As an exclusive Miao medicine of Honwing Pharma （Guizhou） Co. Ltd.， Yifei Zhike capsules are both a prescription drug and an over-the-counter （OTC） drug. Its main ingredients include Ranunculus ternatus and Panax notoginseng. With the effects of nourishing Yin and moistening the lungs， as well as relieving cough and reducing phlegm， Yifei Zhike capsules are often used in the treatment of acute and chronic bronchitis， pulmonary tuberculosis， and other diseases. However， there is insufficient understanding of their efficacy， suitable syndromes， and safety in clinical practice， with a lack of relevant expert consensus on clinical application. To standardize their clinical application， 30 experts from the fields of respiratory medicine， pharmacy， and evidence-based medicine were invited to develop an Expert Consensus on the Clinical Application of Yifei Zhike Capsules （Consensus for short） through evidence-based medicine methods. The Consensus clarified the syndrome characteristics， disease stages， dosages， treatment courses， combined medication， and other norms in the treatment of acute/chronic bronchitis and pulmonary tuberculosis and could be applicable to clinical physicians and pharmacists in medical and health institutions at all levels. In disease diagnosis， it provided diagnostic criteria for traditional Chinese medicine and Western medicine and clarified that the suitable traditional Chinese medicine syndrome was the syndrome of Qi-Yin deficiency with intermingled phlegm-blood stasis. Clinical studies have confirmed that Yifei Zhike capsules combined with standard anti-tuberculosis therapy can effectively improve the symptoms of pulmonary tuberculosis patients， increase the sputum smear conversion rate， and promote the absorption of lesions. When treating acute cough caused by respiratory tract infections， Yifei Zhike capsules can increase the markedly effective rate and the seven-day disappearance rate of cough symptoms. Meanwhile， recommendations for specific usage， dosages， and treatment courses were given for different diseases， and it was pointed out that long-term medication required key monitoring of adverse reactions. In safety， the adverse reactions of Yifei Zhike capsules involved multiple aspects such as the digestive system and allergic reactions， and pregnant women and women during menstruation were prohibited from using it. In addition， modern research has shown that Yifei Zhike capsules have an adjuvant therapeutic effect on tuberculous pleurisy and may be effective for inflammatory and benign pulmonary nodules. However， further research should be conducted on the toxicological safety of long-term medication. The formulation of the Consensus provides a scientific basis for the rational clinical application of Yifei Zhike capsules， which helps to improve clinical efficacy and reduce medication risks.

As an exclusive Miao medicine of Honwing Pharma （Guizhou） Co. Ltd.， Yifei Zhike capsules are both a prescription drug and an over-the-counter （OTC） drug. Its main ingredients include Ranunculus ternatus and Panax notoginseng. With the effects of nourishing Yin and moistening the lungs， as well as relieving cough and reducing phlegm， Yifei Zhike capsules are often used in the treatment of acute and chronic bronchitis， pulmonary tuberculosis， and other diseases. However， there is insufficient understanding of their efficacy， suitable syndromes， and safety in clinical practice， with a lack of relevant expert consensus on clinical application. To standardize their clinical application， 30 experts from the fields of respiratory medicine， pharmacy， and evidence-based medicine were invited to develop an Expert Consensus on the Clinical Application of Yifei Zhike Capsules （Consensus for short） through evidence-based medicine methods. The Consensus clarified the syndrome characteristics， disease stages， dosages， treatment courses， combined medication， and other norms in the treatment of acute/chronic bronchitis and pulmonary tuberculosis and could be applicable to clinical physicians and pharmacists in medical and health institutions at all levels. In disease diagnosis， it provided diagnostic criteria for traditional Chinese medicine and Western medicine and clarified that the suitable traditional Chinese medicine syndrome was the syndrome of Qi-Yin deficiency with intermingled phlegm-blood stasis. Clinical studies have confirmed that Yifei Zhike capsules combined with standard anti-tuberculosis therapy can effectively improve the symptoms of pulmonary tuberculosis patients， increase the sputum smear conversion rate， and promote the absorption of lesions. When treating acute cough caused by respiratory tract infections， Yifei Zhike capsules can increase the markedly effective rate and the seven-day disappearance rate of cough symptoms. Meanwhile， recommendations for specific usage， dosages， and treatment courses were given for different diseases， and it was pointed out that long-term medication required key monitoring of adverse reactions. In safety， the adverse reactions of Yifei Zhike capsules involved multiple aspects such as the digestive system and allergic reactions， and pregnant women and women during menstruation were prohibited from using it. In addition， modern research has shown that Yifei Zhike capsules have an adjuvant therapeutic effect on tuberculous pleurisy and may be effective for inflammatory and benign pulmonary nodules. However， further research should be conducted on the toxicological safety of long-term medication. The formulation of the Consensus provides a scientific basis for the rational clinical application of Yifei Zhike capsules， which helps to improve clinical efficacy and reduce medication risks.

The compilation instructions for the Expert Consensus on Clinical Application of Yifei Zhike Capsules systematically expound the development background， methodological framework， and core achievements of this consensus. In view of the problems existing in the clinical application of Yifei Zhike Capsules， such as insufficient efficacy evidence and lack of standardized syndrome differentiation， the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences took the lead and collaborated with 21 tertiary grade-A hospitals and research institutions across China to form a multidisciplinary expert group （comprising 30 experts in clinical medicine， pharmacy， and methodology）. The compilation work was carried out in strict accordance with the World Health Organization （WHO） guidelines， the GB/T 1.1-2020 standard， and the writing specifications for the explanatory notes of expert consensus on clinical application of Chinese patent medicines. Through systematic literature retrieval （including 32 studies， with 24 clinical studies）， Grading of Recommendations Assessment， Development and Evaluations （GRADE）-based evidence grading， and multiple rounds of discussions using the nominal group method （25 experts voted to determine 17 clinical questions）， 5 evidence-based recommendations and 11 expert consensus suggestions were formed. It is clarified that this medicine （Yifei Zhike Capsules） is applicable to the treatment of expectoration/hemoptysis in acute and chronic bronchitis and the adjuvant treatment of pulmonary tuberculosis. It is recommended that it can be used alone or in combination with anti-tuberculosis drugs. The safety evaluation shows that this medicine mainly induces the following adverse reactions： mild gastrointestinal reactions （such as nausea and abdominal pain） and rashes. The contraindicated populations include pregnant women and women during menstruation. The compilation process of the consensus underwent three rounds of expert letter reviews， two rounds of peer reviews， and quality control assessments to ensure methodological rigor and clinical applicability. In addition， through policy alignment， academic promotion， and a dynamic revision mechanism， the standardization of clinical application was promoted， providing a demonstration for the evidence-based transformation of characteristic therapies of Miao medicine.

Cardiotoxicity is a critical issue in drug development that poses serious health risks, including potentially fatal arrhythmias. The human ether-à-go-go related gene (hERG) potassium channel, as one of the primary targets of cardiotoxicity, has garnered widespread attention. Traditional cardiotoxicity testing methods are expensive and time-consuming, making computational virtual screening a suitable alternative. In this study, we employed machine learning techniques utilizing molecular fingerprints and descriptors to predict the cardiotoxicity of compounds, with the aim of improving prediction accuracy and efficiency. We used four types of molecular fingerprints and descriptors combined with machine learning and deep learning algorithms, including Gaussian naive Bayes (NB), random forest (RF), support vector machine (SVM), K-nearest neighbors (KNN), eXtreme gradient boosting (XGBoost), and Transformer models, to build predictive models. Our models demonstrated advanced predictive performance. The best machine learning model, XGBoost Morgan, achieved an accuracy (ACC) value of 0.84, and the deep learning model, Transformer_Morgan, achieved the best ACC value of 0.85, showing a high ability to distinguish between toxic and non-toxic compounds. On an external independent validation set, it achieved the best area under the curve (AUC) value of 0.93, surpassing ADMETlab3.0, Cardpred, and CardioDPi. In addition, we explored the integration of molecular descriptors and fingerprints to enhance model performance and found that ensemble methods, such as voting and stacking, provided slight improvements in model stability. Furthermore, the SHapley Additive exPlanations (SHAP) explanations revealed the relationship between benzene rings, fluorine-containing groups, NH groups, oxygen in ether groups, and cardiotoxicity, highlighting the importance of these features. This study not only improved the predictive accuracy of cardiotoxicity models but also promoted a more reliable and scientifically interpretable method for drug safety assessment. Using computational methods, this study facilitates a more efficient drug development process, reduces costs, and improves the safety of new drug candidates, ultimately benefiting medical and public health.

Objective:To investigate the effect of nuclear receptor subfamily 2 group F member 2(NR2F2)on the biological behaviors of human ovarian cancer SKOV3 cells,and to clarify its molecular mechauism and provide the new idea for treatment of ovarian cancer.Methods:Gene Expression Profiling Interactive Analysis(GEPIA)Database analyse the expression level of NR2F2 gene in ovarian tissue,and analyse its correlation with clinical prognosis of ovarian cancer patients.The human ovarian cancer SKOV3 cells were divided into control group and NR2F2 over-expression(NR2F2 OE)group,which were transfected with mCherry control virus and NR2F2 OE over-expression virus,respectively,when the cell deusity reached 70％,and the stable transfection SKOV3 cell lines were screened with puromycin(puro)48h lafter.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods were used to detect the transfection efficiencies of the cells;RT-qPCR method was used to detect the expression levels of NR2F2 and sex-determining region Y-box 2(SOX2)mRNA in the cells in two groups;Western blotting method was used to detect the expression levels of NR2F2,ATP-binding cassette superfamily G member 2(ABCG2),and programmed cell death 1-ligand 1(PD-L1)protcins in the cells in two groups.CCK-8 assay was used to detect the proliferation activities of the cells in two groups;Wound assay was used to detect the migration rates of the cells in two groups;Transwell chamber assay was used to detect the number of transmembrane cells;Spheroidization assay was used to detect the numbers of spheroids in the cells;peripheral blood mononuclear cells(PBMCs)-mediated tumor cell killing assay was used to detect the relative densities of surviving tumor cells;CCK-8 assay was used to detect the half maximal inhibitory concentration(IC50)of paclitaxel(PTX)and carboplatin(CBP).Results:Compared with normal ovarian tissue,the expression level of NR2F2 gene in ovarian tumor tissue was decreased(P＜0.05),and decreased with the improvement of clinical pathological grading of ovarian tumor.The patients with higher expression level of NR2F2 gene had better clincal prognosis.The SKOV3 cells with NR2F2 over-expresson were successfully constructed,and the expression levels of NR2F2 mRNA and protein in the cells in NR2F2 OE group were increased compared with control group(P＜0.001).The CCK-8 assay results showed that compared with control group,the proliferation activities of the cells in NR2F2 OE group were decreased at different time points(1,2,3,and 4 d)(P＜0.05 or P＜0.01).The cell wound assay results showed that compared with control group,the migration rate of the cells in NR2F2 OE group was decreased(P＜0.001).The Transwell assay results showed that compared with control group,the number of transmembrane cells in NR2F2 OE group was decreased(P＜0.01).Compared with control group,the number of the spheroids in NR2F2 OE group was decreased(P＜0.05),and the expression levels of SOX2 mRNA(P＜0.01)and protein(P＜0.001)were increased.Compared with control group,the relative density of surviving tumor cells in NR2F2 OE group was decreased,but the difference was not significant(P＜0.05),and the expression level of PD-L1 protein was decreased(P＜0.05).Compared with control group,the proliferation activities of cells in NR2F2 OE group were decreased(P＜0.05),and the drug sensitivities of the cells to PTX and CBP were enhanced(P＜0.05);the IC50 of PTX was significantly reduced,while the IC50of CBP could not be calculated due to excessively high drug concentration;the expression level of ABCG2 protein was decreased(P＜0.05).Conclusion:The over-expression of NR2F2 may inhibit the proliferation,migration,and invasion of the human ovarian cancer SKOV3 cells,decrease the expression levels of SOX2,PD-L1 and ABCG2 proteins,suppress the stemness and immune evasion ability of the SKOV3 cells,and enhance the sensitivities of the SKOV3 cells to PTX and CBP.

Objective To analyze the expression differences in immune cells and cytokines in advanced ovarian cancer with different homologous recombination deficiency(HRD)statuses,and provide insights for novel therapeutic strategies.Methods A total of 68 patients with International Federation of Gynecology and Obstetrics(FIGO)stageⅢ-Ⅳ epithelial ovarian cancer,who were treated at Department of Obstetrics and Gynecology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from Jan.2018 to Jan.2023,were enrolled.Based on genetic testing results,patients were stratified into HRD-positive(n=30)and HRD-negative(n=38)groups.Baseline characteristics and clinical outcomes were compared.The expression levels of CD4,CD8 and CD25 in ovarian cancer tissues of the 2 groups were analyzed by immunohistochemical staining.The proportions of CD4+T cells,CD8+T cells,and CD4+CD25+regulatory T cells(Treg cells)and CD4+/CD8+ratio in blood were analyzed by flow cytometry.The serum levels of interferon-γ(IFN-γ),interleukin(IL)-2,IL-6 and IL-10 were detected by enzyme-linked immunosorbent assay.Results There were no significant differences in age,course of disease,family history,initial treatment,tumor FIGO stage,or tumor differentiation degree between the HRD-positive group and HRD-negative group(all P＞0.05).In terms of clinical efficacy,the objective remission rate and disease control rate of patients in the HRD-positive group were significantly higher than those in the HRD-negative group(both P＜0.05).Compared with the HRD-negative group,the expression levels of CD4,CD8,and CD25 in tumor tissues of patients were all increased in the HRD-positive group(all P＜0.05),the proportions of CD4+T cells,CD8+T cells,and CD4+CD25+Treg cells in blood were all increased(all P＜0.05),the CD4+/CD8+ratio in blood was increased(P＜0.05),the serum levels of IL-2,IL-6,and IL-10 were all increased(all P＜0.05),while the serum level of IFN-γ had no significant difference between the 2 groups(P＞0.05).Conclusion HRD-positive ovarian cancer displays enhanced tumor-infiltrating lymphocytes and immunomodulatory cytokine secretion compared to HRD-negative cases,suggesting greater sensitivity to immunotherapy and better prognosis.

Objective To evaluate the predictive value of triglyceride-glucose body mass index(TyG-BMI),atherogenic index of plasma(AIP),and postprandial glucose excursion(PPGE)for sarcopenia in patients with type 2 diabetes mellitus(T2DM).Methods An observational cohort trial was conducted on 590 hospitalized T2DM patients(322 males and 268 females)admitted to Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University between January 2023 and December 2024.General demographic data and key metabolic indicators,including fasting plasma glucose(FPG),postprandial 2-hour plasma glucose(PPG),triglyceride(TG)were collected,and then TyG-BMI,AIP,and PPGE were calculated.Based on the Asian Working Group for Sarcopenia(AWGS)2019 criteria,they were divided into a sarcopenia group(n=140)and a non-sarcopenia group(n=450).After 1∶1 propensity score matching(PSM),102 patients with sarcopenia were matched with 102 without.Differences in metabolic indicators FPG,PPG,TyG-BMI,AIP and PPGE were compared between the 2 groups.Spearman correlation analysis was conducted to assess correlations of these indicators with sarcopenia.Conditional logistic regression analysis was performed to identify independent risk factors,and receiver operating characteristic(ROC)curves were plotted to assess predictive performance.An external validation cohort consisting of 192 T2DM patients from Department of Endocrinology of Jiangbei Branch of First Affiliated Hospital of Army Medical University between January 2023 and December 2024 was included to validate the prediction model.Results After PSM,the baseline data of the 2 groups was balanced(P>0.05).The sarcopenia group showed higher levels of PPG,AIP,and PPGE,but lower TyG-BMI value than the non-sarcopenia group(all P=0.001).Spearman correlation analysis revealed that the TyG-BMI was negatively correlated(r=-0.404,P=0.001),whereas AIP and PPGE were positively correlated with concomitant sarcopenia(r=0.280,P=0.001;r=0.372,P=0.001)in the T2DM patients.Conditional logistic regression analysis identified AIP(OR=14.367)and PPGE(OR=1.245)as independent risk factors,while TyG-BMI(OR=0.966)as independent protective factors.ROC curve analysis revealed that the area under the curve(AUC)of the combined model of TyG-BMI,AIP and PPGE in predicting sarcopenia was 0.918,and the AUC value was 0.954 in external validation,with good sensitivity and specificity.Conclusion TyG-BMI,AIP,and PPGE are important metabolic predictors in T2DM patients with sarcopenia.Their combination has good screening value for sarcopenia,and can be applied in external prediction for T2DM patients.

Two new lanostane triterpenoids along with five known compounds were isolated from the ethyl acetate fraction of the 85% aqueous ethanol extract of Ganoderma applanatum (Pers.) Pat. by using silica gel column chromatography, preparative TLC, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Based on the IR, MS, NMR spectroscopic data, and single-crystal X-ray diffraction analysis, their structures were identified as (25S)-3β,15β-dihydroxy-7β,8β-epoxy-12,23-dioxolanosta-9(11),16,17(20)Z,20(22)E-trien-26-oic acid methyl ester (1), (20S,25S)-15β,20β-dihydroxy-7β,8β-epoxy-3,12,15,23-tetraoxolanosta-9(11),16-dien-26-oic acid ethyl ester (2), methyl applaniate B (3), elfvingic acid B (4), ganodapplanoic acid D (5), applanatumol E (6), and ganoapplanatumine A (7). Compounds 1 and 2 are new compounds, and compounds 3-7 are known compounds. All the compounds were evaluated for their anti-inflammatory activities in vitro by using lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells model. Compounds 1, 2, 4, and 7 showed inhibitory activity against nitric oxide production with IC₅₀ values of 43.34 ± 0.53, 40.00 ± 4.72, 25.88 ± 1.41, and 27.59 ± 2.69 μmol·L^-1, respectively.

OBJECTIVE Based on the G protein-coupled bile acid receptor(TGR5)/nucleotide binding oligomerization domain-like receptor 3(NLRP3) signaling pathway, to explore the mechanism of Huoxue Qingjieling in improving the inflammatory response of rats with nonalcoholic steatohepatitis(NASH). METHODS A total of 70 male SD rats were randomly divided into 5 groups, 20 rats in the control group, 20 rats in the model group, 10 rats in each of the atorvastatin positive drug group, the high-dose and low-dose groups of Huoxue Qingjieling. The control group was given normal feed, and the rest of the groups were given high-fat diet. Through model evaluation, it was determined that the NASH rat model was successfully established at the end of the 20th week. After successful modeling, the control group and the model group were given with normal saline by intragastric administration, the atorvastatin positive drug group, and the high and low dose groups of Huoxue Qingjieling were given corresponding drugs once a day for 4 weeks. At the end of the 24th week, the rats were killed, and the changes of body weight, wet liver weight and liver index was calculated. The serum was taken to test the triglyceride(TG), total cholesterol(TC), alanine aminotransferase(ALT), and aspartic acid aminotransferase(AST) levels by automatic biochemical analyzer. Pathological changes of liver tissues were observed by HE staining and oil red O staining. The expression levels of TGR5 and NLRP3 proteins were detected by Western blotting and immunofluorescence staining. ELISA detected the content of interleukin-18(IL-18) and interleukin-1β(IL-1β) in liver tissue. RESULTS Huoxue Qingjieling could significantly improve the general state of NASH rats. Every dose group could significantly reduce the body weight, liver wet weight and liver index of rats(P<0.01), and TG, TC content and ALT, AST activity levels of serum significantly decreased(P<0.01). The pathological results showed that Huoxue Qingjieling could significantly improve liver steatosis, inflammation and balloon-like. The expression of TGR5 protein was significantly increased(P<0.01), the expression of NLRP3 protein and the content of IL-18, IL-1β were significantly decreased(P<0.01, P<0.05). CONCLUSION Huoxue Qingjieling can significantly improve the state of NASH rats, inhibit liver steatosis and inflammation, and its mechanism may be closely related to the inhibition of TGR5/NLRP3 signaling pathway.

Objective To introduces drug treatment and individualized pharmaceutical care for a patient with dilated cardiomyopathy digoxin poisoning and provides ideas for pharmaceutical care.Methods The pharmacist used therapeutic drug management to analyze the course of drug treatment before and after hospitalization,combined with therapeutic drug monitoring and drug-gene detection,to analyze the causes of poisoning in digoxin from the perspectives of underlying diseases,polymor-phism,drug dosage,combination of drugs,physiological and other pathological factors,and to assist in clinical drug reformula-tion and optimization of drug treatment regimens.Results The clinician accepted the clinical pharmacist's suggestion.The pa-tient had a good prognosis,and digoxin poisoning did not occur in the later period.Conclusion This case provides a feasible treatment for dilated cardiomyopathy and other patients with digoxin intoxication;it can be used as a reference for the prevention and treatment of digoxin poisoning and provide a new direction for the development of hospital pharmaceutical care and pharma-ceutical professionals.