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 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.

Objective:To investigate the correlation between serum gastrin, C-reactive protein (CRP), tumor necrosis factor α (TNF-α) and the degree of peptic ulcer bleeding.Methods:The clinical data of 90 peptic ulcer bleeding patients (test group) from April 2019 to September 2020 in Hangzhou Hospital of Zhejiang Medical and Health Group were retrospectively analyzed, including 15 cases with low-risk, 40 cases with intermediate-risk and 35 cases with high-risk of Blatchford score; 40 physical examination volunteers were selected as the control group during the same period. The serum levels of CRP and TNF-α were measured by enzyme-linked immunosorbent assay, and the serum level of gastrin was measured by radioimmunoassay. The correlation between CRP, TNF-α, gastrin and the Blatchford score was analyzed by Pearson method; the independent risk factors affecting high-risk peptic ulcer bleeding were analyzed by multivariate Logistic regression; the value of CRP, TNF-α and gastrin in predicting high-risk peptic ulcer bleeding was analyzed by the receiver operating characteristic (ROC) curve.Results:The CRP, TNF-α and gastrin in test group were significantly higher than those in control group: (19.69 ± 3.41) mg/L vs. (2.28 ± 0.64) mg/L, (26.63 ± 4.24) ng/L vs. (1.35 ± 0.31) ng/L and (149.77 ± 21.41) μg/L vs. (72.65 ± 12.39) μg/L, and there were statistical differences ( P<0.01). The hemoglobin and platelets in intermediate-risk and high-risk patients were significantly lower than those in low-risk patients: (59.21 ± 4.63) and (28.94 ± 4.69) g/L vs. (89.68 ± 5.12) g/L, (162.14 ± 12.47) and (122.05 ± 10.39) × 10 9/L vs. (213.58 ± 16.98) × 10 9/L, the indexes in high-risk patients were significantly lower than those in intermediate-risk patients, and there were statistical differences ( P<0.05); the prothrombin time, CRP, TNF-α and gastrin in intermediate-risk and high-risk patients were significantly higher than those in low-risk patients: (13.98 ± 1.29) and (16.97 ± 1.15) s vs. (11.00 ± 2.07) s, (18.87 ± 4.68) and (22.69 ± 2.96) mg/L vs. (15.45 ± 5.54) mg/L, (27.43 ± 5.05) and (31.02 ± 4.56) ng/L vs. (21.39 ± 8.54) ng/L, (140.89 ± 22.36) and (160.58 ± 25.52) μg/L vs. (121.39 ± 15.17) μg/L, the indexes in high-risk patients were significantly higher than those in intermediate-risk patients, and there were statistical differences ( P<0.05). Multivariate Logistic regression analysis result showed that hemoglobin, platelets, CRP, TNF-α and gastrin were independent risk factors for high-risk peptic ulcer bleeding ( OR = 0.224, 0.321, 3.687, 3.058 and 4.051; 95% CI 0.004 to 0.894, 0.121 to 8.547, 1.912 to 5.525, 3.012 to 10.609 and 2.012 to 7.525; P<0.05 or <0.01). Pearson correlation analysis result showed that CRP, TNF-α and gastrin were positive correlation with the Blatchford score ( r = 0.501, 0.526 and 0.542; P<0.01). ROC curve analysis result showed that the areas under the curve of CRP, TNF-α and gastrin for predicting high-risk peptic ulcer bleeding was 0.890, 0.825 and 0.901, with optimal cut-off values of 17.95 mg/L, 22.16 ng/L and 135.36 μg/L, sensitivity of 97.14%, 94.29% and 82.86%, and specificity of 80.00%, 66.67% and 86.67%. Conclusions:CRP, TNF-α and gastrin are correlated to the degree of peptic ulcer bleeding, and can be used as indexes to evaluate the bleeding degree of peptic ulcer.

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 establish UPLC-Q- TOF-MS/MS fingerprint of Fritillaria thunbergii ， and to define its anti-inflammatory quality markers. METHODS ：The determination was performed on Eclipse Plus C 18 column with mobile phase consisted of methanol- 0.1％ formic acid solution （gradient elution ）at the flow rate of 0.4 mL/min. The column temperature was set at 30 ℃，and injection volume was 2 µL. The electrospray ion source was used to scan in the range of m/z 50-1 200 with positive and negative ion detection mode. UPLC-Q-TOF-MS/MS fingerprints of 10 batches of F. thunbergii from different habitats were established by using the Similarity Evaluation System of TCM Chromatographic Fingerprints （2004A edition ）. With ear swelling degree，the serum levels of MDA and NO as anti-inflammatory indexes ，the correlation between the relative area of common peaks in fingerprint and the anti-inflammatory indexes was analyzed by using bivariate correlation analysis and grey correlation analysis ， and the quality markers were screened and identified. RESULTS ：In positive and negative ion mode ，10 batches of F. thunbergii had 26 peaks and 10 peaks. Based on bivariate correlation analysis and grey correlation analysis ，nine quality markers related to anti-inflammatory effect were found ，which were identified as peiminine ，peimine，cyclobalamine，daucidin，polyphyllin Ⅴ， bitumen podophyllotoxin ，phytosterol，ent-kaur-15-en-17-ol，ent-17-norkauran-16-one. CONCLUSIONS ：Established UPLC-Q- TOF-MS/MS fingerprint can be used to evaluate the quality of F. thunbergii ；peiminine，peimine and cyclobalamine and so on may be the quality markers of anti-inflammatory effect of F. thunbergii .

Objective: To investigate clinicopathological features and prognostic factors of gastric neuroendocrine tumors (G-NEN). Methods: Clinical and pathological data of patients with G-NEN diagnosed by pathological examination in Chinese PLA General Hospital from January 2000 to June 2018 were retrospectively analyzed in this case-control study. Patients with complicated visceral lesions, other visceral primary tumors, mental disorders and incomplete clinicopathological data were excluded. Finally, 240 hospitalized patients who met the inclusion criteria were enrolled. Physical examination information, tumor characteristics and pathological characteristics of patients were summarized. The Cox regression models were used to analyze the risk factors affecting G-NEN and the survival conditions were described by Kaplan-Meier survival curves and log-rank test. Results: In 240 patients with G-NEN, the mean age was (60.3±10.1) years; 181 were male (75.4%) and 59 females (24.6%); mean tumor diameter was (4.2±2.8) cm; 51 cases (21.2%) were neuroendocrine tumor (NET), 139 cases (57.9%) neuroendocrine carcinoma (NEC), 50 cases (20.8%) mixed neuroendocrine carcinoma (MANEC); 28 cases (11.7%) were G1 low grades, 34 cases (14.2%) G2 medium grades, and 178 cases (74.2%) G3 high grades; tumor infiltration depth T1 to T4 were 44 cases (18.3%), 27 cases (11.2%), 60 cases (25.0%) and 109 cases (45.4%) respectively; 163 cases (67.9%) developed lymphatic metastasis and 46 patients (19.2%) distant metastasis; tumor stage from stage I to stage IV were 55 cases (22.9%), 42 cases (17.5%), 94 cases (39.2%) and 53 cases (22.1%) respectively. Of the 240 G-NEN patients, 223 cases (92.9%) were followed up. The median survival time of the patients was 39.2 (95% CI: 29.1 to 47.5) months. Univariate survival analysis showed that age ≥ 60 years, tumor diameter ≥ 4.2 cm, tumor grade G3, lymphatic metastasis, distant metastasis, and tumor stage III-IV were risk factors for G-NEN patients. Multivariate survival analysis revealed that lymphatic metastasis (HR=1.783, 95%CI: 1.007-3.155, P=0.047) and distant metastasis (HR=2.288, 95% CI: 1.307-4.008, P=0.004) were independent risk factors of the prognosis. Further analysis of the G3 subgroup of G-NEN showed that the 5-year survival rate of NET-G3 was 76.19%, which was significantly higher than that of NEC-G3 and MANEC-G3 (15.60% and 24.73%, P=0.012). Conclusions Most G-NEN patients are in advanced stage at diagnosis. Lymphatic metastasis and distant metastasis indicate poor prognosis. The prognosis of high proliferation NET-G3 patients is better as compared to those of NEC-G3 and MANEC-G3. This classification is worth further attention.

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.

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.