ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

As people’s attention to health continues to increase, the market demand for traditional Chinese medicine (TCM) is growing steadily. The quality and safety of Chinese medicinal materials have attracted unprecedented social attention. In particular, the issue of exogenous harmful residue pollution in TCM has become a hot topic of concern for both regulatory authorities and society. The Chinese Pharmacopoeia 2025 Edition further refines the detection methods and limit standards for exogenous harmful residues in TCM. This not only reflects China’s high-level emphasis on the quality and safety of TCM but also demonstrates the continuous progress made by China in the field of TCM safety supervision. Basis on this study, by systematically reviewing the development history of the detection standards for exogenous harmful residues in TCM and analyzing the revisions and updates of these detection standards in the Chinese Pharmacopoeia 2025 Edition, deeply explores the key points of the changes in the monitoring standards for exogenous harmful residues in TCM in the Chinese Pharmacopoeia 2025 Edition. Moreover, it interprets the future development directions of the detection of exogenous residues in TCM, aiming to provide a reference for the formulation of TCM safety supervision policies.

ObjectiveTo study the mechanism of compound Xishu granules （CXG） in inhibiting the proliferation of hepatocellular carcinoma cells by regulating ferroptosis. MethodsThe transplanted tumor model of human Huh7 was established with nude mice and the successfully modeled mice were randomized into model， Fufang Banmao （0.21 g·kg^-1）， low-dose （1.87 g·kg^-1） CXG， medium-dose （3.74 g·kg^-1） CXG， and high-dose （7.49 g·kg^-1） CXG groups. Mice were administrated with drinking water or CXG for 28 days， and the body weight and tumor volume were measured every 4 days. Hematoxylin-eosin staining was employed to observe the histopathological changes of tumors. The cell-counting kit-8 （CCK-8） was used to examine the survival rate of Huh7 cells treated with different concentrations （0， 31.25， 62.5， 125， 250， 500， 1 000 mg·L^-1） of CXG for 24 h and 48 h. CA-AM， DCFH-DA， and C11-BODIPY^581/591 fluorescent probes were used to determine the intracellular levels of ferrous ion （Fe²⁺）， reactive oxygen species （ROS）， and lipid peroxide （LPO）， respectively. The colorimetric method was employed to measure the levels of glutathione （GSH） and superoxide dismutase （SOD）. Western blot was employed to determine the protein levels of glutathione peroxidase 4 （GPX4）， transferrin receptor 1 （TFR1）， and ferritin heavy chain 1 （FTH1）， respectively. ResultsIn the animal experiment， compared with the model group， the drug treatment groups showed reductions in the tumor volume from day 12 （P<0.01）. After treatment， the Fufang Banmao and low-， medium-， and high-dose CXG groups had lower tumor volume， relative tumor volume， and tumor weight than the model group （P<0.05）， with tumor inhibition rates of 48.99%， 79.93%， 91.38%， and 97.36%， respectively. Moreover， the CXG groups had lower tumor volume and relative tumor volume （P<0.05 in all the three dose groups） and lower tumor weight （P<0.05 in medium-dose and high-dose groups） than the Fufang Banmao group. Compared with the model group， the drug treatment groups showed reduced number of tumor cells， necrotic foci with karyopyknosis， nuclear fragmentation， and nucleolysis， and the high-dose CXG group showed an increase in the proportion of interstitial fibroblasts. In the cell experiment， compared with the blank group， CXG reduced the survival rate of Huh7 cells in a dose-dependent manner after incubation for 24 h and 48 h （P<0.05）. Compared with the blank group， the RSL3 group and the low-， medium-， and high-dose CXG groups showed a decrease in the relative fluorescence intensity of CA-AM and increases in the fluorescence intensity of DCFH-DA and fluorescence ratio of C11-BODIPY^581/591， which indicated elevations in the levels of Fe²⁺ （P<0.01）， ROS （P<0.05）， and LPO （P<0.01）， respectively. Compared with the blank group， the RSL3 and low-， medium-， and high-dose CXG groups showed lowered levels of GSH and SOD （P<0.05）. In addition， the RSL3 group and the medium- and high-dose CXG groups showed down-regulated expression of GPX4 and FTH1 （P<0.05）， and the low- and high-dose CXG groups presented up-regulated expression of TFR1 （P<0.05）. ConclusionCXG suppresses the proliferation of hepatocellular carcinoma cells by inducing ferroptosis via downregulating the GSH-GPX4 signaling axis and increasing intracellular Fe²⁺and LPO levels.

BACKGROUND:Excessive apoptosis in skeletal muscle cells will destroy the dynamic balance of the number of myocytes,leading to pathological injury of skeletal muscle.Lijin manipulation is effective in treating skeletal muscle injury,but whether it can inhibit apoptosis and promote the repair of skeletal muscle injury is unknown.OBJECTIVE:To explore the mechanism by which Lijin manipulation reduces inflammation and apoptosis during the repair of skeletal muscle injury in rabbits.METHODS:Forty-five healthy adult Japanese white rabbits were randomly divided into blank group,model group and Lijin group(n=15 per group).No intervention was performed in the blank group.Gastrocnemius muscle percussion molding was performed in both the model group and Lijin group.After modeling,the model group was not treated,while the Lijin manipulation(Stroking,kneading,and rubbing)was performed in the Lijin group on the 3rd day,once a day,15 min/time.Sampling in each group was performed on the 7th,14th and 21st days after modeling.The general morphological structure of gastrocnemius was observed by hematoxylin-eosin staining.The ultrastructure of gastrocnemius muscle was observed by transmission electron microscopy.Apoptosis of gastrocnemius cells was observed by TUNEL staining.The expressions of interleukin-1β,interleukin-6 and interleukin-10 in gastrocnemius muscle were detected by ELISA.The protein expressions of BAX,BCL-2 and Caspase3 in gastrocnemius muscle were detected by western blot.The mRNA expression of BAX and BCL-2 was detected by RT-PCR.RESULTS AND CONCLUSION:(1)Hematoxylin-eosin staining results showed that compared with the model group,inflammatory cells decreased in number,myocyte amount increased,and muscle tissue gradually healed in the Lijin group at each observation point.(2)The results of transmission electron microscopy showed that compared with the model group,the arrangement of muscle fibers at each observation point in the Lijin group was gradually orderly,mitochondria were gradually complete,Z-line arrangement was gradually regular,and free ribosomes were gathered.(3)TUNEL staining results showed that compared with the model group,apoptosis rate in the Lijin group was gradually decreased at all observation points(P<0.05).(4)ELISA results showed that compared with the model group,the expression of interleukin-1β and interleukin-6 in the Lijin group continued to decrease(P<0.05),while the expression of interleukin-10 increased on the 7th day after modeling,and then showed a downward trend(P<0.05).(5)Western blot results showed that compared with the model group,the expression of BCL-2 protein/BAX protein in the Lijin group was significantly increased at each observational point(P<0.05).The protein expression of Caspase3 decreased significantly(P<0.001),and was gradually similar to that of the blank group.(6)RT-PCR results showed that compared with the model group,the mRNA expression level of BCL-2/BAX in the Lijin group was significantly higher at each observational point(P<0.05).To conclude,Lijin manipulation can inhibit inflammation,reduce apoptosis,and promote the repair of injured skeletal muscle.

Hyperuricemia(HUA)and gout became typical metabolic disorders characterized by multiple pathogenic factors.Their incidence increased annually,affecting younger populations.Given that uric acid(UA)and inflammation were the primary disease mechanisms,the search for effective and low-side-effect UA-lowering and anti-inflammatory drugs became a pressing scientific priority.Traditional Chinese medi-cine(TCM)encompassed a rich array of theoretical and practical experience,along with a diverse range of chemical substances,making herbs or their components potential sources for therapeutic drugs.Despite the significant role that modern herbal medicines played in treating HUA and gout,the existing research literature remained fragmented,lacking comprehensive and systematic reviews.In this review,we focused on the regulation of UA and summarized the discovery of UA-lowering pharmacodynamic components or ingredients derived from herbs and formulas,as well as their multi-targeted mechanisms of action.Emphasizing this focus,we proposed that,compared to acute inflammation,low-grade inflammation may play a relatively"unnoticed"role in the disease process.In contrast to Western medicine,we discussed the risks and benefits of herbal medicines and their ingredients for treatment,drawing from theoretical insights and clinical practice.This review offered comprehensive perspectives on the research into anti-HUA and gout treatments using herbal medicines and their natural products.Additionally,it provided a forward-looking view on natural product discovery,the exploration of ther-apeutic strategies,and new drug research in this field.

As people's attention to health continues to increase,the market demand for traditional Chinese medi-cine(TCM)is growing steadily.The quality and safety of Chinese medicinal materials have attracted unprecedent-ed social attention.In particular,the issue of exogenous harmful residue pollution in TCM has become a hot topic of concern for both regulatory authorities and society.The Chinese Pharmacopoeia 2025 Edition further refines the detection methods and limit standards for exogenous harmful residues in TCM .This not only reflects China's high-level emphasis on the quality and safety of TCM but also demonstrates the continuous progress made by China in the field of TCM safety supervision.Basis on this study,by systematically reviewing the development history of the detection standards for exogenous harmful residues in TCM and analyzing the revisions and updates of these detec-tion standards in the Chinese Pharmacopoeia 2025 Edition,deeply explores the key points of the changes in the monitoring standards for exogenous harmful residues in TCM in the Chinese Pharmacopoeia 2025 Edition.Moreo-ver,it interprets the future development directions of the detection of exogenous residues in TCM ,aiming to provide a reference for the formulation of TCM safety supervision policies.

Knee osteoarthritis is a common joint disease within osteoarthritis,characterized by pain,swelling,and limited functionality as the main clinical manifestations.In severe cases,it affects daily life and falls under the category of"impediment syndrome"or"bone impediment"in TCM.The author believes that the theory of"bones,tendons,and muscles"is closely related to this disease.Treatment should focus on simultaneously nourishing the liver,spleen and kidneys,considering tendons,bones and muscles,while also dispelling wind,cold and dampness.The clinical application of Sanbi Decoction has shown good efficacy,and this discussion aimed to provide ideas for the diagnosis and treatment of knee osteoarthritis.

Objective To investigate the clinical effect of Nuan'gong decoction in the treatment of cold coagulation and blood stasis type menorrhagia.Methods A total of 120 patients with oligomenorrhea were selected and divided into two groups according to random number table method:estrogen and progesterone group and Nuan'gong decoction.The estrogen and progesterone group was treated with se-quential estrogen and progesterone therapy,while the Nuan'gong decoction group was treated with Nuan'gong decoction on the top of the estrogen and progesterone group.The therapeutic effects,menstrual status,and changes in uterine artery blood flow were compared be-tween the two groups.Results The total effective rate of the Nuan'gong decoction group was 91.67％,which was greatly higher than the 76.67％of the estrogen and progesterone group(P＜0.05).After treatment,the traditional Chinese medicine syndrome score and men-strual distress questionnaire(MDQ)Chinese version score of the Nuan'gong decoction group were lower than those of the estrogen and progesterone group(P＜0.05).After treatment,the duration of menstruation in the Nuan'gong decoction group was longer than that in the estrogen and progesterone group(P＜0.05),and the pictorial blood loss assessment chart(PBAC)score was higher than that in the estrogen and progesterone group(P＜0.05).After treatment,the levels of progesterone(P),estradiol(E2),luteinizing hormone(LH),and follicle stimulating hormone(FSH)in the Nuan'gong decoction group were higher than those in the estrogen and progesterone group(P＜0.05).After treatment,the uterine artery pulsatility index(PI),resistance index(BI)and systolic/diastolic peak flow ve-locity(S/D)in the Nuan'gong decoction group were lower than those in the estrogen and progesterone group.Conclusion For patients with cold coagulation and blood stasis type oligomenorrhea,Nuan'gong decoction for traditional Chinese medicine syndrome differentiation treatment can achieve great therapeutic effects,effectively prolong the duration of menstruation,restore menstrual flow and sex hormone levels,and improve the blood flow parameters of uterine artery.

Objective To investigate the impact of 15 days of complete fasting on individuals'risk decision-making abilities and the role of physical exercise in this process.Methods Twenty-four healthy participants completed a 28-day experiment divided into baseline,complete fasting,calorie restriction,and full recovery phases.Participants were randomly assigned to a light exercise group(EL),moderate exercise group(EM),or control group(CN).Risk decision-making capacity was assessed using the Balloon Analogue Risk Task(BART),with data analyzed via Kruskal-Wallis and Friedman tests.Results Fifteen days of complete fasting did not significantly affect the participants'risk decision-making abilities.Additionally,after fasting,the moderate exercise group was more likely to make risky decisions compared to the light exercise group.Conclusion Long-term fasting has no significant impact on risk decision-making ability,but engaging in physical exercise makes people more likely to make high-risk decisions.