areas under curve (AUCs) of the clinical prediction model after 6, 12, 24, and 36 months treatment were 0.627, 0.719, 0.770, and 0.766, respectively, and in the validation group, they were 0.620, 0.704, 0.759, and 0.765, indicating good discrimination and repeatability of the prediction model. (4) The calibration curve showed that the prediction curve of the clinical prediction model was close to the ideal model's prediction curve, indicating good calibration of the prediction model. CONCLUSIONS: The clinical prediction model for the impact of acupuncture on pregnancy outcomes in POR patients based on the IPRPAM platform has good clinical application value and provides insights into predicting pregnancy outcomes in POR patients undergoing acupuncture treatment.

Analysis of Chinese Medical Syndrome Features of Ischemic Stroke Based on Similarity of Symptoms Subgroup.

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS: There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.

Identification of Hypertension Subgroups through Topological Analysis of Symptom-Based Patient Similarity.

OBJECTIVE: To obtain the subtypes of the clinical hypertension population based on symptoms and to explore the relationship between hypertension and comorbidities. METHODS: The data set was collected from the Chinese medicine (CM) electronic medical records of 33,458 hypertension inpatients in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between July 2014 and May 2017. Then, a hypertension disease comorbidity network (HDCN) was built to investigate the complicated associations between hypertension and their comorbidities. Moreover, a hypertension patient similarity network (HPSN) was constructed with patients' shared symptoms, and 7 main hypertension patient subgroups were identified from HPSN with a community detection method to exhibit the characteristics of clinical phenotypes and molecular mechanisms. In addition, the significant symptoms, diseases, CM syndromes and pathways of each main patient subgroup were obtained by enrichment analysis. RESULTS: The significant symptoms and diseases of these patient subgroups were associated with different damaged target organs of hypertension. Additionally, the specific phenotypic features (symptoms, diseases, and CM syndromes) were consistent with specific molecular features (pathways) in the same patient subgroup. CONCLUSION: The utility and comprehensiveness of disease classification based on community detection of patient networks using shared CM symptom phenotypes showed the importance of hypertension patient subgroups.

Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease.

Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine-based approach was proposed to identify the underlying molecular modules of PSCS complicated with IHD, which could be used for interpreting the pharmacological mechanisms of well-established Chinese herbal formulas (e.g., Tao Hong Si Wu Tang, Dan Shen Yin, Hunag Lian Wen Dan Tang and Gua Lou Xie Bai Ban Xia Tang). In addition, these results delivered novel understandings of the molecular network mechanisms of IHD phenotype subtypes with PSCS complications, which would be both insightful for IHD precision medicine and the integration of disease and TCM syndrome diagnoses.

Detection of herb-symptom associations from traditional chinese medicine clinical data.

Background. Traditional Chinese medicine (TCM) is an individualized medicine by observing the symptoms and signs (symptoms in brief) of patients. We aim to extract the meaningful herb-symptom relationships from large scale TCM clinical data. Methods. To investigate the correlations between symptoms and herbs held for patients, we use four clinical data sets collected from TCM outpatient clinical settings and calculate the similarities between patient pairs in terms of the herb constituents of their prescriptions and their manifesting symptoms by cosine measure. To address the large-scale multiple testing problems for the detection of herb-symptom associations and the dependence between herbs involving similar efficacies, we propose a network-based correlation analysis (NetCorrA) method to detect the herb-symptom associations. Results. The results show that there are strong positive correlations between symptom similarity and herb similarity, which indicates that herb-symptom correspondence is a clinical principle adhered to by most TCM physicians. Furthermore, the NetCorrA method obtains meaningful herb-symptom associations and performs better than the chi-square correlation method by filtering the false positive associations. Conclusions. Symptoms play significant roles for the prescriptions of herb treatment. The herb-symptom correspondence principle indicates that clinical phenotypic targets (i.e., symptoms) of herbs exist and would be valuable for further investigations.

[Combination rules of Chinese herbal prescriptions for treating unstable angina based on complex network].

OBJECTIVE: To explore combination rules of Chinese herbal prescriptions from effective cases for treatment of unstable angina (UA). METHODS: Prescription data from 156 UA patients effectively treated at Cardiovascular Diseases Centre of Xiyuan Hospital were analyzed using complex network method. RESULTS: According to multi-scale analysis of backbone network and pointwise mutual information analysis, core prescriptions from the 156 UA patients were presented as follows: Rhizoma Ligustici wallichii, Radix Paeoniae rubra, Radix Codonopsis, Rhizoma Pinelliae, poria, and Angelica sinensis. Meanwhile, core couplet medicines for these patients covered Rhizoma Ligustici wallichii and Radix paeoniaerubra, Angelica sinensis and Rhizoma Ligustici wallichii, Radix Codonopsis and Rhizoma Ligustici wallichii, Rhizoma Ligustici wallichii and Rhizoma Pinelliae, Rhizoma Atractylodis Macrocephalae and poriacocos, Bulbus Alli Macrostemi and Rhizoma Pinelliae. Among different primary symptoms, there was slightly difference in core prescriptions. CONCLUSION: The core prescriptions for the treatment of UA include blood-activating drug, phlem-resolving drugs. As an exploration of combination rules of Chinese herbal prescriptions in treating UA based on complex network, it can be used as a reference for further researches.

[Optimized treatment program for unstable angina by integrative medicine based on partially observable Markov decision process].

OBJECTIVE: To initially optimize comprehensive treatment program for treating and preventing unstable angina (UA) by integrative medicine (IM). METHODS: Based on partially observable Markov decision process model (POMDP), we chose 3 syndrome elements, i.e., qi deficiency, blood stasis, and phlegm turbidity from UA inpatients. The efficacy of treating UA by IM was objectively assessed by in-depth data mining and analyses. RESULTS: The treatment programs for UA patients of qi deficiency syndrome, blood stasis syndrome, and phlegm turbidity syndrome were recommended as follows: nitrates +statins +clopidogrel +angiotensin II receptor blockers +heparins +Astragalus membranaceus +Condonopsis + poria and large-head atractylodes rhizome (ADR = 0.85077869); nitrates + aspirin + clopidogrel + statins + heparins + Astragalus membranaceus + safflower + peach seed + red peony root (ADR = 0.70773000); nitrates + aspirin + statins + angiotensin-converting inhibitors + snakegourd fruit + onion bulb + ternate pinellia + tangerine peel (ADR = 0.72509600). CONCLUSION: As a POMDP based optimized treatment programs for UA, it can be used as a reference for further standardization and formulation of UA program by integrative medicine.

[Discussion on solutions to ethical issues of clinical researches in a real world].

The paradigm of a real world study has become the frontiers of clinical researches, especially in the field of Chinese medicine, all over the world in recent years. In this paper, ethical issues which probably exist in real-world studies are raised and reviewed. Moreover, some preliminary solutions to these issues such as protecting subjects during the process of real-world studies and performing ethical review are raised based on recent years' practices to enhance the scientificity and ethical level of real-world studies.

Discovery of regularities in the use of herbs in Chinese medicine prescriptions.

Chinese medicine (CM) is a discipline with its own distinct methodologies and philosophical principles. The main method of treatment in CM is to use herbal prescriptions. Typically, a number of herbs are combined to form a formula and different formulae are prescribed for different patients. Regularities in the mixture of herbs in the prescriptions are important for both clinical treatment and novel patent medicine development. In this study, we analyze CM formula data using latent tree (LT) models. Interesting regularities are discovered. Those regularities are of interest to students of CM as well as pharmaceutical companies that manufacture medicine using Chinese herbs.

Patterns of herbal combination for the treatment of insomnia commonly employed by highly experienced Chinese medicine physicians.

OBJECTIVE: To explore the most effective herbal combinations commonly used by highly experienced Chinese medicine (CM) physicians for the treatment of insomnia. METHODS: We collected and analyzed data related to insomnia treatment from the clinics of 7 highly experienced CM physicians in Beijing. The sample included 162 patients and 460 consultations in total. Patient outcomes, such as sleep quality and sleep time per day, were manually collected from the medical records by trained CM clinicians. Three data mining methods, support vector machine (SVM), logistic regression and decision tree, and multifactor dimensionality reduction (MDR), were used to determine and confirm the herbal combinations that resulted in positive outcomes in patients suffering from insomnia. RESULTS: Results show that MDR is the most efficient method to predict the effective herbal combinations. Using the MDR model, we identified several combinations of herbs with 100% positive outcomes, such as stir-fried spine date seed, Szechwan lovage rhizome, and prepared thinleaf milkwort root; white peony root, golden thread, and stir-fried spine date seed; and Asiatic cornelian cherry fruit with fresh rehmannia. CONCLUSIONS: Results indicate that herbal combinations are effective treatments for patients with insomnia compared with individual herbs. It is also shown that MDR is a potent data mining method to identify the herbal combination with high rates of positive outcome.

Topic model for Chinese medicine diagnosis and prescription regularities analysis: case on diabetes.

Induction of common knowledge or regularities from large-scale clinical data is a vital task for Chinese medicine (CM). In this paper, we propose a data mining method, called the Symptom-Herb-Diagnosis topic (SHDT) model, to automatically extract the common relationships among symptoms, herb combinations and diagnoses from large-scale CM clinical data. The SHDT model is one of the multi-relational extensions of the latent topic model, which can acquire topic structure from discrete corpora (such as document collection) by capturing the semantic relations among words. We applied the SHDT model to discover the common CM diagnosis and treatment knowledge for type 2 diabetes mellitus (T2DM) using 3 238 inpatient cases. We obtained meaningful diagnosis and treatment topics (clusters) from the data, which clinically indicated some important medical groups corresponding to comorbidity diseases (e.g., heart disease and diabetic kidney diseases in T2DM inpatients). The results show that manifestation sub-categories actually exist in T2DM patients that need specific, individualised CM therapies. Furthermore, the results demonstrate that this method is helpful for generating CM clinical guidelines for T2DM based on structured collected clinical data.

A study on the basic drugs and points for point application in summer to treat the diseases with attacks in winter.

OBJECTIVE: To study the basic prescriptions of drugs and points for point application in summer to treat the diseases with attacks in winter and the law governing their compatibility. METHODS: A database was set up by collecting and sorting out the relevant literature, and the analysis was made with the complex network. RESULTS: It was found that Bai Jie Zi (Semen Sinapis Albae), Xi Xin (Herba Asari), Gan Sui (Radix Euphorbiae Kansui) and Yan Hu Suo (Rhizoma Corydalis) were used as the basic prescriptions of drugs, Feishu (BL 13), Dazhui (GV 14) and Shanzhong (CV 17) were selected as the basic prescription of points. CONCLUSION: The knowledge obtained from the complex networks on the basic prescriptions of drugs and points for point-application in summer to treat diseases with attacks in winter can provide a data support for working out operation norms and carrying on verification research.

[Analysis of relationships among syndrome, therapeutic treatment, and Chinese herbal medicine in patients with coronary artery disease based on complex networks].

OBJECTIVE: To analyze the relationships among syndrome, therapeutic method and Chinese herbal medicine in patients with coronary artery disease (CAD). METHODS: Using cross-sectional survey, we collected the clinical information of hospitalized CAD patients through individualized Information Acquisition Platform of CAD. The relationships among syndrome, therapeutic treatment and Chinese herbs were excavated by means of complex networks based on theory of correspondence between prescription and syndrome. RESULTS: The fundamental syndrome factors were blood stasis, qi deficiency, phlegm-turbid, yin deficiency, yang deficiency, qi stagnation, and blood deficiency. The therapeutic treatment mainly included activating blood circulation, clearing heat, invigorating qi, resolving turbid and phlegm, nourishing yin, warming yang qi, and dispersing obstruction. These methods constituted an association with major syndrome factors. The major syndrome factors constituted an association with the following Chinese herbal medicines: Huangqi (Radix Astragali Mongolici), Chenpi (Pericarpium Citri Reticulatae), Dihuang (Radix Rehmanniae), Chuanxiong (Rhizoma Chuanxiong), Baizhu (Rhizoma Atractylodis Macrocephalae), Taoren (Semen Persicae), Fuling (Poria), Gancao (Radix Glycyrrhizae), Banxia (Rhizoma Pinelliae), Zexie (Rhizoma Alismatis), Chishao (Radix Paeoniae Rubra), Danggui (Radix Angelicae Sinensis), Danshen (Radix Salviae Miltiorrhizae), Zhiqiao (Fructus Aurantii Submaturus.), Guizhi (Ramulus Cinnamomi) and Maidong (Radix Ophiopogonis Japonici). The efficacy of Chinese berbal medicines constituting association with syndrome factors mainly included alleviating pain, resolving turbid and phlegm, clearing heat, activating blood circulation, invigorating qi, cooling blood, promoting urination, resolving stagnation, removing toxic material, nourishing blood, regulating qi, quieting spirit, invigorating spleen, regulating menstruation, promoting defecation, moistening dryness, and resolving stasis. CONCLUSION: The therapeutic methods for CAD are based on consistency in theory, method, formula and medicines. Therapeutic methods for clearing heat and removing toxical material should be further studied.

[Efficacy evaluation of Shengmai Injection in treating coronary heart disease based on random walk model].

OBJECTIVE: To evaluate the clinical effects of Shengmai Injection in treating coronary heart disease (CHD) based on correct syndrome differentiation and incorrect syndrome differentiation. METHODS: The patients' information was collected through a system of individual diagnosis and treatment of CHD. The score of main symptoms was calculated and recorded during the treatment. Patients were divided into two groups (incorrect syndrome and correct syndrome groups) on the basis of syndrome differentiation treatment or not. The clinical therapeutic effects of the two treatments were evaluated based on statistic theory combined with random walk method. RESULTS: There were 273 patients in the correct syndrome group and 4 patients died (case-fatality rate was 1.47%). There were 297 patients in the incorrect syndrome group and 7 patients died (case-fatality rate was 2.36%). In the correct syndrome group, random fluctuation peak of comprehensive evaluation index, walk steps, positive growth rate of walk, ratio, random fluctuation power-law, increase rate and record times of comprehensive evaluation index were 1 472, 13 617, 0.108 1, 9.25, 0.674 2, 0.470 6 and 3 128 respectively, while in the incorrect syndrome group, 1 030, 14 588, 0.070 6, 14.16, 0.660 6, 0.312 8 and 3 293 respectively. The random fluctuation power-law in both groups exceeded 0.5. CONCLUSION: There is a long-range correlation between the comprehensive evaluation index and therapeutic method as the CHD patients were treated with Shengmai Injection. The clinical therapeutic effects of Shengmai Injection under correct syndrome differentiation are better than the effects of Shengmai Injection under incorrect syndrome differentiation.

[Study on law using Chinese drug of famous old docter of traditional Chinese medicine to coronary heart disease based on association rules].

OBJECTIVE: To analyze the law that famous old doctor of traditional Chinese medicine (TCM) treat angina pectoris using Chinese drugs, explore the method that well-known doctor's experience was arranged. METHOD: Typical medicine case 115 of angina pectoris were collected and well-known doctor coronary heart disease database making a diagnosis was set up, then used association rules to analyze well-known doctor's prescription compatibility law curing coronary heart disease. RESULT: In 175 kinds of traditional Chinese medicinal used, the compatibility among blood-activating drug, phlegm-resolving drug and tonic was the most frequently used medicinal groups, Gualou Xiebai decoction, Huoxue decoction and Shengmai powder were the basic formula that well-known doctor treat coronary heart disease, matching and employing between the three form the universal law that the well-known doctor used medicine. CONCLUSION: Drug groups drew with association rules that well-known doctor treat coronary heart disease reacted well-known doctor's therapeutic thought of curing, would provide the method reference to research in the hereafter.

[Summary of professor Tian Cong-huo's commonly-used acupoint prescriptions].

Clinically, professor TIAN Cong-huo pays attention to treatment based on syndrome differentiation, with acupoint selection based on syndrome differentiation. In this present paper, clinically commonly-used 19 acupoint prescriptions, and relatively fixed indication ranges, manipulation methods, modified acupoint prescriptions, and professor TIAN's experience in application of these acupoints are summarized and introduced.