1.Improvement of myocardial injury by traditional Chinese medicine:mitochondrial calcium homeostasis mediates macrophage autophagy and pyroptosis pathway
Lingyun LIU ; Guixin HE ; Weibin QIN ; Hui SONG ; Liwen ZHANG ; Weizhi TANG ; Feifei YANG ; Ziyi ZHU ; Yangbin OU
Chinese Journal of Tissue Engineering Research 2025;29(6):1276-1284
BACKGROUND:The repair process of myocardial injury involves complex cellular and molecular mechanisms,especially mitochondrial calcium homeostasis,macrophage autophagy and pyroptosis pathways.Traditional Chinese medicine(TCM)has shown significant clinical efficacy in improving myocardial injury,but its mechanism of action needs to be thoroughly investigated. OBJECTIVE:To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury,and to summarize the progress of TCM in this field. METHODS:A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science,PubMed and CNKI.The search terms were"mitochondrial calcium homeostasis,macrophage autophagy,macrophage pyroptosis,traditional Chinese medicine,myocardial injury,myocardial injury reperfusion"in Chinese and English.Through literature review,we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis,explored the mechanism of their roles in myocardial injury,and summarized the pathways of multi-targeted,multi-pathway effects of TCM. RESULTS AND CONCLUSION:The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes.Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways.Autophagy contributes to cell clearance and regulation of inflammatory response,while pyroptosis affects myocardial repair by releasing inflammatory factors.TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms.For example,astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C,and epimedium glycoside plays a role in reducing β-amyloid deposition.In addition,herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways,such as PI3K/AKT and nuclear factor-κB signaling pathways.Future studies should focus on the interactions between mitochondrial calcium homeostasis,autophagy and pyroptosis pathways,as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury.
2.Efficacy of typeⅡ hybrid surgery versus Sun’s surgery in the treatment of acute Stanford type A aortic dissection: A retrospective cohort study in a single center
Jie WANG ; Wei WU ; Long CHENG ; Feifei TANG ; Shilin DAI ; Yuqiang SHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(05):663-669
Objective To compare the clinical efficacy of typeⅡhybrid surgery versus Sun’s surgery in treating acute Stanford A aortic dissection. Methods A retrospective analysis was conducted on the clinical data of patients with acute Stanford A aortic dissection who were treated at the Central Hospital of Wuhan affiliated to Tongji Medical College, Huazhong University of Science and Technology from 2016 to 2022. According to the surgical method, patients were divided into a typeⅡhybrid group and a Sun’s surgery group, and the clinical efficacy of the two groups was compared. Results A total of 52 patients were included, with 22 in the typeⅡhybrid surgery group and 30 in the Sun’s surgery group. The typeⅡhybrid group consisted of 18 males and 4 females, with an average age of (58.18±6.00) years, while the Sun’s surgery group consisted of 22 males and 8 females, with an average age of (53.03±11.89) years. All surgeries were successfully completed. There were 4 (13.3%) perioperative deaths in the Sun’s surgery group, including 2 patients of multiple organ failure, 1 patient of paraplegia, and 1 patient of uncontrollable postoperative bleeding. There was 1 (4.5%) perioperative death in the typeⅡhybrid surgery group, who was suspected of acute coronary syndrome and took a loading dose of dual antiplatelet drugs preoperatively. The patient underwent secondary thoracotomy for hemostasis, was re-cannulated during the operation, and finally died of circulatory failure after implantation of intra-aortic balloon pumping. There was no statistical difference in perioperative mortality between the two groups (P=0.381). Compared with the Sun’s surgery group, the typeⅡhybrid surgery group had shorter cardiopulmonary bypass time [153.00 (135.00, 185.25) min vs. 182.50 (166.50, 196.75) min, P=0.013], aortic cross-clamping time [77.00 (70.50, 92.00) min vs. 102.50 (93.50, 109.75) min, P<0.001], postoperative ICU stay [4.00 (2.83, 6.00) days vs. 8.00 (6.38, 11.78) days, P<0.001], postoperative ventilator support time [72.00 (29.50, 93.25) h vs. 87.65 (39.13, 139.13) h, P=0.138], less intraoperative blood loss [(1586.82±209.41) mL vs. (1 806.00±292.62) mL, P=0.004], postoperative 24 h drainage volume [612.50 (507.50, 762.50) mL vs. 687.50 (518.75, 993.75) mL, P=0.409], and shorter postoperative hospital stay [18.00 (13.00, 20.25) days vs. 22.00 (17.00, 29.25) days, P=0.013]. There was no statistically significant difference in the incidence of other early postoperative complications such as secondary thoracotomy for hemostasis, tracheotomy, renal dysfunction requiring dialysis, stroke, and paraplegia between the two groups (P>0.05). Conclusion For patients with acute Stanford A aortic dissection, typeⅡhybrid surgery is safe and effective; compared with traditional Sun’s surgery, typeⅡhybrid surgery has relatively less trauma, lower incidence of complications, satisfactory short-term results, and further research is needed on long-term prognosis.
3.Hyperoside Alleviates LPS-induced Inflammation in Zebrafish Model via TLR4/MyD88/NF-κB Pathway
Qing LAN ; Anna WANG ; Feifei ZHOU ; Keqian LIU ; Zhao LI ; Wenjing YU ; Shuyao TANG ; Ping LI ; Shaowu CHENG ; Sisi DENG ; Zhenyan SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):63-72
ObjectiveTo investigate the intervention effects and mechanisms of the flavonoid hyperoside (Hyp) on lipopolysaccharide (LPS)-induced inflammation in the zebrafish model. MethodsZebrafish larvae were either microinjected with 0.5 g·L-1 LPS or immersed in 1 g·L-1 LPS for the modeling of inflammation. The larvae were then treated with Hyp at 25, 50, and 100 mg·L-1 through immersion for four consecutive days. The inflammatory phenotypes were assessed by analyzing the mortality rate, malformation rate, body length, and yolk sac area ratio. Behavioral tests were conducted to evaluate the inflammatory stress responses, and macrophage migration was observed by fluorescence microscopy. Additionally, the mRNA levels of inflammation-related genes, including interleukin-1β (IL-1β), interleukin-6 (IL-6), chemokine C-C motif ligand 2 (CCL2), chemokine C-X3-C motif receptor 1 (CX3CR1), chemokine C-C motif receptor 2 (CCR2), and genes associated with the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) signaling pathway, were measured by Real-time quantitative polymerase chain reaction(Real-time PCR). ResultsCompared with the pure water injection group, the model group exhibited increased mortality, malformation rates and yolk sac area ratio (P0.01), reduced body length (P0.01), increased total swimming distance and high-speed swimming duration (P0.01), and up-regulated mRNA levels of TLR4, MyD88, NF-κB, IL-1β, IL-6, CCL2, CX3CR1, and CCR2 (P0.01). Hyp at low, medium and high doses, as well as aspirin, reduced the mortality and malformation rates (P0.05,P0.01), increased the body length (P0.05,P0.01), decreased the yolk sac area ratio (P0.01), reduced the high-speed swimming duration (P0.01), and down-regulated the mRNA levels of TLR4, MyD88, NF-κB, IL-1β, IL-6, CCL2, CX3CR1, and CCR2 (P0.05,P0.01) compared with the model group. ConclusionHyp may modulate the TLR4/MyD88/NF-κB pathway to ameliorate inflammatory phenotypes and alleviate stress conditions in zebrafish, thereby exerting the anti-inflammatory effect.
4.Comparative analysis of small shadow morphology between chest CT and DR images of patients with occupational pneumoconiosis
Zhongxue LI ; Xiazi ZHAO ; Yongzhong TANG ; Qianchang LI ; Shiwen HUANG ; Feifei LI ; Xiaoping LI ; Kunhai QIU
China Occupational Medicine 2024;51(3):303-307
Objective To compare the morphology differences in small shadows of occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis") between computed tomography (CT) and digital radiography (DR) imaging. Methods A total of 1 010 pneumoconiosis patients were selected as the research subjects using a judgment sampling method. Chest DR imaging and CT imaging were performed on patients, and the differences in small shadow morphology between the two images were compared. Results In both DR and CT images of patients, circular small shadows identified as p, q, and r shapes accounted for 76.2%, 11.5%, and 1.3%, respectively, while irregular small shadows were identified in 1.8% of cases. There was medium high consistency between DR and CT in detecting these four types of small shadow morphology (Kappa=0.72, P<0.01). The detection rate of irregular small shadows (including interlobular septal thickening, ground-glass opacity, and/or centrilobular emphysema) by CT images was 54.0% (545/1 010), with 88.6% (483/545) of these cases also showing small circular shadows. Irregular small shadows in CT images were mostly identified as p small circular shadows in DR images, accounting for 88.8% (484/545). The results of DR and CT images for p/p, p/q, q/p, q/q, q/r, r/q and r/r in small circular shadows showed medium high consistency (Kappa =0.52, P<0.01). Conclusion The results of CT and DR imaging for pneumoconiosis with small shadow were of medium high consistency, with CT demonstrating advantages in detecting irregular small shadow morphology of pneumoconiosis. CT images can be used to describe the shape of circular small shadow as DR images, and irregular small shadow can be described as interlobular septal thickening, ground-glass opacity, and/or centrilobular emphysema.
5.The role and mechanism of LncRNA GABPB1-AS1 in regulating proliferation,invasion,migration,and apoptosis of acute myeloid leukemia cells
Yang FEIFEI ; Tang HAO ; Sun HUI ; Sun YIN
Chinese Journal of Clinical Oncology 2024;51(8):392-400
Objective:To explored the role and mechanism of antisense RNA of long non-coding RNA(LncRNA)GA binding protein transcrip-tion factor β subunit 1(GABPB1-AS1)in regulating the proliferation,invasion,migration,and apoptosis of acute myeloid leukemia(AML)cells by targeting the microRNA-497-5p/heat shock protein 8(miR-497-5p/HSPA8)axis.Methods:HL-60 cells were divided into the normal con-trol,si-NC,si-GABPB1-AS1,si-GABPB1-AS1+NC,and si-GABPB1-AS1+miR-497-5p inhibitor groups.Quantitative real time polymerase chain re-action(RT-qPCR)was used to detect the expression levels of LncRNA GABPB1-AS1,miR-497-5p,and HSPA8.Double luciferase reporter gene assay was used to verify the targeting relationship between LncRNA GABPB1-AS1,miR-497-5p,and HSPA8;MTT was used to detect cell viab-ility;while 5-ethynyl-2'-deoxyuridine(EdU)was used to detect proliferation.Transwell chamber experiments were used to detect invasion and migration while flow cytometry was used to detect apoptosis.Western blot was used to detect the levels of proliferating cell nuclear an-tigen(PCNA),HSPA8,metastasis-associated proteins(MTA2),homolog of yeast Atg6(Beclin-1),and Caspase-3 proteins.A mouse trans-planted tumor model was established to verify the effect of LncRNA GABPB1-AS1 on the growth of AML transplanted tumors.Results:Com-pared to human bone marrow monocytes,LncRNA GABPB1-AS1 was highly expressed[(1.29±0.10),(1.58±0.12),(2.02±0.17),(3.17±0.24)vs.(1.02±0.07)]while miR-497-5p was lowly expressed[(0.94±0.07),(0.75±0.03),(0.57±0.03),(0.25±0.01)vs.(1.05±0.09)]in different AML cells(THP-1,NB4,U-937,and HL-60,respectively).The HL-60 cell line was selected for functional verification experiments since LncRNA GABPB1-AS1 expression was highest in the HL-60 cells.Knockdown of LncRNA GABPB1-AS1 reduced HL-60 cell viability,the EdU positive rate,cell in-vasion and migration,the expression of HSPA8 mRNA,and HSPA8,PCNA,and MTA2 protein contents.It increased the apoptosis rate,and the expression of miR-497-5p,Caspase-3 and Beclin-1 protein(P<0.05).miR-497-5p had a targeting relationship with LncRNA GABPB1-AS1 and HSPA8;inhibiting the expression of miR-497-5p reversed the inhibitory effect of LncRNA GABPB1-AS1 knockdown on the malignant bio-logical behavior of HL-60 cells.Meanwhile,inhibiting the expression of LncRNA GABPB1-AS1 constrained the growth of transplanted tumors.Conclusions:Knockdown of LncRNA GABPB1-AS1 inhibits the progression of AML cells,which may be related to the upregulation of miR-497-5p expression and downregulation of HSPA8 expression.
6.Severe cardiotoxic characteristics associated with allogeneic hematopoietic stem cell transplantation preconditioning in patients with aplastic anemia
Xue MING ; Yuanyuan ZHANG ; Tingting HAN ; Jingzhi WANG ; Xiaodong MO ; Fengrong WANG ; Chenhua YAN ; Yu WANG ; Yuhong CHEN ; Zhengli XU ; Feifei TANG ; Ting ZHAO ; Kaiyan LIU ; Xiaohui ZHANG ; Xiaojun HUANG ; Lanping XU
Chinese Journal of Internal Medicine 2024;63(11):1096-1103
Objective:To delineate the clinical characteristics and outcomes associated with severe cardiac toxicity during the preconditioning phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with aplastic anemia (AA).Methods:This retrospective case series study included 31 patients with severe AA who underwent allo-HSCT and were diagnosed with severe cardiac toxicity at the Hematology Department of Peking University People′s Hospital from August 2012 to June 2022. The clinical manifestations of severe cardiac toxicity observed during the preconditioning process were assessed. Patient survival was assessed using the Kaplan-Meier method.Results:In this cohort of 31 patients, the median follow-up period was 9 days (range: 4-365 days). Severe cardiac toxicity manifested within 6 days after the initial cyclophosphamide (Cy) administration. Twenty patients died within 30 days of initiating Cy preconditioning, of which 16 patients died due to severe cardiac toxicity within 25 days. Patients whose cardiac function improved within 30 days post-preconditioning showed a median survival duration of 222 days ( n=11). Troponin I (TNI) levels in patients who died within 30 days of initiating Cy preconditioning began increasing on day 5 post-Cy, peaking sharply by day 9 after a notable rise on day 8. B-type natriuretic peptide (BNP) levels in patients who died within 30 days of initiating Cy preconditioning started to rise from day 1, stabilized between days 2 and 5, and then doubled daily from days 6 to 8, remaining elevated thereafter. Notably, the initial increases in BNP and TNI correlated with electrocardiogram (ECG) signs of low voltage and T-wave inversion in 83.87% of cases ( n=26). Most patients ( n=28, 90.32%) were administered corticosteroid therapy. In those with restored cardiac function, the ejection fraction returned to >50% within 30 days of initiating Cy preconditioning. Conclusions:Patients with severe cardiac toxicity during the preconditioning phase of allo-HSCT typically exhibit early, sustained, and marked elevations in myocardial damage markers, including BNP and TNI, accompanied by ECG abnormalities following Cy administration, with BNP often increasing first. These indicators are associated with rapid disease progression and high mortality. Prompt initiation of treatment upon clinical diagnosis is critical for improving survival outcomes.
7.Effects of facial emotion recognition on prosocial behavior of medical students in mask-obscured scenes:mediating effect of state empathy
Zhenming ZHANG ; Yingcan ZHENG ; Yingdan TANG ; Xinjie TAN ; Feifei WANG ; Jia WANG ; Mengyin ZHU ; Yitong XUE ; Guoyu YANG
Journal of Army Medical University 2024;46(13):1585-1592
Objective To explore the mediating effect of facial emotion recognition on prosocial behavior of medical students in mask-obscured scenes.Methods Fifty-three medical students from a medical university in Chongqing were enrolled from July to September 2023 to complete the facial emotion recognition task,the dictator gaming task and the state empathy test.Spearman correlation analysis was used to examine the correlation between mask wearing and state empathy,trait empathy and prosocial behaviours,and the PROCESS procedure was used to test the mediation of state empathy and the moderating effect of mask wearing or not.Results ①mask wearing,state empathy and prosocial behaviour were significantly correlated(P<0.01);② State empathy exerted mediated effect between facial emotion recognition and prosocial behavior,with the largest effect size(47%)for the relative mediating effect of sadness;③The interaction terms of facial emotion recognition and mask wearing had a significant effect on state empathy(P<0.05).Conclusion Facial emotion recognition can influence prosocial behavior directly and also exert indirect effect on prosocial behavior through state empathy.Compared to the condition without mask wearing,mask wearing can significantly facilitate the effect of happy,sad and neutral emotions on state empathy.
8.Surveillance of antifungal resistance in clinical isolates of Candida spp.in East China Invasive Fungal Infection Group from 2018 to 2022
Dongjiang WANG ; Wenjuan WU ; Jian GUO ; Min ZHANG ; Huiping LIN ; Feifei WAN ; Xiaobo MA ; Yueting LI ; Jia LI ; Huiqiong JIA ; Lingbing ZENG ; Xiuhai LU ; Yan JIN ; Jinfeng CAI ; Wei LI ; Zhimin BAI ; Yongqin WU ; Hui DING ; Zhongxian LIAO ; Gen LI ; Hui ZHANG ; Hongwei MENG ; Changzi DENG ; Feng CHEN ; Na JIANG ; Jie QIN ; Guoping DONG ; Jinghua ZHANG ; Wei XI ; Haomin ZHANG ; Rong TANG ; Li LI ; Suzhen WANG ; Fen PAN ; Jing GAO ; Lu JIANG ; Hua FANG ; Zhilan LI ; Yiqun YUAN ; Guoqing WANG ; Yuanxia WANG ; Liping WANG
Chinese Journal of Infection and Chemotherapy 2024;24(4):402-409
Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33%of which were isolated from sterile body sites,mainly from blood(38.86%)and pleural effusion/ascites(10.21%).The predominant species of Candida were Candida albicans(44.51%),followed by Candida parapsilosis complex(19.46%),Candida tropicalis(13.98%),Candida glabrata(10.34%),and other Candida species(0.79%).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62%).Only 2.97%of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61%and a resistance rate of 9.42%to fluconazole,and susceptibility rates above 90%to other drugs.Candida glabrata had a SDD rate of 92.01%and a resistance rate of 7.99%to fluconazole,resistance rates of 32.27%and 48.24%to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90%to other drugs.Candida tropicalis had resistance rates of 29.55%and 26.24%to fluconazole and voriconazole,respectively,resistance rates of 76.60%and 21.99%to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36%to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.
9.Role of dendritic cells in MYD88-mediated immune recognition and osteoinduction initiated by the implantation of biomaterials.
Zifan ZHAO ; Qin ZHAO ; Hu CHEN ; Fanfan CHEN ; Feifei WANG ; Hua TANG ; Haibin XIA ; Yongsheng ZHOU ; Yuchun SUN
International Journal of Oral Science 2023;15(1):31-31
Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects. Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials. Previous studies have mainly focused on innate immune cells such as macrophages. In our previous work, we found that T lymphocytes, as adaptive immune cells, are also essential in the osteoinduction procedure. As the most important antigen-presenting cell, whether dendritic cells (DCs) can recognize non-antigen biomaterials and participate in osteoinduction was still unclear. In this study, we found that surgical trauma associated with materials implantation induces necrocytosis, and this causes the release of high mobility group protein-1 (HMGB1), which is adsorbed on the surface of bone substitute materials. Subsequently, HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells, and the inflammatory response was activated. Finally, activated DCs release regeneration-related chemokines, recruit mesenchymal stem cells, and initiate the osteoinduction process. This study sheds light on the immune-regeneration process after bone substitute materials implantation, points out a potential direction for the development of bone substitute materials, and provides guidance for the development of clinical surgical methods.
Biocompatible Materials/metabolism*
;
HMGB1 Protein/metabolism*
;
Myeloid Differentiation Factor 88/metabolism*
;
Bone Substitutes/metabolism*
;
Dendritic Cells/metabolism*
10.Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity.
Xin TANG ; Chuanxi WANG ; Lei WANG ; Feifei REN ; Runqiao KUANG ; Zhenhua LI ; Xue HAN ; Yiming CHEN ; Guodong CHEN ; Xiuqing WU ; Jie LIU ; Hengwen YANG ; Xingzhong LIU ; Chen WANG ; Hao GAO ; Zhinan YIN
Acta Pharmaceutica Sinica B 2023;13(9):3930-3944
Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

Result Analysis
Print
Save
E-mail