1.Nanomedicine-driven tumor glucose metabolic reprogramming for enhanced cancer immunotherapy.
Chenwei JIANG ; Minglu TANG ; Yun SU ; Junjie XIE ; Qi SHANG ; Mingmei GUO ; Xiaoran AN ; Longfei LIN ; Ruibin WANG ; Qian HUANG ; Guangji ZHANG ; Hui LI ; Feihu WANG
Acta Pharmaceutica Sinica B 2025;15(6):2845-2866
Tumors exhibit abnormal glucose metabolism, consuming excessive glucose and excreting lactate, which constructs a tumor microenvironment that facilitates cancer progression and disrupts immunotherapeutic efficacy. Currently, tumor glucose metabolic dysregulation to reshape the immunosuppressive microenvironment and enhance immunotherapy efficacy is emerging as an innovative therapeutic strategy. However, glucose metabolism modulators lack specificity and still face significant challenges in overcoming tumor delivery barriers, microenvironmental complexity, and metabolic heterogeneity, resulting in poor clinical benefit. Nanomedicines, with their ability to selectively target tumors or immune cells, respond to the tumor microenvironment, co-deliver multiple drugs, and facilitate combinatorial therapies, hold significant promise for enhancing immunotherapy through tumor glucose metabolic reprogramming. This review explores the complex interactions between tumor glucose metabolism-specifically metabolite transport, glycolysis processes, and lactate-and the immune microenvironment. We summarize how nanomedicine-mediated reprogramming of tumor glucose metabolism can enhance immunotherapy efficacy and outline the prospects and challenges in this field.
2.Research progress on the mechanisms of Tau phosphorylation and its kinases in hypoxic-ischemic brain damage.
Qi-Yi HUANG ; You XIANG ; Jia-Hang TANG ; Li-Jia CHEN ; Kun-Lin LI ; Wei-Fang ZHAO ; Qian WANG
Acta Physiologica Sinica 2025;77(1):139-150
Hypoxic-ischemic brain damage (HIBD) is one of the main causes of disability in middle-aged and elderly people, as well as high mortality rates and long-term physical impairments in newborns. The pathological manifestations of HIBD include neuronal damage and loss of myelin sheaths. Tau protein is an important microtubule-associated protein in brain, exists in neurons and oligodendrocytes, and regulates various cellular activities such as cell differentiation and maturation, axonal transport, and maintenance of cellular cytoskeleton structure. Phosphorylation is a common chemical modification of Tau. In physiological condition, it maintains normal cell cytoskeleton and biological functions by regulating Tau structure and function. In pathological conditions, it leads to abnormal Tau phosphorylation and influences its structure and functions, resulting in Tauopathies. Studies have shown that brain hypoxia-ischemia could cause abnormal alteration in Tau phosphorylation, then participating in the pathological process of HIBD. Meanwhile, brain hypoxia-ischemia can induce oxidative stress and inflammation, and multiple Tau protein kinases are activated and involved in Tau abnormal phosphorylation. Therefore, exploring specific molecular mechanisms by which HIBD activates Tau protein kinases, and elucidating their relationship with abnormal Tau phosphorylation are crucial for future researches on HIBD related treatments. This review aims to focus on the mechanisms of the role of Tau phosphorylation in HIBD, and the potential relationships between Tau protein kinases and Tau phosphorylation, providing a basis for intervention and treatment of HIBD.
Humans
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tau Proteins/physiology*
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Phosphorylation
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Hypoxia-Ischemia, Brain/physiopathology*
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Animals
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Oxidative Stress
3.Antidepressant mechanism of Baihe Dihuang Decoction based on metabolomics and network pharmacology.
Chao HU ; Hui YANG ; Hong-Qing ZHAO ; Si-Qi HUANG ; Hong-Yu LIU ; Shui-Han ZHANG ; Lin TANG
China Journal of Chinese Materia Medica 2025;50(1):10-20
The Baihe Dihuang Decoction(BDD) is a representative traditional Chinese medicine formula that has been used to treat depression. This study employed metabolomics and network pharmacology to investigate the mechanism of BDD in the treatment of depression. Fifty male Sprague-Dawley(SD) rats were randomly assigned to the normal control group, model group, fluoxetine group, and high-and low-dose BDD groups. A rat model of depression was established through chronic unpredictable mild stress(CUMS), and the behavioral changes were detected by forced swimming test and open field test. Metabolomics technology was used to analyze the metabolic profiles of serum and hippocampal tissue to screen differential metabolites and related metabolic pathways. Additionally, network pharmacology and molecular docking techniques were used to investigate the key targets and core active ingredients of BDD in improving metabolic abnormalities of depression. A "component-target-metabolite-pathway" regulatory network was constructed. BDD could significantly improve depressive-like behavior in CUMS rats and regulate 12 differential metabolites in serum and 27 differential metabolites in the hippocampus, involving tryptophan metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, alanine, aspartate, and glutamate metabolism, tyrosine metabolism, and purine metabolism. Verbascoside, isorbascoside, and regaloside B were the key active ingredients for improving metabolic abnormalities in depression. Epidermal growth factor receptor(EGFR), protooncogene tyrosine-protein kinase(SRC), glycogen synthase kinase 3β(GSK3β), and androgen receptor(AR) were the key core targets for improving metabolic abnormalities of depression. This study offered a preliminary insight into the mechanism of BDD in alleviating metabolic abnormalities of depression through network regulation, providing valuable guidance for its clinical use and subsequent research.
Animals
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Drugs, Chinese Herbal/administration & dosage*
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Male
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Rats, Sprague-Dawley
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Rats
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Metabolomics
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Depression/genetics*
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Antidepressive Agents/chemistry*
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Network Pharmacology
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Hippocampus/drug effects*
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Humans
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Molecular Docking Simulation
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Behavior, Animal/drug effects*
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Disease Models, Animal
4.Effect of Duhuo Jisheng Decoction on knee osteoarthritis model rabbits through regulation of cell pyroptosis mediated by PI3K/Akt/mTOR signaling pathway.
Lin-Qin HE ; Peng-Fei LI ; Xiao-Dong LI ; Qi-Peng CHEN ; Zong-Han TANG ; Yu-Xin SONG ; Han-Bing SONG
China Journal of Chinese Materia Medica 2025;50(1):187-197
This study aimed to investigate the underlying mechanisms of Duhuo Jisheng Decoction(DJD) in the prevention and treatment of knee osteoarthritis(KOA). Forty SPF New Zealand rabbits were randomly divided using SPSS 26.0 software into five groups: blank group, model group, low-dose DJD group, high-dose DJD group, and high-dose DJD+phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway activator group(high-dose DJD+740Y-P group), with eight rabbits in each group. Except for the blank group, the KOA model was established in the other groups using papain injection into the knee joint cavity combined with forced flexion of the knee joint. The day after modeling, the blank group and model group were given normal saline at 10 mL·kg~(-1) by gavage, the low-dose DJD group received DJD at 8.8 g·kg~(-1) by gavage, the high-dose DJD group received DJD at 35.2 g·kg~(-1) by gavage, and the high-dose DJD+740Y-P group received DJD at 35.2 g·kg~(-1) by gavage along with 740Y-P at 0.15 μmoL·kg~(-1) injected via the auricular vein. All groups received treatment continuously for four weeks. After modeling and intervention, behavioral observations were performed for all groups, and after the intervention, imaging assessments of the knee joints were conducted. Cartilage from the knee joints was collected, and gross morphological changes were observed. Pathological changes in cartilage tissue were examined using hematoxylin-eosin(HE) staining. The results of these observations were quantitatively evaluated using the Lequesne MG score, Kellgren-Lawrence(K-L) grading, Pelletier score, and Mankin score. ELISA was used to measure the levels of interleukin-1β(IL-1β), interleukin-18(IL-18), and matrix metalloproteinase 13(MMP13) in cartilage tissue. Real-time RT-PCR was used to detect the mRNA expression levels of PI3K, Akt, mTOR, Nod-like receptor protein 3(NLRP3), cysteine protease 1(caspase-1), and gasdermin D(GSDMD) in cartilage tissue. Western blot was employed to measure the protein expression levels of PI3K, Akt, mTOR, NLRP3, caspase-1, and GSDMD. The results showed that compared with the blank group, the model group exhibited significant knee joint degeneration, increased Lequesne MG score, K-L grading, Pelletier score, and Mankin score, elevated levels of IL-1β, IL-18, and MMP13 in cartilage tissue, activation of PI3K, Akt, and mTOR phosphorylation along with increased mRNA expression levels, and elevated protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD. Compared with the model group, these indicators were reversed in both the low-dose and high-dose DJD groups, with the high-dose group showing greater decline degree than the low-dose DJD group. However, compared with the high-dose DJD group, the improvements in knee joint degeneration were less pronounced in the high-dose DJD+740Y-P group, with increased Lequesne MG score, K-L grading, Pelletier score, Mankin score, elevated levels of IL-1β, IL-18, and MMP13, activation of PI3K, Akt, and mTOR phosphorylation along with increased mRNA expression, and increased protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD. In conclusion, DJD is effective and safe in the treatment of KOA, and its mechanism may be related to the inhibition of PI3K/Akt/mTOR signaling pathway-mediated pyroptosis in cartilage tissue, thereby improving knee joint bone structure, reducing the inflammatory response, and preventing cartilage matrix degradation.
Animals
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Drugs, Chinese Herbal/administration & dosage*
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Rabbits
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TOR Serine-Threonine Kinases/genetics*
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Osteoarthritis, Knee/genetics*
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Proto-Oncogene Proteins c-akt/genetics*
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Signal Transduction/drug effects*
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Male
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Disease Models, Animal
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Pyroptosis/drug effects*
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Phosphatidylinositol 3-Kinases/genetics*
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Humans
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Female
5.A comparative study of the diagnostic efficacy of 68Ga-PSMA-617 PET/CT versus mpMRI for prostate cancer with extraprostatic extension and seminal vesicle invasion
Yinzhao WANG ; Xiaomei GAO ; Yongxiang TANG ; Xiaoping YI ; Jinwei ZHANG ; Shuo HU ; Minfeng CHEN ; Lin QI ; Yi CAI
Chinese Journal of Urology 2025;46(1):23-29
Objective:To compare the diagnostic efficacy of 68Ga-prostate-specific membrane antigen (PSMA)-617 PET/CT and multiparametric magnetic resonance imaging (mpMRI) in detecting extraprostatic extension (EPE) and seminal vesicle invasion (SVI) in prostate cancer. Methods:A retrospective analysis was conducted on the clinical data of 113 patients with localized prostate cancer who underwent both 68Ga-PSMA-617 PET/CT and mpMRI at Xiangya Hospital, Central South University, from May 2018 to May 2024 prior to radical prostatectomy (RP). The median age of the patients was 66.0 (61.3, 71.0) years old, with a median body mass index of 28.86 (19.01, 24.77) kg/m 2, and a median prostate-specific antigen (PSA) level of 13.50(9.26, 21.99) ng/ml. The pathological results after RP were used as the gold standard to compare the sensitivity, specificity, positive predictive value, and negative predictive value of the two imaging modalities in diagnosing EPE and SVI. Additionally, the diagnostic value of combining both imaging modalities was explored, employing a parallel strategy where a positive result from either modality was deemed positive, and only when both tests were negative was the result considered negative. Results:Pathological results after RP indicated EPE in 46 cases (40.71%) and SVI in 11 cases (9.70%). In diagnosing EPE, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA-617 PET/CT were 17.39% (8/46), 97.01% (65/67), 80.00% (8/10), and 63.11% (65/103), respectively, while for mpMRI they were 34.78% (16/46), 83.58% (56/67), 59.26% (16/27), and 65.12% (56/86), respectively. The sensitivity of mpMRI was significantly higher than that of 68Ga-PSMA-617 PET/CT ( P=0.048), while the specificity was the opposite ( P=0.008). When combining both imaging modalities, the sensitivity, specificity, positive predictive value, and negative predictive value were 45.65% (21/46), 80.60% (54/67), 61.76% (21/34), and 68.35% (54/79), respectively. In diagnosing SVI, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA-617 PET/CT were 27.27% (3/11), 96.08% (98/102), 42.86% (3/7), and 92.45% (98/106), respectively, while for mpMRI they were 36.36% (4/11), 88.24% (90/102), 25.00% (4/16), and 92.78% (90/97), respectively. The specificity of 68Ga-PSMA-617 PET/CT was significantly higher than that of mpMRI ( P=0.033). When combining both imaging modalities, the sensitivity, specificity, positive predictive value, and negative predictive value were 45.45% (5/11), 85.29% (87/102), 25.00% (5/20), and 93.55% (87/93), respectively. Conclusions:mpMRI has higher sensitivity in diagnosing EPE and SVI in prostate cancer, while 68Ga-PSMA-617 PET/CT shows higher specificity. The combined use of both imaging modalities can increase diagnostic sensitivity but may reduce specificity. PSMA PET/MRI may be a more accurate diagnostic tool for discerning EPE and SVI.
6.Expert recommendations on mass population vaccination
Wen WANG ; Chunhuan ZHANG ; Yong HUANG ; Qi ZHU ; Shiheng CUI ; Yan LIU ; Zhiwei ZHU ; Fang HUANG ; Lin TANG ; Zhoubin ZHANG ; Wenzhou YU
Chinese Journal of Preventive Medicine 2025;59(1):1-7
Mass vaccination represents a highly effective strategy for accelerating disease control while simultaneously reducing incidence and mortality rates. By developing comprehensive plans and standards for mass vaccination, it is feasible to optimize resource allocation and swiftly enhance vaccination coverage, thereby preventing, controlling, or interrupting outbreaks or epidemics of specific infectious diseases. To standardize the mass vaccination process and establish a population immunity barrier in an orderly, efficient, and safe manner, a panel of experts was convened to develop the Recommendations on Mass Vaccination. These recommendations are grounded in the requirements of relevant policies and regulations in China, as well as the insights gained from the mass vaccination campaign for COVID-19 vaccines conducted in the country. The recommendations outline the system requirements pertaining to initiation conditions, departmental coordination, responsibilities, mobilization, operational specifications, and responses to vaccine reactions, among other aspects of mass vaccination implementation, so as to serve as a reference for future mass vaccination initiatives and the formulation of related policies.
7.Ethnic differences in genotype distribution of thalassemia between Han and Li populations in southern Hainan
Yongjing TANG ; Zhixia LI ; Bangruo QI ; Feichen XIU ; Lin YANG ; Qin YANG ; Qinglan TANG ; Xiaopeng LAN ; Yufeng WANG
Chinese Journal of Preventive Medicine 2025;59(9):1540-1545
To analyze the ethnic differences in the genotype distribution of thalassemia between the Han and Li ethnic groups in the Qiongnan region (southern Hainan). A cross-sectional study employing a stratified multistage sampling method was conducted from January 2019 to December 2023. A total of 4 493 high-risk individuals (2 734 Han and 1 759 Li) from southern Hainan (including Sanya, Ledong, Baoting, Lingshui, and other counties) underwent thalassemia genetic testing. The genotype distribution was statistically analyzed. Inter-group comparisons were performed using χ2 test or Fisher′s exact test. The results showed an overall thalassemia positivity rate of 66.70% (2 997/4 493), with carrier, intermediate and major thalassemia rates of 62.01% (2 786/4 493), 3.98% (179/4 493) and 0.71% (32/4 493), respectively. The positivity rates for thalassemia were 87.83% (1 545/1 759) in the Li ethnic group and 53.11% (1 452/2 734) in the Han ethnic group. Among them, the Li ethnic group exhibited significantly higher positivity rates for α-thalassemia (71.12% vs. 40.64%, χ2=398.90, P<0.001) and α/β-compound thalassemia (13.36% vs. 3.33%, χ2=160.06, P<0.001) compared to the Han ethnic group, whereas the Han ethnic group had a higher β-thalassemia rate (9.14% vs. 3.35%, χ2=56.03, P<0.001). Both ethnic groups shared common α-thalassemia alleles (-α 3.7 and -α 4.2), but the -- SEA allele proportion was significantly higher in Han (21.33% vs. 4.34%, χ2=231.45, P<0.001). Six rare -α 21.9 mutations (0.26%) were exclusively identified in the Li ethnic group, whereas none were found in Han. For β-thalassemia, the β CD41-42 allele was predominant in Li (96.60% vs. 71.01%, χ2=77.24, P<0.001), whereas other alleles (β IVS-II-654, β CD71-72, β CD17, and β -28) were more prevalent in Han (11.01%, 6.96%, 4.64%, and 3.19% vs. 1.54%, 0.00%, 0.31%, and 0.62%, respectively),all P<0.05. In conclusion, distinct ethnic disparities in thalassemia genotype distribution are observed in southern Hainan. The Li ethnic group is predominantly characterized by α-thalassemia and α/β-compound genotypes with a predominant β CD41-42 mutation. In contrast, the Han ethnic group displays higher -- SEA proportion and heterogeneous β-thalassemia genotypes.
8.HIV screening for people visiting to a three-A hospital of Sichuan Province and epidemiological characteristics of emerging HIV infection patients complicated witn other infections from 2020 to 2024
Xiaoqin GOU ; Jing TANG ; Xing QI ; Sheng LIN ; Wenqing LIU ; Zhonghai HAN ; Wei LIAO ; Jingying ZHAO ; Huaguo WANG
Chinese Journal of Nosocomiology 2025;35(18):2760-2764
OBJECTIVE To investigate the result of human immunodeficiency virus(HIV)screening for the people visiting to a three-A hospital of Sichuan Province and analyze the prevalence of complications with hepatitis B virus(HBV)infection,hepatitis C virus(HCV)infection and Treponema pallidum(TP)infection in the emerging HIV infection patients.METHODS The result of HIV screening for the people who visited to Ziyang Central Hos-pital from Jan.1,2020 to Dec.31,2024 and the test results of HBV,HCV and TP for the emerging HIV infec-tion patients were collected and were summarized and statistically analyzed by SPSS.0 software.RESULTS Totally 289 891 case-times were tested for HIV,1529 cases were previously diagnosed with HIV,465 of whom were tested posi-tive for the first time,there was significant difference in the positive rate of test for the first time among the 5 years(x2=15.998,P=0.003).Totally 353 cases were confirmed positive among the 465 primary positive screening cases.Among the emerging HIV infection patients,the positive rate was higher in the male than in the female(x2=141.141,P<0.001),and the positive rate was high among the population aged more than 40 year old(x2=11.448,P<0.001),mi-grant workers(x2=270.110,P<0.001)and low education level population(x2=25.911,P<0.001).The detection rate of gp41 was up to 100.00%in strip type testing.The analysis of the ratio of relative light unit(RLU)to Cutoff val-ue(COI)in the initial screening experiment showed that when COI was greater than 50,all of the confirmed tests were positive,when COI ranged between 1 and 5,the false positive rate was 97.06%.The incidence of complica-tion with HBV infection in the emerging HIV infection patients was increased year by year(x2=20.355,P<0.001),and the incidence of complication with HCV infection was increased in recent two years(x2=10.690,P=0.030).CONCLUSIONS There is no obvious rise of positive rate of HIV screening among the people visiting to the hospital in recent 5 years.The sensitivity of the primary screening of clinical laboratory is high without posi-tive missing test.The positive rates of HBV and HCV are increased among the emerging HIV infection patients.
9.Advances in minimally invasive reduction of pelvic fractures
Jie HE ; Jingxin ZHAO ; Wenhao CAO ; Zhiguang CHEN ; Hongzhe QI ; Hao GUO ; Lin QI ; Jiaqi LI ; Hua CHEN ; Peifu TANG
Chinese Journal of Orthopaedic Trauma 2025;27(3):270-276
Conventional surgical management of pelvic fractures entails incision and reduction with internal fixation, a procedure associated with significant bleeding, trauma, and a high surgical risk. The advent of advanced imaging techniques and sophisticated surgical instruments has led to a paradigm shift towards minimally invasive surgery as the prevailing treatment modality for such injuries. The efficacy of reduction is pivotal in determining the clinical prognosis of pelvic fractures, underscoring the importance of enhancing the quality of reduction in the minimally invasive surgery. The advent of 3D printing technology, intelligent orthopaedic surgical robots, mixed reality augmentation technology and high-precision optical localization tracking has catapulted minimally invasive pelvic fracture reduction to the forefront of research in the field of orthopaedics. Studies have demonstrated encouraging outcomes. This paper reviews relevant literature, mainly focusing on the evaluation and measurement, open reduction techniques, minimally invasive closed reduction techniques, and surgical robot assisted reduction techniques in treatment of pelvic fractures, to summarize the technical research progress in minimally invasive closed surgical reduction for pelvic fractures.
10.Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury (version 2025)
Kai HUANG ; Lunhao BAI ; Qing BI ; Hong CHEN ; Jiwu CHEN ; Xuesong DAI ; Wenyong FEI ; Weili FU ; Zhizeng GAO ; Lin GUO ; Yinghui HUA ; Jingmin HUANG ; Suizhu HUANG ; Xuan HUANG ; Jian LI ; Qiang LI ; Shuzhen LI ; Yanlin LI ; Yunxia LI ; Zhong LI ; Ning LIU ; Yuqiang LIU ; Wei LU ; Hongbin LYU ; Haile PAN ; Xiaoyun PAN ; Chao QI ; Weiliang SHEN ; Luning SUN ; Jin TANG ; Zimin WANG ; Bide WANG ; Ru WANG ; Shaobai WANG ; Licheng WEI ; Weidong XU ; Yongsheng XU ; Jizhou YANG ; Liang YANG ; Rui YANG ; Hongbo YOU ; Tengbo YU ; Jiakuo YU ; Bing YUE ; Hua ZHANG ; Hui ZHANG ; Qingsong ZHANG ; Xintao ZHANG ; Jiajun ZHAO ; Lilian ZHAO ; Qichun ZHAO ; Song ZHAO ; Jiapeng ZHENG ; Jiang ZHENG ; Zhi ZHENG ; Jingbin ZHOU ; Jinzhong ZHAO
Chinese Journal of Trauma 2025;41(4):325-338
With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

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