1.Metabolomics as an emerging tool for the pharmacological and toxicological studies on Aconitum alkaloids.
Han DING ; Yamin LIU ; Sifan WANG ; Yuqi MEI ; Linnan LI ; Aizhen XIONG ; Zhengtao WANG ; Li YANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(2):182-190
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*
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Metabolomics/methods*
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Alkaloids/metabolism*
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Humans
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Animals
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Drugs, Chinese Herbal/pharmacology*
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Medicine, Chinese Traditional
2.A high-throughput plant canopy leaf area index inversion model based on UAV-LiDAR.
Yuming LIANG ; Xueyan FAN ; Muqing ZHANG ; Wei YAO ; Xiuhua LI ; Zeping WANG ; Sifan DONG ; Xuechen LI
Chinese Journal of Biotechnology 2025;41(10):3817-3827
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 Sp and the total row point count Ctotal 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 Sp, average height Havg, mid-layer point cloud density Cm, and total row point count Ctotal as input variables, achieved the best performance, with a coefficient of determination (Rv²) of 0.713 and a root mean square error (RMSEv) 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*
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Saccharum/growth & development*
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Algorithms
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Unmanned Aerial Devices
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Remote Sensing Technology/methods*
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Crops, Agricultural/growth & development*
3.COPB1 promotes the development and progression of esophageal squamous cell carcinoma by activating the PI3K/AKT pathway and regulating the tumor immune microenvironment
LIN Yan ; YU Shuangjian ; JIA Sifan ; LI Feiyu ; ZHAO Chenpu ; DONG Zhiming ; SHEN Supeng ; LIANG Jia ; GUO Yanli
Chinese Journal of Cancer Biotherapy 2025;32(12):1236-1246
[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。
4.Risk factor research and risk prediction model establishment for early Q-T interval prolongation after acute myocardial infarction
Sifan LI ; Ying XIAO ; Dongbo WANG ; Sining LIU ; Yadong TANG ; Xuefeng TIAN
Chinese Journal of Primary Medicine and Pharmacy 2024;31(2):175-179
Objective:To establish a prediction model of risk factors for early Q-T interval prolongation after acute myocardial infarction (AMI), which helps prevent and reduce the occurrence of acute malignant events.Methods:This is a case-control study. A total of 100 patients with Q-T interval prolongation after AMI who received treatment at Heilongjiang Provincial Hospital from January 2018 to December 2022 were included in this study. An additional 100 patients without Q-T interval prolongation after AMI who concurrently received treatment in the same hospital were also included in this study. Two model groups, including model group 1 (with Q-T interval prolongation, n = 50) and model group 2 (without Q-T interval prolongation, n = 50), and two test groups, including test group 1 (with Q-T interval prolongation, n = 50) and test group 2 (without Q-T interval prolongation, n = 50), were designated. Logistic regression analysis was performed to construct a prediction model of risk factors for Q-T interval prolongation. The area under the receiver operating characteristic curve was determined to evaluate the prediction model. The value of the prediction model was validated in the test groups. Results:Multivariate logistic regression showed that female gender ( OR = 2.307, 95% CI: 0.09-0.91, P = 0.041) and heart failure ( OR = 3.087, 95% CI: 1.15-8.27, P = 0.025) were independent risk factors for early Q-T interval prolongation after AMI. The area under the receiver operating characteristic curve of the prediction model was 0.770, with a sensitivity of 84.0%, a specificity of 66.0%, the Jordan index of 0.44, and the corresponding optimal critical value of 0.43. This indicates good fit of the model. Conclusion:Female gender and heart failure are independent risk factors for early Q-T interval prolongation after AMI. The model constructed based on the above-mentioned risk factors fits well and has a high predictive value, which helps reduce the occurrence of early Q-T interval prolongation after AMI.
5.Entropy、Dissipative Structure And Health
Sifan DUAN ; Mengmei LIU ; Yani LI ; Dingyun YOU
Journal of Kunming Medical University 2024;45(3):1-6
Dissipative structure refers to a self-organized and orderly structure that exists far from equilibrium.The human body,considered a classical example,generates negative entropy through the exchange of matter,energy,and information with the environment to counteract the increase in entropy.In this paper,we organized theories and related research on dissipative structure and entropy,discussing their significance in regulating various aspects such as the human body,cancer,aging,and more.By selecting the special population of pregnant women,focusing on the information dimension,developing the corresponding information exchange scale(Cronbach's α>0.9),and proposing the information exchange index,we preliminarily explored the influence of the dissipative structure's information dimension on pregnancy health.The results showed a negative correlation between the information exchange index and anxiety scores during pregnancy(r =-0.35,P<0.001),with an OR value of 0.26(95%CI:0.08~0.80),preliminarily confirming the feasibility of conducting empirical research based on dissipative structure theory.If further relevant empirical studies are conducted,it is expected that new disease prevention strategies will be developed and new theories and methods will be provided for the field of public health.
6.Efficacy and safety of chimeric antigen receptor T-cell therapy followed by allogeneic hematopoietic stem cell transplantation in 21 patients with Ph-like acute lymphoblastic leukemia
Haiping DAI ; Hongjie SHEN ; Zheng LI ; Wei CUI ; Qingya CUI ; Mengyun LI ; Sifan CHEN ; Mingqing ZHU ; Depei WU ; Xiaowen TANG
Chinese Journal of Hematology 2024;45(1):35-40
Objective:To evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Ph-like acute lymphoblastic leukemia (Ph-ALL) .Methods:Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included, and their clinical data were retrospectively analyzed.Results:Of the 21 patients, 14 were male and 7 were female. The median age at the time of CAR-T therapy was 22 (6-50) years. Seven patients had ABL1-like rearrangements, and 14 had JAK-STAT rearrangements. Prior to CAR-T therapy, 12 patients experienced hematologic relapse; 7 were multiparameter flow cytometry minimal residual disease (MFC-MRD) -positive and 2 were MFC-MRD-negative. CAR-T cells were derived from patients’ autologous lymphocytes. Nine patients were treated with CD19 CAR-T cells, and 12 were treated with CD19/CD22 CAR-T cells. After assessment on day 28 after CAR-T therapy, 95.2% of the patients achieved complete remission, with an MRD-negative remission rate of 75%. Nineteen patients developed grade 0–2 cytokine release syndrome (CRS) and 2 patients suffered grade 3 CRS, all cases of which resolved after treatment. All patients underwent allo-HSCT after CAR-T therapy. The median time from CAR-T therapy to allo-HSCT was 63 (38-114) days. Five patients experienced relapse after CAR-T therapy, including four with hematologic relapse and one with molecular relapse. The 3-year overall survival (OS) rates in the ABL1 and JAK-STAT groups were (83.3±15.2) % and (66.6±17.2) %, respectively ( P=0.68) . The 3-year relapse-free survival (RFS) rates were (50.0±20.4) % and (55.6±15.4) % in the ABL1 and JAK-STAT groups, respectively. There was no significant difference in 3-year OS or RFS between the two groups. Conclusions:CAR-T therapy followed by allo-HSCT leads to rapid remission in most patients with Ph-ALL and prolongs leukemia-free survival.
7.Visual analysis of research trends and hotspots in Abelmoschus manihot using CiteSpace software
Sifan SUN ; Jinlong AN ; Wei SUN ; Ping LI ; Yanting GU
Journal of Clinical Medicine in Practice 2024;28(18):21-26
Objective To analyze the research literature on Abelmoschus manihot utilizing the CiteSpace visualization software and summarize the current research hotspots and trends in this field. Methods Relevant literature relating Abelmoschus manihot was retrieved from the China National Knowledge Infrastructure (CNKI) database. The CiteSpace 5.7.R5 software was employed to conduct a visual analysis of researchers, research institutions, and key words in the selected literature that met the inclusion criteria. Results A total of 319 relevant articles were retrieved, of which 284 articles were ultimately included for analysis. The earliest research on Abelmoschus manihot could be traced back to 1979. Core authors included LIU Zhihui, TAN Xianhe, ZHU Huayun, etc. Institutions with a higher volume of publications included Nanjing University of Chinese Medicine, the Affiliated Hospital of Nanjing University of Chinese Medicine, Anhui Medical University, Jiangsu Suzhong Pharmaceutical Group, and Jiangsu Provincial Hospital of Traditional Chinese Medicine. Research hotspots encompassed active ingredients, empirical prescriptions, oxidative stress, gut microbiota, Crohn's disease, calcium overload, component identification, and preparation processes. Conclusion The visual analysis of Abelmoschus manihot research presented in the form of knowledge maps reveals that current research spans multiple disciplines. However, collaboration among research institutions needs to be strengthened.
8. Mechanisms of Radix Tetrastigma on anti rheumatoid arthritis via regulating the balance of Th17/Treg
Tiefeng WANG ; Wenrui ZHU ; Jie SU ; Rongshuang XIA ; Sifan LI ; Zhaohuan LOU ; Weidong WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(2):138-146
AIM: To explore the possible mechanism of Radix Tetrastigma (RT) on anti-rheumatoid arthritis (RA). METHODS: The rat model of RA was established by intradermal injection of complete Freund]s adjuvant into the right hind foot of SD rats. RT Extract with different dosage was continuous intragastric administration for 3 weeks, then, the degree of foot swelling, arthritis index score, joint heat and grip of each rat was measured respectively. ELISA was used to detect the expression levels of Interleukin (IL) 6, IL-17, IL-10, tumor necrosis factor-α, and rheumatoid factor. Fully automatic hemorheometer was applied to measure hemorheology indexes. The number of CD4
9.Application of copy number variation sequencing in patients with intellectual disability/developmental delay and autistic spectrum disorder.
Jie LEI ; Gang ZHAO ; Yanke HUANG ; Min LONG ; Wei LI ; Xi DENG ; Zihan XIU ; Yanwei XIAO ; Sifan ZENG ; Jing ZHANG
Chinese Journal of Medical Genetics 2023;40(3):308-316
OBJECTIVE:
To assess the value of copy number variation sequencing (CNV-seq) for the diagnosis of children with intellectual disability (ID), developmental delay (DD), and autistic spectrum disorder (ASD).
METHODS:
Forty patients with ID/DD/ASD referred to Nanshan Maternity and Child Health Care Hospital from September 2018 to January 2022 were enrolled. G-banded karyotyping analysis was carried out for the patients. Genomic DNA was extracted from peripheral blood samples and subjected to CNV-Seq analysis to detect chromosome copy number variations (CNVs) in such patients. ClinVar, DECIPHER, OMIM and other database were searched for data annotation.
RESULTS:
Among the 40 patients (including 30 males and 10 females), 16, 15 and 6 were diagnosed with ID, DD and ASD, respectively. One patient had combined symptoms of ID and DD, whilst the remaining two had combined ID and ASD. Four patients were found with abnormal karyotypes, including 47,XY,+mar, 46,XY,inv(8)(p11.2q21.2), 46,XX,del(5)(p14) and 46,XX[76]/46,X,dup(X)(p21.1q12). Chromosome polymorphism was also found in two other patients. CNV-seq analysis has detected 32 CNVs in 20 patients (50.0%, 20/40). Pathogenic CNVs were found in 10 patients (25.0%), 15 CNVs of uncertain clinical significance were found in 12 patients (30.0%), and 7 likely benign CNVs were found in 4 patients (10.0%).
CONCLUSION
Chromosome CNVs play an important role in the pathogenesis of ID/DD/ASD. CNV-seq can detect chromosomal abnormalities including microdeletions and microduplications, which could provide a powerful tool for revealing the genetic etiology of ID/DD/ASD patients.
Pregnancy
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Child
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Male
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Humans
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Female
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DNA Copy Number Variations
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Intellectual Disability/genetics*
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Autism Spectrum Disorder/genetics*
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Developmental Disabilities/genetics*
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Abnormal Karyotype
10.Drug discovery of sclerostin inhibitors.
Sifan YU ; Dijie LI ; Ning ZHANG ; Shuaijian NI ; Meiheng SUN ; Luyao WANG ; Huan XIAO ; Dingdong LIU ; Jin LIU ; Yuanyuan YU ; Zongkang ZHANG ; Samuel Tin Yui YEUNG ; Shu ZHANG ; Aiping LU ; Zhenlin ZHANG ; Baoting ZHANG ; Ge ZHANG
Acta Pharmaceutica Sinica B 2022;12(5):2150-2170
Sclerostin, a protein secreted from osteocytes, negatively regulates the WNT signaling pathway by binding to the LRP5/6 co-receptors and further inhibits bone formation and promotes bone resorption. Sclerostin contributes to musculoskeletal system-related diseases, making it a promising therapeutic target for the treatment of WNT-related bone diseases. Additionally, emerging evidence indicates that sclerostin contributes to the development of cancers, obesity, and diabetes, suggesting that it may be a promising therapeutic target for these diseases. Notably, cardiovascular diseases are related to the protective role of sclerostin. In this review, we summarize three distinct types of inhibitors targeting sclerostin, monoclonal antibodies, aptamers, and small-molecule inhibitors, from which monoclonal antibodies have been developed. As the first-in-class sclerostin inhibitor approved by the U.S. FDA, the monoclonal antibody romosozumab has demonstrated excellent effectiveness in the treatment of postmenopausal osteoporosis; however, it conferred high cardiovascular risk in clinical trials. Furthermore, romosozumab could only be administered by injection, which may cause compliance issues for patients who prefer oral therapy. Considering these above safety and compliance concerns, we therefore present relevant discussion and offer perspectives on the development of next-generation sclerostin inhibitors by following several ways, such as concomitant medication, artificial intelligence-based strategy, druggable modification, and bispecific inhibitors strategy.


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