Early warning model for stroke recurrence in acute ischemic stroke patients based on traditional Chinese medicine syndrome theory.

OBJECTIVE: This study aimed to establish an early warning model for stroke recurrence in acute ischemic stroke patients based on Traditional Chinese Medicine (TCM) syndrome theory. METHODS: This retrospective study collected the data of 1741 patients with ischemic stroke from 7 clinical centers between July 2016 and November 2019. Distance correlation coefficient, mutual information entropy, and statistical correlation test were used for univariate analysis. Cox proportional hazards regression model was applied to construct and validate the stroke recurrence warning model at different time. The area under the ROC curve (AUC) was used to evaluate the early warning ability of the model. RESULTS: We successfully constructed the early warning model. The median follow-up time was 1.42 years (95% CI [1.37, 1.47]). Recurrence events occurred in 175 patients, with a cumulative recurrence rate of 10.05% (95% CI [8.64, 11.47]). The AUC of the model was 0.64±0.02 in the training set and 0.70±0.03 in the validation set. CONCLUSION: The TCM syndrome model can give an early warning for the recurrence of stroke and provide reference for the secondary prevention of ischemic stroke.

Proteomics analysis of coronary atherosclerotic heart disease with different Traditional Chinese Medicine syndrome types before and after percutaneous coronary intervention.

OBJECTIVE: To investigate the underlying protein molecular mechanisms of "Qi stagnation and blood stasis syndrome" (QS) and "Qi deficiency and blood stasis syndrome" (QD), as two subtypes of coronary artery disease (CAD) in Traditional Chinese Medicine (TCM), following percutaneous coronary intervention (PCI). METHODS: In this study, a total of 227 CAD patients with QS and 211 CAD patients with QD were enrolled; all participants underwent PCI. Label-free quantification proteomics were employed to analyze the changes in serum in two subtypes of CAD patients before and 6 months after PCI, aiming to elucidate the intervention mechanism of PCI in treating CAD characterized by two different TCM syndromes. RESULTS: Biochemical analysis revealed significant changes in tumor necrosis factor-α, high density lipoprotein cholesterol, blood stasis clinical symptoms observation, and Gensini levels in both patient groups post-PCI; Proteomic analysis identified 79 and 95 differentially expressed proteins in the QS and QD patient groups, respectively, compared to their control groups. complement C8 alpha chain, complement factor H, apolipoprotein H, apolipoprotein B, plasminogen, carbonic anhydrase 2, and complement factor I were altered in both comparison groups. Furthermore, enrichment analysis demonstrated that cell adhesion and connectivity-related processes underwent changes in QS patients post-PCI, whereas lipid metabolism-related pathways, including the peroxisome proliferator-activated receptor signaling pathway and extracellular matrix receptor interaction, underwent changes in the QD group. The protein-protein interaction network analysis further enriched 52 node proteins, including apolipoprotein B, lipoprotein (a), complement C5, apolipoprotein A4, complement C8 alpha chain, complement C8 beta chain, complement C8 gamma chain, apolipoprotein H, apolipoprotein A-Ⅱ, albumin, complement C4-B, apolipoprotein C3, among others. The functional network of these proteins is posited to contribute to the pathophysiology of CAD characterized by TCM syndromes. CONCLUSION: The current quantitative proteomic study has preliminarily identified biomarkers of CAD in different TCM subtypes treated with PCI, potentially laying the groundwork for understanding the protein profiles associated with the treatment of various TCM subtypes of CAD.

Traditional Chinese herbal formulas modulate gut microbiome and improve insomnia in patients with distinct syndrome types: insights from an interventional clinical study.

Background: Traditional Chinese medicine (TCM) comprising herbal formulas has been used for millennia to treat various diseases, such as insomnia, based on distinct syndrome types. Although TCM has been proposed to be effective in insomnia through gut microbiota modulation in animal models, human studies remain limited. Therefore, this study employs machine learning and integrative network techniques to elucidate the role of the gut microbiome in the efficacies of two TCM formulas - center-supplementing and qi-boosting decoction (CSQBD) and spleen-tonifying and yin heat-clearing decoction (STYHCD) - in treating insomnia patients diagnosed with spleen qi deficiency and spleen qi deficiency with stomach heat. Methods: Sixty-three insomnia patients with these two specific TCM syndromes were enrolled and treated with CSQBD or STYHCD for 4 weeks. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) every 2 weeks. In addition, variations in gut microbiota were evaluated through 16S rRNA gene sequencing. Stress and inflammatory markers were measured pre- and post-treatment. Results: At baseline, patients exhibiting only spleen qi deficiency showed slightly lesser severe insomnia, lower IFN-α levels, and higher cortisol levels than those with spleen qi deficiency with stomach heat. Both TCM syndromes displayed distinct gut microbiome profiles despite baseline adjustment of PSQI, ISI, and IFN-α scores. The nested stratified 10-fold cross-validated random forest classifier showed that patients with spleen qi deficiency had a higher abundance of Bifidobacterium longum than those with spleen qi deficiency with stomach heat, negatively associated with plasma IFN-α concentration. Both CSQBD and STYHCD treatments significantly improved sleep quality within 2 weeks, which lasted throughout the study. Moreover, the gut microbiome and inflammatory markers were significantly altered post-treatment. The longitudinal integrative network analysis revealed interconnections between sleep quality, gut microbes, such as Phascolarctobacterium and Ruminococcaceae, and inflammatory markers. Conclusion: This study reveals distinct microbiome profiles associated with different TCM syndrome types and underscores the link between the gut microbiome and efficacies of Chinese herbal formulas in improving insomnia. These findings deepen our understanding of the gut-brain axis in relation to insomnia and pave the way for precision treatment approaches leveraging TCM herbal remedies.

[Methods for traditional Chinese medicine syndrome-based efficacy evaluation: a review].

Traditional Chinese medicine(TCM) syndrome-based efficacy is an evaluation index which is unique to TCM and can reflect the advantages of TCM. The development of the methods and measurement tools for evaluating TCM syndrome-based efficacy can provide objective and quantitative evidence for the clinical efficacy evaluation of TCM and the development of new Chinese medicine preparations, being the exploration direction of innovative methods and technologies for evaluating TCM efficacy. The conventional evaluation methods are subjective and limited to the mitigation of symptoms and the improvement of physical signs, which make it difficult to form a unified evaluation standard. In addition, the evaluation methods lack unity, objectivity, and quantitative research. The scientific connotation, evaluation ideas and methods, and key technologies of the evaluation for the therapeutic effect on syndromes remain unclear, which leads to diverse evaluation modes, methods, and indexes. The syndrome-based efficacy scale provides a new idea for the objective quantification and standardization of TCM syndromes. This review systematically summarizes the methods and problems, introduces the research progress in the evaluation scales, and puts forward some thoughts on the characteristics of TCM syndrome-based efficacy evaluation, aiming to provide insights for the research in this field.

Comprehensive effects of traditional Chinese medicine treatment on heart failure and changes in B-type natriuretic peptide levels: A meta-analysis.

BACKGROUND: Heart failure (HF), a common cardiovascular condition, is characterized by significant morbidity and mortality. While traditional Chinese medicine (TCM) is often used as a complementary approach in HF management, systematic evaluations of its impact on clinical outcomes, TCM syndrome scores, and B-type natriuretic peptide (BNP) levels are lacking. This study fills this gap through a comprehensive analysis of randomized controlled trials (RCTs) focusing on TCM for HF treatment. It encompasses an assessment of methodological quality, a meta-analysis, and an evaluation of evidence quality based on established standards. The results offer crucial insights into the potential advantages and constraints of TCM in HF management. AIM: To systematically analyze the effects of TCM on the clinical comprehensive outcomes, TCM syndrome scores, and BNP levels in patients with HF and evaluated the quality of evidence for these trials. METHODS: RCTs on TCM for HF treatment published since the establishment of the database were searched in four Chinese and English databases, including China National Knowledge Infrastructure, Wanfang, VIP Information Chinese Science and Technology Journal, and PubMed. Methodological quality was assessed for the included studies with the Cochrane risk-of-bias assessment tool, and the meta-analysis and publication bias assessment was performed with the RevMan5.3 software. Finally, the quality of evidence was rated according to the GRADE criteria. RESULTS: A total of 1098 RCTs were initially retrieved. After screening, 16 RCTs were finally included in our study, which were published between 2020 and 2023. These RCTs involved 1660 HF patients, including 832 in the TCM group [TCM combined with conventional Western medicine (CMW) treatment] and 828 in the CWM group (CWM treatment). The course of treatments varied from 1 wk to 3 months. TCM syndrome differentiation was analyzed in 11 of the included RCTs. In all included RCTs, outcome indicators included comprehensive clinical outcomes, TCM syndrome scores, and BNP levels. The meta-analysis results showed significant differences between the TCM and CWM groups in terms of comprehensive clinical outcomes [risk ratio = -0.54; 95% confidence interval (CI) = -0.61, -0.47; P < 0.00001], TCM syndrome scores [weighted mean difference (WMD) = -142.07; 95%CI = -147.56, -136.57; P < 0.00001], and BNP levels (WMD = -142.07; 95%CI = -147.56, -136.57; P < 0.00001). According to the GRADE criteria, RCTs where "TCM improves clinical comprehensive outcomes" were rated as low-quality evidence, and RCTs where "TCM reduces TCM syndrome scores" or "TCM decreases BNP levels" were rated as medium-quality evidence. CONCLUSION: TCM combined with CWM treatment effectively improves comprehensive clinical outcomes and diminishes TCM syndrome scores and BNP levels in HF patients. Given the low and medium quality of the included RCTs, the application of these results should be cautious.

Evaluation of A Liver Yin Deficiency Mouse Model Based on Untargeted Metabolomics / 中国实验方剂学杂志

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS）， to evaluate the establishment of a mouse model of liver Yin deficiency by thyroid tablet suspension combined with 10% carbon tetrachloride（CCl4） from the perspective of non-targeted metabolomics， in order to lay the foundation for the establishment of a traditional Chinese medicine（TCM） syndrome model. MethodA total of 24 mice were randomly divided into blank group and model group. The model group was given thyroid tablet suspension（0.003 2 g·kg-1） by gavage for 14 consecutive days， and 10% CCl4（5 mL·kg-1） was intraperitoneally injected once a week to establish a liver Yin deficiency model， while the blank group was injected with an equal amount of olive oil intraperitoneally and gavaged with an equal amount of distilled water， and was fed with normal feed. After the modeling was completed， 6 mice in each group were randomly selected， the levels of alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， cyclic adenosine monophosphate（cAMP）， cyclic guanosine monophosphate（cGMP）， interleukin（IL）-6， IL-10， tumor necrosis factor-α（TNF-α）were measured in the mice serum， and malondialdehyde（MDA）， superoxide dismutase（SOD）， total protein（TP）， hydroxyproline（HYP） and other indicators were measured in the mice liver. Liver tissue sections were taken for hematoxylin-eosin（HE） staining and observing pathological changes. The remaining 6 mice in each group were subjected to UPLC-Q-TOF-MS combined with principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to screen differential metabolites in the liver Yin deficiency mouse model， Kyoto Encyclopedia of Genes and Genomes（KEGG） database was used to analyze the corresponding metabolic pathways of differential metabolites. ResultCompared with the blank group， mice in the model group showed liver Yin deficiency manifestations such as reduced body weight， fatigue and sleepiness， disheveled and lusterless hair， irritability. The levels of ALT， cAMP/cGMP， IL-6， AST， MDA， cAMP， TNF-α significantly increased（P<0.05， P<0.01）， while the levels of SOD， IL-10 and cGMP significantly decreased（P<0.05， P<0.01）， and the changes of HYP and TP were not statistically significant. Hepatic steatosis and distortion of the radial arrangement of the liver plate cells were seen in the section images of the model group， endogenous substances were clearly separated， and 252 differential metabolites were identified in the serum samples， which were mainly involved in the metabolic pathways of purine metabolism， steroid hormone biosynthesis and pyrimidine metabolism. A total of 229 differential metabolites were identified in the liver samples， mainly involving nucleotide metabolism， purine metabolism， steroid hormone biosynthesis， pyrimidine metabolism， antifolate resistance， insulin resistance， primary bile acid biosynthesis， prostate cancer， sulfur relay system， arachidonic acid metabolism and other metabolic pathways. ConclusionThe successful establishment of liver Yin deficiency model in mice by CCl4 combined with thyroid hormone is evaluated through the investigation of serum and liver metabolomics， combined with biochemical indicators， which provides a biological basis and experimental foundation for the Yin deficiency syndrome model of TCM.

Meta-analysis of Distribution Frequency of Traditional Chinese Medicine Syndrome in Primary Osteoporosis / 中国实验方剂学杂志

ObjectiveTo systematically evaluate the distribution of traditional Chinese medicine（TCM） syndromes of primary osteoporosis（POP） in China by using evidence-based medicine methods， and to understand the distribution law of the syndromes. MethodChina National Knowledge Infrastructure（CNKI）， VIP Chinese Science and Technology Journal Database（VIP）， WanFang Data Knowledge Service Platform（WanFang） and China Biology Medicine（CBM） were searched to obtain representative literature， and each database was searched from the 1994 World Health Organization defined diagnostic criteria for osteoporosis until May 1， 2023. Two researchers independently screened literature according to the criteria， extracted data， and cross-checked them. Meta analysis was conducted using R4.1.3， and subgroup analysis was performed. ResultA total of 56 Chinese papers were included， involving 14 415 patients. After standardized classification of syndromes， 11 articles were excluded， and Meta analysis results of the ultimately included 45 Chinese articles showed that the distribution frequencies of liver-kidney Yin deficiency syndrome， spleen-kidney Yang deficiency syndrome and kidney deficiency and blood stasis syndrome in 12 723 patients were 27%［95% confidence interval（CI） 0.24-0.31］， 32%（95% CI 0.29-0.36）， 36%（95% CI 0.30-0.42）. Subgroup analysis showed that there was a statistically significant difference in the distribution of the three TCM syndromes in the north and south（P<0.05）. In addition， the incidence of TCM syndrome fractures in different types of POP was 15%（95% CI 0.09-0.24） for liver-kidney Yin deficiency syndrome， 20%（95% CI 0.12-0.30） for spleen-kidney Yang deficiency syndrome， and 31%（95% CI 0.25-0.39） for kidney deficiency and blood stasis syndrome. ConclusionThe distribution of syndromes in POP patients is mainly kidney deficiency， accompanied by liver and spleen dysfunction. Liver-kidney Yin deficiency syndrome， spleen-kidney Yang deficiency syndrome and kidney deficiency and blood stasis syndrome are all the main syndromes of POP and osteoporotic fractures， and kidney deficiency and blood stasis syndrome is most closely related to the development of osteoporotic fractures. The reference standards for syndrome determination among the included studies are inconsistent， and in the future， it is necessary to focus on their determination standards to obtain consensus research results， at the same time， conduct large-scale syndrome research to obtain representative research results， providing a basis for clinical practice and research.

Application of Animal Models of Corneal Neovascularization Based on Data Mining / 中国实验方剂学杂志

ObjectiveTo provide a reference for the establishment of an ideal corneal neovascularization （CNV） animal model by summarizing the modeling characteristics of CNV animal models. MethodWith "CVN" as the theme word， this paper searched the China National Knowledge Infrastructure （CNKI）， Wanfang， Chinese medical journals full-text database， and PubMed database and screened out relevant literature on CNV animal experiments from 2013 to 2023. The database was established by Excel 2021， and the experimental animal strain， gender， modeling method， detection index， and application category were sorted out. The characteristics of the CNV animal model were analyzed. ResultAfter comparative analysis， it was found that the animal strains were Sprague-Dawley rats （87 times， 29.49%） and New Zealand white rabbits （52 times， 17.63%）. Male animals were recommended. Most modeling methods for efficacy verification and mechanism studies were the alkali burn method. Index detection methods included apparent index observation， histopathological detection， immunohistochemistry （IHC）， Western blot， and various polymerase chain reaction （PCR） tests. Detection indexes included apparent indication， corneal histopathology， CNV regulation， etc. ConclusionThe CNV model of SD rats induced by the alkali burn method is recommended for model replication， and the indexes are mainly selected from the growth of CNV， corneal histopathological test， and vascular endothelial growth factor （VEGF）-related test. In addition， according to the demand， the corneal apparent indication and the basic indexes related to the regulation of CNV， such as vascular endothelial growth factor receptor 2 （VEGFR2）， basic fibroblast growth factor （bFGF）， and secretogranin Ⅲ （Scg3） are also selected. Clinical treatment of CNV relies on anti-inflammatory drugs and anti-VEGF drugs， and there is a lack of application of traditional Chinese medicine （TCM）， so the model needs to be improved by adding elements of TCM syndromes.

Syndrome of liver depression and spleen deficiency is a primary TCM syndrome of response to entecavir + FuZheng HuaYu in patients with HBV-related liver fibrosis.

Objective: Although clinical studies have found that Chinese patent medicine FuZheng HuaYu tablet/capsule can promote the reversal of HBV-related liver fibrosis, not all sufferers have histopathological responses. This study aims to explore the correlation between traditional Chinese medicine (TCM) syndromes and response to entecavir + FuZheng HuaYu (ETV + FZHY) in patients with HBV-related liver fibrosis. Methods: This a multi-center cross-sectional study. According to the different treatment strategies that sufferers have ever received, a total of 437 cases were included and divided into ETV + FZHY group and ETV + placebo group. And based on the relevant efficacy determination criteria, the two groups were subdivided into efficacy responders and non-responders. Then, TCM clinical questionnaire information of these patients were collected for subsequent analysis to acquire relevant syndrome elements and TCM syndromes. Results: No matter what group was, the first three frequency of TCM pathological position in efficacy responders were as follows: Liver > Spleen > Stomach (TCM concepts). As for the ETV + FZHY group, the first three frequency of pathological nature was ranked as Qi deficiency > Dampness > Heat. Compared with the non-responders, the frequency of Spleen, Stomach, Qi deficiency, Heat, and Qi movement stagnation was significantly increased in the efficacy responders (P < 0.05). In terms of TCM syndromes, the frequency increase of Syndrome of liver depression and spleen deficiency (LDSD), in the efficacy responders, changed more obviously than the non-responders (Chi2 = 6.32, P = 0.0006). Conclusions: TCM syndrome elements of Spleen, Stomach, Qi deficiency, Heat, and Qi movement stagnation were closely associated with efficacy responders with HBV-related liver fibrosis in the ETV + FZHY group. Moreover, LDSD was a primary TCM syndrome in these responders.

Research progress on the biological basis of Traditional Chinese Medicine syndromes of gastrointestinal cancers.

Gastrointestinal cancers account for 11.6 % of all cancers, and are the second most frequently diagnosed type of cancer worldwide. Traditional Chinese medicine (TCM), together with Western medicine or alone, has unique advantages for the prevention and treatment of cancers, including gastrointestinal cancers. Syndrome differentiation and treatment are basic characteristics of the theoretical system of TCM. TCM syndromes are the result of the differentiation of the syndrome and the basis of treatment. Genomics, transcriptomics, proteomics, metabolomics, intestinal microbiota, and serology, generated around the central law, are used to study the biological basis of TCM syndromes in gastrointestinal cancers. This review summarizes current research on the biological basis of TCM syndrome in gastrointestinal cancers and provides useful references for future research on TCM syndrome in gastrointestinal cancers.

Chinese traditional herbs enhanced the clinical efficacy of low-molecular-weight heparin in the treatment of recurrent spontaneous abortion complicated with thrombophilia.

Thrombophilia is an important cause of recurrent spontaneous abortion (RSA). The treatment of thrombophilia is beneficial to the prevention of RSA. Therefore, we explored the clinical effect of Chinese traditional herbs with the effects of invigorating the blood, tonifying the kidney and calming the fetus in the treatment of RSA complicated with thrombophilia. We retrospectively analyzed the clinical outcomes of 190 RSA patients combined with thrombophilia using different treatment methods. The traditional Chinese medicine group was treated with kidney-invigorating, blood-activating and fetus-soothing herbs and the western medicine group was treated with low molecular weight heparin (LMWH), and the traditional Chinese medicine combined with western medicine group was treated with LMWH plus Chinese traditional herbs with the effects of kidney tonifying, blood activating and fetus stabilizing. After treatments, platelet aggregation rate, plasma D-dimer and uterine artery blood flow resistance were significantly reduced in the LMWH plus herbs compared to the simple herbs and LMWH group (P < 0.0167). The LMWH plus herbs group significantly accelerated the growth of fetal bud compared with other groups (P < 0.0167). Moreover, the LMWH plus herbs group improved traditional Chinese medicine syndrome scores (P < 0.0167), showing a better clinical efficacy. Adverse reactions occurred in five patients in the LMWH group but not in the simple herbs and LMWH plus herbs group during the treatment period. Therefore, our study shows that for the treatment of RSA complicated with thrombophilia, Chinese traditional herbs plus LMWH can improve the blood supply of the uterus during pregnancy and contribute to a favorable environment for the growth of the fetus. Chinese traditional herbs exert a good curative effect with few adverse reactions.

Role of Traditional Chinese Medicine Syndrome Type, Gut Microbiome, and Host Immunity in Predicting Early and Advanced Stage Colorectal Cancer.

OBJECTIVE: To investigate the role of Traditional Chinese Medicine (TCM) syndrome type, gut microbiome distribution, and host immunity function in predicting the early and advanced clinical stages of colorectal cancer (CRC). METHODS: A cross-sectional case-control study was performed which included 48 early stage and 48 advanced patients with CRC enrolled from March 2018 to December 2020. 16S rRNA gene sequencing was performed to analyze the gut microbiomes of the patients, while T and B lymphocyte subsets in peripheral blood were assessed using flow cytometry. TCM syndrome type was measured using the spleen deficiency syndrome (SDS) scale. RESULTS: The abundance levels of Prevotella, Escherichia-Shigella, and Faecalibacterium in the gut microbiota were significantly increased in the advanced group, while Bacteroides was significantly decreased. Phascolarctobacterium was detectable only in the early metaphase group, whereas Alistipes was detectable only in the advanced group. The lymphocyte (P = .006), T helper cell (TH) (P = .002), cytotoxic T cell (TC) (P = .003), double positive T cell (DPT) (P = .02), and total T counts (P = .001) were significantly higher in the early metaphase group than in the advanced metaphase group. Compared with patients with early stage CRC, the advanced group had a higher SDS score. After adjusting for clinical stage, Spearman's correlation analysis showed interactions among gut microbiome abundance, T cell level, and SDS score. Multivariate logistic analysis showed that after controlling for the SDS score, abundance of Alistipes and Faecalibacterium, and double negative T cell (DNT) level, DPT was significantly associated with a lower risk of advanced-stage disease (hazard ratio, 0.918; P = .022). CONCLUSION: Our study suggested associations between clinical stage, SDS, gut microbiota, and T lymphocytes, which provided insights for a potential prediction model for the disease progression of CRC.

Effects of Modified Baizhu Shaoyao San on Postoperative Diarrhea in Colorectal Cancer Patients: A Single-Blind, Randomized Controlled Trial.

INTRODUCTION: Postoperative gastrointestinal tract dysfunction is considered a common complication affecting patients undergoing intestinal surgery. This research aims to provide evidence to assess the efficacy and safety of Baizhu Shaoyao San (BSS) or modified BSS in treating postoperative diarrhea of colorectal cancer patients. METHODS: Eighty patients with colorectal cancer were randomized within 2 weeks after surgery to receive either modified BSS or Loperamide combined with the respective dummy. The curative effect was evaluated with the traditional Chinese medicine (TCM) syndrome score. Determination of motilin and gastrin in plasma was conducted utilizing ELISA. RESULTS: Compared with Loperamide therapy, the efficacy of modified BSS was statistically significant, the TCM syndrome score decreased, and the total effective rate increased. Levels of motilin and gastrin in plasma decreased. CONCLUSION: The curative effect and safety of modified BSS were statistically significant.

Standardization, objectification, and essence research of traditional Chinese medicine syndrome: A 15-year bibliometric and content analysis from 2006 to 2020 in Web of Science database.

The standardization, objectification, and essence research of traditional Chinese medicine (TCM) syndrome influence the modernization and international development of TCM syndrome. A total of 253 relevant publications collected from the Web of Science Core Collection database from 2006 to 2020 were analyzed by bibliometric and content methods. The co-occurrence analysis of countries, institutions, journals, authors, and keywords analysis were carried out by using Citespace software. The high-yield institutions and high-impact authors contributed to TCM syndrome publications were concentrated in China. Since 2012, driven by some groundbreaking publications, the number of TCM syndrome literatures has increased rapidly. According to the results of bibliometric and content analysis, research hotspots in TCM syndrome in the last 15 years can be summarized in six aspects: (a) objectification research of four TCM diagnostic methods, (b) omics technology for the essence research of TCM syndrome, (c) research on TCM syndrome evaluation scale, (d) metagenomic technology for the essence research of TCM syndrome, (e) data mining technology for TCM syndrome differentiation, and (f) systematic research on TCM syndromes of chronic hepatitis B. Emerging trends can be identified according to the most recent keywords bursts: (a) TCM syndrome diagnostic models with multiple indexes should be constructed to develop personalized medicine. (b) The connotation of TCM syndrome should be verified through "syndrome detecting from recipe used," and the screened potential markers of TCM syndrome need clinical verification. (c) The intervention and integration of multi-disciplines is expected to find a new breakthrough in the research of TCM syndrome.

Psoriasis complicated with metabolic disorder is associated with traditional Chinese medicine syndrome types: a hospital-based retrospective case-control study.

OBJECTIVE: To explore the distribution law of traditional Chinese medicine (TCM) syndrome types in patients with psoriasis vulgaris complicated by metabolic disorders based on the same pathogenic factors as blood-heat and blood-stasis in the pathogenesis of psoriasis and metabolic disorders and to further analyze the correlation between adiponectin and the distribution law. METHODS: From 1 January 2018 to 31 December 2019, patients diagnosed with psoriasis in the inpatient or outpatient department of Dermatology Ward of Shanghai Yueyang Hospital and normal participants who underwent physical examination in the physical examination center over the same period were retrospectively reviewed. Demographic data, medical history, metabolic disorder indices, and TCM syndrome indices of psoriasis patients and healthy volunteers were evaluated. RESULTS: We included 307 patients with psoriasis and 613 healthy controls. On analyzing past medical history, the proportion of overweight and obesity and the comorbidity of diabetes in the psoriasis group (53.42 and 14.66%) were significantly higher than in the control group (43.88 and 7.67%, respectively; p < .05). The abnormal rates of triglyceride (34.20%), high-density lipoprotein cholesterol (50.49%), and HbA1c (18.57%) levels in the psoriasis group were higher than those in the normal control group (26.75, 17.13, and 12.56%, respectively). Overall, the incidence of metabolic disorders in psoriasis patients (267/307, 86.97%) was higher than that in the normal controls (484/613, 78.96%). Among the different syndrome types, the blood-stasis group had significantly higher rates of hypertension, diabetes, and abnormal glycosylated hemoglobin (46.07, 19.10, and 24.72%, respectively) than those of the control group (27.57, 7.67, and 12.56%; p < .05). Patients with blood stasis syndrome had the highest metabolic disorder comorbidity rate (93.26%) and lowest adiponectin level (p < .05). CONCLUSIONS: TCM syndrome differentiation of psoriasis, especially the diagnosis of blood-stasis syndrome, prompts the early screening of patients with metabolic comorbidities. For patients with psoriasis with metabolic disorder, TCM for promoting blood circulation and removing blood stasis can be compatibly applied without contraindications. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (Trial ID: NCT03942185).

Ontology characterization, enrichment analysis, and similarity calculation-based evaluation of disease-syndrome-formula associations by applying SoFDA.

Clinical symptom-based diagnosis and therapy play a crucial role in personalized medicine and drug discovery. The syndromes, distinctive groups of clinical symptoms summarized by traditional Chinese medicine (TCM) theories and clinical experiences, are used as the core diagnostic criteria and therapeutic guidance in TCM. However, there is still a lack of standardized data, information, and intrinsic molecular basis to help TCM syndromes better classify diseases and guide tailored medications. To address this problem, we built the first integrated web platform, SoFDA (http://www.tcmip.cn/Syndrome/front/), with a curated ontology of 319 TCM syndromes, 8045 diseases, and 1359 TCM herbal formulas and their relationships with genes, diseases, and formulas. This platform proposed an association measurement by calculating Jaccard/Cosine similarities between TCM syndromes and their related biomedical entities with case and control validations. On this basis, the SoFDA platform enables biomedical and pharmaceutical scientists to rank and filter the most promising associations for disease diagnosis and tailored interventions. Conversely, the targeted gene sets and symptom sets can also be associated with TCM syndromes, formulas, and diseases for function illustration. Notably, SoFDA explores the multi-way associations among diseases, TCM syndromes, symptom genes, herbal formulas, drug targets, and pathways in heterogeneous biomedical networks with lots of customization. The protocol here implements all the analyses above using the SoFDA platform. Collectively, SoFDA may provide insights into the biological basis of disease-specific TCM syndromes and the underlying molecular mechanisms, as well as a tailored treatment for single or multiple symptoms within a syndrome.

Prediction Model of Treatment Effect of Anlotinib on Extensive-stage Small Cell Lung Cancer Based on Combination of Disease and Syndrome Information / 肿瘤防治研究

Objective To construct a nomogram prediction model for the treatment effect of anlotinib with the participation of traditional Chinese medicine syndrome elements on the patients with extensive-stage small cell lung cancer (ES-SCLC) who previously received multiple lines of chemotherapy. Methods The clinical data of 127 patients with ES-SCLC who received at least two cycles of anlotinib treatment were retrospectively studied. Kaplan-Meier method was used to analyze the relationship between each factor and the overall survival time. Cox regression analysis was applied to screen the independent influencing factors of the prognosis of patients with ES-SCLC. R language was employed to build a nomogram prediction model, C-index was used to evaluate the model, and calibration curve was adopted to verify the accuracy of the model. Results Age, PS score, brain metastases, qi deficiency syndrome, yin deficiency syndrome, and blood stasis syndrome were related risk factors for ES-SCLC treated with anlotinib. PS score, brain metastasis, and blood stasis syndrome were independent prognostic factors. On the basis of these three independent influencing factors, a nomogram model was established to predict the prognosis of patients with ES-SCLC treated with anlotinib. The predicted risk was close to the actual risk, showing a high degree of coincidence. Conclusion The nomogram model established with PS score, blood stasis syndrome elements, and brain metastasis as independent factors can predict the prognosis of patients with ES-SCLC receiving second- and third-line treatment of anlotinib.

Syndrome Differentiation-based Treatment of Diarrhea-predominant Irritable Bowel Syndrome with Chinese Medicine via 5-HT Signaling Pathway： A Review / 中国实验方剂学杂志

Diarrhea-predominant irritable bowel syndrome （IBS-D） is a chronic functional bowel disorder characterized by abdominal pain and diarrhea， with visceral hypersensitivity and abnormal gastrointestinal dynamics as the pathophysiological basis. The brain-gut interaction plays a role in pain-related functional gastrointestinal disorders， especially IBS-D. 5-Hydroxytryptamine （5-HT）， as an important brain-gut peptide regulating gastrointestinal function， affects brain activity， gastrointestinal motility， pain perception， mucosal inflammation， and immune response through brain-gut interaction and is associated with the occurrence and development of IBS-D. In recent years， traditional Chinese medicine （TCM） has shown great potential to mitigate gastrointestinal symptoms and improve the quality of life with its holistic view and treatment based on syndrome differentiation. Studies have shown that TCM treats IBS-D by regulating the 5-HT signaling pathway. With a focus on syndrome differentiation in TCM， this paper systematically describes the efficacy and mechanism of TCM in treating different TCM syndromes of IBS-D via the 5-HT signaling pathway， aiming to provide a scientific basis for TCM treatment of this disease.

Construction and Validation of A Predictive Model Including TCM Pathogenic Syndrome for Short-term Efficacy of PD-1 Inhibitors in Advanced Non-small Cell Lung Cancer / 肿瘤防治研究

Objective To evaluate predictive factors affecting the short-term efficacy of PD-1 inhibitors in non-small cell lung cancer (NSCLC) and to construct a prediction model. Methods From October 2019 to November 2021, 221 patients with advanced NSCLC who met the inclusion criteria and were treated with PD-1 inhibitors were prospectively enrolled. Patients who were enrolled before May 1st, 2021 were included inthe modeling group (n=149), whereas those who enrolled thereafter were included in the validation group (n=72). The general clinical data of patients, information of the four TCM diagnoses were collected, and TCM syndrome elements were identified. R software version 4.0.4 was used in constructing a nomogram clinical prediction model of objective response rate. The predictive ability and discrimination of the model were evaluated and externally validated by using a validation group. Results After two to four cycles of PD-1 inhibitor therapy in 221 patients, the overall objective response rate was 44.80%. Multivariate logistic regression analysis of the modeling group showed that the TPS score (OR=0.261, P=0.001), number of treatment lines (OR=3.749, P=0.002), treatment mode (OR=2.796, P=0.019), qi deficiency disease syndrome elements (OR=2.296, P=0.043), and syndrome elements of yin deficiency disease (OR=3.228, P=0.005) were the independent predictors of the short-term efficacy of PD-1 inhibitors. Based on the above five independent predictors, a nomogram prediction model for the short-term efficacy of PD-1 inhibitors was constructed. The AUC values of the modeling and validation groups were 0.8317 and 0.7535, respectively. The calibration curves of the two groups showed good agreement between the predicted and true values. The mean absolute errors were 0.053 and 0.039, indicating that the model has good predictive performance. Conclusion The nomogram model constructed on the basis of the syndrome elements of Qi-deficiency disease and Yin-deficiency syndrome of TCM, as well as TPS score, number of treatment lines and treatment mode, is a stable and effective tool for predicting the short-term efficacy of PD-1 inhibitors in advanced non-small cell lung cancer.

Medication Rules of Pinelliae Rhizoma Processed Products in Syndrome Differentiation and Treatment of Insomnia Based on Data Mining / 中国实验方剂学杂志

ObjectiveTo analyze and summarize the medication rules of different Pinelliae Rhizoma processed products in the syndrome differentiation and treatment of insomnia using data mining. MethodThe literature on the treatment of insomnia with Pinelliae Rhizoma was retrieved from the China National Knowledge Infrastructure （CNKI）， VIP， and PubMed databases over the past 10 years. An Excel database was constructed to record the prescriptions of different Pinelliae Rhizoma processed products in the treatment of insomnia. SPSS 26.0 software was used for frequency analysis of traditional Chinese medicine （TCM） syndromes related to insomnia， compatibility of drugs， drug effects， and properties. SPSS 26.0 was also used for cluster analysis， factor analysis， and IBM Modeler 18.0 plugin for association rule analysis of the core compatibility of different Pinelliae Rhizoma processed products and combinations. ResultAfter applying inclusion and exclusion criteria， 125 relevant articles were finally included. The commonly used processed products of Pinelliae Rhizoma in the treatment of insomnia were Pinelliae Rhizoma Praeparatum， Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine， and Pinelliae Rhizoma Praeparatum cum Alumine. Among them， Pinelliae Rhizoma Praeparatum was the most frequently used. All three processed products of Pinelliae Rhizoma were often used for insomnia with such TCM syndromes as phlegm-heat disturbing the heart， phlegm-dampness obstructing the interior， and liver Qi stagnation. The compatible drugs were sweet， bitter， and pungent in flavor， cold in nature， and acted on the lung， spleen， heart， and liver meridians， with functions of nourishing deficiency， clearing heat， and calming the mind. The common prescriptions used were Wendantang， Chaihu Longgu Mulitang， Banxia Xiexintang， and Xiaochaihutang， with doses ranging from 6 to 30 g. The core drug combinations were Pinelliae Rhizoma Praeparatum-Poria-Ziziphi Spinosae Semen， Pinelliae Rhizoma Praeparatum Cum Zingibere et Alumine-Jujubae Fructus-Codonopsis Radix， and Pinelliae Rhizoma Praeparatum Cum Alumine-Scutellariae Radix-Bupleuri Radix. ConclusionThis study， for the first time， analyzed and summarized the compatibility and prescription application rules of commonly used processed products of Pinelliae Rhizoma in the treatment of insomnia from the perspective of TCM syndrome differentiation， which provides a theoretical basis for the rational， safe， and effective use of Pinelliae Rhizoma in the treatment of insomnia in TCM.