Aconitum (Ranunculaceae) has a long-standing history in traditional Chinese medicine (TCM), where it has been widely used to treat conditions such as rheumatoid arthritis (RA), myocardial infarction, and heart failure. However, the potency of Aconitum alkaloids, the primary active components of Aconitum, also confers substantial toxicity. Therefore, assessing the efficacy and toxicity of these Aconitum alkaloids is crucial for ensuring clinical effectiveness and safety. Metabolomics, a quantitative method for analyzing low-molecular-weight metabolites involved in metabolic pathways, provides a comprehensive view of the metabolic state across multiple systems in vivo. This approach has become a vital investigative tool for facilitating the evaluation of their efficacy and toxicity, identifying potential sensitive biomarkers, and offering a promising avenue for elucidating the pharmacological and toxicological mechanisms underlying TCM. This review focuses on the applications of metabolomics in pharmacological and toxicological studies of Aconitum alkaloids in recent years and highlights the significant role of metabolomics in exploring compatibility detoxification and the mechanisms of TCM processing, aiming to identify more viable methods for characterizing toxic medicinal plants.
Aconitum/metabolism* ; Metabolomics/methods* ; Alkaloids/metabolism* ; Humans ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional

Objective To explore the value of Delta radiomics based on dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)in the early prediction of pathological complete response(pCR)after neoadjuvant chemotherapy(NAC)for breast cancer.Methods The MRI and clinical data of 107 patients with breast cancer and received NAC treatment were retrospectively collected.The patients were randomly divided into training set(74 cases)and test set(33 cases)in a ratio of 7︰3.The volume of interest(VOI)were marked,and the radiomics features(Pre-features,Post-features)were extracted from the peak images of DCE-MRI before NAC and after the second cycle of NAC.The Delta features were obtained by subtracting Post-features from Pre-features.Subsequently,six machine learning methods including random forest(RF),multi-layer perceptron(MLP),extreme gradient boosting(XGBoost),light gradient boosting machine(LightGBM),K-nearest neighbor(KNN)and logistic regression(LR)were used to consult the model,respectively.The receiver operating characteristic(ROC)curve was used to evaluate the model performance,and the machine learning method and radiomics feature set with the highest area under the curve(AUC)in the test set were selected for further analysis.Univariate and multivariate logistic regression analyses were performed to identify independent clinical predictors and the machine learning method with the best radiomics model was used to construct the clinical model.Combined with tumor radiomics features and independent clinical predictors,the best machine learning method was used to construct a combined model,and the performance of the model was evaluated.Results Progesterone receptor(PR)status was identified as an independent predictor of NAC efficacy in breast cancer.The model established using the RF machine learning method based on the Delta features had the highest AUC of 0.926 in the test set.The AUC of the combined model in the test set was 0.957,which was higher than that of the Pre-radiomics model,Post-radiomics model,Delta-radiomics model,and clinical-features model.Conclusion The combined model of Delta features and clinical features has a good performance in predicting pCR after NAC for breast cancer.

Objective To explore the value of Delta radiomics based on dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)in the early prediction of pathological complete response(pCR)after neoadjuvant chemotherapy(NAC)for breast cancer.Methods The MRI and clinical data of 107 patients with breast cancer and received NAC treatment were retrospectively collected.The patients were randomly divided into training set(74 cases)and test set(33 cases)in a ratio of 7︰3.The volume of interest(VOI)were marked,and the radiomics features(Pre-features,Post-features)were extracted from the peak images of DCE-MRI before NAC and after the second cycle of NAC.The Delta features were obtained by subtracting Post-features from Pre-features.Subsequently,six machine learning methods including random forest(RF),multi-layer perceptron(MLP),extreme gradient boosting(XGBoost),light gradient boosting machine(LightGBM),K-nearest neighbor(KNN)and logistic regression(LR)were used to consult the model,respectively.The receiver operating characteristic(ROC)curve was used to evaluate the model performance,and the machine learning method and radiomics feature set with the highest area under the curve(AUC)in the test set were selected for further analysis.Univariate and multivariate logistic regression analyses were performed to identify independent clinical predictors and the machine learning method with the best radiomics model was used to construct the clinical model.Combined with tumor radiomics features and independent clinical predictors,the best machine learning method was used to construct a combined model,and the performance of the model was evaluated.Results Progesterone receptor(PR)status was identified as an independent predictor of NAC efficacy in breast cancer.The model established using the RF machine learning method based on the Delta features had the highest AUC of 0.926 in the test set.The AUC of the combined model in the test set was 0.957,which was higher than that of the Pre-radiomics model,Post-radiomics model,Delta-radiomics model,and clinical-features model.Conclusion The combined model of Delta features and clinical features has a good performance in predicting pCR after NAC for breast cancer.

Bile acids(BAs)are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps(CGP)and cholesterol gallstones(CGS).To date,there is neither systematic study on BAs profile of CGP or CGS,nor the relationship between them.To explore the metabolomics profile of plasma BAs in healthy volunteers,CGP and CGS patients,an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for simultaneous determination of 42 free and conjugated BAs in human plasma.The developed method was sensitive and reproducible to be applied for the quantification of BAs in the investigation of plasma samples.The results show that,compared to healthy volunteers,CGP and CGS were both characterized by the significant decrease in plasma BAs pool size,furthermore CGP and CGS shared aberrant BAs metabolic characteristics.Cheno-deoxycholic acid,glycochenodeoxycholic acid,λ-muricholic acid,deoxycholic acid,and 7-ketolithocholic acid were shared potential markers of these two cholesterol gallbladder diseases.Subsequent analysis showed that clinical characteristics including cysteine,ornithine and body mass index might be closely related to metabolisms of certain BA modules.This work provides metabolomic information for the study of gallbladder diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to BAs in medical institutions.

Objective: To investigate the effects of miRNA on the expression of paraoxonase 1 (PON1) and its clinical application in the patients with nonalcoholic steatohepatitis (NASH). Methods: Bioinformatics methods were used to analyze and predict PON1 related regulation on miRNA. PON1 luciferase reporter gene vectors were constructed and the activity of dual luciferase was analyzed. The up/down-regulated levels of miRNA in HepG2 cells of different groups were detected by real-time fluorescence quantitative PCR (qRT-PCR), and the levels of PON1 protein in HepG2 cells were detected by western blot. The levels of miR140-5p in the serum of healthy people and NASH patients were also analyzed by qRT-PCR. Results: According to the prediction of TargetScan database, miR140-5p may bind complementarily to the end of PON13′-UTR. The analysis for the activity of dual luciferase reporter gene showed that miR-140-5p mimic significantly downregulated the fluorescence of wild type PON1 vector (P＜0.01). The results of qRT-PCR demonstrated that miR-140-5p mimic group showed high overexpression (P＜0.01) compared with the normal cell control group and the negative mimic control group, while miR-140-5p inhibitor group appeared corresponding low expression (P＜0.05). western blot results suggested that the transfection of miR140-5p mimic significantly down-regulated the expression of PON1 (P＜0.01) while miR140-5p inhibitor up-regulated this expression (P＜0.01). Compared with the healthy control group, the level of miR140-5p was decreased in the serum of NASH patients, and the difference was statistically significant (P＜0.01). Conclusion miR140-5p may be involved in the progression of nonalcoholic steatohepatitis through regulation for the posttranscriptional gene expression of PON1.

Pyrrolizidine alkaloids(PAs)are among the most hepatotoxic natural compounds that are widely distributed throughout the world.Most PAs are metabolically activated to trigger toxicity.Exposure to herbal medicine containing PAs and food supplements contaminated by PAs is considered to be one of the two main causes of hepatic sinusoidal obstruction syndrome(HSOS),which is a rare hepatic vascular disease with a high mortality rate.PAs-induced HSOS cases have been reported worldwide.However,there is no clinically effective therapy for PAs-induced HSOS,which is partially because the toxic mechanism is not fully understood.This review focuses on updating the information on the metabolism and the molecular mechanisms of PAs hepatotoxicity,including oxidative stress,apoptosis,and dysfunction of bile acid metabolism,and their interactions.

Objective:To explore the application value of transcranial magnetic stimulation combined with language training for children with language retardation.Methods:100 children with language retardation who were treated in our hospital from March 2015 to March 2016 were selected as the research object.They were divided into control group and observation group according to the random number table method,50 cases in each group.The control group was treated with routine language training,while the observation group was treated with transcranial magnetic stimulation combined with language training.The treatment of the two groups were 3 months.The therapeutic effects were evaluated by the language development in Chinese children assessment method and the changes of developmental quotient before and after treatment were evaluated by the neuropsychological development test for children.Results:The effective rate of the observation group was 98.0％,which was significantly higher than 87.0％ of the control group (P＜0.05).Compared with before treatment,the language development quotient and development quotient of the two groups after treatment for 1,2 and 3 months were significantly improved,and the observation group was significantly better than the control group (P＜0.05).The normal rate of the observation group was 80.0％,which was significantly higher than 66.0％ of the control group (P＜0.05).Conclusion:The effect oftranscranial magnetic stimulation combined with language training is ideal,which can effectively improve the developmental quotient of children with language retardation,and it is worth promoting in clinical practice.

OBJECTIVE:To explore the role of clinical pharmacists participating in the individualized treatment for purulent meningitis. METHODS:Clinical pharmacists participated in the therapy for a patient with purulent meningitis complicated with Staphylococcus aureus infection. According to patient's condition,clinical pharmacists assisted physicians to formulate preliminary therapeutic plan. Reviewing relevant guidelines,domestic and foreign literatures,clinical pharmacists suggested to combine with dexamethasone so as to relieve inflammatory reaction. According to the results of drug sensitivity test,based on vancomycin plasma concentration monitoring and population pharmacokinetics model fitting,clinical pharmacists suggested to reduce the dose of vanco-mycin to 0.5 g,ivgtt,q12 h. The pharmaceutical care were conducted throughout the therapy,including efficacy evaluation of an-ti-infective therapy,ADR monitoring,renal function monitoring,etc. RESULTS:Physicians adopted some suggestions of clinical pharmacists. The disease condition of the patient was recovred,and no ADR related to vancomycin was found. On the 16th day, the patient was discharged from the hospital. CONCLUSIONS:Clinical pharmacists participate in treatment of purulent meningitis, assist physicians to optimize therapy plan based on relevant guideline,literature,etiological examination,blood concentration moni-toring and pharmacokinetics model fitting results. It not only guarantee therapeutic efficacy of anti-infective therapy,but also pre-vent and reduce the occurrence of ADR.

Objective To summarize the main nursing points of toxic epidermal necrolysis. Methods On the foundation of conventional therapy, an overall assessment was carried out among 10 patients with toxic epidermal necrolysis. On loose skin with erythema, a combination of zinc oxide and talcum powder was externally applied to skin lesions where blisters were not broken in order to promote dry-style exfoliation of the skin lesion. After infrared irradiation, gauze containing MEBO was applied externally to skin lesions with eroded secretions to moisturize them, thus facilitating healing of the skin lesion. Meanwhile, mucosa of special part of patient's body was well nursed. Protective isolation was enhanced in order to reduce secondary infection. The patient's conditions were observed closely. Diet guidance was also done. Results All the patients were dry-style exfoliated with treatment ranges reaching up to 30%to 60%of the affected area. Dry-style exfoliation time was between 5 to 10 days, with an average of 7.20 ±1.69 days. The area of skin lesion erosion ranged from 10% to 60%. Following the external application of MEBO gauze to moisturize and heal, skin lesion healing time ranged from 7 to 18 days with an average of 13.70 ±3.40 days. Conclusion According to the specific situation of toxic epidermal necrolysis, targeted nursing and treatment can promote the dry-style exfoliation of skin lesions, reduce the area of skin erosions, alleviate the suffering of patients and promote healing of the skin lesion.

BACKGROUND: In recent years, the immunoregulatory effects of mesenchymal stem cells (MSCs) can be used to induce immune tolerance. OBJECTIVE: To evaluate the safety and feasibility of human umbilical cord-derived MSCs (hUC-MSCs) in liver transplantation patients. METHODS: hUC-MSCs were cultured and identified. After approved by the Medical Ethics Committee, a total of 50 patients were randomly divided into experimental group and control group according to the proportion of 1:1. In the experimental group, hUC-MSCs were perfused by the portal vein during the operation and infused into the jugular vein on the 3rd day after the operation. The injection dose was 1×106/kg (prepared as 50 mL of cell suspension). Both groups received standard immunosuppressive regimens. Blood biochemistry and immune function indicators were detected preoperatively and at postoperative days 3, 7, months 1, 2, 3, 6, 12. Acute and chronic rejection rates, incidence of infection, and incidence of transplantation-related complications were recorded. RESULTS AND CONCLUSION: (1) At 3 and 7 days after the operation, the percentage of peripheral blood CD4+CD25+ cells (regulatory T cells) in the experimental group was significantly higher than that in the control group (P < 0.05). The percentage of CD4+ cells (helper/inducer T cells) and ratio of CD4+/CD8+ T lymphocytes were significantly lower in the experimental group than the control group (P < 0.05). (2) There was no significant difference in postoperative alanine aminotransferase and total bilirubin levels between the two groups (P > 0.05). (3) The incidence of abnormal liver function in the experimental group was significantly lower than that in the control group (P < 0.05). (4) The incidence of transplantation-related complications and the rate of infection showed no significant difference between the two groups (P > 0.05). Overall, the intravenous infusion of hUC-MSCs is safe and feasible in liver transplantation patients, which in early stage can promote the the proliferation and activation of CD4+CD25+ cells (regulatory T cells), reduce the percentage of CD4+ cells (helper/inducer T cells) and lower the ratio of CD4+/CD8+ T cells, thereby improving the immune status in liver transplantation patients.