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 investigate the therapeutic effects and mechanisms of Aurantii Fructus Immaturus(AFI)on slow-transit constipation(STC)in mice.Methods A STC model was established via intragastric administration of Loperamide Hydrochloride.Successfully modeled mice were randomized into a model group,low-and high-dose AFI groups,a high-dose AFI+Masitinib[tyrosine kinase(c-Kit)inhibitor]group,additionally,a normal group was set up.After intervention,intestinal transit rate,6-hour fecal pellet number,fecal water content,and colonic histomorphology(hematoxylin-eosin staining)were assessed.Enzyme-linked immunosorbent assay(ELISA)was used to measure levels of 5-hydroxytryptamine(5-HT),vasoactive intestinal polypeptide(VIP),substance P(SP),nitric oxide(NO),and nitric oxide synthase(NOS)activity in colon tissue.Quantitative real-time PCR(qRT-PCR)was used to evaluate mRNA expression of stem cell factor(SCF)and c-Kit in colon tissue,Western Blot was used to analyze relative protein expression of aquaporin 3(AQP3),aquaporin 8(AQP8),SCF,and c-Kit in colon tissue.Results Compared with the normal group,there was devere colonic damage observed in the colon tissue of the mice in the model group,the fecal pellet number,fecal water content,intestinal transit rate,colon tissue SP content,c-Kit and SCF gene and protein expression levels were reduced.The contents of 5-HT,VIP and NO,NOS activity and the protein expression levels of AQP3 and AQP8 in colon tissue were increased,and the differences were statistically significant(P＜0.05).Compared with the model group,the colonic injury of mice in the low-and high-does AFI groups showed obvious improvement,the fecal pellet number,fecal water content,intestinal transit rate,colon tissue SP content,c-Kit and SCF gene and protein expression levels were increased,the contents of 5-HT,VIP and NO,NOS activity and the protein expression levels of AQP3 and AQP8 in colon tissue were decreased(P＜0.05).Masitinib partially reversed the laxative effects of AFI(P＜0.05).Conclusion AFI enhances intestinal motility,alleviates colonic injury,and improves defecation in STC mice,potentially via activation of the SCF/c-Kit pathway.

Objective:To explore the risk factors for tubal patency after partial salpingectomy and end-to-end anastomosis,and their impact on pregnancy outcomes.Methods:A total of 300 patients with tubal pregnancy who underwent partial salpingectomy and end-to-end anastomosis in Zhengzhou Maternal and Child Health Hospital from January 2020 to April 2023 were enrolled in the study.Hysterosalpingography was performed after surgical treatment to examine the tubal patency.Lasso-Logistic regression was used to analyze the risk factors for postoperative tubal patency,and Spearman's correlation was used to analyze the impact of each risk factor on the pregnancy rate.Results:Hysterosalpingography showed that the fallopian tube was not obstructed in 225 cases(unobstructed group),the tube was not completely patent(n=54)or blocked(n=21)(obstructed group).Univariate analysis showed that age,diameter of the tubal pregnancy sac,location of tubal pregnancy,timing of surgery,pelvic adhesion,anastomotic method,length of remaining tubal,history of pelvic surgery,number of intraoperative electrocoagulation,intraoperative blood loss,and experience of surgeons were factors affecting postoperative tubal patency(all P＜0.01).Lasso regression analysis identified location of tubal pregnancy,pelvic adhesion,anastomotic method,length of remaining tubal,history of pelvic surgery,number of intraoperative electrocoagulation,and experience of surgeons as influencing factors.Multivariate Logistic regression analysis showed that tubal isthmus pregnancy,pelvic adhesion,open anastomosis surgery,history of pelvic surgery,and number of intraoperative electrocoagulation were independent risk factors for postoperative tubal patency,while length of remaining tubal and years of surgeon's work experience were independent protective factors for postoperative tubal patency(all P＜0.01).A total of 295 patients were followed up for 1 year,192 cases(65.08%)were pregnant,including 172 cases of intrauterine pregnancy(89.58%)and 20 cases of ectopic pregnancy(10.42%).Spearman correlation analysis showed that tubal isthmus pregnancy,pelvic adhesion,open abdominal anastomosis surgery,pelvic surgery history,and times of intraoperative electrocoagulation were negatively correlated with postoperative pregnancy,while the remaining tubal length and years of surgeon's working experience were positively correlated with postoperative pregnancy rate(all P＜0.01).Conclusions:For tubal patency of patients after partial salpingectomy combined with end-to-end anastomosis,the history of tubal isthmus pregnancy,pelvic adhesion,open abdominal anastomosis,pelvic surgery,and the number of intraoperative electrocoagulation are independent risk factors,which are negatively correlated with postoperative pregnancy.The remaining tubal length and the years of surgeon's work experience are independent protective factors,which are positively correlated with postoperative pregnancy.

Objective:To observe the effect of fractional flow reserve derived from computed tomography(FFRcT)measurement system based on iterative algorithm in diagnosing survival prognosis of patients with acute ST-segment elevation myocardial infarction(STEMI)after they underwent emergency percutaneous coronary intervention(PCI).Methods:A total of 98 patients with acute STEMI complicated with multi vessel disease(MVD)were prospectively selected from the Affiliated Hospital of Inner Mongolia Medical University during October 2022 and February 2024.All patients were divided into two groups according to random double-blind method:FFRCT guidance group(49cases)and coronary angiography(CAG)guidance group(49cases).The FFRCT guidance group used FFRCT as the diagnostic basis,which carried out complete revascularization strategy according to FFRCT examination results.CAG guidance group handled infarct-related vessels as the CAG guidance.The basic clinical data,operation details of PCI surgery/technical indicators and utilization indicators of related resource of the two groups were observed,and angina pectoris attack and major adverse cardiovascular events(MACE)and other prognosis indicators of related survival of the two groups were observed and followed up.The primarily observed endpoints were all-cause death,heart failure,stroke,MACE,and composite endpoint event of stroke and revascularization again within 24 months follow-up.Results:The proportion of undergoing PCI on non-infarct-related vessel was 55.10％(27/49)in FFRCT group.In the comparison of operation detail of surgery/technique indicator after PCI surgery between two groups,the operation time of FFRCT guidance group was(65±10)min,which was longer than that[(60±8)min]of CAG guidance group,and the total length of stent was(31±10)mm,which was shorter than that[(36±10)mm]of CAG guidance group.There were statistically significant differences in the above two indicators between the two groups(t=-4.062,-6.710,P＜0.05),respectively.There were no statistically significant differences in the amount of contrast agent,average diameter of stent and length of stay between the two groups(P＞0.05).Compared with the CAG group,the incidences of non-lethal myocardial infarction,primary endpoint events,recurrent angina pectoris,and revascularization of FFRCT group significantly reduced within 24 months follow-up,and the differences of them between two groups were statistically significant(x2=4.926,5.273,6.091,5.804,P＜0.05),respectively.Conclusion:Using FFRCT measurement system based on iterative algorithm in PCI process of emergency for patients with acute STEMI complicated with MVD to examine and guide revascularization is safe and effective,which is worthy of recognition.It has obvious advantages over CAG guidance in reducing the risk of cardiovascular and cerebrovascular events,and in improving prognosis after PCI.

Mastitis is one of the most widespread infectious diseases that adversely affects the profitability of the dairy industry worldwide. Accurate diagnosis and identification of pathogens early to cull infected animals and minimize the spread of infection in herds is critical for improving treatment effects and dairy farm welfare. The major pathogens causing mastitis and pathogenesis are assessed first. The most recent and advanced strategies for detecting mastitis, including genomics and proteomics approaches, are then evaluated .Finally, the advantages and disadvantages of each technique, potential research directions, and future perspectives are reported. This review provides a theoretical basis to help veterinarians select the most sensitive, specific, and cost-effective approach for detecting bovine mastitis early.

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 efficacy of venetoclax-based combined regimen in treatment of adult patients with acute myeloid leukemia (AML).Methods:The data of 50 adult AML (non-acute promyelocytic leukemia) who received venetoclax-based combined regimen in the First Affiliated Hospital of Xiamen University, Dongguan People's Hospital, the First Hospital of Longyan City, Jieyang People's Hospital from December 2018 to May 2021 were retrospectively analyzed. Different doses venetoclax combined with demethylation drugs or low-dose chemotherapy regimen were used to analyze the therapeutic efficacy. The related factors influencing efficacy were analyzed by using logistic regression.Results:The composite complete remission (CR) rate of 50 AML patients was 62.0% (31/50), the overall response rate (ORR) was 76.0% (38/50); 28 patients achieved effectiveness [CR and partial remission (PR)] after the first cycle and could achieve effectiveness by 3 courses of treatment at the latest. Among 50 patients, 28 cases were newly diagnosed AML, the composite CR rate was 60.8% (17/28), ORR was 78.6% (22/28); 22 cases were recurrent and relapsed, the composite CR rate was 63.6% (14/22), ORR was 72.7% (16/22); and there was no statistically significant difference of ORR between the both groups ( χ2 = 0.23, P = 0.743). Logistic regression multivariate analysis showed age was the only independent influencing factor for the treatment effectiveness ( OR = 8.451, 95% CI 1.306-54.697, P = 0.025). The median duration time of patients receiving venetoclax treatment regimen was 4.5 months (1.1-15.0 months); 16 cases who had treatment effectiveness finally relapsed, the median time of maintaining effectiveness was 5 months (1.1-11.0 months). Additionally, the common treatment-related adverse reactions included bone marrow suppression after treatment, followed by some gastrointestinal reactions like nausea, vomiting and stomachache. In addition, no patient stopped medication for more than 1 week due to bone marrow suppression related complications. Conclusion:Venetoclax-based combined regimen shows a good short-term efficacy in treatment of AML. It is also effective and tolerable for elderly patients receiving reduced dose therapy.

Objective:To compare the survival rate of secondary hyperparathyroidism (SHPT) patients with different dialysis modalities after parathyroidectomy (PTX), and analyze the influencing factors of survival prognosis.Methods:Clinical data of dialysis patients diagnosed with SHPT and treated with PTX in the First People′s Hospital of Foshan from April 2014 to May 2019 were retrospectively collected and analyzed. The patients were divided into hemodialysis (HD) group and peritoneal dialysis (PD) group according to preoperative dialysis modalities, and the differences in baseline clinical data and cardiac ultrasound results were compared between the two groups. Kaplan-Meier survival analysis was used to compare the difference in cumulative survival rate between the two groups. Multivariate Cox regression model was used to analyze the influencing factors of all-cause death. Receiver operating characteristic curve (ROC curve) was used to predict the risk of all-cause death.Results:A total of 99 patients were enrolled in this study, and 94 patients completed follow-up, including 23 patients who died. Compared with PD group ( n=45), HD group ( n=54) had higher dialysis age, blood pressure, intact parathyroid hormone, alkaline phosphatase, total heart valve calcification rate, mitral valve calcification proportion, interventricular septal thickness (IVST) and left ventricular mass index (all P<0.05). The median follow-up time was 46.00(32.75, 60.25) months. Kaplan-Meier survival analysis showed that there was no significant difference in cumulative survival rate between HD group and PD group (Log-rank test χ2=0.414, P=0.520). Multivariate Cox regression analysis showed that increasing age ( HR=1.066, 95% CI 1.017-1.118, P=0.008), systolic blood pressure>140 mmHg ( HR=2.601, 95% CI 1.002-6.752, P=0.049) and increasing IVST ( HR=1.269, 95% CI 1.036-1.554, P=0.021) were independent influencing factors for all-cause death in dialysis patients after PTX. ROC curve analysis results showed that the cut-off values of age, dialysis age and IVST for predicting all-cause death after PTX were 51.5 years old ( AUC=0.673, 95% CI 0.545-0.802, P=0.013) and 75.0 months ( AUC=0.654, 95% CI 0.528-0.780, P=0.027) and 13.5 mm ( AUC=0.680, 95% CI 0.557-0.803, P=0.010) respectively. The area under the ROC curve for age, dialysis age, IVST, left ventricular hypertrophy in combination with systolic blood pressure>140 mmHg in the prediction of all-cause death after PTX was 0.776(95% CI 0.677-0.875, P<0.001). Conclusions:There is no significant difference in cumulative survival rate between HD and PD patients with SHPT after PTX. Increasing age, systolic blood pressure>140 mmHg and increasing IVST are independent risk factors for all-cause death in dialysis patients with SHPT after PTX.

Objective:Gastric cancer in adolescents is rare, with only a few cases reported in the literature. The purpose of this study is to investigate the clinicopathological features and prognostic factors of gastric cancer in adolescents aged 10-24 years.Methods:A case-controlled study was performed. The clinicopathological data of gastric cancer patients aged 10-24 years who were treated at the First Medical Center of Chinese PLA General Hospital from February 2000 to February 2017 were retrospectively collected and compared with those patients over 40 years old at the same period, which were randomly selected in a ratio of 1:2. All the patients were followed up until June 2019 and Cox proportional hazard model was used to analyze prognostic factors in the adolescent patients.Results:A total of 63 adolescent gastric cancer patients (0.4% of all 14 794 gastric cancer patients) were enrolled, including 31 males (49.2%) and 32 females (50.8%), with a mean body mass index of (19.5±4.3) kg/m 2. Before diagnosis, Only 35 cases (55.6%) had warning symptoms such as weight loss, ascites, obstruction, hematemesis, black stool, etc.; 5 cases (7.9%) had a family history of gastrointestinal tumor. The median duration of symptoms before diagnosis was 3 months. At diagnosis, 58 cases (92.1%) were poorly differentiated, 57 cases (90.5%) were T3-4 stage, 19 cases (30.2%) were signet ring cell cancer or mucous adenocarcinoma, 57 cases (90.5%) had lymph node metastasis, and 36 cases (57.1%) had distant metastasis. Twenty-nine patients (46.0%) underwent radical surgery, 12 patients underwent palliative surgery, 5 patients underwent exploratory laparotomy, 17 patients were unable to operate due to late stage. Of 56 cases (88.9%) with TNM stage Ⅲ-Ⅳ, 51 patients (81.0%) received chemotherapy. Of the 126 patients over 40 years old, 98 cases (77.8%) were male and 28 cases (22.2%) were female, and the mean body mass index was (23.8±3.2) kg/m 2. There were 60 cases (47.6%) with low differentiation, 90 cases (71.4%) with T3-4, 16 cases (12.7%) with signet ring cell cancer and mucous cell cancer, 79 cases (62.7%) with lymph node metastasis, and 12 cases (9.5%) with distant metastasis. A total of 115 cases (91.3%) underwent radical surgery. Of 74 cases (58.7%) with TNM stage Ⅲ-Ⅳ, 67 cases received (53.2%) chemotherapy. The 63 adolescent gastric cancer patients had lower body mass index, and higher proportion in female, poorly differentiation, signet ring cell cancer and mucous cell cancer, T3-4 stage, lymph node metastasis, distant metastasis, TNM stage Ⅲ-Ⅳ and receiving chemotherapy compared with 126 gastric cancer patients over 40 years old (all P<0.05). Among the 63 adolescent gastric cancer patients, 52 cases (82.5%) were followed up with median follow-up time of 72.1 (36.1, 100.8) months, and the median survival time was 10.4 months (95% CI: 6.5-15.1). The 1-year, 3-year and 5-year survival rates were 44.2%, 25.0% and 18.0%, respectively. Univariate analysis showed that the depth of tumor invasion (HR=7.15, 95% CI:1.71-29.89, P=0.007), lymph node metastasis (HR=6.00, 95% CI:1.42 - 25.42, P=0.015), distant metastasis (HR=7.25, 95% CI: 3.25 - 16.18, P<0.001), TNM stage (HR=5.49, 95% CI: 1.67-18.12, P=0.005) and tumor resection (HR=0.18, 95% CI: 0.09-0.37, P<0.001) were the risk factors affecting the prognosis of adolescent gastric cancer patients. Multivariate survival analysis showed that distant metastasis was an independent factor for gastric cancer survival in adolescents (HR=3.67, 95% CI: 1.32-10.19, P=0.012). Conclusions:Gastric cancer in adolescents is insidious and progresses rapidly. Most of them are in the advanced stage at diagnosis and have low rate of radical excision.

Objective:Gastric cancer in adolescents is rare, with only a few cases reported in the literature. The purpose of this study is to investigate the clinicopathological features and prognostic factors of gastric cancer in adolescents aged 10-24 years.Methods:A case-controlled study was performed. The clinicopathological data of gastric cancer patients aged 10-24 years who were treated at the First Medical Center of Chinese PLA General Hospital from February 2000 to February 2017 were retrospectively collected and compared with those patients over 40 years old at the same period, which were randomly selected in a ratio of 1:2. All the patients were followed up until June 2019 and Cox proportional hazard model was used to analyze prognostic factors in the adolescent patients.Results:A total of 63 adolescent gastric cancer patients (0.4% of all 14 794 gastric cancer patients) were enrolled, including 31 males (49.2%) and 32 females (50.8%), with a mean body mass index of (19.5±4.3) kg/m 2. Before diagnosis, Only 35 cases (55.6%) had warning symptoms such as weight loss, ascites, obstruction, hematemesis, black stool, etc.; 5 cases (7.9%) had a family history of gastrointestinal tumor. The median duration of symptoms before diagnosis was 3 months. At diagnosis, 58 cases (92.1%) were poorly differentiated, 57 cases (90.5%) were T3-4 stage, 19 cases (30.2%) were signet ring cell cancer or mucous adenocarcinoma, 57 cases (90.5%) had lymph node metastasis, and 36 cases (57.1%) had distant metastasis. Twenty-nine patients (46.0%) underwent radical surgery, 12 patients underwent palliative surgery, 5 patients underwent exploratory laparotomy, 17 patients were unable to operate due to late stage. Of 56 cases (88.9%) with TNM stage Ⅲ-Ⅳ, 51 patients (81.0%) received chemotherapy. Of the 126 patients over 40 years old, 98 cases (77.8%) were male and 28 cases (22.2%) were female, and the mean body mass index was (23.8±3.2) kg/m 2. There were 60 cases (47.6%) with low differentiation, 90 cases (71.4%) with T3-4, 16 cases (12.7%) with signet ring cell cancer and mucous cell cancer, 79 cases (62.7%) with lymph node metastasis, and 12 cases (9.5%) with distant metastasis. A total of 115 cases (91.3%) underwent radical surgery. Of 74 cases (58.7%) with TNM stage Ⅲ-Ⅳ, 67 cases received (53.2%) chemotherapy. The 63 adolescent gastric cancer patients had lower body mass index, and higher proportion in female, poorly differentiation, signet ring cell cancer and mucous cell cancer, T3-4 stage, lymph node metastasis, distant metastasis, TNM stage Ⅲ-Ⅳ and receiving chemotherapy compared with 126 gastric cancer patients over 40 years old (all P<0.05). Among the 63 adolescent gastric cancer patients, 52 cases (82.5%) were followed up with median follow-up time of 72.1 (36.1, 100.8) months, and the median survival time was 10.4 months (95% CI: 6.5-15.1). The 1-year, 3-year and 5-year survival rates were 44.2%, 25.0% and 18.0%, respectively. Univariate analysis showed that the depth of tumor invasion (HR=7.15, 95% CI:1.71-29.89, P=0.007), lymph node metastasis (HR=6.00, 95% CI:1.42 - 25.42, P=0.015), distant metastasis (HR=7.25, 95% CI: 3.25 - 16.18, P<0.001), TNM stage (HR=5.49, 95% CI: 1.67-18.12, P=0.005) and tumor resection (HR=0.18, 95% CI: 0.09-0.37, P<0.001) were the risk factors affecting the prognosis of adolescent gastric cancer patients. Multivariate survival analysis showed that distant metastasis was an independent factor for gastric cancer survival in adolescents (HR=3.67, 95% CI: 1.32-10.19, P=0.012). Conclusions:Gastric cancer in adolescents is insidious and progresses rapidly. Most of them are in the advanced stage at diagnosis and have low rate of radical excision.