1.Regulation of Oxidative Stress by Traditional Chinese Medicine in Prevention and Treatment of Myocardial Ischemia-reperfusion Injury: A Review
Haosen ZHAO ; Weijie REN ; Jiahao LI ; Peili WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):268-276
Myocardial ischemia-reperfusion injury (MIRI) is a major complication following coronary revascularization. Studies indicate that its pathophysiological mechanisms of MIRI are closely associated with oxidative stress, iron overload, inflammatory responses, and lipid peroxidation. Oxidative stress refers to an imbalance in redox homeostasis under pathological conditions, characterized by the abnormal accumulation of reactive oxygen species (ROS), which disrupts the dynamic balance between pro-oxidant systems and antioxidant defense networks. In recent years, traditional Chinese medicine (TCM) has demonstrated unique advantages in the prevention and treatment of MIRI due to its multi-target and multi-pathway antioxidant properties. Research reveals that TCM primarily exerts protective effects against oxidative stress-induced MIRI by regulating signaling pathways such as nuclear factor erythroid 2-related factor 2 (Nrf2), adenosine monophosphate-activated protein kinase (AMPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), nuclear factor kappa-B (NF-κB), Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3), and protein kinase C beta Ⅱ/nicotinamide adenine dinucleotide phosphate oxidase 2/reactive oxygen species (PKCβⅡ/NOX2/ROS). This article reviews recent literature on TCM monomers, compound formulas, and their active components, which alleviate oxidative stress to prevent and treat MIRI by modulating the aforementioned signaling pathways. It summarizes a concise overview of the molecular mechanisms by which oxidative stress-related signaling pathways lead to MIRI, discusses how TCM regulates these pathways to reduce oxidative stress-induced MIRI, and explores clinical application prospects and research challenges, aiming to provide a theoretical reference for the research and clinical management of MIRI.
2.Effect of Osteoking on Inflammatory Injury and NF-κB/NFATc1 Signaling Pathway in Model Mice with Postmenopausal Osteoporosis
Tiantian YU ; Ruibing FENG ; Qing WANG ; Chaowen LI ; Jiahao CHEN ; Ruixuan JIANG ; Yinshuai DING ; Yong HUANG ; Hao HU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):62-69
ObjectiveTo explore the possible mechanism of Osteoking (OK) on postmenopausal osteoporosis (PMOP). MethodForty adult female mice were randomly divided into a sham operation (Sham) group, osteoporosis model (OVX) group, estradiol intervention (E2) group, and OK group, with 10 mice in each group. The modeling was completed by conventional back double incision ovariectomy, and the corresponding drugs were given one week later. After 12 weeks, the body mass and uterine index of mice were measured, and the pathological changes of bone tissue and the number of osteoclasts (OCs) were determined by hematoxylin-eosin (HE) and tartrate-resistant acid phosphatase (TRAP) staining, respectively. Bone mineral density (BMD), trabecular number (Tb.N), trabecular separation (Tb.Sp), and bone volume fraction (BV/TV) were measured by microcomputed tomography (Micro-CT). The maximum load of the femur was detected by a three-point bending test. The contents of tumor necrosis factor-α (TNF-α) and bone resorption marker C-terminal telopeptide of type Ⅰ collagen (CTX-1) were measured by enzyme linked immunosorbent assay (ELISA). The protein expression levels of nuclear factor-kappa B p65 (NF-κB p65), phosphorylated nuclear factor-kappa B p65 (p-NF-κB p65), nuclear factor kappa B inhibitor alpha (IκBα), phosphorylated nuclear factor kappa B alpha (p-IκBα), nuclear factor of activated T cells 1 (NFATc1), and proto-oncogene (c-Fos) were detected by Western blot. The mRNA expressions of OCs-related specific genes matrix metalloproteinase-9 (MMP-9), NFATc1, TRAP, cathepsin K (CTSK), and c-Fos were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultCompared with the Sham group, the uterine index decreased significantly in the OVX group, and the body mass (BMI) increased significantly. The structure of bone trabeculae was completely damaged, and the number of OCs increased. BMD, Tb.N, BV/TV, and maximum load decreased, while Tb.Sp was up-regulated. The levels of TNF-α and CTX-1 in serum were up-regulated. The protein expressions of c-Fos, p-NF-κB p65/NF-κB p65, NFATc1, and p-IκBα/IκBα were increased. The mRNA expressions of NFATc1, c-Fos, CTSK, TRAP, and MMP-9 were up-regulated (P<0.05, P<0.01). Compared with the OVX group, the body mass of the OK and E2 groups decreased, and the uterine index increased. The bone trabeculae increased, and the number of OCs decreased. BMD, Tb.N, BV/TV, and maximum load increased, while Tb.Sp decreased. The levels of TNF-α and CTX-1 in serum were decreased. The protein expressions of c-Fos, p-NF-κB p65/NF-κB p65, NFATc1, and p-IκBα/IκBα were decreased, and the mRNA expressions of NFATc1, c-Fos, CTSK, TRAP, and MMP-9 were decreased (P<0.05, P<0.01). ConclusionOK can inhibit the NF-κB/NFATc1 signaling pathway and reduce bone mass loss by reducing the level of inflammatory injury factors in PMOP mice, which is one of the mechanisms for treating PMOP.
3.Establishment of risk prediction model for postoperative liver injury after non-liver surgery based on different machine learning algorithms
Yizhu SUN ; Yujie LI ; Hao LIANG ; Xiang LIU ; Jiahao HUANG ; Xin SHU ; Ailin SONG ; Zhiyong YANG ; Bin YI
Journal of Army Medical University 2024;46(7):760-767
Objective To construct a machine learning prediction model for postoperative liver injury in patients with non-liver surgery based on preoperative and intraoperative medication indicators.Methods A case-control study was conducted on 315 patients with liver injury after non-liver surgery selected from the databases developed by 3 large general hospitals from January 2014 to September 2022.With the positive/negative ratio of 1 ∶3,928 cases in corresponding period with non-liver surgery and without liver injury were randomly matched as negative control cases.These 1243 patients were randomly divided into the modeling group(n=869)and the validation group(n=374)in a ratio of 7∶3 using the R language setting code.Preoperative clinical indicators(basic information,medical history,relevant scale score,surgical information and results of laboratory tests)and intraoperative medication were used to construct the prediction model for liver injury after non-liver surgery based on 4 machine learning algorithms,k-nearest neighbor(KNN),support vector machine linear(SVM),logic regression(LR)and extreme gradient boosting(XGBoost).In the validation group,receiver operating characteristic(ROC)curve,precision-recall curve(P-R),decision curve analysis(DCA)curve,Kappa value,sensitivity,specificity,Brier score,and F1 score were applied to evaluate the efficacy of model.Results The model established by 4 machine learning algorithms to predict postoperative liver injury after non-liver surgery was optimal using the XGBoost algorithm.The area under the receiver operating characteristic curve(AUROC)was 0.916(95%CI:0.883~0.949),area under the precision-recall curve(AUPRC)was 0.841,Brier score was 0.097,and sensitivity and specificity was 78.95%and 87.10%,respectively.Conclusion The postoperative liver injury prediction model for non-liver surgery based on the XGBoost algorithm has effective prediction for the occurrence of postoperative liver injury.
4.Predictors of a forgotten joint after medial open wedge high tibial osteotomy
Yiwei HUANG ; Bo PENG ; Chen ZHANG ; Hao GE ; Jiahao LI ; Yijin LI ; Jinlun CHEN ; Wenjun FENG ; Yirong ZENG
Chinese Journal of Tissue Engineering Research 2024;28(24):3903-3909
BACKGROUND:Medial open wedge high tibial osteotomy is an effective procedure for preserving the knee joint in patients with medial compartmental osteoarthritis.Previous studies have demonstrated that the forgotten joint score provides a lower ceiling effect and consistency of medial open wedge high tibial osteotomy outcomes compared to traditional assessment tools. OBJECTIVE:To identify predictive factors associated with the occurrence of a forgotten joint after medial open wedge high tibial osteotomy. METHODS:117 patients with medial open wedge high tibial osteotomy who were treated at First Affiliated Hospital of Guangzhou University of Chinese Medicine were selected,including 35 males and 82 females,with an average age of 61 years.They were followed up for at least 2 years.Patients were divided into a forgotten joint group(n=28)and a non-forgotten joint group(n=89)by evaluating whether they achieved forgotten joint after surgery.Univariate and multivariate logistic regression analyses were performed with preoperative patient characteristics and surgery-related factors as potential predictors. RESULTS AND CONCLUSION:(1)There were significant differences in the proximal medial tibial angle between the two groups before surgery(P<0.05).There were significant differences in the forgotten joint score,Knee Injury and Osteoarthritis Outcome Score,knee society knee score,function score,and patients joint perception between the two groups after surgery(P<0.05).There was a significant difference between the hip-knee-ankle angle and the medial proximal tibial angle after operation(P<0.05).(2)Univariate Logistic regression analysis showed that the medial proximal tibial angle had a significant influence on the forgotten joint before operation[OR=0.755,95%CI(0.635-0.897),P<0.001].There were significant effects on the forgotten joint of hip-knee-ankle angle and medial proximal tibial angle[OR=1.546,95%CI(1.242-1.924),P<0.001;OR=0.815,95%CI(0.713-0.931),P=0.003].(3)Multivariate logistic regression analysis showed that preoperative K-L grade 1 was a favorable factor for obtaining forgotten joints.Preoperative medial proximal tibial angle and postoperative hip-knee-ankle angle were independent predictors of forgetting joints,and they had a curvilinear relationship with the probability of achieving forgetting joints.When preoperative medial proximal tibial angle increased by 1°,the probability of achieving a forgotten joint decreased by 27.7%[OR=0.723,95%CI(0.593-0.882),P<0.001].Conversely,when postoperative hip-knee-ankle angle increased by 1°,the probability of achieving a forgotten joint increased by 46.4%[OR=1.464,95%CI(1.153-1.860),P=0.002].(4)The results showed that patients with preoperative knee osteoarthritis K-L grade 1,small medial proximal tibial angle(<85.5°),and large postoperative hip-knee-ankle angle(>176.0°)were predictors of forgotten joint.
5.Action mechanism of Bushenhuoxue decoction on promoting nucleus pulposus-like differentiation of adipose-derived stem cells
Zehua GUO ; Zhaoyong LI ; Long CHEN ; Jiahao DUAN ; Haobo JIANG ; Guangxue CHEN ; Youxian SU ; Enxu LIU ; Shaofeng YANG
Chinese Journal of Tissue Engineering Research 2024;28(25):3974-3980
BACKGROUND:Stem cell transplantation is a new way to prevent and cure intervertebral disc degeneration.However,whether the transplanted stem cells can survive,proliferate,differentiate,and restore the function of nucleus pulposus cells after transplantation,is the key and difficult point to overcome. OBJECTIVE:To explore the effects of Bushenhuoxue decoction on survival,proliferation,and nucleus pulposus-like differentiation of adipose-derived stem cells. METHODS:A Transwell chamber was used to construct a co-culture model of human adipose-derived stem cells and human degenerative nucleus pulposus cells.The experiment was divided into control group,model group,drug-containing serum group,and drug-free serum group.Except for the control group,the co-culture system of other groups was treated with 50 μmol/L tert-butyl hydrogen peroxide for 24 hours.The drug-containing serum group and drug-free serum group were treated with DMEM low-glucose complete culture medium containing drug-containing serum of Bushenhuoxue decoction or drug-free serum with 20%volume fraction for 48 hours.The sublayer adipose-derived stem cells were taken.Toluidine blue staining was used to detect proteoglycan synthesis levels.Real-time PCR method was used to detect mRNA expression of type Ⅱ collagen,proteoglycan and SRY-box transcription factor 9.The protein expression of SOX9 was detected by western blot assay.Lactate dehydrogenase assay was used to detect cytotoxicity.Flow cytometry was used to detect reactive oxygen species,and β-galactosidase staining was used to detect cell senescence. RESULTS AND CONCLUSION:(1)Compared with the control group,the proportion of necrotic cells in the model group increased;toluidine blue staining became lighter,and the expression levels of type Ⅱ collagen,proteoglycan,SOX9 mRNA and SOX9 protein decreased(P<0.05).Compared with the model group,the drug-containing serum of Bushenhuoxue decoction could significantly reduce cell injury and promote the expression of type Ⅱ collagen,proteoglycan,SOX9 mRNA,and SOX9 protein(P<0.05),but the improvement in the drug-free serum group was not significant(P>0.05).(2)Compared with the control group,the contents of cytotoxicity,reactive oxygen species,and cell senescence in the model group were significantly increased.Compared with the model group,the microenvironment of the coculture system was significantly improved by drug-containing serum of Bushenhuoxue decoction(P<0.05),while drug-free serum had no significant effect on the microenvironment of the co-culture system(P>0.05).(3)The results show that Bushenhuoxue decoction can promote the survival,proliferation,and nucleus pulposus-like differentiation of adipose-derived stem cells.
6.Systemic therapy for advanced hepatocellular carcinoma
Jiahao XU ; Dongxu YIN ; Yuchen LI ; Fujie CHEN ; Mingda WANG ; Tian YANG
Journal of Clinical Hepatology 2024;40(11):2306-2314
Hepatocellular carcinoma(HCC)is one of the most common malignancies with high morbidity and mortality rates worldwide.With the advances in molecular biology and tumor immunology,molecular-targeted agents represented by tyrosine kinase inhibitors(such as sorafenib and lenvatinib)and immunotherapy represented by PD-1/PD-L1 monoclonal antibodies have brought hope for patients with advanced HCC.The combination of immunotherapy and anti-angiogenic therapy can further improve the treatment outcome of patients.In addition,the optimization and integration of stereotactic body radiotherapy,local treatment,and systemic treatment may maximize the benefits of patients.In the future,through a deep understanding of the heterogeneity of HCC,the development of precision molecular subtyping and individualized treatment,and the establishment of a multidisciplinary collaborative diagnosis and treatment system,systemic therapy is expected to achieve long-term management of advanced HCC.This article reviews the current status and advances in systemic therapy for advanced HCC.
7.Comparison of the clinical efficacy between direct aspiration thrombectomy and stent thrombectomy for acute atherosclerotic occlusion of middle cerebral artery
Yawen CHENG ; Xiangning HAN ; Jiahao LI ; Suhang SHANG ; Sanping CHENG ; Running ZHANG ; Jianfeng HAN ; Fude LIU
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(4):603-608
Objective To compare the clinical efficacy between a direct aspiration first-pass technique(ADAPT)and stent-retriever thrombectomy(SRT)in the treatment for acute ischemic stroke(AIS)caused by intracranial atherosclerotic stenosis related large vessel occlusion(ICAS-LVO).Methods We retrospectively included patients with AIS caused by ICAS-LVO who received endovascular treatment in The First Affiliated Hospital of Xi'an Jiaotong University or The Second Affiliated Hospital of Shaanxi University of Chinese Medicine between January 2020 and January 2023.They were divided into ADAPT group and SRT group according to the first-selected device for thrombectomy.We compared the baseline data,test and examination results,operation process,clinical prognosis and follow-up data of the two groups.Results A total of 117 patients were recruited,including 48 patients in the ADAPT group and 69 patients in the SRT group.There was no significant difference in the baseline data between the two groups.The success rate of both the first-time thrombectomy(P=0.014)and the first-selected device of thrombectomy(P<0.001)was significantly higher in the SRT group than in the ADAPT group.Meanwhile,the incidence of iatrogenic dissection(P<0.001)and vasospasm(P=0.003)was significantly lower in the SRT group than in the ADAPT group.The proportion of patients for whom the device of thrombectomy was changed for remedial treatment in the ADAPT group was significantly higher than that in the SRT group(P<0.001).However,the two groups did not differ significantly in the rate of successful vascular recanalization,incidence of symptomatic/asymptomatic intracranial hemorrhage or the rate of 90-day favorable prognosis.Conclusion For patients with AIS caused by ICAS-LVO of MCA,SRT has a higher rate of immediate successful vascular recanalization with a lower rate of secondary vascular injury compared with ADAPT,but the two techniques have similar efficacy on the 90-day prognosis.
8.Evaluation and Consideration on Equity in Health Technology Assessment
Jiahao HU ; Jiayun WANG ; Xi CHEN ; Yuhan LIU ; Chunlin JIN ; Fen LI
Chinese Health Economics 2024;43(1):11-16
Health technology assessment(HTA)is an important tool to inform health decision-making.Although highly related to ethical issues in the context of HTA,equity has attracted much attention from the academia,a consensus has not yet been reached on how to define and evaluate equity in China and abroad.It introduces the concept of equity,pointes out the necessity to realize health equity and the reflection of equity in healthcare sector,and further elaborates four ways to consider equity,and described the official practice of equity in HTA at home and abroad.It proposes several suggestions for China's HTA:considering equity in HTA and the discussion of equity should depend on specific decision-making scenarios;clarifying what health measurement perspective should be adopted before measuring health equity;paying attention to the value judgment of equity adopted by various stakeholders;conducting basic researches on the general population's preference for health measurement perspectives and value judgments of equity in China in a gesture to improve the evaluation system of equity in HTA.
9.Clinical characteristics of patients >65 years old with acute exacerbation of chronic obstructive pulmonary disease and COVID-19 infection
Yuanzhen JIAN ; Caijun WU ; Li LI ; Jiahao DU ; Aiguo ZHANG ; Zhiyuan NIE ; Qiaojie SUN
Journal of Chinese Physician 2024;26(2):166-171
Objective:To investigate the clinical characteristics of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and corona virus disease 2019 (COVID-19) infection.Methods:Clinical data of AECOPD patients over 65 years old who were diagnosed in the Respiratory and Emergency Departments of the Dongzhimen Hospital, Beijing University of Chinese Medicine from September 2022 to September 2023 were collected. AECOPD patients were divided into a COVID-19 group ( n=29) and a non COVID-19 group ( n=31). The platelet count, white blood cell count, lymphocyte count, neutrophil count, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), C-reactive protein (CRP), procalcitonin (PCT), partial pressure of oxygen (PO 2), partial pressure of carbon dioxide (PCO 2), D-dimer (D-D), and interleukin-6 (IL-6) were compared between two groups of patients upon admission Confusion, Uremia, Respiratory, BP, Age 65 Years (CURB-65) was used to compare length of hospital stay, AECOPD grading, and mortality endpoint days. Results:There was no statistically significant difference in platelet count, white blood cell count, lymphocyte count, neutrophil count, NLR, and PLR between the COVID-19 group and the non COVID-19 group (all P>0.05). The proportion of males, CRP, PCO 2, D-D, IL-6, and CURB-65 scores in the COVID-19 group were higher than those in the non COVID-19 group, while PCT and PO 2 were lower than those in the non COVID-19 group, with statistically significant difference (all P<0.05). The proportion of AECOPD grade Ⅲ in the COVID-19 group was significantly higher than that in the non COVID-19 group, and the progression rate of the disease was higher in the COVID-19 group (37.9% vs 22.6%, P<0.05). COVID-19 was an independent influencing factor for the progression of AECOPD. Conclusions:Patients over 65 years old with AECOPD infected with COVID-19 have a more pronounced inflammatory response, and CRP, IL-6, and CURB-65 scores can be used as indicators to evaluate the degree of inflammation. AECOPD infected with COVID-19 are more prone to coagulation disorders, hypoxemia, more severe illness, and easier progression, suggesting that COVID-19 infection is an independent influencing factor for the progression of AECOPD.
10.Analysis on Mechanism of Huangwu Ganfu Ointment in Relieving Knee Osteoarthritis Pain Based on Network Pharmacology and Experimental Verification
Chuyang JIANG ; Zhaonan WANG ; Jiahao LI ; Qianyu QING ; Le ZHAO ; Ziwei ZHAO ; Yanyan LI
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(1):20-28
Objective To analyze the mechanism of Huangwu Ganfu Ointment in relieving pain of knee osteoarthritis(KOA)based on network pharmacology;To verify it in animal experiments.Methods The active components of Huangwu Ganfu Ointment were obtained by TCMSP database,PubChem database and SwissADME platform,the effective components were screened,and the targets were obtained from SEA database.KOA disease-related targets were obtained from GeneCards,OMIM and other databases,and the intersection targets were obtained.A effective component-target-disease network was constructed using Cytoscape 3.9.0 Software.Protein-protein interaction(PPI)network was constructed by STRING database and core targets were screened.GO and KEGG enrichment analysis of intersection targets were analyzed using DAVID platform.The KOA rat model with cold and damp syndrome was established,and the intervention of Huangwu Ganfu Ointment was carried out.The efficacy was observed and the core target expressions were detected.Results Totally 104 effective components were screened from Huangwu Ganfu Ointment,and 59 potential targets were obtained for treating KOA.PPI network interaction analysis obtained the important targets of IL6,IL1B and PTGS2.KEGG enrichment results showed that Huangwu Ganfu Ointment may involve 84 signaling pathways such as IL-17,TNF,TRP and NF-κB in the treatment of KOA,most of which were related to inflammation.The results of animal experiments showed that Lecuesne MG scores increased in the model rats(P<0.05),and paw withdrawal threshold(PWT)significantly decreased(P<0.05).Compared with model group,PWT in Huangwu Ganfu Ointment medium-and high-dosage groups were significantly recovered,and synovitis Krenn score decreased(P<0.05).The Mankin score of cartilage tissue of Huangwu Ganfu Ointment high-dosage group decreased(P<0.05).The contents of IL-6 and IL-1β in all Huangwu Ganfu Ointment groups decreased(P<0.01).Huangwu Ganfu Ointment medium-and high-dosage groups could down-regulate the expression of TRPV1 protein(P<0.05,P<0.01).Conclusion The mechanism of Huangwu Ganfu Ointment in alleviating the pain of KOA may be related to reducing inflammatory response,reducing the release of inflammatory factors of IL-1β and IL-6,alleviating inflammatory pain sensitivity of KOA,and down-regulating the expression level of TRPV1.

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