In Silico Insights into Micro-Mechanism Understanding of Extracts of Taxus Chinensis Fruits Against Alzheimer's Disease.

BACKGROUND: The taxus chinensis fruit (TCF) shows promises in treatment of aging-related diseases such as Alzheimer's disease (AD). However, its related constituents and targets against AD have not been deciphered. OBJECTIVE: This study was to uncover constituents and targets of TCF extracts against AD. METHODS: An integrated approach including ultrasound extractions and constituent identification of TCF by UPLC-QE-MS/MS, target identification of constituents and AD by R data-mining from Pubchem, Drugbank and GEO databases, network construction, molecular docking and the ROC curve analysis was carried out. RESULTS: We identified 250 compounds in TCF extracts, and obtained 3,231 known constituent targets and 5,326 differential expression genes of AD, and 988 intersection genes. Through the network construction and KEGG pathway analysis, 19 chemicals, 31 targets, and 11 biological pathways were obtained as core compounds, targets and pathways of TCF extracts against AD. Among these constituents, luteolin, oleic acid, gallic acid, baicalein, naringenin, lovastatin and rutin had obvious anti-AD effect. Molecular docking results further confirmed above results. The ROC AUC values of about 87% of these core targets of TCF extracts was greater than 0.5 in the two GEO chips of AD, especially 10 targets with ROC AUC values greater than 0.7, such as BCL2, CASP7, NFKBIA, HMOX1, CDK2, LDLR, RELA, and CCL2, which mainly referred to neuron apoptosis, response to oxidative stress and inflammation, fibroblast proliferation, etc.Conclusions:The TCF extracts have diverse active compounds that can act on the diagnostic genes of AD, which deserve further in-depth study.

A Nomogram model for the early warning of essential hypertension risks based on the principles of traditional Chinese medicine syndrome elements / 数字中医药（英文）

@#[Objective] To construct a Nomogram model for the prediction of essential hypertension (EH) risks with the use of traditional Chinese medicine (TCM) syndrome elements principles in conjunction with cutting-edge biochemical detection technologies. [Methods] A case-control study was conducted, involving 301 patients with essential hypertension in the hypertensive group and 314 without in the control group. Comprehensive data, including the information on the four TCM diagnoses, general data, and blood biochemical indicators of participants in both groups, were collected separately for analysis. The differentiation principles of syndrome elements were used to discern the location and nature of hypertension. One-way analysis was carried out to screen for potential risk factors of the disease. Least absolute shrinkage and selection operator (LASSO) regression was used to identify factors that contribute significantly to the model, and eliminate possible collinearity problems. At last, multivariate logistic regression analysis was used to both screen and quantify independent risk factors essential for the prediction model. The “rms” package in the R Studio was used to construct the Nomogram model, creating line segments of varying lengths based on the contribution of each risk factor to aid in the prediction of risks of hypertension. For internal model validation, the Bootstrap program package was utilized to perform 1000 repetitions of sampling and generate calibration curves. [Results] The results of the multivariate logistic regression analysis revealed that the risk factors of EH included age, heart rate (HR), waist-to-hip ratio (WHR), uric acid (UA) levels, family medical history, sleep patterns (early awakening and light sleep), water intake, and psychological traits (depression and anger). Additionally, TCM syndrome elements such as phlegm, Yin deficiency, and Yang hyperactivity contributed to the risk of EH onset as well. TCM syndrome elements liver, spleen, and kidney were also considered the risk factors of EH. Next, the Nomogram model was constructed using the aforementioned 14 risk predictors, with an area under the curve (AUC) of 0.868 and a 95% confidence interval (CI) ranging from 0.840 to 0.895. The diagnostic sensitivity and specificity were found to be 80.7% and 85.0%, respectively. Internal validation confirmed the model’s robust predictive performance, with aconsistency index (C-index) of 0.879, underscoring the model’s strong predictive ability. [Conclusion] By integrating TCM syndrome elements, the Nomogram model has realized the objective, qualitative, and quantitative selection of early warning factors for developing EH, resulting in the creation of a more comprehensive and precise prediction model for EH risks.

TCM herbal prescription recommendation model based on multi-graph convolutional network.

ETHNOPHARMACOLOGICAL RELEVANCE: The recommendation of herbal prescriptions is a focus of research in traditional Chinese medicine (TCM). Artificial intelligence (AI) algorithms can generate prescriptions by analysing symptom data. Current models mainly focus on the binary relationships between a group of symptoms and a group of TCM herbs. A smaller number of existing models focus on the ternary relationships between TCM symptoms, syndrome-types and herbs. However, the process of TCM diagnosis (symptom analysis) and treatment (prescription) is, in essence, a "multi-ary" (n-ary) relationship. Present models fall short of considering the n-ary relationships between symptoms, state-elements, syndrome-types and herbs. Therefore, there is room for improvement in TCM herbal prescription recommendation models. PURPOSE: To portray the n-ary relationship, this study proposes a prescription recommendation model based on a multigraph convolutional network (MGCN). It introduces two essential components of the TCM diagnosis process: state-elements and syndrome-types. METHODS: The MGCN consists of two modules: a TCM feature-aggregation module and a herbal medicine prediction module. The TCM feature-aggregation module simulates the n-ary relationships between symptoms and prescriptions by constructing a symptom-'state element'-symptom graph (Se) and a symptom-'syndrome-type'-symptom graph (Ts). The herbal medicine prediction module inputs state-elements, syndrome-types and symptom data and uses a multilayer perceptron (MLP) to predict a corresponding herbal prescription. To verify the effectiveness of the proposed model, numerous quantitative and qualitative experiments were conducted on the Treatise on Febrile Diseases dataset. RESULTS: In the experiments, the MGCN outperformed three other algorithms used for comparison. In addition, the experimental data shows that, of these three algorithms, the SVM performed best. The MGCN was 4.51%, 6.45% and 5.31% higher in Precision@5, Recall@5 and F1-score@5, respectively, than the SVM. We set the K-value to 5 and conducted two qualitative experiments. In the first case, all five herbs in the label were correctly predicted by the MGCN. In the second case, four of the five herbs were correctly predicted. CONCLUSIONS: Compared with existing AI algorithms, the MGCN significantly improved the accuracy of TCM herbal prescription recommendations. In addition, the MGCN provides a more accurate TCM prescription herbal recommendation scheme, giving it great practical application value.

Exploration of a Brain-Liver-Communication-Related Mechanism Involved in the Experimental Perimenopausal Depression Rat Model using Chaihu-Shugan-San.

Existing research suggests the involvement of a brain-liver-communication-related mechanism in the occurrence of depression. In this study, we selected Chaihu-Shugan-San (CSS), a traditional Chinese herbal medicine that can simultaneously affect liver and depression, as a probe to investigate the involvement of the brain-liver-communication-related mechanism in perimenopausal depression. A total of 50 experimental perimenopausal depression rat models were established by ovariectomy surgery (PMS) followed by chronic unpredictable mild stress (CUMS) processes. Animals underwent CSS treatment or treatments with CSS + Ly294002, an inhibitor of the PI3K/Akt signalling pathway. We observed the behavioural performances of depression and anxiety, serum concentrations of biochemical indices, serum estrogen two levels, hippocampal 5-HT and NE levels and the morphological changes in liver tissues. The protein and mRNA expressions of PI3K and Akt were also evaluated. CSS treatment significantly ameliorated the behavioural performance, partial biochemical indices and the morphological changes in the liver tissues of PMS + CUMS rats. Ly294002 partially inhibited the CSS effects. The expressions of PI3K and Akt were significantly downregulated by PMS + CUMS processes but upregulated by CSS treatment, which could be significantly suppressed by Ly294002. A brain-liver-communication-related mechanism may be involved in perimenopausal depression, where the PI3K/Akt signalling pathway plays a vital role.

Exploring miRNA-related Molecular Targets of Erchen Decoction against Lipid Metabolism Disorder using a Network Pharmacologic Approach.

BACKGROUND: Erchen Decoction (ECD) is a complex herbal formulation widely used for treating lipid metabolism disorder (LMD) in China. This study aims to explore the microRNA (miRNA)-related molecular targets of ECD against LMD using a network pharmacology approach (NPA) Methods: We randomly divided 20 male Sprague Dawley rats into two groups; 10 rats were normal controls, and the other 10 rats were fed a high-fat diet (HFD) for 12 weeks to establish an LMD model. Differentially expressed miRNAs (DE-miRs, HFD vs. Control) in the rats' liver tissues were identified by miRNA sequencing and validated with qRT-PCR. Finally, the miRNArelated molecular targets for ECD activity against LMD were identified using a standard NPA by finding the intersection between identified DE-miRs-related targets and ECD-related targets. RESULT: We identified 8 DE-miRs and 968 targets and compared them to 262 ECD-related targets. A final list of 22 candidate targets was identified. Using a confidence score of >0.4, the network of (protein-protein interaction) PPI relationships exhibited 22 nodes and 67 edges. The GO and KEGG enrichment analyses revealed 171 molecular targets and 59 pathways, which were associated with ECD against LMD. CONCLUSION: The identified molecular targets and pathways suggest that complex mechanisms are involved in ECD's mechanism of action, and immune-inflammation-related mechanisms are closely associated with the effects of ECD. The targets obtained in this study will guide future studies on the pharmacologic effects of ECD.

Role of Parameter Setting in Electroacupuncture: Current Scenario and Future Prospects.

Acupuncture is an ancient therapeutic method based on the theory of Chinese medicine (CM). Traditional acupuncture has many limitations; it is subjective and relies more on the experience of an acupuncturist, and the efficacy is sometimes irreproducible. In contrast, electroacupuncture (EA) has special characteristics in terms of objectivity and stability, thereby gaining considerable attention. Parameter setting plays a crucial role in EA practice. The current paper summarizes the current situation and limitations of parameter setting in EA practice. Objectification is the tendency and future of CM as well as EA. With the development of computerized technologies, such as wearable sensors, vast data, and artificial intelligence, CM syndromes can be successfully objectified. We propose the development of a novel self-feedback-adjust EA system, which may improve the parameter setting in EA and be beneficial to both the patients and clinicians.

An Effective Treatment of Perimenopausal Syndrome by Combining Two Traditional Prescriptions of Chinese Botanical Drugs.

Ethnopharmacological relevance: Two types of traditional Chinese formulas of botanical drugs are prescribed for treating perimenopausal syndrome (PMS), a disorder in middle-aged women during their transition to menopause. One is for treating PMS as kidney deficiency (KD) due to senescence and declining reproductive functions, and the other is for treating it as liver qi stagnation (LQS) in association with stress and anxiety. Despite the time-tested prescriptions, an objective attestation to the effectiveness of the traditional Chinese treatment of PMS is still to be established and the associated molecular mechanism is still to be investigated. Materials and methods: A model for PMS was generated from perimenopausal rats with chronic restraint stress (CRS). The effectiveness of traditional Chinese formulas of botanical drugs and a combination of two of the formulas was evaluated based on 1H NMR plasma metabolomic, as well as behavioral and physiological, indicators. To investigate whether the formulas contained ligands that could compensate for the declining level of estrogen, the primary cause of PMS, the ligand-based NMR technique of saturation transfer difference (STD) was employed to detect possible interacting molecules to estrogen receptors in the decoction. Results: Each prescription of the classical Chinese formula moderately attenuated the metabolomic state of the disease model. The best treatment strategy however was to combine two traditional Chinese formulas, each for a different etiology, to adjust the metabolomic state of the disease model to that of rats at a much younger age. In addition, this attenuation of the metabolomics of the disease model was by neither upregulating the estrogen level nor supplementing an estrogenic compound. Conclusion: Treatment of PMS with a traditional Chinese formula of botanical drugs targeting one of the two causes separately could ameliorate the disorder moderately. However, the best outcome was to treat the two causes simultaneously with a decoction that combined ingredients from two traditional prescriptions. The data also implicated a new paradigm for phytotherapy of PMS as the prescribed decoctions contained no interacting compound to modulate the activity of estrogen receptors, in contrast to the treatment strategy of hormone replacement therapy.

The important herbal pair for the treatment of COVID-19 and its possible mechanisms.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is an unprecedented disaster for people around the world. Many studies have shown that traditional Chinese medicine (TCM) are effective in treating COVID-19. However, it is difficult to find the most effective combination herbal pair among numerous herbs, as well as identifying its potential mechanisms. Herbal pair is the main form of a combination of TCM herbs, which is widely used for the treatment of diseases. It can also help us to better understand the compatibility of TCM prescriptions, thus improving the curative effects. The purpose of this article is to explore the compatibility of TCM prescriptions and identify the most important herbal pair for the treatment of COVID-19, and then analyze the active components and potential mechanisms of this herbal pair. METHODS: We first systematically sorted the TCM prescriptions recommended by the leading experts for treating COVID-19, and the specific herbs contained in these prescriptions across different stages of the disease. Next, the association rule approach was employed to examine the distribution and compatibility among these TCM prescriptions, and then identify the most important herbal pair. On this basis, we further investigated the active ingredients and potential targets in the selected herbal pair by a network pharmacology approach, and analyzed the potential mechanisms against COVID-19. Finally, the main active compounds in the herbal pair were selected for molecular docking with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) 3CLpro and angiotensin converting enzyme II (ACE2) for further verification. RESULT: We obtained 32 association rules for the herbal combinations in the selection of TCM treatment for COVID-19. The results showed that the combination of Amygdalus Communis Vas (ACV) and Ephedra sinica Stapf (ESS) had the highest confidence degree and lift value, as well as high support degree, which can be used in almost all the stages of COVID-19, so ACV and ESS (AE) were selected as the most important herbal pair. There were 26 active ingredients and 44 potential targets, which might be related to the herbal pair of AE against COVID-19. The main active ingredients of AE against COVID-19 were quercetin, kaempferol, luteolin, while the potential targets were Interleukin 6 (IL-6), Mitogen-activated Protein Kinase 1 (MAPK)1, MAPK8, Interleukin-1ß (IL-1ß), and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) p65 subunit (RELA). The protein-protein interaction (PPI) cluster demonstrated that IL-6 was the seed in the cluster, which plays an important role in connecting other nodes in the PPI network. The potential pathways mainly involved tumor necrosis factor (TNF), Toll-like receptor (TLR), hypoxia-inducible factor-1 (HIF-1), and nucleotide-binding oligomerization domain (NOD)-like receptor (NLRs). The molecular docking results showed that the main active ingredients of AE have good affinity with SARS-COV-2 3CLpro and ACE2, which are consistent with the above analysis. CONCLUSIONS: There were 32 association rules in the TCM prescriptions recommended by experts for COVID-19. The combination of ACV and EAS was the most important herbal pair for the treatment of COVID-19. AE might have therapeutic effects against COVID-19 by affecting the inflammatory and immune responses, cell apoptosis, hypoxia damage and other pathological processes through multiple components, targets and pathways.

Modeling of diagnosis for metabolic syndrome by integrating symptoms into physiochemical indexes.

BACKGROUND: Metabolic syndrome (MS) is a major global health concern comprising a cluster of co-occurring conditions that increase the risk of heart disease, stroke and type 2 diabetes. MS is usually diagnosed using a combination of physiochemical indexes (such as BMI, abdominal circumference and blood pressure) but largely ignores clinical symptoms when investigating prevention and treatment of the disease. Exploring predictors of MS using multiple diagnostic indicators may improve early diagnosis and treatment of MS. Traditional Chinese medicine (TCM) attaches importance to the etiology of disease symptoms and indications using four diagnostic methods, which have long been used to treat metabolic disease. Therefore, in this study, we aimed to develop predictive indicators for MS using both physiochemical indexes and TCM methods. METHODS: Clinical information (including both physiochemical and TCM indexes) was obtained from a cohort of 586 individuals across 4 hospitals in China, comprising 136 healthy controls and 450 MS cases. Using this cohort, we compared three classic machine learning methods: decision tree (DT), support vector machine (SVM) and random forest (RF) towards MS diagnosis using physiochemical and TCM indexes, with the best model selected by comparing the accuracy, specificity and sensitivity of the three models. In parallel, the best proportional partition of the training data to the test data was confirmed by observing the changes in evaluation indexes using each model. Next, three subsets containing different categories of variables (including both TCM and physicochemical indexes combined - termed the "fused indexes", only physicochemical indexes, and TCM indexes only) were compared and analyzed using the best performing model and optimum training to test data proportion. Next, the best subset was selected through comprehensive comparative analysis, and then the important prediction variables were selected according to their weight. RESULTS: When comparing the three models, we found that the RF model had the highest average accuracy (average 0.942, 95%CI [0.925, 0.958]) and sensitivity (average 0.993, 95%CI [0.990, 0.996]). Besides, when the training set accounted for 80% of the cohort data, the specificity got the best value and the accuracy and sensitivity were also very high in RF model. In view of the performance of the three different subsets, the prediction accuracy and sensitivity of models analyzing the fused indexes and only physicochemical indexes remained at a high level. Further, the mean value of specificity of the model using fused indexes was 0.916, which was significantly higher than the model with only physicochemical indexes (average 0.822) and the model with only TCM indexes (average 0.403). Based on the RF model and data allocation ratio (8:2), we further extracted the top 20 most significant variables from the fused indexes, which included 14 physicochemical indexes and 6 TCM indexes including wiry pulse, chest tightness, spontaneous perspiration, greasy tongue coating etc. CONCLUSION: Compared with SVM and DT models, the RF model showed the best performance, especially when the ratio of the training set to test set is 8:2. Compared with single predictive indexes, the model constructed by combining physiochemical indexes with TCM indexes (i.e. the fused indexes) exhibited better predictive ability. In addition to common physicochemical indexes, some TCM indexes, such as wiry pulse, chest tightness, spontaneous perspiration, greasy tongue coating, can also improve diagnosis of MS.

The Metabolomic Rationale for Treating Perimenopausal Syndrome as Kidney Deficiency.

BACKGROUND: Traditional Chinese medicine (TCM) typically attributes the etiopathogenesis of perimenopausal syndrome (PMS) to kidney deficiency in the TCM stratification system for diagnosis. However, the molecular basis of this classical attribution remains to be investigated. Aim of the Study. By unraveling the responses to TCM treatment for kidney deficiency, the metabolomic link between PMS and kidney deficiency can be evaluated for in-depth understanding of the mechanism of TCM treatment and development of better treatment protocols. MATERIALS AND METHODS: With naturally aged rats as a model for PMS, the metabolomic response to TCM treatment for kidney deficiency was investigated by 1H NMR. RESULTS: 1H NMR metabolomic evidence of plasma samples demonstrates that treatments with two classical TCM prescriptions for kidney deficiency, decoctions of Yougui and Zuogui, result in modulating the metabolic state of the disease model towards that of rats of younger age. CONCLUSION: The data support the notion that kidney deficiency is responsible, in part at least, for PMS, and the relevant prescriptions are helpful in dampening the changes in the body's metabolic states to alleviate symptoms of the disorder.

A Microcosmic Syndrome Differentiation Model for Metabolic Syndrome with Multilabel Learning.

BACKGROUND: Metabolic syndrome (MS) is a complex multisystem disease. Traditional Chinese medicine (TCM) is effective in preventing and treating MS. Syndrome differentiation is the basis of TCM treatment, which is composed of location and/or nature syndrome elements. At present, there are still some problems for objective and comprehensive syndrome differentiation in MS. This study mainly proposes a solution to two problems. Firstly, TCM syndromes are concurrent, that is, multiple TCM syndromes may develop in the same patient. Secondly, there is a lack of holistic exploration of the relationship between microscopic indexes, and TCM syndromes. In regard to these two problems, multilabel learning (MLL) method in machine learning can be used to solve them, and a microcosmic syndrome differentiation model can also be built innovatively, which can provide a foundation for the establishment of the next model of multidimensional syndrome differentiation in MS. METHODS: The standardization scale of TCM four diagnostic information for MS was designed, which was used to obtain the results of TCM diagnosis. The model of microcosmic syndrome differentiation was constructed based on 39 physicochemical indexes by MLL techniques, called ML-kNN. Firstly, the multilabel learning method was compared with three commonly used single learning algorithms. Then, the results from ML-kNN were compared between physicochemical indexes and TCM information. Finally, the influence of the parameter k on the diagnostic model was investigated and the best k value was chosen for TCM diagnosis. RESULTS: A total of 698 cases were collected for the modeling of the microcosmic diagnosis of MS. The comprehensive performance of the ML-kNN model worked obviously better than the others, where the average precision of diagnosis was 71.4%. The results from ML-kNN based on physicochemical indexes were similar to the results based on TCM information. On the other hand, the k value had less influence on the prediction results from ML-kNN. CONCLUSIONS: In the present study, the microcosmic syndrome differentiation model of MS with MLL techniques was good at predicting syndrome elements and could be used to solve the diagnosis problems of multiple labels. Besides, it was suggested that there was a complex correlation between TCM syndrome elements and physicochemical indexes, which worth future investigation to promote the development of objective differentiation of MS.

Verification of the Efficacy and Safety of Qi-Replenishing Chinese Medicine in Treating Prediabetes: A Meta-Analysis and Literature Review.

BACKGROUND: Qi-replenishing Chinese medicines (QCMs) are used for treating prediabetes in the traditional Chinese medicine (TCM) clinical practice. The aims of this meta-analysis were to (i) verify the efficacy and safety of QCMs in treating prediabetes and (ii) investigate the clinical outcomes between the trials complying with and not complying with the principle of "syndrome differentiation." METHODS: We included only randomized controlled clinical trials (RCTs) whose Jadad scores were not less than 4. The overall clinical outcomes, including the incidence rate of diabetes, normalization of blood glucose, changes in fasting blood glucose (FBG), 2 h postprandial blood glucose, HbA1c, and occurrence of adverse events, were evaluated. Subgroup analyses were performed. RESULTS: A total of 11 RCTs that enrolled 2210 patients with prediabetes were included. We observed that overall treatment with QCMs significantly ameliorated the clinical outcomes of prediabetes without increasing incidence of adverse events. The results of subgroup analyses revealed that prescribing QCMs complying with syndrome differentiation ameliorated all the clinical indices, whereas prescribing not complying with syndrome differentiation could not achieve significant amelioration in FBG and HbA1c levels. Furthermore, the subgroup with syndrome differentiation reported more adverse events. CONCLUSIONS: The overall results suggested that QCMs are effective and safe in treating prediabetes. Results of subgroup analyses indicated that the groups with syndrome differentiation presented better efficacy but had a higher occurrence of adverse events. This study indicated the important role of the principle of syndrome differentiation in TCM and that the adverse events of QCMs cannot be ignored in TCM clinical practice.

Factor and Cluster Analysis for TCM Syndromes of Real-World Metabolic Syndrome at Different Age Stage.

BACKGROUND: Traditional Chinese medicine (TCM) has the characteristics of multitarget and overall regulation, which has certain advantages in preventing and treating of metabolic syndrome (MS). The aim of the present study was to evaluate the similarities and differences of TCM syndrome distribution in different age groups to promote the optimization of treatment strategies. METHODS: This study was based on a real-world survey conducted in 3 hospitals in China. There are 1262 collected cases of MS meeting the inclusion criteria, which were divided into the young group, middle-aged group, and elderly group. Factor analysis (FA) was conducted for syndrome element extraction, and K-means cluster analysis was processed for syndrome type classification. Frequency analysis and Chi-square test were used to compare the syndrome characteristics of each group. RESULTS: Common factors extracted were assigned to 18 syndrome elements including 11 nature syndrome elements and 7 location syndrome elements. Phlegm and dampness are the most frequent syndrome elements in general. Compared with the middle-aged group and elderly group, the young group has more obvious nature syndrome elements in heat and Qi deficiency, and location syndrome elements in the stomach. As for the middle-aged group, the frequency of location syndrome in kidney syndrome was higher than that in other groups. When it comes to the elderly group, it is shown that the symptoms of Yin deficiency and blood deficiency increase with age and the old patients may have more location syndrome elements in the lung and gallbladder. CONCLUSION: The TCM syndrome of MS is complex in that there may be the characteristics of deficiency and excess syndrome simultaneously. The main pathological factors of MS were phlegm and dampness. Besides, MS patients at different age periods may have their own syndrome distribution features. So, it is reasonable to adhere to the method of resolving phlegm and removing dampness and, at the same time, adopt the ways of clearing heat, promoting Qi, nourishing Yin, supplementing blood as well as regulating the liver, promoting the lung, transporting the spleen, nourishing the heart, and nourishing the kidney based on the syndrome feature of MS in different age stages.

Problems lowering the study quality in traditional medicine, introspection from an example of meta-analysis of acupuncture.

BACKGROUND: Most randomized controlled trials (RCTs) of traditional medicine (such as traditional Chinese medicine (TCM), psychotherapy or behavioral therapy, and dietary interventions, etc.) have reported that they could not provide convincing evidence to support the efficacy because of the low quality of their studies. Here, we aimed to determine the underlying problems of the study quality using standards of evidence-based medicine (EBM) to evaluate the efficacy of traditional medicine. METHODS: We conducted an example of meta-analysis to evaluate the efficacy of acupuncture, a classical treatment of TCM, for treatment of intracerebral hemorrhage (ICH). The quality of the included studies was evaluated by using a Jadad score. RESULTS: A total of 24 Chinese RCTs that enrolled 1815 patients with ICH were included. Although the results suggested that acupuncture had good efficacy for relief of neurological deficits and improvement of the activities of daily living despite the high heterogeneity of the included studies, the low quality of the included literature reduced the worthiness of the evidence. Two systematic problems (lack of blinding and allocation concealment and high heterogeneity) and one non-systematic problem (lack of reports on adverse events and follow-up) of the TCM studies were found in this illustrational meta-analysis. We believed that other interventions of traditional medicine also suffer from these problems. CONCLUSIONS: Non-systematic problems can be improved by perfecting the experimental design, educating the researcher, and improving the reporting system. However, systematic problems are derived from the characteristics of traditional medicine that are difficult to be corrected. We propose that adoption of objective indexes might be a better solution to improve the systematic problems of traditional medicine. We summarized the problems and the underlying solutions, which may contribute to improve the study quality of systematic review in traditional medicine, strictly complying with the principles of EBM.

Traditional Chinese Medicine-Guided Dietary Intervention for Male Youth Undergoing Drug Detoxification: A Randomized Controlled Trial.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of traditional Chinese medicine- (TCM-) guided dietary interventions in improving yang-qi deficiency and yin-blood deficiency TCM syndromes according to the principles of TCM syndrome differentiation theory in male youths undergoing drug detoxification during the rehabilitation period who stayed in a compulsory isolation detoxification center. METHODS: Male youths undergoing drug detoxification who met the criteria to be included in the study were randomly divided into the intervention group (n = 62) and the control group (n = 61) according to a random number table in a 1 : 1 ratio. The intervention group received a TCM-guided diet, and the control group received routine food support. Over an intervention period of 3 months, we observed changes in the TCM syndrome element scores in the two groups before and after intervention. RESULTS: After 3 months, the qi deficiency, yin deficiency, blood deficiency, and yin-blood deficiency syndrome in the intervention group improved significantly (P values 0.009, 0.000, 0.005, and 0.001, respectively). In the control group, yang deficiency, qi deficiency, and yang-qi deficiency syndromes worsened significantly (P values 0.003, 0.032, and 0.009, respectively). The differences (post-pre) in yang deficiency, qi deficiency, yang-qi deficiency, yin deficiency, blood deficiency, and yin-blood deficiency syndromes between the two groups were statistically significant (P values 0.003, 0.003, 0.003, 0.001, 0.005, and 0.002, respectively). CONCLUSION: A TCM-guided diet can delay the worsening of yang-qi deficiency syndrome symptoms and improve yin-blood deficiency syndrome and the prognosis of male youth undergoing drug detoxification during the rehabilitation period.

Mechanisms Underlying the Prevention and Treatment of Cholelithiasis Using Traditional Chinese Medicine.

Cholelithiasis is a major public health concern that necessitates highly effective, feasible, and recurrence-preventing therapies. Currently available surgical treatments and medications cannot effectively avoid the recurrence of cholelithiasis. Hence, several Chinese herbal compounds (CHCs) are considered for the treatment of cholelithiasis, considering that they can effectively discharge gallstones and prevent the recurrence of such condition. In the present narrative review, we aim to summarize the underlying mechanisms of currently used CHCs in the treatment of cholelithiasis and to describe the current situation of traditional Chinese medicine (TCM) use for cholelithiasis. Several commonly used CHCs were used to illustrate these issues. We found that the mechanisms underlying the CHC treatments rely on the amelioration of the biliary dynamics factors, maintenance and protection of the liver function, reduction of the cholesterol and bilirubin levels, and regulation of the inflammatory reactions. CHCs as treatments based on TCM can ameliorate the overall bodily function, thereby preventing the recurrence of cholelithiasis. Appropriate application of CHCs would be beneficial for patients and clinicians, although the safety and efficacy of CHCs need further verification.

An in vitro validation of the therapeutic effects of Tougu Xiaotong capsule on tunicamycin-treated chondrocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Tougu Xiaotong capsule (TXC) is a Chinese herbal compound that belongs to a range of Chinese herbs functioning as 'kidney invigorators and liver softeners' commonly used to treat osteoarthritis (OA) in China. AIMS OF THE STUDY: The aims of the present study are to confirm the therapeutic effects of TXC in an OA cell model and to determine the mechanisms involved in such effects. MATERIALS AND METHODS: A tunicamycin (Tm)-exposed OA cell model was employed, and the effects of TXC were confirmed by observing cell viability and apoptosis. The reduced cell viability and increased apoptosis caused by Tm were improved by TXC, confirming the cellular protection of TXC. We then investigated the expression of biomarkers related to the endoplasmic reticulum (ER) stress pathway, including microRNA-211 (miR-211), a regulator in the ER stress pathway. RESULTS: Downregulation of X-box binding protein 1 (Xbp-1) and miR-211 expression following Tm administration was reversed by TXC. Moreover, the upregulation by Tm of the expression levels of binding immunoglobulin protein, Xbp-1, activating transcription factor 4, C/EBP-homologous protein, Caspase-9 and Caspase-3 was downregulated by TXC. These results indicated that the ER stress pathway-related mechanism may play a potential role in the therapeutic effects of TXC. CONCLUSIONS: The present study provides evidence of the therapeutic effects of TXC at the cell level and describes a cellular model for establishing the mechanisms of the effects of TXC used in the treatment of OA.

Effects of the Chinese herb formula Yufeining on stable chronic obstructive pulmonary disease: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: A Chinese herb formula Yufeining (YFN) has showed promise in the treatment of stable chronic obstructive pulmonary disease (COPD), less is known that the impact of YFN in combination with standard Western treatments on lung inflammation. This study evaluated the safety and efficacy of YFN as a treatment for stable COPD and as an anti-inflammatory agent. METHODS: Sixty patients with stable COPD were randomly assigned to two treatment groups (YFN treatment, N = 30; placebo treatment, N = 30). Both groups received inhaled steroids and bronchodilators during an 8-week intervention, and patient status was assessed at 8 weeks later and 4 months after treatment. The primary outcome included clinical efficacy. The secondary outcomes involved CAT score, mMRC grade, six-minute walking distance (6MWD). IL-8, TNF-α, IL-17A, LTB4, TGF-ß1 and CRP were also detection in peripheral serum, as well as adverse reaction conditions. RESULTS: The YFN group demonstrated a significant improvement in clinical efficacy (compare 89.3% to 63.3% in the placebo group; P < 0.05). CAT scores and mMRC grades significantly decreased (P < 0.05, P < 0.01), and 6MWD significantly increased (P<0.05), after YFN treatment. The levels of IL-8, TNF-α, LTB4 and CRP decreased significantly after 8 weeks of treatment compared to baseline levels in both groups. Only in the YFN treatment group, the levels of IL-17A decreased significantly after treatment compared to baseline levels (P < 0.05). No changes were observed inTGF-ß1 from pre-to post-treatment in either group (P > 0.05). Serum levels of IL-8, TNF-α, IL-17A, LTB4 and CRP decreased significantly after YFN treatment compared to the placebo group (P < 0.05). CONCLUSION: A combinatorial treatment approach with YFN, inhaled steroids and bronchodilators produced a clinically effective treatment for stable COPD, leading to a significant decrease in circulating inflammatory mediators. The study appeared YFN was safety. CLINICAL TRIAL REGISTRATION NUMBER: No. ChiCTR-IOR-17013577.

Sirt1/Foxo Axis Plays a Crucial Role in the Mechanisms of Therapeutic Effects of Erzhi Pill in Ovariectomized Rats.

Background. Erzhi pill (EZP), a traditional Chinese herbal formula, has been widely used to treat postmenopausal osteoporosis (PMOP) in China. However, its molecular mechanisms remain unclear. The aim of the present study is to investigate the antiosteoporotic effect of EZP on an ovariectomized rat model of PMOP. We performed the biomarkers of bone metabolism disorder, bone morphology, bone mineral density (BMD), and bone biomechanics to confirm the successful establishment of the PMOP model. We then investigated the expression of biomarkers related to the Sirt1/Foxo axis. We also examined microRNA-132 (miR-132), a regulator in the Sirtuin1 (Sirt1) expression. The bone metabolism disorder, bone morphology, BMD, and bone biomechanics in ovariectomized rats were improved by EZP administration. The antiosteoporotic effect of EZP was confirmed. We also found that the expressions of Sirt1, Runx2, Foxo1, and Foxo3a were downregulated in ovariectomized rats, while being then upregulated by EZP administration. And the expression of PPAR-γ and miR-132 was upregulated in ovariectomized rats and then downregulated by EZP administration. These results provided evidence that Sirt1/Foxo axis related mechanism may play a crucial role in the therapeutic effects of EZP, indicating that Sirt1/Foxo axis can be considered as a potential therapeutic target for PMOP in the future.

The antidepressant-like effects of Chaihu Shugan San: Dependent on the hippocampal BDNF-TrkB-ERK/Akt signaling activation in perimenopausal depression-like rats.

Chaihu Shugan San (CSS), a traditional Chinese medicine formula, has been used to treat depression for hundreds of years. Recently, the antidepressant-like mechanism of CSS has been increasingly evaluated and demonstrated. However, there are few studies focused on the involvement of the neurotrophic system in mediating the antidepressant-like effects of CSS. Considering the high prevalence of perimenopausal depression around the world, the goal of the present study was to determine whether brain-derived neurotrophic factor (BDNF) signaling is required for the antidepressant-like effects of CSS in perimenopausal depressive-like rats. The results indicate that CSS reverses depressive-like behaviors and attenuates the downregulation of BDNF in the hippocampus of perimenopausal rats exposed to chronic unpredictable mild stress (CUMS). We found that the TrkB antagonist K252 not only blocks the effects of CSS on behavioral improvement but also abolishes the activation of CSS in BDNF-TrkB signaling. As a result, the downstream targets of BDNF signaling, such as the ERK and Akt pathways, are significantly inhibited by K252a. Furthermore, CSS increases hippocampal neurogenesis, while K252a fully prevents this action. In conclusion, the present results demonstrate that the activation of the hippocampal BDNF-TrkB-ERK/Akt signaling pathway is required for the antidepressant-like effects of CSS on the depressive-like state during perimenopause. Additionally, this study also demonstrates that neurogenesis is required for the effects of antidepressants in aging perimenopausal animals and provides fundamental evidence for the clinical application of CSS.