BACKGROUND:A large number of studies have found that pyroptosis is closely related to the occurrence and development of motor system diseases,but there are few studies and reviews on pyroptosis in motor system diseases.OBJECTIVE:To review the current clinical and preclinical studies,summarize the role of pyroptosis in motor system diseases and related molecular mechanisms,and provide reference for the pyroptosis-targeted treatment for motor system diseases in the future.METHODS:The relevant literatures in PubMed and CNKI database were searched by computer from January 2000 to January 2024.The English search terms were"pyroptosis,tendons,ligaments,cartilage,muscles,bones"and the Chinese search terms were"pyroptosis,tendon,ligament,cartilage,skeletal muscle,bone"in Chinese.A combination of subject terms and free search terms was used.There were a total of 422 documents,including 334 in English and 88 in Chinese.After excluding duplicate literature and irrelevant literature,the literature without inclusion value was further excluded by reading the whole paper,and finally 78 documents were included for review and analysis.RESULTS AND CONCLUSION:Different pathways of pyroptosis and subsequent inflammatory responses can affect the progression of motor system diseases and the repair process of injuries.Excessive pyroptosis can not only cause a large number of tissue cells to die,but also aggravate tissue inflammation and degrade the extracellular matrix through substances such as inflammatory factors released after cell lysis,and damaging related molecular patterns can act as upstream signals to further aggravate pyroptosis.Current methods for preventing and treating motor system diseases mainly include NOD-like receptor thermal protein domain-associated protein 3 inhibitors,Chinese herbal extracts,exosome therapy,mesenchymal stem cell therapy,and exercise therapy.The review suggests that targeted intervention of some key factors in the process of pyroptosis may be a new direction for the treatment and prevention of motor system diseases.

Objective:To evaluate the efficacy and safety of upadacitinib in the real-world treatment of difficult-to-treat Crohn's disease (DTT-CD) .Methods:This multicenter, retrospective cohort study included patients diagnosed with DTT-CD according to the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) criteria, and treated at eight Chinese inflammatory bowel disease centers between January 2023 and March 2025. Clinical outcomes were assessed after 12 weeks of induction therapy with upadacitinib (45 mg qd), including clinical remission rate, clinical response rate, and incidence of adverse events.Results:Among 151 enrolled DTT-CD patients, the clinical remission rate was 47.0%, and the clinical response rate was 90.7% after 12 weeks of treatment. Adverse events occurred in 42 cases (27.8%) .Conclusion:Upadacitinib demonstrated favorable efficacy in inducing clinical remission in DTT-CD patients, with a good safety profile at the induction dose (45 mg qd) .

Objective:To explore the impact of a comprehensive fall prevention training program on early postural con-trol disorders in elderly patients with Parkinson's disease(PD).Method:Thirty-five early PD patients were randomized into two groups:a conventional training group(n=18)and a fall prevention training group(n=17).Both groups received standard pharmacological therapy and routine functional training,which included strength training and aerobic exercise.The fall prevention training group ad-ditionally received posture control training based on central regulatory mechanisms.All the training were con-ducted 5 sessions per week over an 8-week period.Assessments were performed using a dynamic and static balance training system prior to the program and again after 8 weeks of intervention.The evaluation comprised the sensory organization test(SOT),limits of stability(LOS),and timed up and go test(TUG),as well as the unified Parkinson's disease rating scale Ⅲ(UPDRS-Ⅲ)and Parkinson's disease questionnaire 39(PDQ-39).Result:Within-group comparisons:the total SOT score,SOT proprioception,SOT vestibular function,and the max excursions(MXE)in forward,backward,leftward,and rightward directions in the fall prevention training group were significantly higher after treatment(P<0.05).The visual dependency and visual scores of the SOT in the fall prevention training group did not show significant differences compared to before treat-ment(P>0.05).In the conventional training group,there were no significant differences in total SOT scores,SOT proprioception,SOT visual dependence,SOT vestibular function,or visual scores before and after treat-ment(P>0.05).The leftward MXE in the conventional training group showed a significant increase after treat-ment(P<0.05),while there were no significant differences in forward,backward,and rightward MXE(P>0.05).Both groups exhibited significant decreased TUG,UPDRS-Ⅲ,and PDQ-39 scores after treatment(P<0.05).Between-group comparisons:the total SOT score and vestibular function score in the fall prevention training group was higher than in the conventional training group after treatment(P<0.05,P<0.01).The TUG score in the fall prevention training group was lower than in the conventional training group after treatment(P<0.05).Prior to treatment,there were no significant differences in all indicators between the two groups(P>0.05).There were no significant differences in SOT proprioception,SOT visual dependence,SOT visual scores,MXE in forward,backward,leftward,and rightward directions,UPDRS-Ⅲ,and PDQ-39 after treat-ment between the two groups(P>0.05).Conclusion:The fall prevention training program designed for early PD patients in this study can significantly improve the balance-related sensory integration,proprioception,and vestibular function in these patients,en-hance their MXE in LOS.However,the effects on functional mobility,motor function,and quality of life re-main unclear.Further studies are needed to explore the long-term efficacy of this training program on early postural control disorders in PD patients and its effects on PD patients with cognitive impairments.

Objective:To evaluate the efficacy and safety of upadacitinib in the real-world treatment of difficult-to-treat Crohn's disease (DTT-CD) .Methods:This multicenter, retrospective cohort study included patients diagnosed with DTT-CD according to the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) criteria, and treated at eight Chinese inflammatory bowel disease centers between January 2023 and March 2025. Clinical outcomes were assessed after 12 weeks of induction therapy with upadacitinib (45 mg qd), including clinical remission rate, clinical response rate, and incidence of adverse events.Results:Among 151 enrolled DTT-CD patients, the clinical remission rate was 47.0%, and the clinical response rate was 90.7% after 12 weeks of treatment. Adverse events occurred in 42 cases (27.8%) .Conclusion:Upadacitinib demonstrated favorable efficacy in inducing clinical remission in DTT-CD patients, with a good safety profile at the induction dose (45 mg qd) .

BACKGROUND:A large number of studies have found that pyroptosis is closely related to the occurrence and development of motor system diseases,but there are few studies and reviews on pyroptosis in motor system diseases.OBJECTIVE:To review the current clinical and preclinical studies,summarize the role of pyroptosis in motor system diseases and related molecular mechanisms,and provide reference for the pyroptosis-targeted treatment for motor system diseases in the future.METHODS:The relevant literatures in PubMed and CNKI database were searched by computer from January 2000 to January 2024.The English search terms were"pyroptosis,tendons,ligaments,cartilage,muscles,bones"and the Chinese search terms were"pyroptosis,tendon,ligament,cartilage,skeletal muscle,bone"in Chinese.A combination of subject terms and free search terms was used.There were a total of 422 documents,including 334 in English and 88 in Chinese.After excluding duplicate literature and irrelevant literature,the literature without inclusion value was further excluded by reading the whole paper,and finally 78 documents were included for review and analysis.RESULTS AND CONCLUSION:Different pathways of pyroptosis and subsequent inflammatory responses can affect the progression of motor system diseases and the repair process of injuries.Excessive pyroptosis can not only cause a large number of tissue cells to die,but also aggravate tissue inflammation and degrade the extracellular matrix through substances such as inflammatory factors released after cell lysis,and damaging related molecular patterns can act as upstream signals to further aggravate pyroptosis.Current methods for preventing and treating motor system diseases mainly include NOD-like receptor thermal protein domain-associated protein 3 inhibitors,Chinese herbal extracts,exosome therapy,mesenchymal stem cell therapy,and exercise therapy.The review suggests that targeted intervention of some key factors in the process of pyroptosis may be a new direction for the treatment and prevention of motor system diseases.

Objective:To explore the impact of a comprehensive fall prevention training program on early postural con-trol disorders in elderly patients with Parkinson's disease(PD).Method:Thirty-five early PD patients were randomized into two groups:a conventional training group(n=18)and a fall prevention training group(n=17).Both groups received standard pharmacological therapy and routine functional training,which included strength training and aerobic exercise.The fall prevention training group ad-ditionally received posture control training based on central regulatory mechanisms.All the training were con-ducted 5 sessions per week over an 8-week period.Assessments were performed using a dynamic and static balance training system prior to the program and again after 8 weeks of intervention.The evaluation comprised the sensory organization test(SOT),limits of stability(LOS),and timed up and go test(TUG),as well as the unified Parkinson's disease rating scale Ⅲ(UPDRS-Ⅲ)and Parkinson's disease questionnaire 39(PDQ-39).Result:Within-group comparisons:the total SOT score,SOT proprioception,SOT vestibular function,and the max excursions(MXE)in forward,backward,leftward,and rightward directions in the fall prevention training group were significantly higher after treatment(P<0.05).The visual dependency and visual scores of the SOT in the fall prevention training group did not show significant differences compared to before treat-ment(P>0.05).In the conventional training group,there were no significant differences in total SOT scores,SOT proprioception,SOT visual dependence,SOT vestibular function,or visual scores before and after treat-ment(P>0.05).The leftward MXE in the conventional training group showed a significant increase after treat-ment(P<0.05),while there were no significant differences in forward,backward,and rightward MXE(P>0.05).Both groups exhibited significant decreased TUG,UPDRS-Ⅲ,and PDQ-39 scores after treatment(P<0.05).Between-group comparisons:the total SOT score and vestibular function score in the fall prevention training group was higher than in the conventional training group after treatment(P<0.05,P<0.01).The TUG score in the fall prevention training group was lower than in the conventional training group after treatment(P<0.05).Prior to treatment,there were no significant differences in all indicators between the two groups(P>0.05).There were no significant differences in SOT proprioception,SOT visual dependence,SOT visual scores,MXE in forward,backward,leftward,and rightward directions,UPDRS-Ⅲ,and PDQ-39 after treat-ment between the two groups(P>0.05).Conclusion:The fall prevention training program designed for early PD patients in this study can significantly improve the balance-related sensory integration,proprioception,and vestibular function in these patients,en-hance their MXE in LOS.However,the effects on functional mobility,motor function,and quality of life re-main unclear.Further studies are needed to explore the long-term efficacy of this training program on early postural control disorders in PD patients and its effects on PD patients with cognitive impairments.

BACKGROUND:Various clinical strategies for the treatment of tendinopathy have good short-term effects but poor long-term effects,and some studies have proven that mitochondria are closely related to the occurrence and development of tendinopathy.However,the relationship between mitochondria and tendinopathy and mitochondria-targeting therapeutic strategies for tendinopathy have not been summarized so far,which is not good for specialists and scholars in related fields to understand the recent research situation.OBJECTIVE:To review the existing clinical or preclinical original studies,in order to summarize the relationship between mitochondrial dysfunction and tendinopathy and the mitochondria-targeting methods for the treatment of tendinopathy,and to provide certain prospects for the evaluation and management of mitochondria in tendinopathy in the future.METHODS:The relevant literatures in PubMed,Web of Science,CNKI,WanFang and VIP databases were searched.The search time was from January 2009 to March 2024,and the search terms were"tendinopathy,tendon injuries,tendon,tendons,mitochondria,mitochondria dysfunction,mitochondria disease"both in English and Chinese.According to the exclusion and inclusion criteria,62 articles were finally included for review and analysis.RESULTS AND CONCLUSION:(1)In clinical tendinopathy patients or tendinopathy models,mitochondrial dysfunction is common,mainly represented by excessive production of reactive oxygen species,decreased activity of superoxide dismutase,ridge clutter and decreased number of mitochondria,which indicates that mitochondrial dysfunction will occur due to tendon injury,thus further worsening tendinopathy and forming a vicious cycle.(2)When the tendon has not been injured or tendinopathy has not yet occurred,the mitochondrial function will be affected by various internal and external factors,resulting in tendinopathy.This indicates that the normal tendon will be damaged,lesioned or even ruptured due to the abnormal function of the mitochondria.(3)Mechanical tensile stress,advanced glycosylation end products,aging and other internal and external factors are the main causes of mitochondrial dysfunction,and these factors will damage and weaken the biological activity and mechanical properties of normal tendons through molecular mechanisms such as apoptosis,inflammation and respiratory chain damage,and thereby induce tendinopathy.(4)According to molecular mechanisms,mitochondria-targeting therapies mainly include mitochondrial transfer/transplantation,transplantation,targeted antioxidants,etc.(5)This review mainly aims at clinical patients with tendinopathy or animal models with similar modeling methods,providing a reliable idea for clinical exploration of the pathogenesis of tendinopathy and targeted therapies for tendinopathy.However,the disadvantage is that the included studies are mainly animal experiments,and there is a lack of more clinical trials for verification.

BACKGROUND:Various clinical strategies for the treatment of tendinopathy have good short-term effects but poor long-term effects,and some studies have proven that mitochondria are closely related to the occurrence and development of tendinopathy.However,the relationship between mitochondria and tendinopathy and mitochondria-targeting therapeutic strategies for tendinopathy have not been summarized so far,which is not good for specialists and scholars in related fields to understand the recent research situation.OBJECTIVE:To review the existing clinical or preclinical original studies,in order to summarize the relationship between mitochondrial dysfunction and tendinopathy and the mitochondria-targeting methods for the treatment of tendinopathy,and to provide certain prospects for the evaluation and management of mitochondria in tendinopathy in the future.METHODS:The relevant literatures in PubMed,Web of Science,CNKI,WanFang and VIP databases were searched.The search time was from January 2009 to March 2024,and the search terms were"tendinopathy,tendon injuries,tendon,tendons,mitochondria,mitochondria dysfunction,mitochondria disease"both in English and Chinese.According to the exclusion and inclusion criteria,62 articles were finally included for review and analysis.RESULTS AND CONCLUSION:(1)In clinical tendinopathy patients or tendinopathy models,mitochondrial dysfunction is common,mainly represented by excessive production of reactive oxygen species,decreased activity of superoxide dismutase,ridge clutter and decreased number of mitochondria,which indicates that mitochondrial dysfunction will occur due to tendon injury,thus further worsening tendinopathy and forming a vicious cycle.(2)When the tendon has not been injured or tendinopathy has not yet occurred,the mitochondrial function will be affected by various internal and external factors,resulting in tendinopathy.This indicates that the normal tendon will be damaged,lesioned or even ruptured due to the abnormal function of the mitochondria.(3)Mechanical tensile stress,advanced glycosylation end products,aging and other internal and external factors are the main causes of mitochondrial dysfunction,and these factors will damage and weaken the biological activity and mechanical properties of normal tendons through molecular mechanisms such as apoptosis,inflammation and respiratory chain damage,and thereby induce tendinopathy.(4)According to molecular mechanisms,mitochondria-targeting therapies mainly include mitochondrial transfer/transplantation,transplantation,targeted antioxidants,etc.(5)This review mainly aims at clinical patients with tendinopathy or animal models with similar modeling methods,providing a reliable idea for clinical exploration of the pathogenesis of tendinopathy and targeted therapies for tendinopathy.However,the disadvantage is that the included studies are mainly animal experiments,and there is a lack of more clinical trials for verification.

BACKGROUND:Reactive oxygen species may be closely related to the occurrence and development of tendinopathy,but its exact role and related signal transduction mechanism have not been fully summarized. OBJECTIVE:To review current clinical or preclinical original studies,summarize the role of reactive oxygen species in tendinopathy and related signal transduction pathways and to explore its characteristics and whether there is a unified downstream pathway. METHODS:Relevant original studies in PubMed,Embase,Web of Science,as well as CNKI,WanFang,and VIP databases were searched by computer and the search results were screened and excluded according to the inclusion criteria.Ninety articles were finally included for review and analysis. RESULTS AND CONCLUSION:Reactive oxygen species affects the direction of tendon healing by simultaneously acting on tendon cells and the extracellular matrix,and it exhibits a bifacial effect in the treatment of tendinopathy.Concentration of reactive oxygen species may be the key to determining its direction of action.The possibility that low-dose reactive oxygen species can participate in the normal physiological healing of tendons or that tendon tissues are adaptive to stimulations may be the underlying mechanism that produces this characteristic effect.Reactive oxygen species affect the composition and structure of the extracellular matrix and normal tendon repair as well as maintain viability in response to external stimulations through matrix metalloproteinases,mitogen-activated protein kinases,mitochondrial apoptosis,the forkhead transcription factor O family,autophagy,inflammation,and antioxidant signaling pathways.Different reactive oxygen species stimulation intensities,durations,and external environments may cause different alterations in downstream molecular pathways and thus have different effects on the tendon.Due to the large gap in the number of literature included in the evaluation of the positive and negative effects of reactive oxygen species,it may cause some analytical error in the search for factors behind the characteristics of the action of reactive oxygen species in tendon.In addition,most experimental intervention conditions and results of interest are relatively homogeneous;therefore,the temporal and quantitative mechanisms of reactive oxygen species and the synergistic effects with other intervention factors have not been clarified,and the overall system of molecular actions of reactive oxygen species in tendinopathy has not been constructed.To conclude,reactive oxygen species might be involved in the treatment and prevention of tendinopathies as a beneficial factor in the future,and facilitate the exploration of oxidative stress signaling pathways and overall molecular action systems in tendinopathies thereafter,as well as lay the foundation for research on the therapeutic strategies of different antioxidants in tendinopathies to better prevent and treat tendon injury and degeneration.

BACKGROUND:Increasing studies have found that estrogen has a certain correlation with tendinopathy,but for a long time,there are few experiments and summaries of estrogen in tendinopathy,which makes it difficult for specialists and scholars in related fields to fully understand the research status. OBJECTIVE:To summarize the current clinical or preclinical original research,so as to summarize the role of estrogen in tendinosis,and make a certain prospect for the evaluation and management of estrogen in tendinosis in the future. METHODS:Relevant literature in PubMed,Web of Science,CNKI,WanFang,and VIP databases were searched by computer.Search time was from January 2008 to September 2023.The search terms were"oestrogen,estrogen,estrogen receptor,tendinopathy,tendonopathy,sinew,tendon,tendons,myotenositis"in English and"estrogen,estrogen receptor,tendinosis,tendon,tendinitis"in Chinese.According to the selection criteria,the search results were screened and excluded,and finally 60 documents were included for review and analysis. RESULTS AND CONCLUSION:In vivo studies have shown that estrogen can promote tendon anabolism.In vitro experiments have also proved that various estrogens can promote the proliferation of tendon cells and reduce inflammation and apoptosis,but most of the experiments are limited to animal models.Estrogen receptor β acts more in tendon injury and repair processes,but estrogen receptor α has not been found to have a major impact on tendon injury.The expression of estrogen receptor β can repair the tendon by affecting the formation of fat,the deposition of type I collagen and reducing the apoptosis of tendon cells,while its over-expression may promote inflammation and angiogenesis,thus promoting the inflammatory process and playing a role in tendon injury.Animal studies have shown that estrogen deficiency may reduce the synthesis efficiency of collagen in the tendon,decrease the elasticity of tendon,inhibit the synthesis and metabolism of the tendon,which is not conducive to the repair of tendon injury,while normal level of estrogen may stimulate the synthesis of type I collagen in tendon and promote the proliferation and metabolism of tendon cells.At present,the molecular mechanism of estrogen in tendon injury has not been fully explained.More experiments focus on tendon collagen synthesis,cell proliferation and apoptosis.Only a few documents have studied the molecular mechanisms of estrogen receptor β deficiency regulating interferon regulatory factor 5-chemokine ligand 3 axis,E2 regulating estrogen receptor α and PI-3K-Akt signaling pathways,and high levels of estradiol reducing the level of free-circulating insulin-like growth factor.Various estrogens,including endogenous estrogens and phytoestrogens,are beneficial to the repair of tendinopathy at normal levels,and estrogen receptor β mainly affects the formation of fat,the deposition of type I collagen and the reduction of apoptosis of tendon cells through,which lays a foundation for the future treatment of tendinopathy with different subtypes of estrogens in vivo and the influence of estrogen membrane receptors on tendinopathy.