1.Screen of FDA-approved drug library identifies vitamin K as anti-ferroptotic drug for osteoarthritis therapy through Gas6
Yifeng SHI ; Sunlong LI ; Shuhao ZHANG ; Caiyu YU ; Jiansen MIAO ; Shu YANG ; Yan CHEN ; Yuxuan ZHU ; Xiaoxiao HUANG ; Chencheng ZHOU ; Hongwei OUYANG ; Xiaolei ZHANG ; Xiangyang WANG
Journal of Pharmaceutical Analysis 2025;15(5):1033-1047
Ferroptosis of chondrocytes is a significant contributor to osteoarthritis(OA),for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis.Here,we screen for anti-ferroptotic drugs in Food and Drug Administration(FDA)-approved drug library via a high-throughput manner in chondrocytes.We identified a group of FDA-approved anti-ferroptotic drugs,among which vitamin K showed the most powerful protective effect.Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix(ECM)degradation in chondrocytes.Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus(DMM)mouse model.Mechanistically,transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6(Gas6).Furthermore,exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase(AXL)/phosphatidylinositol 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)axis.Together,we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis,indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.
2.Hearing loss prevalence and burden of disease in China: Findings from provincial-level analysis.
Yu WANG ; Yang XIE ; Minghao WANG ; Mengdan ZHAO ; Rui GONG ; Ying XIN ; Jia KE ; Ke ZHANG ; Shaoxing ZHANG ; Chen DU ; Qingchuan DUAN ; Fang WANG ; Tao PAN ; Furong MA ; Xiangyang HU
Chinese Medical Journal 2025;138(1):41-48
BACKGROUND:
Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China's aging society.
METHODS:
We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China.
RESULTS:
An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015.
CONCLUSIONS
The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.
Humans
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China/epidemiology*
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Hearing Loss/epidemiology*
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Prevalence
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Middle Aged
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Male
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Female
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Adult
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Aged
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Adolescent
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Young Adult
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Child
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Child, Preschool
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Infant
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Aged, 80 and over
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Cost of Illness
3.Clinical guideline for diagnosis and treatment of nonunion of osteoporotic vertebral fractures (version 2025)
Haipeng SI ; Le LI ; Junjie NIU ; Wencan ZHANG ; Fuxin WEI ; Jinqiu YUAN ; Qiang YANG ; Hongli WANG ; Guangchao WANG ; Shihong CHEN ; Yunzhen CHEN ; Xiaoguang CHENG ; Jianwen DONG ; Shiqing FENG ; Rui GU ; Yong HAI ; Tianyong HOU ; Bo HUANG ; Xiaobing JIANG ; Lei ZANG ; Chunhai LI ; Nianhu LI ; Hua LIN ; Hongjian LIU ; Peng LIU ; Xinyu LIU ; Sheng LU ; Shibao LU ; Chunshan LUO ; Lvy CHAOLIANG ; Lvy WEIJIA ; Xuexiao MA ; Wei MEI ; Chunyang MENG ; Cailiang SHEN ; Chunli SONG ; Ruoxian SONG ; Jiacan SU ; Honglin TENG ; Hui SHENG ; Beiyu WANG ; Bingwu WANG ; Liang WANG ; Xiangyang WANG ; Nan WU ; Guohua XU ; Yayi XIA ; Jin XU ; Youjia XU ; Jianzhong XU ; Cao YANG ; Maowei YANG ; Zibin YANG ; Xiaojian YE ; Hailong YU ; Xijie YU ; Hua YUE ; Zhili ZENG ; Xinli ZHAN ; Hui ZHANG ; Peixun ZHANG ; Wei ZHANG ; Zhenlin ZHANG ; Jianguo ZHANG ; Tengyue ZHU ; Qiang LIU ; Huilin YANG
Chinese Journal of Trauma 2025;41(10):932-945
Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.
4.The rehabilitation outcomes and medical expenditures of stroke patients in the neurology and rehabilitation departments using the International Classification of Functioning, Disability and Health′s Rehabilitation Set
Xiu XU ; Tanyao JIANG ; Tiebin YAN ; Sizhen CHEN ; Na YU ; Xiangyang CHEN ; Xinting ZHANG ; Zhongping ZHANG
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(9):847-852
Objective:To evaluate the outcomes of stroke treatment in neurology and rehabilitation departments using the International Classification of Functioning, Disability and Health′s Rehabilitation Set (ICF-RS).Method:The functional status of stroke survivors before and after treatment in the neurology and rehabilitation departments was evaluated using the ICF-RS (30 items). Each patient′s functioning was graded (normal, mild, moderate or severe dysfunction) by an experienced clinical evaluator and also by the intelligent evaluation model in the ICF-RS app. Medical expenditure data during hospitalization were extracted from the hospital′s case records. Rank sum tests compared the functional changes in a patient before and after their rehabilitation. Kappa coefficients were computed to evaluate the consistency of the functional grades assigned by the evaluators and the app.Results:Before the rehabilitation treatment, all 30 items of the ICF-RS were abnormal for all of the patients from the neurology and rehabilitation departments. After their rehabilitation treatment, 25 items had improved significantly for the neurology patients and 8 had improved significantly for those from the rehabilitation department. After their rehabilitation treatment, the average functional improvement among the neurology patients was 25%. For the rehabilitation patients it was 13%. The total expenditure for every 1% improvement in function was Y977 for the neurology patients (including Y143 for rehabilitation) and Y1, 481 for the rehabilitation patients (including Y862 of actual rehabilitation). The proportions of rehabilitation expenditure were thus 14% and 58% respectively. The kappa coefficients quantifying overall consistency were both greater than 0.8.Conclusion:The national standard ICF-RS can be used to evaluate functional changes, rehabilitation efficacy and the composition of stroke patients′ medical expenditures in the early stage of neurology and the recovery period in the rehabilitation department. The consistency of the functional level evaluations between the app and human evaluators is good.
5.Textual Research on Classical Formula Mulisan
Dongsen HU ; Xiangyang ZHANG ; Canran XIE ; Jiawei SHI ; Ziyi WANG ; Zhuoyan ZHOU ; Lin ZHANG ; Yexin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):191-200
The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas (second batch) of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha, Astragali Radix, Ephedrae Radix et Rhizoma, and wheat, with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution, composition, dosage, original plants and their processing methods, decocting method, efficacy, indications, and modern clinical application of Mulisan by tracing, comparative analysis, and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition, dosage, efficacy, and indications of Mulisan were first recorded in the Treatise on Diseases, Patterns, and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods, Ostreae Concha is the shell of Ostrea rivularis, which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica, respectively, the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum, which can be used without processing, while the stir-fried fruit, being thin and deflated, demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g, Astragali Radix 8.26 g, Ephedrae Radix et Rhizoma 8.26 g, and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL, and the decoction should be taken warm. In modern clinical practice, Mulisan has a wide range of indications, including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases, neurological diseases, respiratory system diseases, and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research, development, and clinical application of Mulisan.
6.Textual Research on Classical Formula Mulisan
Dongsen HU ; Xiangyang ZHANG ; Canran XIE ; Jiawei SHI ; Ziyi WANG ; Zhuoyan ZHOU ; Lin ZHANG ; Yexin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):191-200
The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas (second batch) of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha, Astragali Radix, Ephedrae Radix et Rhizoma, and wheat, with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution, composition, dosage, original plants and their processing methods, decocting method, efficacy, indications, and modern clinical application of Mulisan by tracing, comparative analysis, and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition, dosage, efficacy, and indications of Mulisan were first recorded in the Treatise on Diseases, Patterns, and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods, Ostreae Concha is the shell of Ostrea rivularis, which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica, respectively, the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum, which can be used without processing, while the stir-fried fruit, being thin and deflated, demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g, Astragali Radix 8.26 g, Ephedrae Radix et Rhizoma 8.26 g, and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL, and the decoction should be taken warm. In modern clinical practice, Mulisan has a wide range of indications, including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases, neurological diseases, respiratory system diseases, and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research, development, and clinical application of Mulisan.
7.Effects of Inhibiting the NKCC1/AQP4 Pathway on Neurological Injury Improvement in a Rat Model of High-Altitude Cerebral Edema
Huali GENG ; Baichuan LI ; Xu SONG ; Yilin XIA ; Xiangyang ZHOU ; Jing GAO ; Lei CHEN
Journal of Sichuan University (Medical Sciences) 2025;56(1):156-165
Objective To investigate the pathogenesis of high-altitude cerebral edema(HACE)and develop new therapeutic strategies.Methods Male Sprague-Dawley(SD)rats of 6 weeks old were selected and placed in a hypobaric chamber.The rats were exposed to the high-altitude environment of 7000 m above sea level for 3 days for HACE modeling.Whether the HACE model was successfully established in the rats was evaluated by measuring brain water content,the degree of disruption to the blood-brain barrier(BBB),and brain tissue Nissl staining.The experimental animals were divided into four groups,with 28 rats in each group.The blank control group was exposed to a normobaric and normoxic environment simulating the conditions at 500 m above sea level for 3 d.The other groups,including a model group(the HACE group),a bumetanide group(the positive control group),and a XH-6003 treatment group,were placed at an altitude of 7 000 m above sea level and were injected with normal saline,bumetanide,and XH-6003,a new type of Na-K-2C1 cotransporter 1(NKCC1)inhibitor,via the tail vein,respectively,twice daily for 3 d.The experimental animals were taken out of the hypobaric chamber for testing after 3 d.The primary outcome measures included brain water content,BBB permeability,changes in brain tissue morphology,and the expression levels of aquaporin-4(AQP4)and NKCC1.The secondary outcome measures included behavioral changes,apoptosis,and oxidative stress markers.Results The HACE rat model was successfully established.The model group exhibited increased brain water content(P<0.0001),BBB disruption(P<0.0001),impairment in learning skills and memory(P<0.001),and anxiety/depression-like behaviors(P<0.01).qPCR results showed significantly increased expression of NKCC1 and AQP4 in the brain tissue of the model group(P<0.01).Pathology examination revealed neuronal and glial cell damage in the hippocampus of the model group(P<0.01).Treatment with XH-6003,the NKCC1 inhibitor,reversed brain water content,BBB disruption,and neuronal and glial cell damage to a certain degree(P<0.05),decreased the expression of NKCC1 and AQP4 in the brain tissue(P<0.01),and inhibited apoptosis-related proteins.Among the oxidative stress indices,only glutathione(GSH)showed improvement(P<0.001).Rats treated with XH-6003 showed functional improvement only in the time spent exploring novel objects,while other behavioral outcomes remained unchanged.Conclusion HACE is associated with the activation of the NKCC1/AQP4 pathway.Inhibition of this pathway alleviates brain edema,BBB disruption,and neuronal and glial cell damage.These findings suggest that XH-6003 holds potential as a therapeutic strategy for HACE at the cellular and molecular levels,but its effects in improving HACE-related behavioral disorders warrant further investigation.
8.Effect of patellar morphology on functional recovery and patellofemoral joint alignment after unicompartmental knee arthroplasty
Yingjin SUN ; Ning LIU ; Long HUANG ; Shuo FENG ; Xiangyang CHEN
Chinese Journal of Tissue Engineering Research 2025;29(27):5826-5832
BACKGROUND:There are few studies on the effect of different patellar morphologies on the outcome after unicompartmental knee arthroplasty.OBJECTIVE:To investigate the effect of different patellar morphologies on functional recovery and patellofemoral joint alignment after unicompartmental knee arthroplasty based on patellar Wiberg classification.METHODS:A retrospective study was conducted in 186 patients with medial knee osteoarthritis who underwent unicompartmental knee arthroplasty at Affiliated Hospital of Xuzhou Medical University between January 2022 and March 2023.Patients were categorized into group A(type Ⅰ,n=43),group B(typeⅡ,n=104),and group C(type Ⅲ,n=39)according to the Wiberg classification.The Hospital for Specia Surgery knee score,Feller score,and incidence of anterior knee pain,as well as radiologic data(patellar index,patellar tilt angle,and lateral patellofemoral angle)were compared among the three groups.RESULTS AND CONCLUSION:(1)There was no significant difference in the Feller patellar score and Hospital for Specia Surgery score at the final postoperative follow-up in patients with Wiberg type Ⅰ,type Ⅱ,and type Ⅲ patellae(P>0.05).(2)Although there was no significant difference in the incidence of anterior knee pain among the three groups at the final follow-up,patients with type Ⅲ patellae were significantly more likely to have experienced anterior knee pain early in the postoperative period.(3)Different patellar morphologies can improve patellar position to some extent after unicompartmental knee arthroplasty,but type Ⅲ had greater patellar tilt than types Ⅰ and Ⅱ,both preoperatively and postoperatively.(4)This finding highlights the need for tailored morphological adjustments to the Wiberg Ⅲ patella during unicompartmental knee arthroplasty to improve surgical outcomes.
9.Efficacy and safety of high-frequency repetitive transcranial magnetic stimulation in postherpetic neuralgia
Yu ZHAO ; Xiangyang TANG ; Zuosheng CHEN ; Fengming YAO ; Wei JIANG ; Fei XU
Chinese Journal of Neuromedicine 2025;24(8):799-805
Objective:To evaluate the efficacy and safety of high-frequency repetitive transcranial magnetic stimulation (hrTMS) in postherpetic neuralgia (PHN).Methods:A prospective randomized controlled trial was performed; 63 PHN patients treated in Department of Neurology and Department of Dermatology and Venereology of Anqing Municipal Hospital from June 2024 to March 2025 were enrolled; they were randomly assigned to 2 groups: an hrTMS group ( n=32) received hrTMS (frequency: 10 Hz; total pulses: 2,400; intensity: 90% of resting motor threshold) to the contralateral primary motor cortex (M1), and a sham stimulation group ( n=31) received sham stimulation using a sham figure-of-eight coil generating no actual magnetic field. Scores of short-form McGill pain questionnaires (pain rating index [PRI] total score, PRI sensory subscore, PRI affective subscore, visual analogue scale [VAS] score, present pain intensity [PPI] score) and N100 amplitude were collected before treatment and at 1, 2, 3, and 4 weeks after treatment. Adverse events during treatment were recorded. Results:At 2 weeks after treatment, significant difference was observed between the hrTMS group and sham stimulation group in PRI total score, VAS score, and N100 amplitude ( P<0.05). At 3 and 4 weeks after treatment, significant differences were found between the two groups in PRI total score, PRI sensory subscore, PRI affective subscore, VAS score, PPI score and N100 amplitude (3 weeks after treatment: 8.59±1.13 vs. 9.61±1.20, 5.34±0.79 vs. 5.90±0.94, 3.25±0.57 vs. 3.71±0.46, 5.78±0.66 vs. 6.42±0.92, 2.16±0.37 vs. 2.55±0.51, and [2.53±0.51] μV vs. [2.13±0.34] μV; 4 weeks after treatment: 7.53±0.92 vs. 9.68±1.35, 4.94±0.62 vs. 6.00±1.07, 2.59±0.56 vs. 3.68±0.60, 5.06±0.67 vs. 6.23±1.06, 1.97±0.17 vs. 2.52±0.51, and [2.81±0.40] μV vs. [2.16±0.52] μV, P<0.05). In the hrTMS group, PRI total score, PRI sensory subscore, PRI affective subscore, VAS score, PPI score and N100 amplitude were significantly different at 2, 3, and 4 weeks after treatment compared with those before treatment ( P<0.05). Incidence of adverse events (headache, dizziness or tinnitus) did not differ significantly between the two groups ( P>0.05). Conclusion:The hrTMS applied to the M1 region in PHN patients is effective by obviously reducing pain intensity and improving negative emotional states, with favorable safety profile.
10.Optimal rotational alignment of the tibial component during Oxford unicompartmental knee arthroplasty
Ning LIU ; Yingjin SUN ; Long HUANG ; Shuo FENG ; Xiangyang CHEN
Chinese Journal of Tissue Engineering Research 2025;29(33):7158-7164
BACKGROUND:Unicompartmental knee arthroplasty effectively addresses medial knee osteoarthritis.The accurate tibial component rotational alignment is crucial to ensure the best surgical outcome.OBJECTIVE:To assess the impact of tibial component rotational alignment on short-term outcomes after unicompartmental knee arthroplasty in medial knee osteoarthritis patients.METHODS:From February 2021 to February 2023,91 patients who underwent mobile-bearing unicompartmental knee arthroplasty in Affiliated Hospital of Xuzhou Medical University were selected.According to the rotational alignment of tibial prosthesis relative to Akagi's line measured by postoperative CT,the patients were divided into three groups.Group A had internal rotation greater than 0°,group B had external rotation from 0° to 5°,and group C had external rotation greater than 5°.The knee range of motion,Oxford knee score,and forgotten joint score were recorded and compared among three groups preoperatively,at the last follow-up after surgery.RESULTS AND CONCLUSION:(1)At the last follow-up after surgery,the Oxford knee score of group B was significantly lower than that of group A(P=0.003)and group C(P=0.025).The knee range of motion of group B was higher than that of group A(P=0.011)and group C(P=0.024),and the forgotten joint score of group B was higher than that of group A(P=0.001)and group C(P=0.049).(2)The forgotten joint score in group C was significantly higher than that in group A at the last follow-up(P=0.044).(3)Patients were followed up for 12-36 months after arthroplasty.There were 2 and 7 cases of postoperative knee pain in groups B and C,and the difference was statistically significant(P=0.033).(4)It is indicated that external rotation of the tibial prosthesis by 0°-5° is ideal for achieving satisfactory short-term clinical outcomes,so we should avoid intraoperative tibial prosthesis malrotation.

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