1.Effects of Modified Buyang Huanwu Tang on Mice with Cerebral Ischemia-reperfusion Injury by Regulating PINK1/Parkin Signaling Pathway-mediated Mitochondrial Autophagy
Li GUO ; Hengwen CHEN ; Cun ZHAN ; Zhenzhen YING ; Zuomin WU ; Shaoju JIN ; Shangmei CAO ; Shengming HUANG ; Jin WANG ; Xiaotao YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):34-43
ObjectiveTo investigate the effects of modified Buyang Huanwu Tang on cerebral ischemia-reperfusion injury (CI/RI) in mice via the PTEN-induced putative kinase 1/E3 ubiquitin ligase (PINK1/Parkin) signaling pathway-mediated mitophagy, and to explore the underlying mechanism by which modified Buyang Huanwu Tang improves CI/RI. MethodsSeventy-two male C57BL/6J mice were randomly divided into six groups (n = 12 per group): Sham-operated group, middle cerebral artery occlusion/reperfusion (MCAO/R) model group, low-, medium-, and high-dose modified Buyang Huanwu Tang groups (8.84, 17.68, 35.36 g·kg-1·d-1), and an aspirin group (13.00 mg·kg-1·d-1). Neurological deficit scores were assessed using the Zea-Longa method. Cerebral infarct volume ratio was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Histopathological changes and neuronal injury in brain tissues were observed using hematoxylin-eosin (HE) staining and Nissl staining. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Mitochondrial ultrastructure in brain tissue was observed by transmission electron microscopy (TEM). Serum levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expression levels of PINK1, Parkin, microtubule-associated protein 1 light chain 3B (LC3B, LC3Ⅱ/Ⅰ), and p62 in brain tissues were detected by real-time quantitative reverse transcription PCR (Real-time PCR) and Western blot, respectively. ResultsCompared with the sham-operated group, the MCAO/R model group showed significantly increased neurological deficit scores and cerebral infarct volume ratios (P<0.01). Severe cortical injury on the infarct side was observed, characterized by decreased neuronal density, cytoplasmic vacuolation, nuclear pyknosis, a marked reduction in Nissl bodies, dissolution of Nissl bodies in the cytoplasm of some pyramidal neurons, and blurred cellular boundaries. The number of TUNEL-positive cells increased significantly (P<0.01). Mitochondria exhibited cristae membrane rupture and matrix vacuolation, with rupture of the outer mitochondrial membrane and formation of autophagosomes, the number of which increased significantly. Serum SOD activity decreased significantly (P<0.01), while MDA content increased significantly (P<0.01). In infarcted brain tissues of model mice, the relative mRNA expression and protein levels of PINK1, Parkin and LC3B were significantly increased (P<0.05, P<0.01), whereas p62 mRNA and protein expression were significantly decreased (P<0.05, P<0.01), showing statistical significance. Compared with the model group, all treatment groups showed significantly decreased neurological deficit scores and cerebral infarct volume ratios (P<0.01). Neuronal density increased significantly, cytoplasmic vacuolation was alleviated, nuclear morphology tended to be more regular and clearer, Nissl body density increased significantly with reduced dissolution and improved contour clarity. The mitochondrial cristae structure was partially restored, with some mitochondria showing autophagosome encapsulation, and the degree of mitochondrial damage was alleviated. Serum SOD activity increased significantly (P<0.01), while MDA content decreased significantly. The mRNA and protein expression levels of PINK1, Parkin, and LC3Ⅱ/Ⅰ were significantly increased (P<0.05, P<0.01), while p62 mRNA and protein expression in the low- and medium-dose modified Buyang Huanwu Tang groups were significantly decreased (P<0.05, P<0.01), showing statistical significance. ConclusionModified Buyang Huanwu Tang can upregulate the protein expression levels of PINK1, Parkin, and LC3Ⅱ/Ⅰ and downregulate p62 protein expression, suggesting that it may improve CI/RI by regulating the expression of proteins related to the PINK1/Parkin signaling pathway. Regulation of the mitophagy pathway may be one of the mechanisms by which modified Buyang Huanwu Tang alleviates CI/RI in mice.
2.Preliminary study on the role of TM9SF2 knockdown in promoting the activity of the type I interferon signaling pathway to inhibit vesicular stomatitis virus replication.
Kang LI ; Xinyu WANG ; Ran YE ; Lingyun GUO ; Linxu WANG ; Nuo XU ; Tong ZHANG ; Xiaotao DUAN
Chinese Journal of Cellular and Molecular Immunology 2025;41(6):481-487
Objective To explore the effect of the knockdown of transmembrane 9 superfamily protein member 2 (TM9SF2) on the replication of vesicular stomatitis virus (VSV), and investigate its role in the mechanism of antiviral innate immunity. Methods Small interfering RNA (siRNA) was used to knock down the TM9SF2 gene in human non-small cell lung cancer A549 cells. The CCK-8 method was used to assess cell proliferation. A VSV-green fluorescent protein (VSV-GFP) infected cell model was established. The plaque assay was used to measure the viral titer in the supernatant. RT-qPCR and Western blotting were employed to quantify the mRNA and protein levels of VSV genome replication in A549 cells following VSV infection, as well as the expression of interferon β (IFN-β) mRNA and interferon regulatory factor 3 (IRF3) protein phosphorylation following polyinosinic-polycytidylic acid (poly(I:C)) stimulation. Results Compared to the negative control, the knockdown of TM9SF2 exhibited a significant effect, with no observed impact on A549 cell proliferation. The VSV-GFP infected A549 cell model was successfully established. After viral stimulation, fluorescence intensity was reduced following TM9SF2 knockdown, and the mRNA and protein levels of VSV were significantly downregulated. The viral titer of VSV was decreased. After poly(I:C) stimulation, TM9SF2 knockdown significantly upregulated the mRNA level of IFN-β and the phosphorylation level of IRF3 protein. Conclusion The knockdown of TM9SF2 inhibits the replication of vesicular stomatitis virus, and positively regulates the type I interferon signaling pathway, thus enhancing the host's antiviral innate immune response.
Humans
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Virus Replication/genetics*
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Signal Transduction
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Membrane Proteins/metabolism*
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A549 Cells
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Vesiculovirus/physiology*
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Interferon-beta/metabolism*
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Interferon Regulatory Factor-3/genetics*
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Interferon Type I/metabolism*
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Vesicular Stomatitis/immunology*
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Gene Knockdown Techniques
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Vesicular stomatitis Indiana virus/physiology*
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RNA, Small Interfering/genetics*
3.Research on MRI Gradient Coil Magnetic Field Induced Eddy Current Method.
Xiaotao ZHANG ; Yicheng LI ; Zhanping ZHENG ; Mingke WANG ; Like FENG ; Congbo LI
Chinese Journal of Medical Instrumentation 2025;49(3):263-268
After the production of the gradient coil of the magnetic resonance imaging system, electromagnetic field testing is required to verify whether the assembly accuracy meets the electromagnetic field requirements. Since the passive magnetic field B z satisfies the Laplace ,s equation and is a harmonic function, and according to the extreme value principle of harmonic function, the maximum or minimum values of B z can only appear on the boundaries, so the observation points of the magnetic field are generally selected on the surface of the spherical imaging area. For superconducting magnets used for human body magnetic resonance imaging, a spherical area with a center diameter of 40~50 cm is generally selected as the shimming target area. Only the field value of the target area needs to be measured, and the spherical harmonic coefficients obtained after data processing are used to determine the magnetic field performance of the gradient coil. There are many testing principles and methods for electromagnetic fields, so there is no unified way and method in the field of commercial applications. This article is based on the Gauss-Legendre numerical integration, measures and analyzes the magnetic field performance of gradient coils by building a data acquisition system, and this article applies numerical analysis methods to calculate the spherical harmonic coefficients of the magnetic field using discrete test data, providing a feasible method for the production and testing of gradient coils.
Magnetic Resonance Imaging/methods*
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Magnetic Fields
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Electromagnetic Fields
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Equipment Design
4.Efficacy of Weiyan Tongluo Granules in Patients with Chronic Atrophic Gastritis of Spleen Deficiency and Blood Stasis Type:A Multi-Center,Double-Blind,Double-Dummy,Randomized Controlled Trial
Xiaotao JIANG ; Jie LIN ; Yushan ZOU ; Zehong YANG ; Jinglin PAN ; Zhekun XIONG ; Changlong WANG ; Yuancheng HUANG ; Shuye WANG ; Yanhua YAN ; Junhui ZHENG ; Yi WEN ; Fengbin LIU ; Peiwu LI
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(6):822-831
OBJECTIVE To evaluate the efficacy and safety of Weiyan Tongluo Granules in treating chronic atrophic gastritis(CAG)and explore its potential mechanisms.METHODS From June 2020 to December 2022,100 CAG patients with spleen defi-ciency and blood stasis syndrome were enrolled and randomly divided into a trial group(n=50)and a control group(n=50)using a random number table.The trial group received Weiyan Tongluo Granules plus a folic acid placebo,while the control group received fo-lic acid tablets plus a traditional Chinese medicine granule placebo.The treatment course for both groups was 24 weeks,with 8 and 10 dropouts in the trial and control groups,respectively.Post-treatment comparisons included OLGA/OLGIM staging reversal rates,low-grade intraepithelial neoplasia regression rate,SSDPRO-CG(Patient-Reported Outcome Scale for Chronic Gastritis in Spleen-Stomach Diseases)scores,TCM syndrome scores,and safety indicators.Serum levels of PG I,PGⅡ,PGR,and G-17 were measured via ELISA before and after treatment.Gastric mucosal p-NF-κB and CDX2 protein expression levels were analyzed by Western blot,while mRNA levels of IL-1β,IL-6,VIL1,and MUC2 were quantified via qPCR.RESULTS After treatment,the trial group showed sig-nificantly higher OLGA and OLGIM stage reversal rates than the control group(P<0.05,P<0.01),though no significant difference was observed in low-grade intraepithelial neoplasia regression.Both groups exhibited significant improvements in physiological domain scores and total SSDPRO-CG scores(P<0.01),with the trial group outperforming the control group in physiological,independence,psychological domains,and total scores(P<0.05,P<0.01).TCM syndrome scores(total and sub-items:gastric distension,pain,poor appetite,bloating)decreased significantly in both groups(P<0.01),while the trial group showed greater reductions in loose stools and dull complexion(P<0.01).After-treatment,the trial group had significantly lower TCM syndrome scores than the control group(P<0.05,P<0.01).Serum PG I,PGⅡ,PGR,G-17,gastric mucosal p-NF-κB,CDX2,and IL-1β,IL-6,VIL1,MUC2 mRNA levels improved significantly in the trial group(P<0.05,P<0.01),while the control group improved only in PGⅡ(P<0.05,P<0.01).The trial group's improvements in these biomarkers surpassed the control group's(P<0.05,P<0.01).No treatment-related adverse events occurred in either group.CONCLUSION Weiyan Tongluo Granules ameliorate gastric mucosal pathology,clinical symptoms,psychological state,and quality of life in CAG patients without significant adverse effects.Its mechanism may involve sup-pressing the NF-κB pathway to reduce IL-1β and IL-6 expression,downregulating CDX2 to inhibit VIL1 and MUC2 transcription,thereby reversing the vicious cycle of inflammation-intestinal metaplasia.
5.Research on the role and mechanism of mitochondrial targeting peptide SS-31 in inflammation-in-duced senescence and pyroptosis of nucleus pulposus cells
Xin PENG ; Zhiqiang WANG ; Tong ZHANG ; Guang YANG ; Xiaotao WU ; Yanzheng GAO
Chinese Journal of Spine and Spinal Cord 2025;35(4):399-407
Objectives:To investigate the effect and mechanism of mitochondrial targeting peptide SS-31 on senescence and pyroptosis of nucleus pulposus(NP)cells induced by inflammation.Methods:NP cells were isolated and cultured in vitro from 6-week-old male SD rats,and were divided into control group,lipopolysaccharide(LPS)group,and LPS+SS-31 group;And the control group of cells received no treatment,LPS group of cells were treated with 100μg/mL LPS for 24h,and LPS+SS-31 group of cells were pre-treated with SS-31 30min before LPS intervention.The levels of cellular senescence and pyroptosis were assessed in each group using β-galactosidase(SA-β-Gal)staining and westem blot(WB)assay;Transmission electron mi-croscopy and oxygen consumption rate(OCR)assay were used to analyze the mitochondrial function of NP cells in each group;The expressions of phosphorylated nuclear factor-κB-p65(p-NF-κB-p65),cyclic GMP-AMP synthase(cGAS),and interferon stimulating gene(STING)in each group were detected by WB and im-munofluorescence;Hematoxylin-eosin(HE)staining,immunohistochemistry(IHC)staining and WB assay were performed to analyze the effects of in vivo injection of SS-31 on intervertebral disc degeneration,senescence,and pyroptosis.Results:The positive SA-β-Gal staining of NP cells,expression of senescence marker pro-teins(p53,p21),and pyroptosis-related molecules(NLRP3,Caspase-1 p20)were significantly lower in the LPS+SS-31 group compared with the LPS group(P<0.05);Transmission electron microscopy(TEM)showed that the mitochondrial swelling of NP cells was round,the matrix was translucent,and the interstitial lumen of the mitochondrial cristae was dilated in the LPS group,while the mitochondrial swelling was subsided,and the morphology of mitochondria tended to be normalized in the LPS+SS-31 group.Meanwhile,the maximum respi-ration level of NP cells was significantly enhanced in the LPS+SS-31 group compared with the LPS group(P<0.05).The results of WB and immunofluorescence showed that LPS significantly up-regulated the expression of p-NF-κB-p65,cGAS,and STING(P<0.05),while SS-31 pretreatment significantly inhibited the expression of p-NF-κB-p65,cGAS and STING in NP cells induced by LPS(P<0.05).Finally,in vivo experiments con-firmed that local injection of SS-31 reduced the senescence and pyroptosis of NP cells,and alleviated the degeneration of intervertebral disc induced by annulus fibropuncture.Conclusions:SS-31 alleviates inflamma-tion-induced senescence and pyroptosis of NP cells,which is related to the inhibition of NF-κB signaling pathway and cGAS/STING signaling pathway.
6.Multiple Organ Failure Caused by Sodium Valproate:A Case Report
Baoping XU ; Huaiwen PENG ; Xiantao ZHANG ; Xiaotao WANG
Herald of Medicine 2025;44(1):134-138
The patient,male,42 years old,was given 1.5 mg·kg-1·h-1 sodium valproate via intravenous infusion due to epilepsy,resulting in multiple organ failure.The diagnosis and treatment process of the patient was retrospectively analyzed.The relevance evaluation was carried out using Naranjo's ADR evaluation probability scale,and the relevant literatures were reviewed to provide a reference for the clinical safety of sodium valproate.
7.Pathogenesis and treatment progress of flap ischemia-reperfusion injury
Bo HE ; Wen CHEN ; Suilu MA ; Zhijun HE ; Yuan SONG ; Jinpeng LI ; Tao LIU ; Xiaotao WEI ; Weiwei WANG ; Jing XIE
Chinese Journal of Tissue Engineering Research 2025;29(6):1230-1238
BACKGROUND:Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects,but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury.Therefore,it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE:To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024.The search terms used were"flap,ischemia-reperfusion injury,inflammatory response,oxidative stress,Ca2+overload,apoptosis,mesenchymal stem cells,platelet-rich plasma,signaling pathways,shock wave,pretreatment"in Chinese and English.After elimination of irrelevant literature,poor quality and obsolete literature,77 documents were finally included for review. RESULTS AND CONCLUSION:Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response,oxidative stress response,Ca2+overload,and apoptosis,which can cause apoptosis of vascular endothelial cells,vascular damage and microcirculation disorders in the flap,and eventually lead to flap necrosis.Studies have found that mesenchymal stem cell transplantation,platelet-rich plasma,signaling pathway modulators,shock waves,and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees,and reduce the necrosis rate and necrosis area of the grafted flap.Although there are many therapeutic methods for skin flap ischemia/reperfusion injury,a unified and effective therapeutic method has not yet been developed in the clinic,and the advantages and disadvantages of various therapeutic methods have not yet been compared.Most of the studies remain in the stage of animal experiments,rarely involving clinical observations.Therefore,a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic.
8.Optimization of water extraction technology of Kaixin granules
Zuomin WU ; Shuxian BAI ; Meng NING ; Yunzhi WANG ; Huifen MA ; Jingyuan DONG ; Zhongjie YANG ; Zhishen XIE ; Zhenqiang ZHANG ; Xiaotao YU
China Pharmacy 2025;36(22):2790-2795
OBJECTIVE To optimize the water extraction technology for Kaixin granules. METHODS UPLC-MS/MS method was established for the simultaneous determination of ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, tenuifolin, polygalaxanthone Ⅲ and 3, 6′-disinapoyl-sucrose. An orthogonal test was designed with extraction times, extraction duration, and the volume of added water as factors. Using the contents of the aforementioned six indicator components and the extract yield as evaluation indexes, analytic hierarchy process-entropy weight method was employed to determine the combined weights of each indicator. Subsequently, process optimization and validation were conducted by integrating grey relational analysis (GRA) and back propagation (BP) neural network. RESULTS The water extraction technology optimized by the orthogonal test and GRA was 10- fold water for the first decoction and 8-fold water for the subsequent two, extracting 3 times,extracting for 1 h each time; the average comprehensive score of the validation experiment was 91.10 (RSD=0.31%, n=3). The water extraction technology optimized by BP neural network was extracting 3 times with 10-fold water added each time, extracting for 1.5 h each time; the average comprehensive score of the validation experiment was 95.89 (RSD=0.73%, n=3). Considering practical production requirements, the optimal water extraction technology was extraction performed three times, with 10-fold water for the first decoction and 8-fold water for the subsequent two extractions, with an extraction time of 1 h each. CONCLUSIONS The optimized water extraction technology for Kaixin granules is stable and feasible.
9.Epidemiological characteristics of cross-county imported dengue fever cases within Yunnan Province in 2023
Yerong TANG ; Hongning ZHOU ; Chao WU ; Chun WEI ; Xiaotao ZHAO ; Xuefei WANG ; Xiaolian GUO ; Jinyong JIANG
Chinese Journal of Schistosomiasis Control 2025;37(5):524-529
Objective To investigate the epidemiological characteristics of cross-county imported dengue fever cases within Yunnan province in 2023, so as to provide insights into formulation of preventive and control measures for intra-provincial spread of dengue fever. Methods All data pertaining cross-county imported dengue fever cases within Yunnan Province in 2023 were collected, and the temporal, regional and population distributions of the cases were descriptively analyzed. Results A total of 1 664 intra-provincial cross-county imported dengue fever cases were reported in 95 counties (cities, districts) cross 16 profectures (cities) in Yunnan Province in 2023, accounting for 12.34% of total cases in the province. Cross-county imported dengue fever cases were predominantly reported during the period between August and October (1 516 cases, 91.11% of total cases), and peaked in September (659 cases), with a single-day peak on October 8 (36 cases). During the period from September 4 to 10, five counties (cities) with local dengue fever epidemics, including Jinghong City of Xishuangbanna Dai Autonomous Prefecture, Gengma Dai and Wa Autonomous County of Lincang City, Ruili City of Dehong Dai and Jingpo Autonomous Prefecture, Mengla Coun ty of Xishuangbanna Dai Autonomous Prefecture, and Zhenkang County of Lincang City, exported 165 cross-county imported dengue fever cases to the rest of the province. Among the 1 644 intra-provincial cross-county imported dengue fever cases, the male to female ratio was 1.40∶1.00, and 1 329 cases were at ages of 15 to 55 years (79.87%), with farmers as the predominant occupation (886 cases, 53.25%). The top 5 counties (cities/districts) reporting the highest number of intra-provincial cross-county imported dengue fever cases included Simao District (266 cases) and Lancang Lahu Autonomous County (118 cases) of Pu’er City, Mengla County (91 cases) and Menghai County (91 cases) of Xishuangbanna Dai Autonomous Prefecture, and Mangshi City (73 cases) of Dehong Dai and Jingpo Autonomous Prefecture, which accounting for 38.40% of total imported cases. These intra-provincial cross-county imported dengue fever cases originated from 7 counties (cities/districts) in 4 prefectures (cities), including 1 261 cases (76.70%) from Jinghong City of Xishuangbanna Dai Autonomous Prefecture, 224 cases (13.63%) from Ruili City of Dehong Dai and Jingpo Autonomous Prefecture, 103 cases (6.27%) from Gengma Dai and Wa Autonomous County of Lincang City, 31 cases (1.89%) from Mengla County of Xishuangbanna Dai Autonomous Prefecture, 30 cases (1.82%) from Zhenkang County of Lincang City, 10 cases (0.61%) from Cangyuan Wa Autonomous County of Lincang City, and 5 cases (0.30%) from Mohan-Boten Economic Cooperation Zone of Kunming City. In addition, local dengue fever epidemics following intra-provincial cross-county importation of dengue fevers cases in Simao District, Jinggu Dai and Yi Autonomous County, Mangshi City, Longchuan County, and Cangyuan Wa Autonomous County. Conclusions Farmers and students are high-risk populations for intra-provincial cross-county imported dengue fever cases in Yunnan Province, and health education pertaining personal protection against dengue fever should be strengthened among these high-risk populations by governments at all levels. There is a high risk of local out-break of dengue fever following continuous introduction of intra-provincial cross-county imported cases. Standardized management of intra-provincial cross-county imported dengue fever cases should be reinforced to reduce the risk of local epidemics.
10.Progress on the Main Mechanism Affecting Flap Survival
Jinpeng LI ; Jie GUO ; Tao LIU ; Xiaotao WEI ; Yuan SONG ; Weiwei WANG ; Zhijun HE
Medical Journal of Peking Union Medical College Hospital 2025;16(2):416-422
Flap surgery is a complex surgical procedure that has become an effective method for the treatment of many diseases and traumas.Flap survival is closely related to a variety of factors including cellular autophagy,oxidative stress,inflammatory response,mesenchymal stem cells(MSCs)function,and vascular regeneration.Cellular autophagy maintains intracellular homeostasis and plays a key role in reducing oxidative stress and inflammation and promoting injury repair.Excessive oxidative stress and inflammatory responses pose a threat to flaps,affecting their survival and successful transplantation.Endothelial cells are involved in vascu-lar regeneration through proliferation,migration,and production of angiogenic factors,and vascular endothelial growth factor directly promotes blood vessel formation and maintains endothelial cell function.MSCs play an important role in promoting flap survival and tissue repair due to their unique biological properties and multiple mechanisms of action.The multiple roles played by cellular autophagy,oxidative stress,inflammatory response,MSCs function,and vascular regeneration in influencing postoperative flap survival are hereby elaborated.The aim is to provide a basis for the clinical application of regulating the above factors to improve postoperative flap survival,improve the success rate of flap surgery,reduce complications,and bring more hope for the recovery and quality of life of patients.

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