1.Rhodiolae Crenulatae Radix et Rhizoma protects brain microvascular endothelial cells from ischemia and hypoxia injury by regulating PI3K/AKT/GSK3β pathway.
Li TANG ; Qiu-Yue YANG ; Hong-Fa CHENG ; Ya-Hui XIE ; Qiu-Xia ZHANG
China Journal of Chinese Materia Medica 2025;50(11):3127-3136
This study elucidates the mechanism of Rhodiolae Crenulatae Radix et Rhizoma(RCRR) in protecting brain microvascular endothelial cells from oxygen-glucose deprivation(OGD) injury and reveals the modern pharmacological mechanism of RCRR's traditional use in nourishing Qi and promoting blood circulation to protect endothelial cells. The scratch assay was employed to assess the migratory capacity of endothelial cells. Immunofluorescence and Western blot techniques were employed to assess the protein expression of tight junction proteins zonula occludens-1(ZO-1), occludin, claudin-5, and proteins of the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase-3beta(GSK3β) pathway. The results demonstrated that 63 bioactive components and 125 potential core targets of RCRR were identified from the ETCM, TCMBank, and SwissTargetPrediction databases, as well as from the literature. A total of 1 708 brain microvascular endothelial cell-related targets were identified from the GeneCards and OMIM databases, and 52 targets were obtained by intersecting drug components with cell targets. The protein-protein interaction(PPI) network analysis revealed that AKT1, epidermal growth factor receptor(EGFR), matrix metalloproteinase 9(MMP9), estrogen receptor 1(ESR1), proto-oncogene tyrosine-protein kinase(SRC), peroxisome proliferator-activated receptor gamma(PPARG), GSK3β, and matrix metalloproteinase 2(MMP2) were considered hub genes. The KEGG enrichment analysis identified the PI3K/AKT pathway as the primary signaling pathway. Cell experiments demonstrated that RCRR-containing serum could enhance the migratory capacity of brain microvascular endothelial cells and the expression of tight junction proteins following OGD injury, which may be associated with the downregulation of the PI3K/AKT/GSK3β pathway. This study elucidates the pharmacological mechanism of RCRR in protecting brain microvascular endothelial cells through network pharmacology, characterized by multiple components and targets. These findings were validated through in vitro experiments and provide important ideas and references for further research into the molecular mechanisms of RCRR in protecting brain microvascular endothelial cells.
Endothelial Cells/cytology*
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Glycogen Synthase Kinase 3 beta/genetics*
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Proto-Oncogene Proteins c-akt/genetics*
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Drugs, Chinese Herbal/pharmacology*
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Phosphatidylinositol 3-Kinases/genetics*
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Signal Transduction/drug effects*
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Brain/metabolism*
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Humans
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Animals
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Rhizome/chemistry*
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Microvessels/metabolism*
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Brain Ischemia/drug therapy*
2.Mechanism of antidepressant action of kaji-ichigoside F1 based on metabolomics.
Mao-Yang HUANG ; Fa-Ju CHEN ; Lang ZHOU ; Qi-Ji LI ; Xiao-Sheng YANG
China Journal of Chinese Materia Medica 2025;50(16):4574-4583
In this study, serum metabolomics techniques and molecular biology methods were used to investigate the intervention effect of kaji-ichigoside F1 on chronic unpredictable mild stress(CUMS) depression mouse model and its mechanism. The CUMS depression mouse model was constructed, and the mice were divided into blank group, model group, escitalopram(ESC, 10 mg·kg~(-1)) group, and low-dose, medium-dose, and high-dose kaji-ichigoside F1 groups(1, 2, and 4 mg·kg~(-1)). CUMS modeling was performed on all mice except the blank group, and the cycle was four weeks. At the end of modelling, ESC and kaji-ichigoside F1 were administered by gavage once a day for 28 days. After the end of the administration, behavioral testing(sucrose preference test, open field test, forced swimming test, and tail suspension test) was conducted to evaluate the improvement of depression symptoms of different doses of kaji-ichigoside F1 on CUMS depression mouse model. The morphology of neurons and the number of Nissl bodies in the hippocampus were observed by Nissl staining. Metabolomics technique was used to analyze the changes in serum differential metabolites in mice. Protein expression levels of P2X7 purinergic receptor(P2X7R), adenosine A1 receptor(A1R), and adenosine receptor A2A(A2AR) in mouse hippocampus were detected by Western blot. The results showed that compared with that in the blank group, the body weight of mice in the model group was significantly decreased, and the sucrose preference rate was significantly decreased. The immobility time was significantly increased in the forced swimming and tail suspension tests, and the total moving distance was significantly decreased in the open field test. The number of Nissl bodies was significantly decreased, and the depression-like behavior and the number of Nissl bodies in the hippocampus of mice were significantly improved after administration of kaji-ichigoside F1. In the metabonomics analysis, the purine metabolism of serum after kaji-ichigoside F1 administration was involved in the metabolic passage of depression, and Western blot analysis verified the expression of P2X7R, A1R, and A2AR proteins in purine metabolic pathways. The results show that kaji-ichigoside F1 significantly decreases the expression of P2X7R and A2AR proteins in the hippocampus of CUMS model mice and increases the expression level of A1R proteins. It is suggested that kaji-ichigoside F1 may play an antidepressant role by regulating the expression of P2X7R, A1R, and A2AR proteins in the purine metabolism pathway.
Animals
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Mice
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Antidepressive Agents/administration & dosage*
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Metabolomics
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Depression/genetics*
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Male
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Drugs, Chinese Herbal/administration & dosage*
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Disease Models, Animal
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Hippocampus/metabolism*
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Behavior, Animal/drug effects*
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Humans
3.AI-Ready Competency Framework for Biomedical Scientific Data Literacy.
Zhe WANG ; Zhi-Gang WANG ; Wen-Ya ZHAO ; Wei ZHOU ; Sheng-Fa ZHANG ; Xiao-Lin YANG
Chinese Medical Sciences Journal 2025;40(3):203-210
With the rise of data-intensive research, data literacy has become a critical capability for improving scientific data quality and achieving artificial intelligence (AI) readiness. In the biomedical domain, data are characterized by high complexity and privacy sensitivity, calling for robust and systematic data management skills. This paper reviews current trends in scientific data governance and the evolving policy landscape, highlighting persistent challenges such as inconsistent standards, semantic misalignment, and limited awareness of compliance. These issues are largely rooted in the lack of structured training and practical support for researchers. In response, this study builds on existing data literacy frameworks and integrates the specific demands of biomedical research to propose a comprehensive, lifecycle-oriented data literacy competency model with an emphasis on ethics and regulatory awareness. Furthermore, it outlines a tiered training strategy tailored to different research stages-undergraduate, graduate, and professional, offering theoretical foundations and practical pathways for universities and research institutions to advance data literacy education.
Artificial Intelligence
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Humans
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Biomedical Research
4.Surgical approaches to varicocele: a systematic review and network meta-analysis.
Lin-Jie LU ; Kai XIONG ; Sheng-Lan YUAN ; Bang-Wei CHE ; Jian-Cheng ZHAI ; Chuan-Chuan WU ; Yang ZHANG ; Hong-Yan ZHANG ; Kai-Fa TANG
Asian Journal of Andrology 2025;27(6):728-737
Surgical methods for varicocele remain controversial. This study intends to evaluate the efficacy and safety of different surgical approaches for treating varicocele through a network meta-analysis (NMA). PubMed, Embase, Cochrane, and Web of Science databases were thoroughly searched. In total, 13 randomized controlled trials (RCTs) and 24 cohort studies were included, covering 9 different surgical methods. Pairwise meta-analysis and NMA were performed by means of random-effects models, and interventions were ranked based on the surface under the cumulative ranking curve (SUCRA). According to the SUCRA, microsurgical subinguinal varicocelectomy (MSV; 91.6%), microsurgical retroperitoneal varicocelectomy (MRV; 78.2%), and microsurgical inguinal varicocelectomy (MIV; 76.7%) demonstrated the highest effectiveness in reducing postoperative recurrence rates. In this study, sclerotherapy embolization (SE; 87.2%), MSV (77.9%), and MIV (67.7%) showed the best results in lowering the risk of hydrocele occurrence. MIV (82.9%), MSV (75.9%), and coil embolization (CE; 58.7%) were notably effective in increasing sperm motility. Moreover, CE (76.7%), subinguinal approach varicocelectomy (SV; 69.2%), and SE (55.7%) were the most effective in increasing sperm count. SE (82.5%), transabdominal laparoscopic varicocelectomy (TLV; 76.5%), and MRV (52.7%) were superior in shortening the length of hospital stay. The incidence rates of adverse events for MRV (0), SE (3.3%), and MIV (4.1%) were notably low. Cluster analyses indicated that MSV was the most effective in the treatment of varicocele. Based on the existing evidence, MSV may represent the optimal choice for varicocele surgery. However, selecting clinical surgical strategies requires consideration of various factors, including patient needs, surgeon experience, and the learning curve.
Humans
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Male
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Embolization, Therapeutic/methods*
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Microsurgery/methods*
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Randomized Controlled Trials as Topic
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Sclerotherapy/methods*
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Treatment Outcome
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Urologic Surgical Procedures, Male/methods*
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Varicocele/surgery*
5.Shexiang Tongxin Dropping Pill Improves Stable Angina Patients with Phlegm-Heat and Blood-Stasis Syndrome: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.
Ying-Qiang ZHAO ; Yong-Fa XING ; Ke-Yong ZOU ; Wei-Dong JIANG ; Ting-Hai DU ; Bo CHEN ; Bao-Ping YANG ; Bai-Ming QU ; Li-Yue WANG ; Gui-Hong GONG ; Yan-Ling SUN ; Li-Qi WANG ; Gao-Feng ZHOU ; Yu-Gang DONG ; Min CHEN ; Xue-Juan ZHANG ; Tian-Lun YANG ; Min-Zhou ZHANG ; Ming-Jun ZHAO ; Yue DENG ; Chang-Jiang XIAO ; Lin WANG ; Bao-He WANG
Chinese journal of integrative medicine 2025;31(8):685-693
OBJECTIVE:
To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents.
METHODS:
This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs).
RESULTS:
This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed.
CONCLUSION
STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans
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Double-Blind Method
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Drugs, Chinese Herbal/adverse effects*
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Male
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Female
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Middle Aged
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Angina, Stable/physiopathology*
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Aged
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Syndrome
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Treatment Outcome
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Placebos
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Tablets
6.Nonsurgical Treatment of Chronic Subdural Hematoma Patients with Chinese Medicine: Case Report Series.
Kang-Ning LI ; Wei-Ming LIU ; Ying-Zhi HOU ; Run-Fa TIAN ; Shuo ZHANG ; Liang WU ; Long XU ; Jia-Ji QIU ; Yan-Ping TONG ; Tao YANG ; Yong-Ping FAN
Chinese journal of integrative medicine 2025;31(10):937-941
7.Influencing factors and the Nomogram model to predict early hematoma expansion of intracranial hemorrhage
Fa WU ; Yu-Lin YANG ; Ting-Ting WU ; Rui JIANG ; Jie WU ; Peng WANG ; Fei-Zhou DU ; Hong-Mei YU ; Jian-Hao LI
Medical Journal of Chinese People's Liberation Army 2024;49(5):504-510
Objective To investigate factors influencing the occurrence of early haematoma expansion(HE)in patients with spontaneous intracerebral hemorrhage(sICH),to develop a predictive model and evaluate its predictive efficacy.Methods A retrospective cohort of 238 patients with sICH,admitted to General Hospital of Western Theater Command between January 2017 and December 2022,was analyzed.Patients were categorized into two groups based on the criteria of HE exceeding 33%in relative volume or 6 ml in absolute volume:HE group(n=62)and non-haematoma expansion(NHE)group(n=176).Clinical characteristics,laboratory findings,Non-contrast Computed Tomography(NCCT)imaging,and Glasgow Coma Scale(GCS)scores were compared between the two groups.Multifactorial logistic regression analysis was employed to identify risk factors for HE and to model the probability of its occurrence.The R language rms package was utilized to construct a nomogram model for predicting HE in sICH patients,Additionally,the related clinical,NCCT,and GCS models were constructed.The predictive efficacy of each model for HE in sICH patients was evaluated using area under Receive Operative Characteristic(ROC)curve(AUC),and the clinical application value of each model was assessed using accuracy,sensitivity,specificity,and Jordon's index.The Delong test was applied to analyze differences in the predictive values of the models.Results Significant differences in satellite sign,vortex sign,and history of anticoagulant treatment were observed between two groups(P<0.05).Multifactorial logistic regression analysis revealed independent risk factors for HE in sICH patients,including the first CT examination time,homogeneity,history of anticoagulant medication,volume,maximal diameter,hypodensity sign,island sign,satellite sign,and vortex sign(P<0.05).The AUCs for the constructed clinical model,NCCT model,GCS model and nomogram model in predicting the occurrence of HE in sICH patients were 0.672,0.706,0.518 and 0.754,respectively.The nomogram model demonstrated higher accuracy,sensitivity,Jordon's index and AUC compared with those in the clinical and NCTT models.Conclusions The first CT examination time,homogeneity,history of anticoagulant treatment,volume,maximum diameter,hypodensity sign,island sign,satellite sign,and vortex sign are independent predictors of early HE in sICH patients.The nomogram model,constructed with the above parameters,demonstrated high predictive efficacy for HE and holds potential for clinical application.
8.Tamoxifen inducing differentiation of oligodendrocyte lineage cells in the central nervous system
Ting XU ; Hai-Yan LÜ ; Qing-Ting YU ; Zui-Su YANG ; Fa-Lei YUAN
Acta Anatomica Sinica 2024;55(6):685-692
Objective To investigate the differentiation of oligodendrocyte precursor cells after neural injury utilizing Sox10 cell lineage tracing in the cortical tissue.Methods C57BL/6 mice and Sox10-CreERT2/red fluorescent protein(RFP)model mice were used in the current study.The Sox10-CreERT2/RFP model mice generated by crossing Sox10-CreERT2 and Ai9 were 8-week-old F1 mice(n=16),which were randomly divided into control group(n=4)and 7 days(n=4),14 days(n=4),and 30 days feed groups(n=4).Tamoxifen(TAM)was used to induce the expression of RFP.The control group received tamoxifen dissolved in sunflower seed oil by gavage(40 mg/kg once daily for three consecutive days)and the brain tissues were obtained after 4 days.The feed group mice were fed with tamoxifen-containing feed to induce RFP expression,and the brain tissues were obtained after 7,14,and 30 days,respectively.Immunofluorescent staining was performed to detect the expressions of neuronal nuclei(NeuN),microtubule-associated protein 2(MAP2),phosphorylated histone 2AX(γ-H2AX),cluster of differentiation 13(CD 13),γ-aminobutyric acid(GABA),glial fibrillary acidic protein(GFAP),cluster of differentiation 11b(CD11b),vesicular glutamate transporter 2(VGLUT2),and adenomatous polyposis coli(APC,CC-1)in the brains of each group mice.The number of positive cells was counted,and the proportion was calculated.Eight-week-old male C57BL/6 mice were randomly divided into wild type(WT)group(n=4)and WT+TAM group(n=4).They were fed with regular feed and tamoxifen-containing feed for 30 days,respectively,and then brain tissues were obtained.Immunofluorescent double-labeling was used to detect the expressions of γ-H2AX positive neurons in the cortex of mice in both groups.Results In the control group,feed 7 days,14 days,and 30 days groups,the proportions of RFP+pericytes among all RFP+cells in the cortical tissue were(0.8±0.1)%,(2.7±0.1)%,(3.2±0.1)%,(4.0±0.1)%,respectively,and the proportion of mature oligodendrocytes(CC-1+RFP+)in the feed 7 days group was(51.2±0.7)%.The proportions of RFP-positive neurons in the cortex after 14 and 30 days of tamoxifen feed were(0.7±0.1)%and(1.5±0.1)%,respectively,while no conversion to RFP-positive neurons was observed in the gavage group and 7 days feed group.RFP cells in the cortex of the 7 days or 30 days feed group did not express GFAP or CD11b.Extensive γ-H2AX+NeuN+staining was observed in the WT group and WT+TAM group.Conclusion Long-term administration of tamoxifen can promote the differentiation of Sox10 cells into pericytes and neurons.Further investigation into the role of OPC in the neurovascular unit repair mechanism may contribute to a better understanding of the pathogenesis underlying AD.
9.Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics
Yu-long CHEN ; You ZHAI ; Xiao-yan WANG ; Wei-xia LI ; Hui ZHANG ; Ya-li WU ; Liu-qing YANG ; Xiao-fei CHEN ; Shu-qi ZHANG ; Lu NIU ; Ke-ran FENG ; Kun LI ; Jin-fa TANG ; Ming-liang ZHANG
Acta Pharmaceutica Sinica 2024;59(2):382-394
Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and

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