This paper systematically reviews the development history of clinical trials for new TCM drugs in China and identifies the main existing problems. It proposes that, under the "three-combination" regulatory review evidence system for TCM, clinical trials of new TCM drugs should leverage the advantages of human use experience, adhere to a clinical value-oriented approach, and flexibly select clinical development pathways without necessarily following the traditional phase Ⅱ and Ⅲ staging model. Based on human use experience data to clarify the clinical advantages of prescriptions, trial objectives should be established by determining clinical positioning, and risk-benefit assessments should be conducted to support subsequent clinical trial design. While adhering to the fundamental principles of clinical trials, new design methodologies should be introduced, including the use of adaptive designs to achieve seamless phase Ⅱ and Ⅲ integration; analysis of human use experience data to identify advantageous patient populations, providing a scientific basis for inclusion and exclusion criteria; clarification of the clinical therapeutic characteristics of TCM to guide the selection of appropriate efficacy and safety endpoints; and, based on human use experience data, estimation of sample size and determination of dosing regimens, treatment duration, visit schedules, and follow-up periods. In addition, clinical trial quality control and risk management plans should be developed, and "patient-centered" clinical trials should be implemented. These approaches aim to shorten the development timeline of new TCM drugs, reduce R&D costs, and improve the success rate of drug development.

In recent years, China's new round of institution reform has further optimized the drug regulatory system. Relevant departments and institutions involved in traditional Chinese medicine (TCM) regulation have been strengthened. TCM regulatory science, as an emerging interdisciplinary field, has received high regard and experienced rapid development, significantly enhancing TCM regulatory capabilities. Simultaneously, accelerated progress in emerging technologies and production innovation for TCM drug discovery, coupled with the implementation of the National Major Scientific and Technological Special Project for ''Significant New Drugs Development'' and its translational achievements, have led to a historic turning point in the development of innovative natural TCM drugs over the past five years. Driven by the dual engines of ''regulatory science'' and ''policy restructuring'', the development of new TCM drugs has entered a fast lane. Both the quantity and quality of investigational new drug (IND) and new drug application (NDA) registrations and approvals for new natural TCM drugs have shown rapid growth, effectively meeting the public's health demands for TCM products and unmet clinical needs of patients. This study focuses on the development of new TCM drugs during the significant historical phase from 2021 to 2025. It provides a comprehensive overview of new TCM and natural drug applications and regulatory reviews over the past five years, delves into the implementation of the National Drug Regulatory Science Action Plan, and highlights the importance of TCM regulatory science as an emerging interdisciplinary field in accelerating the creation of new TCM drugs. It systematically summarizes the effects of regulatory policies and regulations, the reform of TCM registration classification, specialized TCM registration provisions, and incentive measures such as the National Major Scientific and Technological Special Project for ''Significant New Drugs Development''. Based on an international perspective, it provides a focused review of recent highlights in TCM new drug development and regulation. This holds significant importance for promoting breakthroughs in TCM new drugs across more disease areas and advancing the international coordination of TCM regulation. The challenge faced in managing the registration of new TCM drugs lies in resolving the conflict between TCM theory and modern drug attributes, while balancing the rapid advancement of traditional medical theory and emerging technologies with the robustness of the drug regulatory framework. In the future, actively advancing research and translation in TCM regulatory science, innovatively establishing benefit-risk assessment systems and standards for new TCM drugs, and accelerating the development of a globally leading regulatory system with Chinese characteristics that aligns with the unique nature of TCM will be particularly crucial for global coordination of TCM regulatory policies, and the modernization and internationalization of TCM.

The triglyceride glucose–Chinese visceral adiposity index (TyG-CVAI), an integrated marker of insulin resistance and visceral adiposity, has been associated with cardiovascular outcomes. However, the longitudinal cardiovascular implications of cumulative TyG-CVAI exposure and directional changes in TyG-CVAI remain insufficiently characterized. This study aimed to examine the associations of cumulative TyG-CVAI exposure and longitudinal TyG-CVAI change patterns with incident cardiovascular disease (CVD) among middle-aged and older Chinese adults. This prospective study included 4,338 participants from the China Health and Retirement Longitudinal Study (CHARLS) who were free of CVD during the exposure assessment period from 2011 to 2015 and had complete TyG-CVAI data in 2011 and 2015. Participants were categorized into four TyG-CVAI change patterns (low–low, low–high, high–low, and high–high). Cumulative TyG-CVAI was calculated using repeated measurements from 2011 to 2015 and analyzed as both a standardized continuous variable and quartiles. Incident CVD was defined as new-onset heart disease or stroke during follow-up. Kaplan–Meier analysis, multivariable Cox proportional hazards models, and restricted cubic spline (RCS) analysis were performed. During a mean follow-up of 5 years, 845 incident CVD events occurred among 4,338 participants. Compared with the low–low group, the fully adjusted hazard ratios (HRs) and 95

TET2-mediated clonal hematopoiesis of indeterminate potential (CHIP) is a known cardiovascular risk factor, but its role in cardiac aging and potential for pharmacological intervention remain unclear. Herein, Mendelian randomization using large-scale genome-wide association studies (GWAS) data assessed CHIP's causal impact on aging and cardiovascular disease that revealed significant causal associations between TET2-CHIP, CVD, and aging biomarkers. Transcriptome-guided screening identified oridonin as a candidate compound reversing CHIP- and aging-associated gene signatures. Multi-tiered target prediction combining chemical structure-based algorithms and transcriptomic correlation identified KDM5C as a key target, validated by enzymatic inhibition and surface plasmon resonance assays. In vivo and in vitro administration of oridonin significantly ameliorated cardiac dysfunction and pathological remodeling in the CHIP model. Epigenetic regulation was profiled via ChIP-seq and RNA-seq, focusing on H3K4me3-mediated transcription. Tet2+/−BMT mice exhibited age-progressive myocardial fibrosis, inflammation, senescence, and functional decline. Mechanistically, oridonin inhibited KDM5C histone demethylase, restored H3K4me3 levels, and activated the SIRT2 anti-aging pathway. Rescue experiments using gene overexpression and recombinant protein supplementation confirmed the functional role of the KDM5C–H3K4me3–SIRT2–S100A8 axis in mediating oridonin's effects. Overall, TET2-driven CHIP promotes cardiac aging, as evidenced by human genetic analyses and long-term BMT models. Oridonin, by inhibiting KDM5C and restoring H3K4me3-dependent SIRT2 signaling, mitigates CHIP–induced myocardial aging.

Aging is increasingly viewed as an organism-wide process marked by systemic decline and multimorbidity. This Review frames immunosenescence as a context-dependent mediator, amplifier, or consequence of multi-organ dysfunction, integrating niche-centered mechanisms, bidirectional immune-organ interactions, innate-adaptive remodeling, immune-tissue axes, and multidimensional biomarkers. We also highlight current limitations, including context heterogeneity and unresolved causality, and discuss senolytic, senomorphic, and other therapeutic strategies with potential relevance and limitations for healthspan extension.

This study aimed to explore the therapeutic effects of psoralen(PSO)on skeletal muscle atrophy in chronic heart failure(CHF)and its underlying mechanisms.Male mice were randomly assigned to control,CHF,high-dose PSO,low-dose PSO,and empagliflozin(empa)groups.A CHF model was established by ligating the left anterior descending coronary artery,which was followed by 8 weeks of treatment starting 2 weeks post-surgery.In vitro,C2C12 myoblasts were cultured and exposed to angiotensin Ⅱ(Ang Ⅱ)to induce skeletal muscle injury,and divided into control,Ang Ⅱ,low-/medium-/high-dose PSO,and pyroptosis induction(nigericin)groups.General conditions,body weight,and skeletal muscle mass were recorded.The left ventricular ejection fraction(LVEF)was assessed by echocardiography.Skeletal muscle function was evaluated using grip strength and rotarod tests.Histopathological changes were examined by hematoxylin-eosin(HE)staining.Levels of interleukin IL-1β and tumor necrosis factor-α(TNF-α)in skeletal muscle tissue were measured.Transcriptomic profiling was performed to observe gene changes of mice and thereby predict relevant biological processes.Immunohistochemistry was used to evaluate NOD-like receptor family pyrin domain containing 3(NLRP3),cleaved-Caspase-1(c-Caspase-1),and N-terminal fragment of gasdermin D(GSDMD-N)expression.Western blot quantified NLRP3,GSDMD,GSDMD-N,Caspase-1,c-Caspase-1,and IL-1β protein levels.Immunofluorescence was employed to assess myotube diameter and NLRP3 expression,while quantitative polymerase chain reaction(qPCR)detected Nlrp3,Caspase-1,and Gsdmd mRNA levels.Results showed that compared with the control group,the CHF group exhibited significantly reduced LVEF,gastrocnemius-to-body weight ratio,forelimb grip strength,rotarod time,and running distance,along with decreased myofiber cross-sectional area.IL-1β and TNF-α levels,as well as NLRP3,GSDMD,GSDMD-N,Caspase-1,c-Caspase-1,and IL-1β protein expression,were significantly increased in gastrocnemius.Compared with the CHF group,PSO at all doses improved LVEF,muscle mass,forelimb grip strength,and exercise endurance,increased myofiber cross-sectional area,and reduced inflammatory cytokine levels(IL-1β and TNF-α),with the high-dose group showing the most pronounced effects.Transcriptomic analysis revealed that PSO significantly downregulated pyroptosis-related genes.The Western blot results showed that PSO significantly decreased the protein expression of NLRP3,GSDMD,GSDMD-N,Caspase-1,c-Caspase-1,and IL-1β.The qPCR results indicated the significant decreases in mRNA expression of NLRP3,Caspase-1,and GSDMD.In vitro,PSO at 20 and 40 μmol·L-1 significantly increased myotube diameter of Ang Ⅱ-induced C2C12 cells and reduced expression of NLRP3,GSDMD,GSDMD-N,Caspase-1,c-Caspase-1,and IL-1β.Compared with the 40 μmol·L-1 PSO group,nigericin treatment reversed these effects.In conclusion,PSO effectively attenuates skeletal muscle atrophy in CHF mice,potentially through suppression of skeletal muscle cell pyroptosis via downregulation of the NLRP3/Caspase-1/GSDMD pathway.

With the in-depth implementation of Opinions of the Central Committee of the Communist Party of China and the State Council on promoting the inheritance, innovation, and development of TCM and Special provisions for the registration administration of TCM, the evidence system of registration, review, and evaluation of TCM, which integrates TCM theory, human use experience, and clinical trials(hereinafter referred to as "three combinations"), has broken through the traditional evaluation model and established a research and development pathway aligns with the characteristics of TCM, and has become a pivotal reform driving the research and development of new TCM drugs. Against this backdrop, experts and representatives from hospitals and enterprises of research and development have developed this consensus through multiple rounds of discussions, aiming to provide a reference for the scientific design, standardized conduct and efficient advancement of clinical trials for new TCM drugs under this system. Centering on human use experience, this consensus elaborated on rational clinical trial planning strategies according to the evidence level of human use experience, the innovative design approaches of trials based on human use experience, the integration and optimized application of domestic and international regulations and technical guidelines, and a full-process communication mechanism and an efficient collaborative framework with clearly defined roles of three parties. It is expected to promote the high-quality development of new TCM drugs in research and development and better meet clinical needs.

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.

OBJECTIVE:To develop a core outcome set (COS) for clinical trials on post COVID-19 condition (PCC), that is, what, when, and how to measure PCC. METHOD:A comprehensive collection of outcomes (including their measurement methods and phases) was launched via literature review and clinician and patient surveys. Two rounds of Delphi surveys were conducted under the predefined criteria for rating, followed by a consensus meeting to finalize the COS for PCC (COS-PCC). RESULTS:Fifty-two outcomes within 7 categories and 206 measurement methods were identified. Sixty participants from five stakeholder groups completed the first round of the Delphi survey and 41 the second. Consensus was reached among 36 representatives on four domains of respiratory, physical, neuropsychological, and health conditions, including nine core outcomes and their respective measurement methods of priority: dyspnea (modified Medical Research Council scale), cough (Leicester Cough Questionnaire), exercise capacity (6-min walk test), fatigue (Fatigue Severity Scale), pain (Numerical Rating Scale), sleeping disturbance (Pittsburgh Sleep Quality Index), anxiety (Generalized Anxiety Disorder Scale-7), depression (Patient Health Questionnaire-9), and health status (36-item Short Form Health Survey); 16 optional measurement methods achieved consensus for supplement. Measuring phases of each core outcome were prioritized by importance through short and long terms of PCC. CONCLUSIONS:The COS-PCC highlights the key PCC concerns and provides an essential outcome set for PCC assessment in clinical trials and evidence synthesis. With improving the understanding of PCC and accumulating research evidence, the COS-PCC needs to be continuously updated and improved in practice.

The study was conducted to investigate the mechanism of Xinyang Tablets( XYP) in modulating the fat mass and obesity-associated protein(FTO)/N6-methyladenosine(m6A) signaling pathway to ameliorate ventricular remodeling in heart failure(HF). A mouse model of HF was established by transverse aortic constriction(TAC). Mice were randomized into sham, model, XYP(low, medium, and high doses), and positive control( perindopril) groups(n= 10). From day 3 post-surgery, mice were administrated with corresponding drugs by gavage for 6 consecutive weeks. Following the treatment, echocardiography was employed to evaluate the cardiac function, and RT-qPCR was employed to determine the relative m RNA levels of key markers, including atrial natriuretic peptide( ANP), B-type natriuretic peptide( BNP), β-myosin heavy chain(β-MHC), collagen type I alpha chain(Col1α), collagen type Ⅲ alpha chain(Col3α), alpha smooth muscle actin(α-SMA), and FTO. The cardiac tissue was stained with Masson's trichrome and wheat germ agglutinin(WGA) to reveal the pathological changes. Immunohistochemistry was employed to detect the expression levels of Col1α, Col3α, α-SMA, and FTO in the myocardial tissue. The m6A modification level in the myocardial tissue was measured by the m6A assay kit. An H9c2 cell model of cardiomyocyte injury was induced by angiotensin Ⅱ(AngⅡ), and small interfering RNA(siRNA) was employed to knock down FTO expression. RT-qPCR was conducted to assess the relative m RNA levels of FTO and other genes associated with cardiac remodeling. The m6A modification level was measured by the m6A assay kit, and Western blot was employed to determine the phosphorylated phosphatidylinositol 3-kinase(p-PI3K)/phosphatidylinositol 3-kinase(PI3K) and phosphorylated serine/threonine kinase(p-Akt)/serine/threonine kinase(Akt) ratios in cardiomyocytes. The results of animal experiments showed that the XYP treatment significantly improved the cardiac function, reduced fibrosis, up-regulated the m RNA and protein levels of FTO, and lowered the m6A modification level compared with the model group. The results of cell experiments showed that the XYP-containing serum markedly up-regulated the m RNA level of FTO while decreasing the m6A modification level and the p-PI3K/PI3K and p-Akt/Akt ratios in cardiomyocytes. Furthermore, FTO knockdown reversed the protective effects of XYP-containing serum on Ang Ⅱ-induced cardiomyocyte hypertrophy. In conclusion, XYP may ameliorate ventricular remodeling by regulating the FTO/m6A axis, thereby inhibiting the activation of the PI3K/Akt signaling pathway.

BACKGROUND:Atherosclerosis (AS) serves as the primary pathological basis for various cardiovascular and cerebrovascular diseases. Impaired efferocytosis by macrophages within AS plaques exacerbates lipid metabolism disorders and inflammatory responses. Huoxue Tongluo Tablet (HXTL), a traditional Chinese medicine formula, has shown efficacy in treating AS and modulating macrophage function. However, its underlying mechanisms remain unclear. It is hypothesized that HXTL ameliorates AS by enhancing macrophage efferocytosis. PURPOSE:To assess the efficacy and mechanisms of HXTL in treating AS at the single-cell level. METHODS:Ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) was used to analyze the constituents of HXTL. HXTL was administered to ApoE⁻/⁻ mice maintained on a high-fat diet. The progression of AS was evaluated by measuring atherosclerotic plaque area, necrotic core formation, collagen depletion, lipid accumulation, lipid profiles, pro-inflammatory mediators, and oxidative stress markers. Transcriptomic analysis was performed to explore the mechanisms underlying the therapeutic effects of HXTL on AS. Efferocytosis-related marker expression was evaluated using immunohistochemistry and quantitative PCR (qPCR), and the efferocytosis index was determined by the co-localization of apoptotic cells and macrophages. Efferocytosis inhibition was induced using Cytochalasin D. Single-cell sequencing was utilized to investigate alterations in Trem2⁺ macrophages following HXTL treatment. Trem2 expression was accessed by immunohistochemistry and qPCR, while flow cytometry and immunofluorescence staining confirmed the changes in Trem2⁺ macrophages. Bioinformatic analyses were conducted to investigate the mechanism through which HXTL enhances efferocytosis by regulating Trem2⁺ macrophage subsets. Western blotting and qPCR were used to assess the expression levels of PPARγ signaling, and the regulatory role of PPARγ signaling in macrophage subpopulation generation and efferocytosis function was accessed using GW9662. RESULTS:UPLC-MS/MS analysis identified 99 major components in HXTL. In vivo, medium and high doses of HXTL significantly reduced atherosclerotic plaque area, improved lipid profiles, decreased pro-inflammatory mediators and reactive oxygen species (ROS), and enhanced the efferocytosis function. Inhibition of efferocytosis reversed these beneficial effects. Single-cell sequencing and in vivo validation revealed that HXTL upregulated Trem2⁺ macrophages and efferocytosis-related genes. Bioinformatics and in vivo experiments demonstrated that HXTL activated PPARγ signaling, and inhibition of PPARγ signaling negated the pro-efferocytosis effects and the upregulation of Trem2⁺ macrophage upregulation induced by HXTL. CONCLUSIONS:HXTL activates the PPARγ pathway, upregulates Trem2⁺ macrophages, and enhances macrophage efferocytosis, thereby ameliorating AS. This study is the first to demonstrate the regulatory effects of HXTL on macrophage subpopulations and its pro-efferocytosis activity.

In the development of traditional Chinese medicine(TCM), the concept of "preventive treatment of disease" has a long history and plays a crucial role in bridging the past and the future. With the continuous growth of public health needs and the ongoing transformation of the registration management of TCM, its position in the research and development of new drugs has become increasingly significant. As one of the important sources of new drug innovation, the new TCM for "preventive treatment of diseases" represents a new thinking proposed based on the current routine registration and research and development. The research and development of TCM for "preventive treatment of diseases" mainly cover four stages: prevention(before the onset of disease), early intervention(when the disease is about to occur), interruption and reversal(when the disease has already occurred), and prevention of recurrence after recovery(after the disease). This study aims to comprehensively analyze the positioning, key points, and difficulties in the research and development of TCM for "preventive treatment of diseases" and explore effective paths to promote the innovative development of TCM through relevant cases. The research and development of new TCM for "preventive treatment of disease" require researchers to seize the opportunities for innovation before the start of the research and development, accurately grasp the key issues at different stages, and pay attention to the full lifecycle evaluation of the drugs. Meanwhile, in the design of the research plan, the optimal effectiveness evaluation indicators should be explored; key and difficult areas such as chronic diseases and rare diseases should be taken seriously, and the limitations of new drug development only based on the diagnosed diseases should be broken, so as to cater to more patients. In addition, through relevant representative cases in China and abroad, the unique advantages of TCM for "preventive treatment of diseases" should be fully leveraged. By learning from the past, all aspects of key points in the evaluation of new drug research and development should be strengthened. Finally, this study proposed that TCM for "preventive treatment of diseases" can employ novel methods and advanced technologies such as new biomarkers and innovative clinical design protocols, as well as new perspectives on disease research and health management. This can provide new paths for the innovation of TCM and public health management.

Traditional Medicine(TM),particularly Traditional Chinese Medicine(TCM),is an indispensable compo-nent of the global healthcare system,offering unique insights to modern medical science.Clinical efficacy is the bedrock for the inheritance and development of TM.To meet the growing demand for high-quality healthcare,it is imperative to integrate TM with mod-ern technology to address the issue of insufficient evi-dence for the efficacy of TM.To evaluate the clinical efficacy of TM,clinical trials are necessary,especially good clinical trials,which conform to the general prin-ciples of scientific research and also take into account the characteristics of traditional therapies.To promote the development of high-quality clinical trials that are in line with the features of TM,the attending experts held an in-depth discussion and reached the Rome con-sensus on"Good Clinical Trials for TM(GCT-TM),"at the 18th Academic Annual Meeting of the Clinical Efficacy Evaluation Committee of the World Federation of Chinese Medicine Societies and the 8th International Forum on Evidence-Based Chinese Medicine,held in Rome on June 26,2025.

BACKGROUND:Heart failure remains a leading cause of mortality worldwide with limited therapeutic options. Xinyang Tablet (XYT), a clinically used traditional Chinese medicine, demonstrates cardioprotective effects, but its mechanisms against cardiac hypertrophy remain unclear. This study aimed to elucidate the therapeutic mechanisms of XYT in heart failure with a focus on oxidative stress and hypertrophy pathways. METHODS:Pressure-overload heart failure was induced by transverse aortic constriction (TAC) in mice. Cardiac function was assessed via histology (hematoxylin-eosin [H&E], Masson's trichrome), oxidative stress markers (dihydroethidium [DHE] staining, superoxide dismutase [SOD]/malondialdehyde [MDA]/glutathione peroxidase [GSH-Px] assays), and molecular analyses. In vitro, angiotensin II (AngII)-treated HL-1 cardiomyocytes evaluated hypertrophy and oxidative stress responses. Multiomic approaches, including ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS), network pharmacology, RNA sequencing (RNA-seq), and single-cell RNA sequencing (scRNA-seq), identified XYT's bioactive compounds and hub targets, validated by AKT inhibitor (MK-2206) experiments. RESULTS:XYT attenuated TAC-induced cardiac hypertrophy and fibrosis, reducing heart volume, cardiomyocyte cross-sectional area, and fibrotic markers (collagen type I alpha 1 [COL1A1]/collagen type III alpha 1 [COL3A1]). XYT suppressed oxidative stress by decreasing reactive oxygen species (ROS)/NADPH oxidase 2 (NOX2)/NOX4 while increasing superoxide dismutase 2 (SOD2)/GSH-Px in vivo and in vitro. Bioinformatics identified 18 hub genes (e.g., histone deacetylase 2 [HDAC2], SOD2) and enriched phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)/oxidative stress pathways. XYT inhibited HDAC2/AKT/glycogen synthase kinase-3β (GSK-3β) phosphorylation, while AKT inhibition with MK-2206 mimicked XYT's protective effects. CONCLUSION:XYT ameliorates heart failure by targeting HDAC2 to suppress AKT/GSK-3β signaling, mitigating oxidative stress, cardiac hypertrophy, and fibrosis, providing mechanistic evidence for clinical translation.

OBJECTIVE:Xinyang Tablet (XYAT) and Xinyin Tablet (XYIT) have been used to treat chronic heart failure (CHF) for 20 years. This study investigated their pharmacodynamic material basis and underlying mechanisms of action. METHODS:Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS) was used to identify the components of XYAT and XYIT, and to profile their metabolites in plasma and urine samples from both rats and human volunteers. Furthermore, the prototype compounds and their pharmacokinetics were evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Network pharmacology predicted potential targets and pathways, which were subsequently validated through flow cytometry and Western blot. The efficacy of XYAT, XYIT and their active components was evaluated in oxidative stress and cardiotoxicity models. RESULTS:A total of 162 and 130 compounds were detected in XYAT and XYIT, respectively; among these, 148 from XYAT and 119 from XYIT were structurally identified. A validated HPLC-MS/MS method quantified 20 key exposure components, five of which showed high systemic exposure and underwent pharmacokinetic analysis. Pharmacokinetic results indicated that the systemic exposure of most compounds was higher for XYAT than for XYIT. Using network pharmacology, seven candidate active compounds were identified, along with their predicted therapeutic targets and associated signaling pathways. Flow cytometry and Western blot confirmed that XYAT, XYIT, and their bioactive components alleviate CHF by modulating calcium signaling and phosphoinositide 3-kinase/protein kinase B signaling. Pharmacodynamic assays demonstrated that XYAT provides protection against hydrogen peroxide-induced injury, while XYIT mitigates doxorubicin-induced cytotoxicity. Further validation confirmed that 20(S)-ginsenoside Rg2 and 20(R)-ginsenoside Rh1 effectively reduced the H2O2-induced oxidative stress, while 20(S)-ginsenoside Rg2 and calycosin-7-O-β-d-glucoside significantly protected against doxorubicin-induced cytotoxicity. CONCLUSION:These findings provide mechanistic insights into the pharmacodynamic material basis and anti-CHF mechanisms of XYAT and XYIT. The integrated strategy established herein offers robust evidence that the superior systemic exposure of key components underpins the rationale for XYAT's formulation and warrants its continued development in modern cardiology. Please cite this article as: Lan YL, Chen SM, Dai BX, Wu CS, Wei Y, Yang L, Yan JL, Guo YQ, Wang DW, Li QG, Yang ZQ, Xian SX, Yuan TH. Bioactive components of Xinyang and Xinyin tablets for treating chronic heart failure: pharmacokinetics, network pharmacology and experimental validation. J Integr Med. 2026; 24(2):265-278.

Based on latent structure model and association rule analysis, this study investigates the prescription patterns used by professor YANG Zhong-qi in treating hypertension with traditional Chinese medicine(TCM) and infers the associated TCM syndromes, providing a reference for clinical syndrome differentiation and treatment. The observation window spanned from January 8, 2013, to June 26, 2024, during which qualified herbal decoction prescriptions meeting efficacy criteria were extracted from the outpatient medical record system of the First Affiliated Hospital of Guangzhou University of Chinese Medicine and compiled into a standardized database. Statistical analysis of high-frequency herbs included frequency counts and herbal property-channel tropism analysis. Latent structure modeling and association rule analysis were performed using R 4.3.2 and Lantern 5.0 software to identify core herbal combinations and infer TCM syndrome patterns. A total of 2 436 TCM prescriptions were included in the study, involving 263 drugs with a cumulative frequency of 29 783. High-frequency herbs comprised Uncariae Ramulus cum Uncis, Poria, Glycyrrhizae Radix et Rhizoma, Puerariae Lobatae Radix, and Alismatis Rhizoma, predominantly categorized as deficiency-tonifying, heat-clearing, and blood-activating and stasis-resolving herbs. Latent structure analysis identified 18 latent variables, 74 latent classes, 5 comprehensive clustering models, and 15 core herbal combinations, suggesting that the core syndrome clusters include liver Yang hyperactivity pattern, Yin deficiency with Yang hyperactivity pattern, phlegm-stasis intermingling pattern, and liver-kidney insufficiency pattern. Association rule analysis revealed 22 robust association rules. RESULTS:: indicate that hypertension manifests as a deficiency-rooted excess manifestation, significantly associated with functional dysregulation of the liver, lung, spleen-stomach, heart, and kidney. Key pathogenic mechanisms involve liver Yang hyperactivity, phlegm-stasis interaction, and liver-kidney insufficiency. Therapeutic strategies should prioritize liver-calming, spleen-fortifying, and deficiency-tonifying principles, supplemented by dynamic regulation of Qi-blood and Yin-Yang balance according to syndrome evolution, alongside pathogen-eliminating methods such as phlegm-resolving and stasis-dispelling. Synergistic interventions like mind-tranquilizing therapies should be tailored to individual conditions.

Because of the unclear active substances,metabolic pathways,and targets of new drugs of traditional Chinese medicine(TCM),non-clinical safety evaluation often fails to accurately locate the target organs and tissue exposed to medicinal toxicity.The human use experience(HUE)contains important safety information of TCM,while the clinical safety data in the past HUE are few and have not been effectively applied.Standardized prospective HUE studies should be carried out to collect the clinical safety data,in which appropriate physical and chemical indicators(including blood,urine,and stool routine),liver biochemical indicators,kidney biochemical indicators,and cardiovascular biochemical indicators should be selected for safety evaluation,and the detection time point and sample size should be rationally designed.Importance should be attached to the observation of symptoms and signs of adverse events/reactions in patients as well as the safety information of special groups such as the elderly,children,and pregnant women.The adverse events of TCM should be observed,judged,and treated according to the theory and the diagnosis and treatment mode of TCM.The clinical safety information about the HUE should be comprehensively collected for new drugs of TCM to make up for the lack of extrapolation of toxicological test results to humans.The unique advantages of clinical origin of new drugs of TCM should be given full play for cross-reference of the results of toxicological research and the conclusions of HUE safety evaluation.In addition,benefit-risk assessment should be conducted based on HUE,and a panoramic safety evaluation system characterized by macro and micro combination and in line with the characteristics of TCM should be established to improve the success rate in the research and development of new drugs of TCM.

BACKGROUND:While there are numerous benefits to tea consumption, its long-term impact on patients with chronic kidney disease (CKD) remains unclear. METHOD:Our analysis included 17,575 individuals with CKD from an initial 45,019 participants in the National Health and Nutrition Examination Survey (NHANES) (1999-2018). Individuals with extreme dietary habits, pregnancy, or non-CKD conditions were excluded. Key cohort demographics revealed a mean age of 62.3 years, with 52.1% female participants, and 57.3% identified as non-Hispanic White. A total of 5,835 deaths were recorded during follow-up, including 1,823 cardiovascular-related deaths. Cox and restricted cubic spline regression was used to examine the linear or nonlinear association of tea consumption with mortality. The substitution analysis explored the effects of replacing a specific type of tea with another type of tea. Subgroup analysis stratified by sex, age, body mass index (BMI), diabetes, cancer, cardiovascular disease (CVD), and urinary albumin. Sensitivity analysis was performed to ensure the reliability of our findings. RESULTS:After adjusting for age, sex, race, education level, marital, annual household income, energy intake, total water intake, protein intake, carbohydrate intake, dietary fiber, sugar beverages, milk whole, total monounsaturated fatty acids, total polyunsaturated fatty acids, total saturated fatty acids, smoking, metabolic equivalent of task for physical activity level (MET-PA), BMI, diabetes, hypertension, urinary albumin, estimated glomerular filtration rate (eGFR), CVD, cancer, serum sodium, serum potassium, and serum phosphorus, setting the individuals without tea consumption record as reference. Consuming up to 4 cups of tea per day was significantly associated with lower all-cause mortality compared with that never drinking tea, among CKD patients at 1-2 stages [Hazard Ratio (HR) = 0.89; 95% Confidence Interval (CI) = 0.79, 0.99; p = 0.04], while the association between tea consumption and CVD mortality didn't reach statistical significance. Dose-response effect was observed, showing that consuming up to three to five cups of tea per day was associated with mitigated risks of all-cause mortality, particularly in early CKD stages (non-linear p > 0.05). A 1 cup per day higher intake of oxidized tea was associated with a 10% lower risk of all-cause mortality in CKD stage 1-2 [HR = 0.90; 95%CI = 0.82, 0.99; p = 0.03]. Replacing 1 cup of green tea with 1 cup of oxidized tea per day was associated with an 8% and 11% lower risk of all-cause mortality [HR = 0.92; 95%CI = 0.86, 0.98; p = 0.01] and CVD mortality [HR = 0.89; 95%CI = 0.80, 1.00; p < 0.05], respectively, in individuals with CKD stages 1-2. CONCLUSION:Tea consumption showed protective effects on all-cause mortality in CKD population, with potential benefits observed in terms of both the cups quantity and types of tea consumed. These findings appeared to be more prominent among early stages CKD population.

The guidelines for clinical research on new drugs provide unified standards for drug developers, researchers, and regulatory authorities, playing a crucial role in new drug development. This article systematically reviews the evolution of guidelines for clinical research on new traditional Chinese medicine(TCM) drugs in China, with a focus on analyzing the current status of these guidelines and the problems that exist. It also provides interpretations of three important guidelines. The article points out that with the continuous emergence of new clinical trial design methods, development concepts, and tools, and under the background of the &quot;three combinations&quot; evidence evaluation system for new TCM drugs, it is imperative to revise existing guidelines, formulate new ones, and develop new tools for clinical efficacy evaluation. It is hoped that relevant departments will adopt an open attitude and work together to build a technical system of clinical research guidelines for new TCM drugs that aligns with the characteristics of TCM.

Background Oral microbiota can reflect physiological functions and pathological conditions in human body. Patients with chronic heart failure (CHF) exhibit distinct oral health status compared to healthy controls (HCs), which is attributed to the differences in dominant microbial communities present in the oral cavity. Up to date, there are few studies examined the association between CHF and dominant oral microbiota. To fill in this research gap, this study aimed to investigate the differences of oral microbiota between CHF patients and HCs, to identify valuable novel biomarkers for CHF. Methods Chronic heart failure patients and healthy volunteers were recruited. Oral microbiota samples were then collected using oral swabs, and 16S rRNA sequencing was employed to analyze the microbiota. Statistical analysis was conducted to identify key bacteria at multiple taxonomic levels in the oral microbiota samples from both the CHF patient and healthy control groups, with a focus on core genera to identify potential biomarkers and evaluate their diagnostic efficacy. Results There were 60 CHF patients and 30 HCs were recruited, with 42 CHF patients with New York Heart Association (NYHA) functional class II-IV and 28 HCs were included in the final analysis. The alpha diversity was higher in HCs, while beta diversity was higher in CHF patients. The CHF patients showed significant differences from HCs at five gene (phylum, class, order, family and genus) levels by analyzing the relative richness of microbiota at different taxomal levels. Altogether 14 microbes could distinguish CHF patients from HCs, i.e., Abiotrophia , Butyrivibrio , Lactobacillus , Capnocytophaga and Neisseria which are more abundant in CHF patients, and Actinomyces , Anaerovorax , Eubacterium , Kingella , Mogibacterium , Peptococcus , Peptostreptococcus , Solobacterium and TM7\_genus\_incertae_sedis which are more abundant in HCs. Furthermore, the AUC of their combined diagnosis was 83.7% (95% confidential interval 74.1%–93.3%), which have high reliability for the diagnostic significance. In accordance to Spearman’s correlation, Eubacterium, Solobacterium and Rhizobium were core genera and the abundance of Eubacterium and Solobacterium exhibited downward trends as NYHA class increases. Conclusion This study revealed the dysbiosis of the oral microbiota in CHF patients and identified potential biomarkers for CHF diagnosis and management. ![Figure][1] * CHF : chronic heart failure HCs : healthy controls NYHA : New York Heart Association NT-proBNP : N-terminal pro-b-type natriuretic peptide LEfSe : Linear discriminant analysis effect size OTUs : operational taxonomic units AUC : Area Under the Curve TMAO : trimethylamine N-oxide. [1]: pending:yes