Effects of Bushen-Jiangya granules on blood pressure and pharmacogenomic evaluation in low-to-medium-risk hypertensive patients: study protocol for a randomized double-blind controlled trial

Introduction Hypertension is one of the most important risk factors for cardiovascular disease, and its control rates remain low worldwide. The most effective strategy is that patients with hypertension should be diagnosed and treated early. Preliminary studies showed that the Bushen Jiangya granule (BSJY) could suppress ventricular hypertrophy and inflammatory responses, lower blood pressure, and protect the target organs of hypertension. We designed a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of BSJY in patients with low-to-medium risk hypertension. Methods and analysis This trial is a one-center, randomized, double-blind, placebo-controlled study. A total of 260 participants will be randomized in a 1:1 ratio to an experimental group (BSJY plus amlodipine) and a control group (placebo plus amlodipine). The trial cycle will last 8 weeks. The primary outcome is the change in 24-h average systolic and diastolic blood pressure. The secondary outcomes include heart rate variability, pharmacogenomic evaluation, improvement in TCM syndrome, and serum pro-inflammatory/anti-inflammatory cytokines between the two groups. The safety of medication will also be evaluated. All the data will be recorded in electronic case report forms and analyzed by SPSS V.22.0. Ethics and dissemination This study has been approved by the Research Ethics Committee of Guang’anmen Hospital, China Academy of Chinese Medical Sciences in Beijing, China (No. 2019-186-KY-01). The participants are volunteers, understand the process of this trial, and sign an informed consent. The results of this study will be disseminated to the public through peer-reviewed journals and academic conferences. Discussion We hypothesize that patients with low-to-medium-risk hypertension will benefit from BSJY. If successful, this study will provide evidence-based recommendations for clinicians. Trial registration Chinese Clinical Trial Registry ChiMCTR1900002876. Registered in November 2019

Syndrome Differentiation and Treatment Regularity in Traditional Chinese Medicine for Type 2 Diabetes: A Text Mining Analysis

ObjectiveThe goal of this study was to systematically summarize and categorize the syndrome differentiation, medication rules, and acupoint therapy in the domestic traditional Chinese medicine (TCM) literature on type 2 diabetes mellitus (T2DM), such that guidelines and new insights can be provided for future practitioners and researchers.MethodsTaking randomized controlled trials (RCTs) on the treatment of T2DM in TCM as the research theme, we searched for full-text literature in three major clinical databases, including CNKI, Wan Fang, and VIP, published between 1990 and 2020. We then conducted frequency statistics, cluster analysis, association rules extraction, and topic modeling based on a corpus of medical academic words extracted from 3,654 research articles.ResultsThe TCM syndrome types, subjective symptoms, objective indicators, Chinese herbal medicine, acupuncture points, and TCM prescriptions for T2DM were compiled based on invigorating the kidney and Qi, nourishing Yin, and strengthening the spleen. Most TCM syndrome differentiation for T2DM was identified as “Zhongxiao” (the lesion in the spleen and stomach) and “Xiaxiao” (the lesion in the kidney) deficiency syndromes, and most medications and acupoint therapies were focused on the “Spleen Channel” and “Kidney Channel.” However, stagnation of liver Qi was mentioned less when compared with other syndromes, which did not have symptomatic medicines.ConclusionThis study provides an in-depth perspective for the TCM syndrome differentiation, medication rules, and acupoint therapy for T2DM and provides practitioners and researchers with valuable information about the current status and frontier trends of TCM research on T2DM in terms of both diagnosis and treatment.

Clinical Effects of Jiawei Danggui Beimu Kushen Pills in the Treatment of Prostate Cancer and Their Influence on the Expression of Serum Prostate Specific Antigen

Objective. To observe the clinical effects of Jiawei Danggui Beimu Kushen pills in treating prostate cancer and their influence on the expression of serum prostate specific antigen. Methods. A total of 234 prostate cancer patients were selected and randomly divided into observation group and control group, with 117 cases in each group. The control group was given oral bicalutamide tablets, while the observation group was treated with Jiawei Danggui Beimu Kushen pills on the basis of the control group. The treatment efficacy, IPSS score, TCM syndrome score, VAS score, quality-of-life score, and immune function of the two groups were compared before and after treatment. The serum PSA and f-PSA levels of patients before treatment and after 30 days, 90 days, and 180 days of treatment in the two groups were compared. The five-year cumulative survival rate and the incidence of adverse reactions were compared between the two groups. Results. After treatment, the total effective rate of the observation group was 88.03% (103/117), which was higher than that of the control group 69.23% (81/117); the difference was statistically significant ( P < 0.05 ). After treatment, the IPSS score, TCM syndrome score, and VAS score of the two groups were reduced, and those in the observation group were lower than those in the control group; the difference was statistically significant ( P < 0.05 ). After treatment, the quality-of-life scores of the two groups increased, and the observation group was higher than the control group; the difference was statistically significant ( P < 0.05 ). Before treatment, there was no significant difference in serum PSA levels and f-PSA levels when comparing between the two groups of patients ( P > 0.05 ). With the increase of treatment time, the two index levels of the two groups were gradually decreased. After 180 days of treatment, the two index levels of the two groups of patients were significantly lower than those before treatment, and the two index levels of the observation group were significantly lower than those of the control group; the difference was statistically significant ( P < 0.05 ). After treatment, the levels of IgM and IgA in the two groups were decreased, and the level of IgG was increased. The difference between the two groups in the levels of each index before and after treatment was statistically significant ( P < 0.05 ), and the difference between the two groups in the levels of each index after treatment was also statistically significant ( P < 0.05 ). The five-year cumulative survival rate of the observation group was 69.23%, and the five-year cumulative survival rate of the control group was 46.15% ( P < 0.05 ). There was no statistically significant difference between the two groups in the incidence of dizziness, fatigue, and gastrointestinal reactions ( P > 0.05 ), but the difference in the incidence of dysuria as well as dysuria and hematuria was statistically significant ( P < 0.05 ). Conclusion. Jiawei Danggui Beimu Kushen pills are effective in treating prostate cancer, which can effectively reduce the patients’ IPSS score and TCM syndrome scores, relieve the pain, and improve the quality of life of patients. They also have a potential role in regulating serum PSA levels, clearing tumor lesions, reducing postoperative complications, and improving related symptoms.

Correlation between TCM Syndromes and Type 2 Diabetic Comorbidities Based on Fully Connected Neural Network Prediction Model

Objective. To predict the major comorbidities of type 2 diabetes based on the distribution characteristics of syndromes, and to explore the relationship between TCM syndromes and comorbidities of type 2 diabetes. Methods. Based on the electronic medical record data of 3413 outpatient visits from 995 type 2 diabetes patients with comorbidities, descriptive statistical methods were used to analyze the basic characteristics of the population, the distribution characteristics of comorbidities, and TCM syndromes. A neural network model for the prediction of type 2 diabetic comorbidities based on TCM syndromes was constructed. Results. Patients with TCM syndrome of blood amassment in the lower jiao were diagnosed with renal insufficiency with 95% test sensitivity. The patients with spleen deficiency combined with ascending counterflow of stomach qi and cold-damp patterns were diagnosed with gastrointestinal lesions with 92% sensitivity. The patients with TCM syndrome group of spleen heat and exuberance of heart fire were diagnosed as type 2 diabetes complicated with hypertension with a sensitivity of 91%. In addition, the prediction accuracy of combined neuropathy, heart disease, liver disease, and lipid metabolism disorder reached 70∼90% in TCM syndrome groups. Conclusion. The fully connected neural network model study showed that syndrome characteristics are highly correlated with type 2 diabetes comorbidities. Syndrome location is commonly in the heart, spleen, stomach, lower jiao, meridians, etc., while syndrome pattern manifests in states of deficiency, heat, phlegm, and blood stasis. The different combinations of disease location and disease pattern reflect the syndrome characteristics of different comorbidities forming the characteristic syndrome group of each comorbidity. Major comorbidities could be predicted with a high degree of accuracy through TCM syndromes. Findings from this study may have further implementations to assist with the diagnosis, treatment, and prevention of diabetic comorbidities at an early stage.

Exploring biological basis of Syndrome differentiation in coronary heart disease patients with two distinct Syndromes by integrated multi-omics and network pharmacology strategy

Background Traditional Chinese Medicine (TCM) is distinguished by Syndrome differentiation, which prescribes various formulae for different Syndromes of same disease. This study aims to investigate the underlying mechanism. Methods Using a strategy which integrated proteomics, metabolomics study for clinic samples and network pharmacology for six classic TCM formulae, we systemically explored the biological basis of TCM Syndrome differentiation for two typical Syndromes of CHD: Cold Congealing and Qi Stagnation (CCQS), and Qi Stagnation and Blood Stasis (QSBS). Results Our study revealed that CHD patients with CCQS Syndrome were characterized with alteration in pantothenate and CoA biosynthesis, while more extensively altered pathways including D-glutamine and D-glutamate metabolism; alanine, aspartate and glutamate metabolism, and glyoxylate and dicarboxylate metabolism, were present in QSBS patients. Furthermore, our results suggested that the down-expressed PON1 and ADIPOQ might be potential biomarkers for CCQS Syndrome, while the down-expressed APOE and APOA1 for QSBS Syndrome in CHD patients. In addition, network pharmacology and integrated analysis indicated possible comorbidity differences between the two Syndromes, that is, CCQS or QSBS Syndrome was strongly linked to diabetes or ischemic stroke, respectively, which is consistent with the complication disparity between the enrolled patients with two different Syndromes. These results confirmed our assumption that the molecules and biological processes regulated by the Syndrome-specific formulae could be associated with dysfunctional objects caused by the Syndrome of the disease. Conclusion This study provided evidence-based strategy for exploring the biological basis of Syndrome differentiation in TCM, which sheds light on the translation of TCM theory in the practice of precision medicine.

Study protocol: Traditional Chinese Medicine (TCM) syndrome differentiation for heart failure patients and its implication for long-term therapeutic outcomes of the Qiliqiangxin capsules

Background Syndrome differentiation is a commonly used methodology and practice in Traditional Chinese Medicine (TCM) guiding the diagnosis and treatment of diseases including heart failure (HF). However, previous clinical trials seldom consider the impact of syndrome patterns on the outcome evaluation of TCM formulae. Qiliqiangxin (QLQX) capsule is a TCM formula with cardiotonic effect to improve the cardiovascular function for heart failure with proven efficacy from well-designed clinical trials. Though, there is no clinical trial with a large sample size and long assessment period that considers the relationship between TCM syndrome differentiation and the treatment efficacy of QLQX. In the present study, we design a study protocol to evaluate the relationship between TCM syndrome differentiation and the severity of heart failure as well as its progression. Furthermore, we will evaluate the impact of the TCM syndrome patterns on the efficacy of QLQX in the outcome of heart failure. Methods This is a clinical study conducted in conjunction with an ongoing clinical trial (QUEST Study) by sharing the parent patient populations but with different aims and independent designed roadmaps to investigate the TCM syndrome pattern distributions and the impacts of syndrome pattern types on the efficacy of QLQX in HF treatment. The clinical trial involves over 100 hospitals in mainland China and Hong Kong SAR with 3080 HF patients. By assessing the morbidity and re-hospitalization, we will verify and apply a modified TCM Questionnaire to collect the clinical manifestations of HF and acquire the tongue images of the patients to facilitate the syndrome differentiation. We will base on the “2014 Consensus from TCM experts on diagnosis and treatment of chronic heart failure” to evaluate the TCM syndromes for the patients. A pilot study with at least 600 patients will be conducted to evaluate the reliability, feasibility and validity of the modified TCM questionnaire for syndrome differentiation of HF and the sample size is calculated based on the confidence level of 95%, population size of 3080 and 5% margin of error. Secondly, we will investigate the characteristic of TCM syndrome distribution of HF patients and its correlation with the functional and biochemical data. Furthermore, we will evaluate the relationship between the TCM syndrome patterns and the efficacy of QLQX in the treatment of heart failure. Lastly, we will investigate the implication of tongue diagnosis in the severity and therapeutic outcome of HF. Expect outcomes To our knowledge, this is the first large scale clinical trial to evaluate the impacts of TCM syndrome differentiation on the progression and therapeutic outcome of HF patients and explore the diagnostic value of TCM Tongue Diagnosis in HF patients. We expect to obtain direct clinical evidence to verify the importance of TCM syndrome differentiation for the diagnosis and treatment of HF. Trial Registration: The trial was registered at Chinese Clinical Trial Registry, http://www.chictr.org.cn. (Registration No.: ChiCTR1900021929); Date: 2019-03-16.

On the Modern Clinical Application of Wendan Decoction

Wendan Decoction is one of the commonly used prescriptions in clinical practice.it has a wide range of applications. On the basis of traditional Chinese medicine (TCM) syndrome differentiation, as long as it can be added or subdivided flexibly, it can be used to conquer various difficult and miscellaneous diseases seen in daily life.

Metabolomics-Based Clinical Efficacy of Compound Shenlu Granule, a Chinese Patent Medicine, in the Supportive Management of Aplastic Anemia Patients: A Randomized Controlled Pilot Trial

Objective. To explore the clinical efficacy and mechanism of compound Shenlu granule (SLG) treatment in patients with aplastic anemia (AA). Methods. A total of 89 AA patients were randomly divided into an SLG supportive group (group A, n = 44) and a control group (group B, n = 45) while continuing Western medical management. After 6 months, hemograms, traditional Chinese medicine (TCM) syndrome scores, and overall clinical efficacy rate were assessed. Serum metabolomics characteristics were observed using ultraperformance liquid chromatography-mass spectrometry after SLG intervention. Results. The levels of red blood cell (RBC), hemoglobin (Hb), and platelet (PLT) were increased in both groups after treatment for 6 months ( P < 0.05 ), and in group A, the elevation of PLT became much more significant ( P < 0.01 ). The TCM syndrome score was lower in group A than in group B after treatment ( P < 0.05 ). Metabolomics data showed a significant difference in the patients using SLG after 6 months, and 14 biomarkers were identified. Conclusion. SLG supportive treatment showed positive results in patients with AA, and metabolomics data indicated that SLG influenced aminoacyl-tRNA biosynthesis and glycerophospholipid metabolism to gradually return to normal.