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

To explore the feasibility of using UAV-LiDAR for measuring the leaf area index (LAI) of crop canopies, we employed UAV-LiDAR to scan sugarcane canopies during the tillering and elongation stages, acquiring canopy point cloud data. Subsequently, features such as average row height, projected row area, point cloud density at different canopy layers, and the ratios between these parameters were extracted. Three feature selection methods-partial least squares regression (PLSR), XGBoost feature importance (XGBoost-FI), and random forest-recursive feature elimination (RF-RFE)-were adopted to evaluate and identify the optimal input variables for modeling. With these selected variables, LAI inversion models were developed based on random forest (RF) and adaptive boosting (AdaBoost) algorithms, and their performance was assessed. Among the extracted features, the projected row area S_p and the total row point count C_total exhibited strong correlations with LAI, with correlation coefficients of 0.73 and 0.72, respectively. The AdaBoost-based LAI inversion model, using the projected row area S_p, average height H_avg, mid-layer point cloud density C_m, and total row point count C_total as input variables, achieved the best performance, with a coefficient of determination (R_v²) of 0.713 and a root mean square error (RMSE_v) of 0.25 on the validation set. This study provides an effective method for high-throughput acquisition of LAI in field crops, offering valuable scientific support for sugarcane field management and breeding efforts.
Plant Leaves/growth & development* ; Saccharum/growth & development* ; Algorithms ; Unmanned Aerial Devices ; Remote Sensing Technology/methods* ; Crops, Agricultural/growth & development*

[摘 要] 目的：探究包被蛋白复合体β1亚基（COPB1）在食管鳞状细胞癌（ESCC）中的表达，及其对ESCC细胞恶性生物学行为的影响、作用机制及临床意义。方法：采用2014～2018年间在河北医科大学第四医院生物样本库中82例ESCC组织及癌旁组织，常规培养正常食管鳞状上皮细胞HEEC和食管癌细胞KYSE-150、KYSE-170、Eca109、TE1、KYSE-30、KYSE-450，用转染试剂将pcDNA3.1-vector（空载体）、pcDNA3.1-COPB1载体，si-NC和si-COPB1转染至KYSE-150、TE1细胞中，记为NC、COPB1-OE、si-NC和si-COPB1组。用数据库数据分析COPB1 mRNA在泛癌组织中的表达及其表达与免疫细胞浸润的关系，qPCR法检测ESCC组织和细胞中COPB1、PIK3CB、CD68、CD163、CD206、ARG1、IL-10 mRNA水平表达情况，WB法检测ESCC组织和各组细胞中的COPB1、PI3K、CD68、CD163、CD206、p-AKT蛋白表达，克隆形成实验和MTS实验检测各组细胞的增殖能力，划痕愈合实验和Transwell实验检测各组细胞的迁移和侵袭能力，免疫组织化学染色（IHC）法检测ESCC组织中COPB1和CD206蛋白表达。以人单核细胞白血病细胞（THP-1）构建巨噬细胞模型，用佛波酯（PMA）和IL-3和IL-4和ESCC细胞上清液诱导巨噬细胞转型，用qPCR和WB法检测CD68和CD206m RNA和蛋白的表达。结果：COPB1在泛癌组织和ESCC组织中均呈高表达且与淋巴结转移和TNM分期有关联（均P < 0.01），COPB1高表达的ESCC患者总生存期短（P < 0.05），COPB1是潜在的ESCC的诊断标志物。COPB1在KYSE-150和TE1细胞中也呈高表达（均P < 0.05），过表达或敲减COPB1可明显抑制或促进KYSE-150和TE1细胞的增殖能力、迁移和侵袭能力（均P < 0.05）。COPB1表达变化诱导的差异表达基因主要富集于PI3K/AKT通路（均P < 0.001）, COPB1可促进PI3K/AKT通路的活化（P < 0.05），COPB1高表达可导致M2型巨噬细胞浸润增加（P < 0.05），COPB1高表达促进TAM/M2极化（P < 0.05）。结论：COPB1在ESCC组织中呈高表达，其可激活PI3K/AKT通路及调控肿瘤免疫微环境促进 ESCC发生发展，COPB1有望成为ESCC诊断和预后的生物标志物及治疗靶点。

Objective:To explore the effect of heme-binding protein 1(HEBP1)down-regulation on the function of microglia BV2,and to clarify the key role of HEBP1 in the microglia.Methods:Negative control and HEBP1 knockdown small interfering RNA(siRNA)were constructed to knockdown HEBP1 gene in mouse-derived microglial BV2,and the HEBP1 knockdown BV2 cell models were obtained.The BV2 cells were divided into si-NC group,si-HEBP1-1 group,si-HEBP1-2 group,and si-HEBP1-3 group.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods were used to detect the expression levels of HEBP1 mRNA and protein in the BV2 cells after knockdown;the siRNA with the most significart knockdown effect was selected for stlbsequent expreriments.The proliferation abilities of the cells in si-NC group and si-HEBP1 group were detected by cell counting kit-8(CCK-8)assay,and the cell migration rates were assessed by scratch assay;the cellular mitochondrial membrane potential and reactive oxygen species(ROS)levels were detected by kits;the cellular mitochondrial respiratory function was detected by mitochondrial respirometer.The BV2 cells were divided into si-NC group,si-NC+lipopolysacch aride(LPS)group,si-HEBP1 group,and si-HEBP1+LPS group.RT-qPCR method was used to detect the expression levels of HEBP1,interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)mRNA in the BV2 cells in various groups,and Western blotting method was used to detect the expression levels of HEBP1 protein in the BV2 cells in various groups.Results:When the BV2 cells were transfected with siRNA carrying with red fluorescence tag CY3,the transfect effricacy was above 90％;compared with si-NC group,the expression levels of HEBP1 protein in the BV2 cells in si-HEBP1-1 group,si-HEBP1-2 group,and si-HEBP1-3 group were significantly decreased(P<0.05 or P<0.01),especially in si-HEBP1-1 group.Compared with si-NC group,the expression levels of HEBP1 mRNA in the BV2 cells in si-HEBP1-1 group,si-HEBP1-2 group,and si-HEBP1-3 group were significantly decreased(P<0.01),especially in si-HEBP1-1 group;indicating that si-HEBP1-1 was the siRNA with best HEBP1 knowdown effect,and the HEBP1 knockdown BV2 cell model was successfully constructed.The CCK-8 resuts showed that compared with si-NC group,the proliferation activities of the BV2 cells in si-HEBP1 group were decreased(P<0.05 or P<0.01);from 90 min,the differences in proliferation activities of the BV2 cells in two groups were obvious.The cell scratch experiment results showed that compared with si-NC group,the cell migration rate in si-HEBP1 group was significantly decreased(P<0.05).The fluorescence microscope results showed that compared with si-NC group,the mitochondrial membrane potential of the BV2 cells in si-HEBP1 group was significantly decreased(P<0.05);compared with si-NC group,the ROS level in the BV2 cells in si-HEBP1 group was significantly increased(P<0.05).The mitochondrial respiration function testing results showed that compared with si-NC group,routine respiration(ROUNTINE)and leak respiration(LEAK)in si-HEBP1 group were significautly decreased(P<0.05 or P<0.01),and electron transfer system capacity(ETS)and residual oxygen consumption(ROX)had no significant differences(P>0.05);the ATP amount was decreased(P<0.05).The RT-qPCR results showed that compared with si-NC group,the expression levels of IL-1β,TNF-α,and IL-6 mRNA in the BV2 cells in si-NC+LPS group were significantly decreased(P<0.01);compared with si-HEBP1 group,the expression levels of IL-1β,TNF-α,and IL-6 mRNA in the BV2 cells in si-HEBP1+LPS group were significantly decreased(P<0.01);compared with si-NC+LPS group,the expression levels of IL-1β,TNF-α,and IL-6 mRNA in the BV2 cells in si-HEBP1+LPS group were significantly increased(P<0.01).Conclusion:Knockdown of HEBP1 gene can decrease the proliferation and migration abilities of the microglia BV2 and increase inflammatory response to LPS stimulus,and their mechanisms may be related to mitochondrial function damage and decreased ATP production of the BV2 cells.

Objective To investigate the risk factor for adverse events(AEs)after non-sedated esophagogastroduodenoscopy(EGD).Methods The data on clinical manifestations,adverse events after non-sedated EGD and common risk factors were collected and retrospectively analyzed with statistical methods in patients who underwent non-sedated EGD from May 2018 to June 2019.These patients were divided into AEs group and non-AEs group.Results Of 2 384 patients,57.67%(1 375/2 384)presented with nausea,12.79%(305/2 384)vomiting,and 5.79%(138/2 384)presented with pharyngalgia.Multivariate Logistic regression analysis was performed.Advanced age(≥65 years old)(OR=0.683,95%CI:0.506-0.921)was protective factors for nausea after non-sedated EGD.Hypertension(OR=1.361,95%CI:1.026-1.806),overweight(OR=1.399,95%CI:1.154-1.695),obesity(OR=2.594,95%CI:1.760-3.823)and inspection duration>15 min(OR=3.107,95%CI:2.296-4.206)were independent risk factors for nausea after non-sedated EGD.Advanced age(OR=0.393,95%CI:0.221-0.699)and imported equipment(OR=0.697,95%CI:0.546-0.890)were protective factors for vomiting after non-sedated EGD.Moreover,inspection duration>15 min(OR=1.641,95%CI:1.008-2.699)was independent risk factors for vomiting after non-sedated EGD.There was no difference in success rate of non-sedated EGD between two groups(P<0.05).Conclusion Hypertension,overweight and obesity were independent risk factors for nausea after non-sedated EGD.The advanced age and imported equipment were protective factors for vomiting after non-sedated EGD.In addition,inspection duration over 15 min is a risk factor for AEs such as nausea and vomiting after nonsedative EGD.Whether AEs occurred or not is non-related to success rate of non-sedated EGD.

Gastric cancer is a common clinical tumor,and its incidence and mortality rates rank among the top of malignant tumors.Helicobacter pylori(Hp)is an important carcinogenic factor for gastric cancer.Studies have found that in addition to Hp,other microorganisms in the stomach also play a key role in the progression of gastric cancer.The composition and diversity of the gastric microbiota vary significantly under different gastric disease conditions,which may affect the progression of gastric cancer.Hp can induce gastric epithelial inflammation and oxidative stress through various virulence factors,thereby promoting the occurrence of gastric cancer.Non-Hp microorganisms can be involved in the process of gastric cancer through pathways such as metabolic changes and immune regulation.In recent years,with the development of high-throughput sequencing technology,the complexity of gastric microbiota has gradually been revealed,which provides new insights for the early warning and intervention of gastric cancer.This article comprehensively review the role of gastric microbiota in the progression of gastric cancer.

Objective To investigate effects of prophylactic laparoscopic and transvaginal cervical cerclage in the treatment of twin pregnancy complicated with cervical insufficiency.Methods A retrospective analysis was performed on 57 patients with twin pregnancy complicated with cervical insufficiency undergoing elective surgery from March 2021 to April 2024.The patients were fully informed of two surgical methods and their advantages and disadvantages before surgery.According to the patient's wishes,26 cases underwent transvaginal cervical cerclage(vaginal cerclage group)and 31 cases underwent laparoscopic cervical cerclage(abdominal cerclage group).The operation time,intraoperative blood loss and other surgery-related conditions,pregnancy outcomes such as gestational age of delivery and incidence of spontaneous miscarriage,neonatal prognosis such as neonatal birth weight and the Apgar score,and complications of childbirth such as cervical laceration,premature rupture of membranes,chorioamnionitis were compared between the two groups.Results No serious complications occurred in both groups.The operation time[(62.8±19.0)min vs.(79.7±20.5)min,t=-3.212,P=0.002]and intraoperative blood loss[15(10,20)ml vs.50(20,50)ml,Z=-3.757,P=0.000]in the vaginal cerclage group were less than those in the abdominal cerclage group.There were no significant differences in hospital stay,incidence of postoperative premature rupture of membranes,and postpartum hemorrhage between the two groups.The incidence of chorioamnionitis in the vaginal cerclage group was significantly higher than that in the abdominal cerclage group[19.2%(5/26)vs.0.0%(0/31),P=0.016].The prolong gestational weeks in the abdominal cerclage group were longer than those in the vaginal cerclage group[(21.9±4.4)gestational weeks vs.(18.6±5.8)gestational weeks,t=-2.377,P=0.021].The delivery rate<32 gestational weeks in the abdominal cerclage group was significantly lower than that in the vaginal cerclage group[6.5%(2/31)vs.30.8%(8/26),χ2=4.222,P=0.040].Compared with the vaginal cerclage group,the abdominal cerclage group had higher birth weight[(2247.4±370.3)g vs.(2037.5±542.0)g,t=-2.289,P=0.025],1-minute Apgar score[(8.9±1.1)points vs.(7.9±1.8)points,t=-3.130,P=0.002]and 5-minute Apgar score[(9.4±0.7)points vs.(8.9±1.2)points,t=-2.912,P=0.004],and lower incidences of 5-minute Apgar score≤7 points[1.7%(1/60)vs.18.8%(9/48),χ2=7.341,P=0.007],neonatal intensive care unit admission[28.3%(17/60)vs.60.4%(29/48),χ2=11.226,P=0.000]and hyperbilirubinemia[21.7%(13/60)vs.43.8%(21/48),χ2=6.029,P=0.014].Conclusions Prophylactic transvaginal cervical cerclage and laparoscopic cervical cerclage are both safe and effective for twin pregnancy complicated with cervical insufficiency.Compared with transvaginal cervical cerclage,laparoscopic cervical cerclage can reduce the incidence of postoperative chorioamnionitis,prolong the gestational week of delivery,reduce the risk of spontaneous preterm birth<32 gestational weeks,and achieve better pregnancy outcomes and neonatal prognosis.

Objective:To investigate the prognostic and predictive value of tertiary lymphoid structures (TLS) in gastric cancer patients undergoing immunotherapy.Methods:Clinical and pathological data, along with tumor tissue samples, were collected from 33 gastric cancer patients who received immunotherapy at Zhongda Hospital, Southeast University from January 2020 to December 2024. The density of tertiary lymphoid structures (TLS) and expression patterns of CD3, CD20, PNAd, and BCL6 were systematically evaluated using hematoxylin-eosin (H&E) staining and immunohistochemical (IHC) analysis. Statistical analyses were performed to determine the associations between TLS characteristics and clinical outcomes, including objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS).Results:Patients in the TLS-high infiltration group (TLS High) demonstrated significantly better outcomes compared to that of the TLS-low group (TLS Low), with higher ORR (58.8% vs 18.8%, P=0.019), DCR (94.1% vs 37.5%, <0.001), and markedly prolonged median PFS (276 vs 67 days, P＜0.000 1). Similarly, the BCL6-high expression group (BCL6 High) showed superior treatment responses versus the BCL6-low group (BCL6 Low), with significantly higher ORR (64.7% vs 12.5%, P=0.002), DCR (100.0% vs 31.3%, P＜0.001), and extended PFS ( P＜0.001). Univariate and multivariable Cox regression confirmed TLS infiltration level as an independent favorable prognostic factor for gastric cancer patients receiving immunotherapy ( HR=0.147, 95% CI: 0.022-0.964, P=0.046). Receiver operating characteristic (ROC) curve analysis revealed excellent predictive accuracy for both TLS infiltration [area under the curve (AUC)=0.885, P＜0.001] and the BCL6 scoring model (AUC=0.890, P＜0.001) in anticipating immunotherapy response. Conclusion:TLS density and BCL6 expression may serve as dual predictive and prognostic biomarkers for gastric cancer immunotherapy, highlighting their clinical utility in patient stratification and treatment guidance.

BACKGROUND:Total flavonoids from Sophora flavescens have a variety of pharmacological effects,including anti-inflammatory,immunomodulatory,antioxidant,and anti-hepatic injury,but the therapeutic effects and mechanisms in non-alcoholic fatty liver disease are not clear.OBJECTIVE:To reveal the mechanism of total flavonoids from Sophora flavescens in the treatment of non-alcoholic fatty liver disease using bioinformatics,network pharmacology and zebrafish experimental validation.METHODS:A zebrafish model of non-alcoholic fatty liver disease was constructed to observe lipid accumulation,pathomorphologic changes,and expression of inflammatory genes in the liver of zebrafish after treatment with total flavonoids from Sophora flavescens.The active ingredients of total flavonoids from Sophora flavescens and non-alcoholic fatty liver disease-related targets were obtained from TCMSP,Swiss Target Prediction,and Bat-man databases.STRING was used to perform protein-protein interaction network analysis,GO functional enrichment and KEGG pathway enrichment analysis.Based on the GSE33814 dataset,the differentially expressed genes of total flavonoids from Sophora flavescens and non-alcoholic fatty liver disease intersection targets were screened out.Correlation analysis and receiver operating characteristic curve were performed using R4.3.2 software.Core genes were verified by the validation set GSE89632.RT-qPCR and western blot assays were performed to verify the expression of core pathway-related genes and proteins.RESULTS AND CONCLUSION:(1)Total flavonoids from Sophora flavescens could improve lipid accumulation in the liver of zebrafish with non-alcoholic fatty liver disease,significantly inhibited the elevation of lipid and aminotransferase levels in zebrafish(P<0.05),and regulated the expression of genes related to inflammation and lipid metabolism.(2)A total of 168 common targets were obtained using the network pharmacology,and top 10 core genes,identified by Cytoscape topology analysis,were HSP90AA1,STAT3,PIK3R1,MAPK1,AKT1,RXRA,PIK3CA,EGFR,JAK2,and ESR1.GO and KEGG analysis pathways mainly included insulin resistance,lipids,and atherosclerosis.There were a total of 59 differentially expressed genes after intersection of total flavonoids from Sophora flavescens and non-alcoholic fatty liver disease targets.The receiver operating characteristic curve and validation set analyses yielded six core targets that were significantly different between healthy individuals and patients with non-alcoholic fatty liver disease(P<0.01).(3)RT-PCR and western blot results verified that total flavonoids from Sophora flavescens inhibited the activation of the JAK2/STAT3 signaling pathway in zebrafish.To conclude,total flavonoids from Sophora flavescens may alleviate the inflammatory response through the JAK2/STAT3 signaling pathway,thus inhibiting lipid accumulation and improving non-alcoholic fatty liver disease.

Objective To investigate the risk factor for adverse events(AEs)after non-sedated esophagogastroduodenoscopy(EGD).Methods The data on clinical manifestations,adverse events after non-sedated EGD and common risk factors were collected and retrospectively analyzed with statistical methods in patients who underwent non-sedated EGD from May 2018 to June 2019.These patients were divided into AEs group and non-AEs group.Results Of 2 384 patients,57.67%(1 375/2 384)presented with nausea,12.79%(305/2 384)vomiting,and 5.79%(138/2 384)presented with pharyngalgia.Multivariate Logistic regression analysis was performed.Advanced age(≥65 years old)(OR=0.683,95%CI:0.506-0.921)was protective factors for nausea after non-sedated EGD.Hypertension(OR=1.361,95%CI:1.026-1.806),overweight(OR=1.399,95%CI:1.154-1.695),obesity(OR=2.594,95%CI:1.760-3.823)and inspection duration>15 min(OR=3.107,95%CI:2.296-4.206)were independent risk factors for nausea after non-sedated EGD.Advanced age(OR=0.393,95%CI:0.221-0.699)and imported equipment(OR=0.697,95%CI:0.546-0.890)were protective factors for vomiting after non-sedated EGD.Moreover,inspection duration>15 min(OR=1.641,95%CI:1.008-2.699)was independent risk factors for vomiting after non-sedated EGD.There was no difference in success rate of non-sedated EGD between two groups(P<0.05).Conclusion Hypertension,overweight and obesity were independent risk factors for nausea after non-sedated EGD.The advanced age and imported equipment were protective factors for vomiting after non-sedated EGD.In addition,inspection duration over 15 min is a risk factor for AEs such as nausea and vomiting after nonsedative EGD.Whether AEs occurred or not is non-related to success rate of non-sedated EGD.