1.Platelet-derived growth factor BB-loaded chitosan/reduced graphene oxide scaffold for repairing alveolar bone defects
Xiangyu BAI ; Feng HUO ; Yan HAO ; Zecheng WANG ; Xiaoyu GUO
Chinese Journal of Tissue Engineering Research 2026;30(2):329-337
BACKGROUND:Studies have shown that platelet-derived growth factor BB can stimulate the proliferation and osteogenic differentiation of mesenchymal stem cells and accelerate the calcification process of osteoblast-like cells.However,its clinical application has problems such as short half-life and easy decomposition.Loading the growth factor onto a suitable biomaterial scaffold can enable its slow and continuous release and maintain an effective concentration,which has become a hot topic in current research.OBJECTIVE:To observe the effect of chitosan/reduced graphene oxide scaffolds loaded with platelet-derived growth factor BB on the repair of alveolar bone defect in rats.METHODS:(1)Chitosan/reduced graphene oxide scaffolds(referred to as CS/rGO scaffolds)and chitosan/reduced graphene oxide scaffolds loaded with different mass concentrations(5,10,15,and 20 mg/L)of platelet-derived growth factor BB(referred to as CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds)were prepared respectively.The five groups of scaffolds were co-cultured with rat periodontal ligament stem cells.The cell proliferation and migration were detected by CCK-8 assay and Transwell chamber assay,respectively,to screen the appropriate growth factor loading mass concentration for subsequent experiments.CS/rGO scaffolds(or extracts)and CS/rGO/PDGF-BB-15 scaffolds(or extracts)were co-cultured with rat periodontal ligament stem cells,and the osteogenic differentiation and angiogenic ability of the cells were detected.(2)The alveolar bone defect model was prepared in front of the bilateral maxillary first molars of 16 SD rats,and the rats were randomly divided into 4 intervention groups:the blank control group did not receive any intervention,the simple scaffold group was implanted with CS/rGO/PDGF-BB-15 scaffold,the control group was implanted with CS/rGO scaffold and rat periodontal ligament stem cell complex,and the experimental group was implanted with CS/rGO/PDGF-BB-15 scaffold and rat periodontal ligament stem cell complex,with 4 rats in each group.Twelve weeks after surgery,the bone repair of the alveolar bone defect was observed by Micro CT scanning and hematoxylin-eosin staining.RESULTS AND CONCLUSION:(1)CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds could promote the proliferation and migration of rat periodontal ligament stem cells.Among them,the CS/rGO/PDGF-BB-15 scaffold had the most significant effect on promoting cell proliferation and migration,and this scaffold was used for subsequent experiments.Compared with the CS/rGO scaffold,the CS/rGO/PDGF-BB-15 scaffold could promote the osteogenic and angiogenic differentiation of rat periodontal ligament stem cells.(2)Micro CT scanning and hematoxylin-eosin staining results showed that the experimental group had the best alveolar bone defect repair effect,and a large amount of new bone tissue and blood vessel formation could be seen.(3)The chitosan/reduced graphene oxide scaffold loaded with platelet-derived growth factor BB can effectively promote the repair of rat alveolar bone defects by promoting the proliferation,migration,angiogenic and osteogenic differentiation of rat periodontal ligament stem cells.
2.Platelet-derived growth factor BB-loaded chitosan/reduced graphene oxide scaffold for repairing alveolar bone defects
Xiangyu BAI ; Feng HUO ; Yan HAO ; Zecheng WANG ; Xiaoyu GUO
Chinese Journal of Tissue Engineering Research 2026;30(2):329-337
BACKGROUND:Studies have shown that platelet-derived growth factor BB can stimulate the proliferation and osteogenic differentiation of mesenchymal stem cells and accelerate the calcification process of osteoblast-like cells.However,its clinical application has problems such as short half-life and easy decomposition.Loading the growth factor onto a suitable biomaterial scaffold can enable its slow and continuous release and maintain an effective concentration,which has become a hot topic in current research.OBJECTIVE:To observe the effect of chitosan/reduced graphene oxide scaffolds loaded with platelet-derived growth factor BB on the repair of alveolar bone defect in rats.METHODS:(1)Chitosan/reduced graphene oxide scaffolds(referred to as CS/rGO scaffolds)and chitosan/reduced graphene oxide scaffolds loaded with different mass concentrations(5,10,15,and 20 mg/L)of platelet-derived growth factor BB(referred to as CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds)were prepared respectively.The five groups of scaffolds were co-cultured with rat periodontal ligament stem cells.The cell proliferation and migration were detected by CCK-8 assay and Transwell chamber assay,respectively,to screen the appropriate growth factor loading mass concentration for subsequent experiments.CS/rGO scaffolds(or extracts)and CS/rGO/PDGF-BB-15 scaffolds(or extracts)were co-cultured with rat periodontal ligament stem cells,and the osteogenic differentiation and angiogenic ability of the cells were detected.(2)The alveolar bone defect model was prepared in front of the bilateral maxillary first molars of 16 SD rats,and the rats were randomly divided into 4 intervention groups:the blank control group did not receive any intervention,the simple scaffold group was implanted with CS/rGO/PDGF-BB-15 scaffold,the control group was implanted with CS/rGO scaffold and rat periodontal ligament stem cell complex,and the experimental group was implanted with CS/rGO/PDGF-BB-15 scaffold and rat periodontal ligament stem cell complex,with 4 rats in each group.Twelve weeks after surgery,the bone repair of the alveolar bone defect was observed by Micro CT scanning and hematoxylin-eosin staining.RESULTS AND CONCLUSION:(1)CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds could promote the proliferation and migration of rat periodontal ligament stem cells.Among them,the CS/rGO/PDGF-BB-15 scaffold had the most significant effect on promoting cell proliferation and migration,and this scaffold was used for subsequent experiments.Compared with the CS/rGO scaffold,the CS/rGO/PDGF-BB-15 scaffold could promote the osteogenic and angiogenic differentiation of rat periodontal ligament stem cells.(2)Micro CT scanning and hematoxylin-eosin staining results showed that the experimental group had the best alveolar bone defect repair effect,and a large amount of new bone tissue and blood vessel formation could be seen.(3)The chitosan/reduced graphene oxide scaffold loaded with platelet-derived growth factor BB can effectively promote the repair of rat alveolar bone defects by promoting the proliferation,migration,angiogenic and osteogenic differentiation of rat periodontal ligament stem cells.
3.Expression characteristics and prognostic value of CENPM, and its mechanisms in regulating malignant phenotypes in glioma
YUAN Hao ; ZHANG Siwei ; WANG Mengyue ; SUN Qiaoxin ; BAI Zili ; CHEN Peng
Chinese Journal of Cancer Biotherapy 2026;33(4):418-428
[摘 要] 目的:探究着丝粒蛋白M(CENPM)在脑胶质瘤中的表达特征、临床预后价值及其对肿瘤恶性生物学行为的调控机制,为脑胶质瘤的精准治疗提供潜在靶点。方法:基于中国胶质瘤基因组图谱(CGGA)和癌症基因组图谱(TCGA)数据库分析CENPM在胶质瘤中的表达及其与患者临床病理特征和预后的相关性。通过基因本体论(GO)分析、京都基因与基因组百科全书(KEGG)富集分析和单细胞转录组分析探索CENPM的生物学功能和作用机制。WB法检测CENPM在胶质瘤细胞(LN-18、LN-229、U-138MG、U-251MG)和正常胶质细胞(HEB)中的表达;构建CENPM敲低细胞后,通过CCK-8、集落形成、Transwell和划痕实验评估恶性表型改变。结果:CENPM在WHO高级别胶质瘤中呈高表达(P < 0.05),与肿瘤恶性程度正相关。高表达组患者总体生存期显著短于低表达组(P < 0.01),Cox回归证实CENPM是影响胶质瘤患者预后的独立危险因素(P < 0.05)。功能富集分析结果显示CENPM相关基因主要富集于细胞周期调控、PI3K-Akt通路和免疫相关过程。单细胞分析结果显示CENPM主要在CD8⁺ T细胞高表达,并通过PTN-PTPRZ1/NCL配受体调控细胞通信。体外实验证实CENPM在胶质瘤细胞表达高于正常胶质细胞(LN-18:P < 0.01,LN-299:P < 0.05);敲低CENPM显著抑制迁移(P < 0.05),但增强集落形成,提示其在肿瘤进展中的双重调控作用。结论:CENPM作为胶质瘤独立预后危险因子,通过调控细胞周期、PTN通路和免疫微环境驱动肿瘤进展,其差异化调控机制(抑制迁移、促进增殖)具有潜在的临床转化价值,可作为分子分型和靶向治疗候选标志物。
4.Efficacy of MitraClip in functional versus degenerative mitral regurgitation: A systematic review and meta-analysis
Xuhua LI ; Qiyuan BAI ; Zhili WEI ; Shidong LIU ; Hao CHEN ; Yang CHEN ; Bing SONG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(05):807-814
Objective To systematically evaluate the differences in outcomes between functional mitral regurgitation (FMR) and degenerative mitral regurgitation (DMR) in patients treated with transcatheter edge-to-edge repair (TEER) using the MitraClip device. Methods A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, Web of Science, the CNKI, Wanfang Database, VIP Database, and the CBM from their inception to January 2024. Two researchers independently performed study selection, data extraction, and risk of bias assessment. The quality of cohort studies was evaluated using the Newcastle-Ottawa Scale (NOS). A meta-analysis was performed using Stata 18.0 software. Results A total of 13 cohort studies involving 6 402 patients were included, comprising 4 161 patients in the FMR group and 2 241 in the DMR group. All included studies had NOS scores of ≥6 points. The meta-analysis revealed that compared to the DMR group, the FMR group had a higher 1-year all-cause mortality rate [OR=1.53, 95%CI (1.30, 1.81), P<0.01] and a higher 1-year rehospitalization rate for heart failure [OR=1.90, 95%CI (1.60, 2.26), P<0.01]. Conversely, the FMR group had a lower post-procedural mean transmitral gradient [SMD=–0.47, 95%CI (–0.65, –0.30), P<0.01] and a lower rate of subsequent mitral valve surgery [OR=0.41, 95%CI (0.20, 0.83), P=0.01]. Conclusion Following MitraClip therapy, patients with FMR exhibit favorable short-term outcomes, but their mid- to long-term outcomes are inferior to those of patients with DMR. When determining the treatment strategy with MitraClip, the specific etiology of mitral regurgitation should be considered for a more accurate prediction of therapeutic efficacy and prognosis.
5.Analysis of soil-borne nematode infection status among rural communities in Yubei, Chongqing
Dan JIANG ; Yong-dong HAO ; Sen-ping YANG ; Xiao-yuan SU ; Hua-jun BAI ; Bo LYU ; Ya-ling RAN ; He-yi GUAN ; Ling HU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):85-89
Objective To analyze the infection status and epidemic trends of soil-borne nematode infections in Yubei, Chongqing City, in 2010,2021, and 2022. Methods The local populations from four survey sites of four towns in 2010 and five sites of five towns in 2021 and 2022 were surveyed regarding their basic information using a unified form. Fecal samples of the participants were collected and tested for soil-borne nematode infections using the modified Kato-Katz thick smear method. Results In 2010, 2 049 participants were surveyed, followed by 1 000 participants in 2021 and 2022. The overall prevalence of parasitic infections declined significantly from 3.86% to 0.20%. In 2010, soil-transmitted nematode included hookworms(3.81%) and roundworms(0.29%). In 2021, the infection rates of roundworms and hookworms were 1.70% and 0.10% respectively. Notably, only Ascaris was identified in 2022(0.20%). The≥60 age group consistently exhibited the highest infection rates across all surveys, followed by the 40-59 age group. The infection rates of males in the three surveys were 3.31%,1.92%, and 0.20% respectively, and those of females were 4.37%, 1.46%, and 0.20% respectively. There was no statistically significant difference in the infection rates between males and females. Educational attainment was inversely associated with infection; in 2010, the highest prevalence was observed among those with primary education or below, whereas in 2021, illiterate or semi-literate individuals showed the highest susceptibility. The occupational distribution of infections in 2010 indicated that retirees (8.33%), farmers(4.86%), and homemakers or unemployed individuals(3.45%)were the most affected. However, in 2021 and 2022, farmers emerged as the predominant occupational group with soil-transmitted nematode infections. Conclusions The infection rate of soil-borne nematodes showed a decreasing trend in Yubei, and the infection species changed from hookworms in 2010 to Ascaris in 2022. Farmers, the elderly, and people with low education levels should continue to be the focus of preventive and control efforts.
6.Research progress on traditional Chinese medicine remodeling the immune microenvironment in ischemic stroke by regulating HIF-1α-mediated glycolytic reprogramming
Jiayu DU ; Senyu WANG ; Chen BAI ; Yingxu HAO ; Xiangzhe LIU
China Pharmacy 2026;37(17):2332-2337
Ischemic stroke (IS) is a serious cerebrovascular disease with high clinical incidence. Cerebral ischemia and hypoxia can induce metabolic reprogramming of cellular glycolysis. Hypoxia-inducible factor-1α (HIF-1α) serves as the core transcription factor in the hypoxic response. This article systematically reviews the molecular mechanisms of HIF-1α-mediated glycolytic reprogramming, elaborates on the effects of this metabolic alteration on the functional status of different immune cells, and summarizes the research progress of traditional Chinese medicine (TCM) interventions in this pathological process. HIF-1α reshapes glucose metabolic flux and shifts cellular metabolism toward glycolysis by regulating the transcription of key genes, including glucose transporters, glycolytic rate-limiting enzymes, and mitochondrial oxidative inhibitors. This metabolic disturbance can regulate the activation status, phenotypic differentiation, and functional remodeling of microglia, astrocytes, and peripherally infiltrated immune cells, thereby participating in the mediation of neuroinflammatory responses after IS. Moreover, multiple signaling pathways and the metabolite of glycolysis lactate can exert feedback regulation on this metabolic-immune process. Various active components of TCM and herbal formulas, such as astragaloside Ⅳ, salvianolic acid C, Ginkgo biloba extract, and Mailuo shutong pills, can inhibit abnormal glycolysis, reduce lactate accumulation, and restore the homeostasis of glucose oxidative metabolism by regulating signaling pathways including AMP-activated protein kinase/mammalian target of rapamycin/HIF-1α, HIF-1α/pyruvate kinase M2, and HIF-1α/lactate dehydrogenase A. Consequently, they effectively alleviate neuroimmune inflammation and attenuate ischemic brain injury.
7.Distribution and epidemiological characteristics of single and mixed viral infections in patients with acute respiratory tract infection
Langlang LIU ; Tiao BAI ; Yanhu WEI ; Hao WANG ; Shaoting SONG ; Chanchan MIAO
Journal of Public Health and Preventive Medicine 2026;37(5):77-81
Objective To explore the distribution and epidemiological characteristics of single virus infection and mixed virus infection in patients with acute respiratory tract infection. Methods A retrospective study was conducted on 320 patients with acute respiratory tract infections who visited sentinel hospitals from January 2022 to January 2025. All patients underwent common virus detection and atypical pathogen human rhinovirus (HRV) detection. Results In this study, there were 204 patients (71.83%) with single virus infection, including 87 cases (42.65%) of atypical pathogen human rhinovirus (HRV) infection, 28 cases (13.73%) of influenza A virus infection, 35 cases (17.16%) of influenza B virus infection, 21 cases (10.29%) of respiratory syncytial virus (RSV) infection, 17 cases (8.33%) of adenovirus (ADV) infection, and 16 cases (7.84%) of parainfluenza virus (PIV) infection. There were 80 patients (28.17%) with mixed virus infection, including 57 cases (71.25%) of influenza virus+RSV mixed infection and 23 cases (28.75%) of ADV+PIV mixed infection. There were significant differences in the detection rates of HRV, RSV, influenza virus+RSV, and ADV+PIV among different age groups (P<0.05). The detection rates of HRV, RSV single and mixed virus were high in age of 0-5 years old, while the detection rate of ADV was high in age of ≥60 years old. Statistical differences were found in the detection rates of HRV, influenza A virus, influenza B virus, ADV, influenza virus+RSV, and ADV+PIV among different seasons (P<0.05). The detection rates of HRV, influenza A virus, influenza B virus, and RSV were high in spring and winter, the detection rates of ADV and ADV+PIV were high in summer, the detection rate of PIV was high in spring and autumn, and the detection rate of influenza virus+RSV was high in winter. There were no statistical differences in the detection rates of viral pathogens among patients with different genders (P>0.05). Conclusion Acute respiratory tract infection is mainly caused by single virus infection (HRV is the most common). Mixed infection is more common in influenza virus with RSV. Children aged 0-5 years old and elderly people over 60 years old are susceptible populations. Children have a higher risk of mixed infection, and the epidemic peak is concentrated in winter and spring.
8.Multiparametric MRI to Predict Gleason Score Upgrading and Downgrading at Radical Prostatectomy Compared to Presurgical Biopsy
Jiahui ZHANG ; Lili XU ; Gumuyang ZHANG ; Daming ZHANG ; Xiaoxiao ZHANG ; Xin BAI ; Li CHEN ; Qianyu PENG ; Zhengyu JIN ; Hao SUN
Korean Journal of Radiology 2025;26(5):422-434
Objective:
This study investigated the value of multiparametric MRI (mpMRI) in predicting Gleason score (GS) upgrading and downgrading in radical prostatectomy (RP) compared with presurgical biopsy.
Materials and Methods:
Clinical and mpMRI data were retrospectively collected from 219 patients with prostate disease between January 2015 and December 2021. All patients underwent systematic prostate biopsy followed by RP. MpMRI included conventional diffusion-weighted and dynamic contrast-enhanced imaging. Multivariable logistic regression analysis was performed to analyze the factors associated with GS upgrading and downgrading after RP. Receiver operating characteristic curve analysis was used to estimate the area under the curve (AUC) to indicate the performance of the multivariable logistic regression models in predicting GS upgrade and downgrade after RP.
Results:
The GS after RP was upgraded, downgraded, and unchanged in 92, 43, and 84 patients, respectively. The AUCs of the clinical (percentage of positive biopsy cores [PBCs], time from biopsy to RP) and mpMRI models (prostate cancer [PCa] location, Prostate Imaging Reporting and Data System [PI-RADS] v2.1 score) for predicting GS upgrading after RP were 0.714 and 0.749, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, tPSA, PCa location, and PIRADS v2.1 score) was 0.816, which was larger than that of the clinical factors alone (P < 0.001). The AUCs of the clinical (age, percentage of PBCs, ratio of free/total PSA [F/T]) and mpMRI models (PCa diameter, PCa location, and PI-RADS v2.1 score) for predicting GS downgrading after RP were 0.749 and 0.835, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, F/T, PCa diameter, PCa location, and PI-RADS v2.1 score) was 0.883, which was larger than that of the clinical factors alone (P < 0.001).
Conclusion
Combining clinical factors and mpMRI findings can predict GS upgrade and downgrade after RP more accurately than using clinical factors alone.
9.Trajectories of body mass index for age z-score and its influencing factors among children with congenital hypothyroidism
CHENG Lingling ; YAN Yaqiong ; BAI Zenghua ; ZHANG Xiaogang ; HAO Liting ; YANG Huiying
Journal of Preventive Medicine 2025;37(8):858-863
Objective:
To analyze the trajectories of body mass index for age z-score (BAZ) and its influencing factors among children with congenital hypothyroidism (CH) based on latent class growth modeling (LCGM), so as to provide the evidence for improving treatment measures and optimizing growth management among children with CH. Methods Children with CH aged 0 to 3 years from the Newborn Disease Screening Center of Shanxi Children's Hospital (Shanxi Maternal and Child Health Hospital) between 2017 and 2022 were selected as the research subjects. Basic information, height and weight data from 3 to 36 months of age, age at treatment initiation, thyroid-stimulating hormone (TSH) levels at diagnosis, and family information were retrospectively collected. BAZ for children with CH at each month of age was calculated based on the WHO Child Growth Standards. The trajectories of BAZ were analyzed using LCGM, and factors affecting the trajectories of BAZ among children with CH were analyzed using a multinomial logistic regression model.
Methods:
Children with CH aged 0 to 3 years from the Newborn Disease Screening Center of Shanxi Children's Hospital (Shanxi Maternal and Child Health Hospital) between 2017 and 2022 were selected as the research subjects. Basic information, height and weight data from 3 to 36 months of age, age at treatment initiation, thyroid-stimulating hormone (TSH) levels at diagnosis, and family information were retrospectively collected. BAZ for children with CH at each month of age was calculated based on the WHO Child Growth Standards. The trajectories of BAZ were analyzed using LCGM, and factors affecting the trajectories of BAZ among children with CH were analyzed using a multinomial logistic regression model.
Results:
A total of 299 children with CH were included. There were 140 boys (46.82%) and 159 girls (53.18%). The median of BAZ was 0.50 (interquartile range, 1.68). The LCGM analysis categorized the subjects into three groups: the persistent high-growth pattern group with 24 cases (8.03%), the slow-growth pattern group with 39 cases (13.04%), and the appropriate-growth pattern group with 236 cases (78.93%). Multinomial logistic regression analysis showed that compared to the children with CH in the appropriate-growth pattern group, those who started treatment at the age of 30 to 60 days (OR=0.109, 95%CI: 0.016-0.732; OR=0.166, 95%CI: 0.032-0.852) had a lower risk of persistent high-growth and slow-growth patterns; CH children with TSH levels of 50 to 150 mIU/L at diagnosis (OR=3.554, 95%CI: 1.201-10.514) and those whose paternal had a senior high school/technical secondary school education (OR=2.975, 95%CI: 1.003-8.823) exhibited a higher risk of the persistent high-growth pattern. Conversely, CH children whose paternal reproductive age was 30 to 35 years (OR=0.166, 95%CI: 0.034-0.806) had a lower risk of the persistent high-growth pattern.
Conclusions
The BAZ trajectory of children with CH aged 0 to 3 years exhibited three patterns: persistent high-growth, slow-growth, and appropriate-growth. The persistent high-growth and slow-growth patterns were associated with treatment timing, TSH levels at diagnosis, paternal reproductive age, and paternal education level. It is recommended to strengthen early treatment interventions and provide family follow-up guidance.
10.Exploring the mechanism of jolkinolide B in gastric cancer treatment based on network pharacology and molecular docking approach
Hao ZHANG ; Ling-Min LI ; Nan WU ; Ning-Ning WANG ; Xue-Yan LI ; Bai-Yu JIAN
Acta Anatomica Sinica 2025;56(1):37-42
Objective To explore the mechanism of action of jolkinolide B in the treatment of gastric cancer by network pharmacology combined with molecular docking technique.Methods The SwissTargetPrediction database was used to obtain the targets of the active compounds.Search Genecards,OMIM,Drugbank,TTD,and PharmGKB databases to obtain targets for gastric cancer.The intersection between the targets of jolkinolide B and those of gastric cancer was identified pinpoint potential targets for jolkinolide B in treating gastric cancer.The String database was utilized construct a protein-protein interaction(PPI)network.Bioconductor bioinformatics packages with R software was employed conduct Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on the shared targets.This process revealed significant regulatory pathways crucial for jolkinolide B's efficacy in treating gastric cancer.Cytoscape 3.7.1 software was utilized create the core network of"Potential Targets of Triptolide B in Gastric Cancer Treatment",and SYBYL-X2.1.1 software was employed conduct molecular docking validation of the selected main active ingredients and critical targets.Results Jolkinolide B may target multiple proteins,including MAPK1,glycogen synthase kinae-3β(GSK-3β),and JUN,impacting the proliferation,invasion,and metastasis of gastric cancer,ultimately inhibiting its growth.Conclusion We predicted the possible molecular mechanism of jolkinolide B in the treatment of gastric cancer to provide guide information for the subsequent experimental research and clinical application.


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