Tremor is a movement disorder that significantly impacts an individual’s physical stability and quality of life, and conventional medication or surgery often falls short in providing a cure. Rehabilitation training is, therefore, used as an auxiliary method to mitigate the exacerbation of individual tremors. Video-based rehabilitation training is a form of therapy that allows patients to exercise at home, reducing pressure on rehabilitation institutions’ resources. However, it has limitations in directly guiding and monitoring patients’ rehabilitation, leading to an ineffective training effect. This study proposes a low-cost rehabilitation training system that utilizes optical see-through augmented reality (AR) technology to enable tremor patients to conduct rehabilitation training at home. The system provides one-on-one demonstration, posture guidance, and training progress monitoring to achieve an optimal training effect. To assess the system’s effectiveness, we conducted experiments comparing the movement magnitudes of individuals with tremors in the proposed AR environment and video environment, while also comparing them with standard demonstrators. Participants wore a tremor simulation device during uncontrollable limb tremors, with tremor frequency and amplitude calibrated to typical tremor standards. The results showed that participants’ limb movement magnitudes in the AR environment were significantly higher than those in the video environment, approaching the movement magnitudes of the standard demonstrators. Hence, it can be inferred that individuals receiving tremor rehabilitation in the AR environment experience better movement quality than those in the video environment. Furthermore, participant experience surveys revealed that the AR environment not only provided a sense of comfort, relaxation, and enjoyment but also effectively guided them throughout the rehabilitation process. A tremor is a type of involuntary muscle contraction that results in shaking or trembling. It is a common symptom of movement disorders that affects a large number of people . There aTremors can significantly impact an individual’s quality of life by affecting their ability to perform everyday activities such as eating, writing, and using a phone. These challenges can lead to feelings of frustration and a loss of independence. Therefore, it is crucial to invest in research and technological support to develop effective treatments, Rehabilitation, and support technologies that can alleviate the effects of tremors.Pharmacotherapy has long been the conventional approach for managing tremors in patients with ET and PT, but its effectiveness is often hindered by various factors, including drug-drug interactions, intolerable side effects, and inadequate therapeutic response. For example, dopaminergic drugs, which are commonly prescribed for PT, only alleviate tremors in about half of the patients . SimilarRehabilitation is an important adjunct to clinical medical treatment for tremors, particularly in patients with mild to moderate disease who are reluctant to undergo surgery and can benefit from physical therapy programs. Various approaches have been studied, including flexibility and strength training. Sajjad Farashi et al.  conducteVirtual reality or augmented reality technology can overcome the limitations of video-based rehabilitation training methods by providing interactive visuals and personalized guidance, thus increasing patient engagement and motivation during the rehabilitation process. Hueso et al.  developeAugmented reality refers to the combination of digital information from a virtual world with the physical environment of the real world to create a more interactive and immersive user experience. Wang et al. ,24 conduConsidering the lack of a specialized augmented reality system for rehabilitation training specifically designed for patients with tremors and the need to improve the effectiveness and experience of rehabilitation training that can be conducted at home by patients with tremors, including one-on-one demonstration, posture guidance, and monitoring of training progress, we developed a low-cost augmented reality tremor rehabilitation training system using Oculus Quest 2. This study used Optitrack to record standard Yapa-PBGA movements and incorporated them into the system, creating a one-on-one virtual model for rehabilitation training. By designing natural interaction logic in the system, individuals with tremors can be guided to perform accurate limb movements during rehabilitation training. The patients’ actual limb movement data can also be recorded and analyzed in real-time by the system.’s position (posture) during rehabilitation training.In this study, an optical see-through AR system based on Yapa-PBGA is proposed to support individuals with tremors in rehabilitation training. The system employs Oculus Quest 2 and its self-contained controller, Oculus Touch. As illustrated in In the system environment, the user is rehabilitated as if he/she were playing Frisbee. The user can not only see his/her body and hands, but also a human-like avatar, virtual targets, and visual prompting for hand positions. This avatar is designed so that it simulates the gymnastic posture of the instructor in Yapa-PBGA and is registered in the physical environment to demonstrate the physical movements of rehabilitation training See a. A virtYapa Parkinson balance and gait aerobics abbreviated as Yapa-PBGA is a video-based dexterity training gymnastics for tremor patients that is proposed by the National Clinical Research Center for Geriatric Disorder, XiangYa Hospital , to imprTo create an immersive rehabilitation training experience that simulates the presence of a virtual demonstrator performing gymnastics in front of the user, we have designed a gymnastics demonstrator Avatar. According to the Yapa-PBGA posture model, a motion actor who underwent extensive Yapa-PBGA training was arranged to carefully choreograph and record the movements of Aatar, ensuring the accuracy of the postures.In ’s sense of achievement. (6) The actual landing position of the frisbee is dynamically adjusted according to the user’s 3D spatial coordinate position to ensure accurate landing on the user’s hand position. Using this natural interaction logic can promote users to maintain standard limb postures during training, improving the quality of rehabilitation training.To guide users to maintain standard limb postures during rehabilitation training and make the training more engaging, a natural interaction logic of catching frisbees is designed for the rehabilitation training system. Specifically, the interaction logic includes (1) The rehabilitation training system first presents the standard limb postures to guide users to maintain the correct posture. (2) Frisbees fly from a distance and reach only the hand positions corresponding to the standard limb movements. (3) Users need to catch the virtual frisbees within a specified time. (4) Users receive visual feedback from the frisbees when they successfully catch them, enhancing their perceptual experience. (5) When the user successfully catches a virtual frisbee, the system emits Vibration Feedback to enhance the userp is the position of the user’s hand/Oculus Touch relative to the helmet.The user’s motion data are tracked by Oculus Touch. In light of the fact that a tremor patient’s vibration frequency is generally less than 10 Hz, according to the Shannon theorem, the actual detection frequency that was set at 20 Hz was sufficient to meet the motion data collected without any distortions. User quality of movement in each gymnastic posture is measured by comparing user motion data with Frisbee positions. As shown in Equation (1), when the Euler distance between the Frisbee and the handle is less than 100 mm, i.e., when the user’s limb is close to the specified position. The system offers the user both visual feedback on the frisbee’s disappearance and haptic feedback through vibrations.’s disease (PT) and primary tremor (ET), participants were asked to wear a tremor simulator. Our study used a tremor simulator, shown in ’s left and right hands, 3 cm from the elbow joint and 2 cm from the wrist joint. To replicate the tremor experienced by patients with PT and ET, we used a tremor simulator to randomly apply two types of electrical pulses to the participants’ upper limbs. One signal caused the limb to tremble at a fixed frequency of approximately 5 Hz, while the other allowed the limb to oscillate voluntarily at a frequency of 4 to 7 Hz. We assessed their limb tremor status with Oculus Touch before each experiment to ensure that participants’ involuntary limb tremors met tremor criteria.As part of the study, experiments were conducted to test the efficacy of the proposed system in helping people with tremor during rehabilitation. To simulate patients with ParkinsonThe experiment will record participants’ motions in the video and AR environments, respectively. To objectively compare the effects of rehabilitation training in the video and AR environments, this study further processed the sampled data and analyzed the magnitude of the body movements of the participants as they performed the rehabilitation postures in Q1: I feel comfortable doing rehabilitation training in this environment.Q2: I feel interested in rehabilitating in this environment.Q3: I find it easy to do rehabilitation in this environment.Q4: I think I can tolerate rehabilitation in this environment.Q5: I feel unburdened by rehabilitation in that environment.Q6: I feel that the body movements are standard in this environment.Q7: I feel like I can follow the pace of rehabilitation training in this environment.Q8: I feel like the environment can guide my body movements.Q9: I feel as if rehabilitation in that environment would have good results.Q10: I am satisfied with my rehabilitation training in this environment.Q11 (SO): Sense of Ownership: I felt as if I was touching the virtual object directly with my hands, forgetting the existence of the handle.Q12 (SA) SA: The human-computer interaction is easy to control without a sense of dissonance in the AR rehabilitation system.An in-depth survey of the participants’ rehab experiences was conducted through the use of the following questionnaire. The psychological feelings in relation to questions from Q1 to Q12 were rated based on a seven-point Likert scale, ranging from 0 (strongly disagree) to 7 (strongly agree).Firstly, we invited a physically healthy Yapa-PBGA demonstrator to perform a set of standard exercises. Throughout the entire training routine, the demonstrator wore an Oculus Touch, and the 3D positional coordinates of his upper limb movements were fully recorded. Subsequently, we extracted data from the movements in the postures shown in As a way of clearly describing, analyzing, and comparing the two rehabilitation modalities in the following sections, “Video” and “AR” represent the video and AR rehabilitation conditions, respectively, “Q1” to “Q10”, the experience investigations, and “G1” to “G9” , the rehab postures.p < 0.05 level for G2, G3, G4, G5, G7, and G9. In groups G1 and G8, significant differences were commonly found in the L group, but not found in the R group. The results revealed that for most rehab postures, the magnitude of human motion in the AR condition was significantly greater than that in the video environment. As shown in A compared T-test was conducted to compare the magnitude of the mean body movement of participants making G1 to G9 under the “video” and “AR” conditions see . There wp < 0.01. The results showed that the participants felt comfortable and easy doing rehabilitation, did not perceive the physical burden, and were able to tolerate the intensity of the rehabilitation training. In the analysis, we compared the differences between the two conditions on the basis of Q6 to Q8 and found significant differences at p < 0.01. The result shows that the participants were more likely to be guided by rehabilitation training. Thus, the participants were more confident in performing standard rehabilitation training movements in the AR environment. There are no significant differences between the conditions in Q7, however, as the participants generally rated it very well  and the sense of agency (SA) are two central aspects of bodily self-awareness; the sense of ownership would be considered a direct perceptual experience, while the sense of agency is the sense of controlling and causing the body to act through volition, two important properties of operational logic in human-computer interaction. As we calculated the mean and standard deviation on the questionnaire of Q11 (SO) and Q12 (SA), we found a mean of 5.5 with a variation of 0.48, and a mean of 5.7, with a deviation of 0.3. This implies that participants are prone to the illusion that they are touching virtual objects, that the interaction can be easily controlled, and that users do not experience a strong sense of dissonance in the AR environment.Rehabilitation is an important way to reduce the severity and progression of tremors, and Yapa-PBGA provides a low-cost video rehabilitation program that can be used by patients at home. However, this program has limitations in providing face-to-face guidance for patients and does not track the quality of movements during rehabilitation. To address these limitations and better assist tremor patients with their rehabilitation at home, a low-cost AR system has been demonstrated to create an immersive rehab experience. This system simulates an instructor demonstrating gymnastics in front of the user, while also guiding the user’s body movements during the rehabilitation process.To evaluate the effectiveness of the proposed AR system in supporting individuals with tremors to achieve better results in Yapa-PBGA gymnastics, experiments were conducted to compare and analyze the magnitude of body movements of individuals with tremors in the video and AR environments, as well as that of the control group. The magnitude of movement is an objective measure of how well the movement achieves the correct posture, and the greater the magnitude, the better the rehabilitation will be. In most rehabilitation postures, participants demonstrated significantly greater magnitudes of limb movement in the AR environment, approaching the demonstrator’s level, compared to the video environment. However, no statistically significant differences were observed in G1 (R) and G8 (R). Further analysis revealed that this was due to the fact that these two groups used poses involving hands on the waist, which are easy to assume and least influenced by experimental conditions. Therefore, G1 (R) and G8 (R) were not considered in the final experimental conclusion. It can be concluded that the proposed AR method is effective in improving the quality of movement for individuals with tremors. User experience surveys showed that participants felt more relaxed, comfortable, and engaged when using the proposed AR system compared to the video environment. The proposed AR system was also effective in providing rehabilitation guidance to individuals with tremors. Although there was no significant difference between the AR environment and the video environment in Q7, the actual evaluation revealed that participants could follow the pace of rehabilitation training under AR conditions. Additionally, an analysis of the sense of ownership and agency of participants with tremors found that the AR system was effective in providing them with a natural rehabilitation experience without causing dissatisfaction.This study aimed to develop a low-cost augmented reality rehabilitation training system that would enable tremor patients to receive training at home with guidance. We created a set of rehabilitation posture models by extracting basic movements from Yapa-PBGA and established a one-to-one avatar demonstration training action through three-dimensional reconstruction and virtual mapping. To make rehabilitation training more engaging, we designed a natural interaction logic using a frisbee interaction mode to guide rehabilitation trainees’ posture and provide necessary visual and tactile interaction feedback. We evaluated the effectiveness of our proposed tremor rehabilitation system by conducting simulated experiments and comparing it with traditional video rehabilitation methods. The results showed that our system significantly improved the movement quality of tremor patients while providing a more relaxed, comfortable, guided, and controllable rehabilitation experience than video rehabilitation methods. However, due to the limited number of patients tested, further optimization and discussion are still necessary for clinical settings. Long-term tracking and evaluation of the system’s effectiveness are also essential. Therefore, we plan to continue improving the system and expanding the sample size in future research to further validate its effectiveness and feasibility.


Aim: The objective of this study is to evaluate the safety, utilisation, and effectiveness of a novel, virtual rehabilitation programme for survivors of SARS‑CoV‑2 infection (COVID-19) and intensive care admission.Methods: A service evaluation was performed. Adults admitted to a United Kingdom intensive care unit with COVID-19-induced respiratory failure and surviving hospital discharge were invited to an eight-week rehabilitation programme. The programme consisted of virtually delivered exercise classes and support groups led by critical care physiotherapists and follow-up nurses.p < 0.001), perceived breathlessness , shoulder disability , anxiety , depression , and psychological distress . No adverse events or injuries were recorded during the programme.Results: Thirty-eight of 76 eligible patients (50%) agreed to participate, of which 28 (74%) completed the rehabilitation programme. On completion of the rehabilitation programme, there were significant improvements in exercise capacity (one-minute sit-to-stand test; 20 stands vs. 25 stands, Conclusion: It is feasible to recruit and retain survivors of COVID-19-induced respiratory failure for virtual post-intensive-care rehabilitation. It appears that the virtual rehabilitation programme is safe and improves physical and psychological morbidity. Critical illness's physical and psychological sequelae are well documented and collectively known as post-intensive care syndrome (PICS) . PICS isMuscle weakness and reduced exercise capacity contribute to delayed physical recovery due to an ongoing cycle of reduced physical activity and the propagation of sarcopenia and frailty . NeuropsAcute respiratory failure following a SARS‑CoV‑2 infection (COVID-19) has resulted in a sudden surge in ICU admissions worldwide . The phyRehabilitation has been recognised as an essential component in the recovery from PICS and COVID-19 -10. HoweThe post-intensive-care follow-up service at our institution formerly consisted of a weekly rehabilitation class and support group led by ICU physiotherapists and ICU follow-up nurses in the hospital's outpatient department. Due to the demands of the pandemic, the follow-up service was suspended to enable the repurposing of staff and resources for frontline emergency services. Although some outpatient services have since reopened, national laws regarding social distancing and infection-control procedures have restricted face-to-face group activities.To meet the needs of a rapidly increasing post-intensive-care population amidst the unprecedented circumstances of a pandemic, services were required to adapt and work virtually -11. The This service evaluation aimed to assess the safety, utilisation , and potential impact on the recovery from physical and neuropsychiatric sequelae of an innovative virtual post-intensive-care rehabilitation programme for survivors of COVID-19.This article was previously presented as a meeting abstract at the 2021 European Society of Intensive Care Medicine (ESICM) Lives Conference on October 4, 2021, and the 2021 Association of Chartered Physiotherapists in Respiratory Care (ACPRC) ACPRC Virtual Conference on April 23, 2021 -15.DesignThis was a single-centre service evaluation and has therefore been reported in accordance with Revised Standards for Quality Improvement Reporting Excellence (SQUIRE) guidance .Ethical considerationsThis single-centre ) service evaluation used anonymised linked databases  with a waiver of ethical approval according to the national guidance [SettingA major tertiary hospital in Birmingham, United Kingdom ), with one of the largest co-located ICUs in Europe. Between March 2020 and April 2020, the ICU at QEHB admitted 177 patients with COVID-19, of whom 110 survived ICU discharge [SampleConsecutive adult patients (≥18 years of age) who were admitted to the ICU with a confirmed diagnosis of COVID-19 between March 2020 and April 2020 and survived to hospital discharge were identified by a senior ICU physiotherapist. Patients were excluded if they had unstable medical conditions contraindicating their safety to exercise, a severe neurological injury impeding their ability to cooperate with rehabilitation, or an inability to provide informed consent for the programme as required by our hospital.After hospital discharge, patients were invited to participate via telephone by a senior ICU physiotherapist. If patients declined to participate, the primary reason was recorded. Baseline data, including demographics, ventilation days, and length of stay, were obtained from patient notes and electronic health databases.InterventionPatients were invited to participate in an eight-week post-intensive-care rehabilitation programme. The programme consisted of a once-weekly exercise class followed by a support group, completed virtually via video call using Microsoft Teams. Patients were able to complete the programme in their own homes using either a smartphone, tablet device, laptop, or computer, with a group of up to six patients on each call. Verbal and written patient information was provided, including the risks and benefits .Exercise ComponentA structured, interval exercise approach was adopted, consisting of a warm-up, 20 minutes of circuit-based exercises, and a cool-down, delivered by the class physiotherapist . The proSupport Group ComponentFollowing the exercise component, patients were invited to participate in a support group. The structure of these sessions is based on recommendations from the patient support charity 'ICU Steps' . In linePrimary outcome measuresThe primary outcomes assessed the utilisation of the virtual rehabilitation programme; including recruitment, retention, and adherence rates. Recruitment was defined as the percentage of eligible patients who attended. Retention was defined as the number of patients who completed rehabilitation. Adherence was defined as completing a minimum of 75% of the available virtual rehabilitation sessions. All adverse events were recorded.Secondary outcome measuresSecondary outcomes assessed the impact of the virtual rehabilitation programme on patient clinical outcomes . The characteristics of the patient cohorts who attended and did not attend were summarised, with continuous variables reported as means ± standard deviations (SDs) where normally distributed and medians and interquartile ranges (IQRs) reported otherwise. Comparisons between patients who attended and did not attend were then performed using Mann-Whitney U tests for ordinal or continuous variables and chi-squared tests for nominal variables. Data for all outcomes post-intervention were assessed for normality using the Sharipo-Wilk test, and non-parametric tests were used as appropriate. Continuous variables were reported as medians and IQRs, and the Wilcoxon matched-pairs signed rank test was used to assess for statistical significance, with p<0.05 deemed to be indicative of statistical significance throughout.Eighty-seven patients out of 110 patients (79%) who were admitted to the ICU at QEHB with COVID-19 between March and April 2020 and survived hospital discharge were screened for their eligibility for virtual post-intensive-care rehabilitation during a three-month period , and impact on the recovery from physical and neuropsychiatric sequelae with an innovative virtual post-intensive-care rehabilitation programme in survivors of COVID-19. To the best of our knowledge, this is the first known report of innovative, virtually delivered post-intensive-care follow-up specifically for survivors of severe COVID-19 requiring ICU admission.This service evaluation has demonstrated that it is feasible to recruit survivors of an ICU admission with severe COVID-19 to a virtual, post-intensive-care rehabilitation programme. During the three-month recruitment period, 79% of patients were approached and offered rehabilitation. Patients were approached an average of 79 days post-hospital discharge, in accordance with national guidelines, which advise follow-up at two to three months . Twenty-Of those approached during the period of the service evaluation, 50% participated in the virtual post-intensive-care rehabilitation programme. The primary reason for declining was that rehabilitation was not required due to independent self-management. This may be reflective of a working-age cohort (mean age 54 years) and pre-admission Clinical Frailty Score (median 2 = well); however, in our study, the demographics of those who attended and those who declined showed no significant differences. The physical and non-physical outcomes of those who declined rehabilitation were not investigated in this study, yet previous literature suggests that PICS affects 50% of critical care survivors ,8. PrediOf those who attended, we found 73.6% retention (defined as completion of the programme) and 82% adherence (defined as attending a minimum of 75% of rehabilitation sessions) to an eight-week programme; demonstrating patient acceptability of the programme. The virtual nature of the programme has enabled accessibility to rehabilitation and the ability to overcome the challenges of social restrictions and infection control procedures during the COVID-19 pandemic. However, it is important that rehabilitation services do not discriminate against those who do not have access to technology. Almost one-third of patients declined participation due to a lack of technology access, and 18.2% due to language barriers. Further work is required to ensure rehabilitation and post-intensive care follow-up are accessible to all patients, expanding to all socioeconomic and ethnic regions.The programme was found to be safe, with no adverse or safety events recorded. The participants who completed the rehabilitation programme demonstrated improvements in all physical and non-physical outcomes. Despite being delivered virtually, with patients self-directing their exercise intensity based on perceived breathlessness, the rehabilitation programme remained effective. This supports existing work that virtual rehabilitation is feasible and effective, yet this is the first known report of virtual rehabilitation specifically for survivors of COVID-19 following critical care admission -13,23-24The rehabilitation programme aimed to improve physical fitness through an interval training approach. Baseline data identified poor levels of exercise capacity prior to rehabilitation, with the mean 1MSTS score for the group equivalent to the 2.5th percentile for healthy 65- to 69-year-olds, despite a mean age of 54 years . FollowiIn addition to physical fitness, the programme also aimed to improve upper-limb strength. Shoulder impairment and its associated functional disability are common in survivors of critical illness . PronounIn contrast to previous ICU literature, overall, our cohort demonstrated normal scores for anxiety, depression, and psychological distress ,3. DespiLimitationsThere are several limitations to this service evaluation. First, this is a non-randomised trial that does not have a control group for comparison. We recognise that this reduces the validity of the study findings as the results may be subject to temporal changes, acknowledging that activity levels between hospital discharge and follow-up were not monitored and that the advice given to patients by ward physiotherapists was not standardised. The results are also open to bias as they only reflect those who consented to participate and are therefore representative of a cohort that is motivated and engaged with rehabilitation. As this service evaluation did not collate qualitative data, the results do not account for the experiences, needs, or preferences of patients. Participant numbers were small, and the service evaluation was performed at a single centre; therefore, results may not be representative of the wider population.The COVID-19 pandemic has placed overwhelming demand on healthcare services and has subsequently led to the repurposing of resources and staff to bolster frontline emergency departments. As we face the secondary impacts of the pandemic, the optimisation of recovery as a therapeutic objective should be prioritised over patient survival alone. For many survivors of critical illness, their discharge from the ICU is the start of an uncertain journey, facing numerous physical and non-physical limitations. It is essential that critical care rehabilitation and follow-up services are protected in order to optimise patient recovery and quality of life after critical illness.This service evaluation demonstrates that with protection and prioritisation of rehabilitation, post-intensive-care follow-up services can be adapted using innovative and virtual methods. This is the first known report of virtual post-intensive-care rehabilitation for survivors of COVID-19, providing accessible critical care follow-up despite the restrictions faced by healthcare services during the pandemic. This service evaluation has demonstrated that it is feasible to recruit and retain intensive care survivors for virtual rehabilitation and that the programme is safe and effective. For those who attended the virtual post-intensive-care rehabilitation programme, there was a significant improvement in all physical and non-physical outcomes. Further research, including an appropriately powered multi-centre randomised clinical trial with longitudinal follow-up, is required to further validate these findings.


Androgen receptor (AR) is a receptor found on many breast cancer cells, and drugs can be used to target AR in the treatment of advanced breast cancers. We aim to better understand how AR is expressed in breast cancer that has spread to the brain, i.e., brain metastases (BrM). We used a technique called immunohistochemistry to study AR expression in BrM from 57 breast cancer patients. We found that AR was expressed in the majority of BrM, and was expressed at different frequencies across different types of breast cancer. We did not find an association between AR expression and measures of survival. In most patients, AR expression in breast tumours and BrM was comparable. This study shows that AR is expressed in the majority of breast cancer BrM, and may be a useful target for treating breast cancer patients who have BrM.p = 0.003). Patients with AR positive versus AR negative BrM had similar overall survival , brain-specific progression-free survival , and time from breast cancer diagnosis to BrM diagnosis . AR is expressed in the majority of breast cancer BrM and represents a potential therapeutic target.We aimed to evaluate the expression of the “targetable” androgen receptor (AR) in breast cancer brain metastases (BrM). An established, retrospective 57-patient cohort with metastatic breast cancer who underwent surgery for BrM at the Sunnybrook Odette Cancer Centre between 1999–2013 was studied. AR expression in BrM samples was assessed in triplicate using immunohistochemistry (IHC). AR positive status was defined as nuclear AR expression ≥ 10% by IHC using the SP107 antibody. The median age of patients was 52 years (range 32–85 years). 28 (49%) of BrM were HER2+, 17 (30%) were hormone receptor positive (HR+)/HER2−, and 12 (21%) were triple negative breast cancers (TNBCs). 56% (n = 32/57) of BrM were AR positive, and median AR expression was 20% (CI 1.6–38.3%). AR expression was different across breast cancer subtypes; AR was most frequently expressed in HER2+ (n = 21/28), followed by HR+/HER2− (n = 9/17), and lowest in TNBC (n = 2/12) BrM ( Androgen receptor (AR) is a nuclear steroid hormone receptor that functions as a ligand-activated transcription factor and regulates the expression of downstream genes involved in cellular proliferation and apoptosis ,2. AR isGiven that breast cancer is the second most common cause of brain metastases (BrM), which are associated with high rates of morbidity and mortality, there is interest in evaluating novel treatment approaches with central nervous system (CNS) activity . The antWe aimed to evaluate the expression of AR using a clinically validated and commercially available antibody in an established cohort of patients with metastatic breast cancer who underwent surgery for BrM at our institution. This study used a retrospective cohort of breast cancer patients who underwent surgery for BrM at Sunnybrook Odette Cancer Centre (SOCC) in Toronto, Ontario, Canada, consecutively between July 1999 and June 2013. The Anatomic Pathology Laboratory Information System was searched for metastatic carcinoma of breast origin. Patients with a personal history of previous or concurrent breast carcinoma and BrM and no evidence of another primary tumor were included if their breast primary pathology was available in the archives of the Pathology Department. Clinical information as well as information on BrM and matched primary breast tumours were obtained from the patients’ electronic medical records. Mean followup time was 11.4 months. Research Ethics Board approval was obtained from the Sunnybrook Research Institute.Immunohistochemistry (IHC) was assessed on BrM samples using an established tissue microarray (TMA) consisting of 1 um tissue cores in triplicates. AR expression was assessed using the SP107 antibody ) and was scored as a continuous variable as percentage of positive nuclei. Positive status was defined as nuclear AR expression ≥10% of tumor cells. GATA3 expression was assessed using the sc-268 antibody ) and Ki-67 expression was assessed using the clone 30-9 antibody ). Both GATA3 and Ki-67 expression were scored as a continuous variable as percentage of positive nuclei, and we defined low expression as 1–24%, intermediate expression as 25–49%, and high expression as ≥50%. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2) status of the BrM was evaluated based on 2020 and 2018 ASCO/CAP guidelines respectively [p-value of <0.05. Data was analyzed using R version 4.2.1 (23 June 2022) and visualized using the ggplot2 package.Brain-specific progression-free survival (bsPFS), OS, and time from diagnosis of breast cancer to diagnosis of BrM were estimated using the Kaplan–Meier method and compared across groups using the log-rank test. Independence between categorical variables was assessed using the χ2 test. Mean AR expression across breast cancer subtypes was compared using ANOVA, and post-hoc analysis using Tukey HSD. Difference between AR expression in primary breast samples and matched BrM was tested using the Wilcoxon signed rank test. bsPFS was defined as the duration of time in months from the time of BrM surgery to the time of BrM progression or death. Overall survival (OS) was defied as the duration of time in months from the time of BrM surgery to the time of death due to any cause. Time from diagnosis of breast cancer to diagnosis of BrM was defined as the duration of time in months from first diagnosis of primary breast cancer to the time of BrM surgery. For all analyses, statistical significance was defined as a A search was conducted on 25 January 2023 on the clinicaltrials.gov website using the search terms “Breast cancer” and “Androgen” and filtered for studies that were “Recruiting”, “Not yet recruiting” or “Active not recruiting”. This search yielded 37 trials, which were manually reviewed. Only trials including women ≥18 years with advanced or metastatic breast cancer, with the primary intervention being an androgen-targeted therapy either alone or in combination with other systemic therapies were selected for review. 16 trials met the inclusion criteria and are included in 57 patients with metastatic breast cancer who underwent surgical resection of BrM were included in this study . The medAR expression by IHC using the SP107 antibody was quantified for all 57 BrM, and is shown in In subsequent analyses, cases with AR expression ≥10% were labelled as “AR positive (AR+)”, while those with AR expression <10% were labelled as “AR negative (AR−)”. This was based on a previous study that found that AR expression threshold of 10% is associated with clinical response to enzalutamide in TNBC . 56% n .p = 0.003)  (We found a significant association between AR expression and primary breast cancer subtype. AR was most frequently expressed in BrM from HER2+ breast cancer (n = 21/28 BrM were AR+), followed by HR+/HER2− breast cancer (n = 9/17), and least frequently in TNBC (n = 2/12) (= 0.003) b. Mean as. TNBC) c.p = 0.020) and mean absolute AR expression (p = 0.005). The subgroup with high (50% or above) Ki-67 expression had the lowest AR expression (p = 0.005 for Tukey HSD between Ki-67 high vs. Ki-67 intermediate groups) (We found a significant association between Ki-67 expression by IHC and both frequency of AR expression ( groups) b.p = 0.003) and mean absolute AR expression (p = 0.005). The subgroup with high (50% or above) GATA3 expression had the highest AR expression   d.p < 0.05). 90% (n = 9/10) of primary breast cancers were AR+, whereas 70% (n = 7/10) of BrM were AR+. AR status was concordant in 7 of 10 cases. Among the 3 cases for which AR status differed in the primary cancer and BrM, AR was “gained” in the BrM in one case and “lost” in the BrM in two cases  (p = 0.95)  a. Patien = 0.95) b. These p = 0.16)  c.AR expression in breast cancer BrM is of interest due to readily available androgen-targeted therapies that can cross the blood brain barrier. This study demonstrated in a retrospective Canadian cohort that AR is expressed by IHC in the majority of breast cancer BrM, and that HER2+ BrM most frequently expressed AR, while TNBC BrM least frequently expressed AR. AR status was concordant between the majority of BrM and matched primary breast tumours. AR status of the BrM was not associated with OS or bsPFS, although patients with AR+ BrM had a trend towards developing BrM later in the course of their disease. In our study, AR expression by IHC was expressed  in 64.9% of breast cancer BrM. This is higher than what was reported in a previous study which demonstrated that AR expression was expressed  in 35.1% of breast cancer BrM in a similar-sized cohort . The antWith respect to AR expression by IHC in primary breast cancers, our results are comparable to those of other studies, which consistently report that AR is expressed in 72–79% of primary breast cancers ,4,5. In p < 0.001) with AR reverse phase protein assay, and AR mRNA expression was associated with lower grade disease and lower risk of recurrence [While AR expression by IHC is the gold standard, previous studies have also investigated mRNA expression of AR in primary breast cancer, although to our knowledge there have been no such studies in breast cancer BrM. A study of 101 primary TNBCs found that qRT-PCR detected AR expression in 34% of cases compared to 15% of cases using IHC , with 75% concordance between the two methods; this study found that AR mRNA expression was associated with shorter distant metastases free survival, which is consistent with previous studies employing IHC in TNBC . Anothercurrence . Interescurrence , and ≥40currence . PresentOur study found no significant association between AR expression with either OS or bsPFS, which is not surprising given that our cohort consisted of multiple different breast cancer subtypes, which inherently portend different prognoses; the number of patients within each subtype was too small to draw meaningful conclusions. Additionally, no patients in our study received AR-targeted therapies. AR signaling plays a different biological role in different breast cancer types . In ER+ Many of the associations that we found between the expression of AR and the expression of other prognostic and proliferation markers (GATA3 and Ki-67) are in keeping with what is known about the biology of breast carcinomas. Ki-67 is a nuclear protein associated with cellular proliferation, and is associated with higher histological grade and shorter survival . The facThe fact that our study shows a high proportion of breast cancer BrM are AR-positive using a biomarker predictive of response to anti-androgen therapies, supports the evaluation of AR-targeted therapies in breast cancer patients BrM. Our study is limited by the small retrospective single centre design, and the fact that no anti-androgen therapies were prescribed to our patients. The small number of patients with matched primary and BrM tissue is another limitation. In the future, pre-clinical models of AR-positive BrM would be useful in validating these findings.This study used a clinically validated antibody (SP107) to show in a 57-patient retrospective Canadian cohort that the majority of breast cancer BrM were AR positive (defined as AR ≥ 10% by IHC). Furthermore, AR expression was most frequently expressed in HER2+ BrM and least frequently expressed in TNBC BrM. These findings are comparable to AR expression previously reported in primary breast cancers. HER2+ BrM most frequently express AR, yet there are no active clinical trials evaluating AR-directed therapies in patients with HER2+ BrM; hence, additional trials for this population are warranted. While AR-targeted therapies may be most clinically useful in the treatment of TNBC, AR is expressed least frequently in TNBC BrM, suggesting a need for improved biomarkers to judiciously guide patient selection. Overall, our study shows that AR is a frequently expressed and promising intracranial molecular target, supporting the investigation of androgen-targeted therapies in the treatment of patients with breast cancer BrM.


Using the social support theory for reference, a subject-object influencing mechanism model of China's rehabilitation assistance system for disabled children is built based on the survey data on 1,698 disabled children in 243 designated rehabilitation institutions in Hu'nan Province as well as the topic of the assessment and optimization of the rehabilitation assistance system for disabled children. The analysis using the structural equation modeling reveals that the inclusive welfare effect of the rehabilitation assistance system for disabled children has emerged, and disabled children receiving free rehabilitation in the designated institutions have achieved good rehabilitation results as a whole, however, disabled children of different age groups have generational differences in the rehabilitation effects, and the preferential aspect of the system needs to be strengthened. Government support, institutional support, and social support have positive non-equilibrium effects in enhancing the rehabilitation effects of disabled children. Institutional support plays a partial mediating role between government support, family support, and disabled children's rehabilitation effects, showing that the current social support system for the rehabilitation assistance of disabled children is experiencing structural, social and kernel changes, to evolve from the traditional closed and disconnected one-way resource support to open, coordinated, and interactive multi-support, and gradually become a comprehensive and efficient interactive support system with families as the foundation, institutions as the main body, and the government as the core. Rehabilitation of disabled children refers to the treatment process of helping disabled children to recover and improve their functional status, reduce dysfunction, and enhance their abilities to take care of themselves in daily life, learn, and socialize through the combination of rehabilitation training, surgery, assistive device adaptation, education, psychological counseling, etc. From the perspective of rehabilitation medicine, childhood is the most economical and effective rehabilitation period with the most far-reaching influence . DisableSince the 1980s, the Chinese government has been highly valuing the rehabilitation of disabled children and has made improving the welfare and promoting rehabilitation services for disabled children to be a people's livelihood support project. The rehabilitation of disabled children has been included in the outlines of five-year plans from the 8th Five-Year Plan to the 13th Five-Year Plan for the cause of disabled people in China, and the work of rehabilitation of disabled children has been advanced in order. In particular, the work for disabled children has formally entered the stage of system building since the 19th National Congress of the Communist Party of China (CPC) proposed to “develop programs for disabled people and work to provide better rehabilitation services for them”. Acting on the policy requirements to help those most in need, to build a tightly woven safety net, and to build the necessary institutions, the State Council of China introduced China's first special system in the field of rehabilitation of disabled people, i.e., the rehabilitation assistance system for disabled children, in 2018. This system fills in gaps in China's rehabilitation service guarantee system for disabled children and transforms the salvage rehabilitation work for disabled children from project-based operation to institutional guarantee. This system also comprehensively expands the rehabilitation service objects, establishes the rehabilitation assistance principle of doing everything within the capacity to basically realize the salvage of disabled children as much as possible, and comprehensively enhances the rehabilitation welfare of disabled children. According to statistics, from 2018–2021, the annual number of people enjoying rehabilitation assistance for children with disabilities in China is 157,000, 181,000, 237,000, and 363,000, respectively; the total number of disability rehabilitation institutions in China is 9,036, 9,775, 10,440, and 11,260, respectively; the annual number of people in employment in rehabilitation institutions in China is 250,000, 264,000, 295,000, and 318,000, respectively  to specialize in providing treatment training services for the rehabilitation of disabled children, which receive rehabilitation funds from the DPFs or other social entities, receive objects of rehabilitation from the families of disabled children, and play a bridge role in the rehabilitation of disabled children. This is a factor that must be considered in studying the relationships between the rehabilitation effects of and rehabilitation services for disabled children.In order for the rehabilitation assistance system for disabled children to produce good rehabilitation effects, in this paper, a field survey and empirical research on the rehabilitation assistance system for disabled children have been conducted, with improving the implementation effects of the rehabilitation assistance system for disabled children as the objective, the social support theory as the theoretical basis, and the rehabilitation effects of disabled children as the metric of the system's operation performance. In this paper, “measurement” and “analysis” are combined and structural equation modeling is used to explore from multiple dimensions the action paths and mechanisms of related social subjects' participation in the rehabilitation assistance system for disabled children, dig the deep causes of the unsatisfactory implementation effects of the rehabilitation assistance system for disabled children, and propose pertinent strategies to optimize the effectiveness of the rehabilitation assistance system for disabled children. Therefore, the core questions of this paper are three: Firstly, how effective is the current implementation of the rehabilitation assistance system for children with disabilities in China? Secondly, what is the mechanism through which the support provided by different actors affects the effectiveness of the rehabilitation assistance for children with disabilities? Third, how can the rehabilitation assistance system for children with disabilities be further optimized from the perspective of the support provided by different actors?The International Classification of Functioning, Disability and Health (ICF), published by the World Health Organization in 2001, is now widely used in disability statistics and social services as a global and universal standard for terminology, classification and coding for the classification of functioning and disability. The classification is based on a “biopsychosocial” medical model, which states that an individual's functioning in a given domain is the result of the interaction between his or her health status and contextual factors. It sees disability not only as an attribute of the individual, but also as a complex collection of conditions, many of which are caused by environmental factors in the context. Contextual factors refer to all aspects of the external or extrinsic world that form the background to an individual's life, including nature and its features, the man-made natural world, other people with whom the individual has different relationships and roles, attitudes and values, social institutions and services, and policies, rules and laws. These factors are external to the individual, and an environment that facilitates has a positive impact on the individual's performance, ability to move and body structure and function, while an environment that has barriers or lacks enabling factors has a negative impact on the individual's performance, ability to move and body structure and function. Therefore, the solution to disability-related problems needs to focus on the external environment in which people with disabilities live, with the aim of transforming it to enable them to participate in social life and integrate into the social community. Social support, as an important component of the environment, has a corresponding impact on the rehabilitation effectiveness of disabled people. Therefore, in order to further analyse the intrinsic impact of social support on the rehabilitation of disabled children, this paper chooses social support theory as the logical basis and analytical framework.Originating from the social etiology of mental disorders in the 1970s, the social support theory has rapidly expanded to economics, sociology, pedagogy, etc. owing to its strong explanatory power, to become an important scientific paradigm in these fields. In the social support theory, social support refers to a selective social behavior where a social network helps socially vulnerable groups without compensation through material and spiritual means such as information, laws, finance, and psychology . Social In the rehabilitation support framework for disabled children in China today, the government is the main policy and fund supporter of the rehabilitation cause of disabled children. Based on the definition of the terms “services, institutions and policies for health” and “support and interlinkages” in the ICF main categories of environmental factors and the relevant literature. Government support is effectively the sum of policies, institutions and services provided by the public sector, with government at the center, to address the rehabilitation of children with disabilities, to provide medical rehabilitation and to promote healthy lifestyles . In the H1: Government support positively promotes the rehabilitation effects of disabled children.In the rehabilitation support framework for disabled children in China today, designated rehabilitation institutions are the main service supporter for the rehabilitation of disabled children. A designated rehabilitation institution for disabled children (“rehabilitation institution”) is a medical rehabilitation institution registered according to law to undertake rehabilitation assistance programs for disabled children and provide basic rehabilitation services, such as clinical diagnosis, functional assessment, rehabilitation therapy, function training, and device adaptation for children with various disabilities, which is accredited by a DPF at or above the county level together with education, civil affairs, health, market regulation departments, etc., and signs a rehabilitation service agreement therewith. The common carriers for rehabilitation institutions are mainly hospitals, rehabilitation centers, maternity and childcare hospitals, special education schools and rehabilitation device companies with strong rehabilitation service capacities . Staff iH2: Institutional support positively promotes the rehabilitation effects of disabled children.In the rehabilitation support framework for disabled children in China today, families of disabled children are the main composite supporter for the rehabilitation of disabled children. Families are basic living units with high internal cohesion and formed based on blood and relationships, and are the main carriers of daily life for disabled children. Based on the definition of the terms “immediate family” and “support and interconnectedness” in the ICF main categories of environmental factors, family support actually refers to the practical material or emotional support, nurturing, protection and assistance in the rehabilitation of disabled children provided by individuals associated with birth, marriage or other culturally recognized immediate family relationships, such as parents and grandparents. Family support is more direct, selfless and sustainable than other forms of support, and is the most fundamental element in the rehabilitation of disabled children . SpecifiH3: Family support positively promotes the rehabilitation effects of disabled children.In the previous project-based social support system for the rehabilitation of disabled children, the government directly provided financial support and purchased assistive devices for disabled children in some archived poverty-stricken households and low-income households by mainly relying on specific service projects, such as the Ministry of Civil Affairs' “Tomorrow Plan” and “Rebirth Action,” and the CDPF's “Public Welfare Lotteries for Rehabilitation” and “Colorful Dream Action Plan” ; rehabilH4: Institutional support plays a mediating role between family support or government support and the rehabilitation effects of disabled children.To further verify the above research hypotheses, the structural equation modeling (SEM) is selected in this paper to measure the relationships between variables, with the specific model equations as follows:Where, Equation (1) is a structural model representing the relationships between the exogenous latent variable and the endogenous latent variable, with S representing the endogenous latent variable, i.e., the rehabilitation effects of disabled children, L representing the three exogenous latent variables , Γ representing the path coefficient (the influence of the exogenous latent variables on the endogenous latent variable), and ζ representing the residual term (reflecting the unexplained part of the equation).Equations (2) and (3) are measurement models that connect the latent variables and the observed variables, where, Y represents the observed variable under the endogenous latent variable, X represents the observed variable under the exogenous latent variable, Λ y and Λ x represent the factor loading matrix of the observed variable under the endogenous latent variable and that of the observed variable under the exogenous latent variable, respectively, ε represents the measurement error of the observed variable under the endogenous latent variable, and δ represents the measurement error under the exogenous latent variable.Rehabilitation effects of disabled children. The rehabilitation effects of disabled children refer to the specific situation of functional improvement of disabled children after various rehabilitation activities and represent an important metric of the implementation situation and effects of the rehabilitation assistance system for disabled children. According to the existing studies, there are various scales to measure the rehabilitation effects, such as the Nottingham Health Profile (NHP) , the IntGovernment support refers to the sum of various systems and services provided by public departments with the government as the axis for socially vulnerable groups and is an important measure of vulnerable groups' access to support resources. Government support was mainly measured from the dimensions of institutional guarantee, behavior coordination, and public opinion support based on the various preferential policies provided for the rehabilitation of disabled children in the Implementation Opinions on the Establishment of Rehabilitation Assistance System for Disabled Children in Hu'nan Province and Xu's definition of government support for children . The dimFamily support refers to the help provided by other family members for the vulnerable members. In the light of disabled children's psychological similarities to preschool children and physiological similarities to the disabled older adult, in this study, based on the measurement of family support for preschool children by Yue and Zhang and the measurement of family support for the disabled older adult by Chen et al. , 42, famRehabilitation institution support refers to the sum of various services provided by medical rehabilitation institutions such as hospitals, rehabilitation centers, maternity and childcare hospitals, and special education schools for the rehabilitation population, being an important metric of the institution-based rehabilitation level. In the light of the special requirements of disabled children for institution-based rehabilitation, in this study, after synthesizing the detailed indicators for designated rehabilitation institutions in the Notice on the Exit and Access of Designated Rehabilitation Institutions for Disabled Children as well as the evaluation dimensions put forward by Mi et al. for rehabilitation institutions , two dimThis study was based on the results of a questionnaire survey conducted in 243 designated rehabilitation institutions in 14 prefectural-level cities in Hu'nan Province from June to December 2020, with the respondents mainly being the parents of disabled children who have received rehabilitation in the designated rehabilitation institutions. Considering that the number of people who have received rehabilitation in the designated institutions in each prefectural-level city was different, in order to ensure the representativeness of the survey and the reasonableness of the samples, the equal probability sampling method was mainly adopted in the survey. Firstly, the number of designated rehabilitation institutions for disabled children in each city of the province  was used as the sampling basis, the theoretical number of questionnaires to be distributed in each county and city was determined based on eight questionnaires per institution , then, with the assistance of the Hu'nan Disabled Persons' Federation, surveyors were dispatched to each designated rehabilitation institution in the province to conduct a structured questionnaire survey, and finally, 1,944 questionnaires were distributed in total. After invalid questionnaires were eliminated, a total of 1,698 valid questionnaires were recovered, with a valid recovery rate of 87.4%.As shown in P < 0.05), indicating significant generational differences in the rehabilitation effects of different age groups. Also, it is worth noting that, except for disabled children aged 3–6 who score more than 3 in the improvement of all abilities, disabled children aged 0–3 score <3 in the improvement of self-care ability, psychological development ability, and verbal communication ability, which is poor. Disabled children aged 6–14 also score <3 in the improvement of psychological development ability and verbal communication ability, which is at average and below. The above result reflects, to some extent, that the system lacks specificity in the specific implementation and fails to effectively respond to the rehabilitation content of disabled children of different age groups, and the system's preferential aspect needs to be strengthened.The rehabilitation effects of disabled children are the most direct and effective metric of the implementation effects of the rehabilitation assistance system for disabled children. The better the rehabilitation effects achieved by disabled children receiving free rehabilitation training in designated institutions, the better the implementation effects of the rehabilitation assistance system for disabled children. Therefore, to better measure the rehabilitation effects of disabled children and the implementation effects of the system, in this study, efforts were made to attempt to further explore the improvement of disabled children in physical, psychological, communication, perception and overall abilities and then the five scores were summed to obtain the comprehensive improvement score of disabled children, to comprehensively highlight the rehabilitation effects of disabled children. One-way ANOVA was used to further analyze the differences in rehabilitation effects among different age groups. The results are shown in p < 0.001), showing that the sample data was suitable for factor analysis. Then, the principal component analysis method and the varimax rotation method were adopted to solve the common factors, a total of four common factors were extracted based on the principle of eigenvalues greater than one, all common factor loads were >0.65, and the cumulative variance explained reached 74.505%, showing that the extracted four common factors could effectively cover the basic information on each measurement indicator and had a strong generalization ability. Also, seen from the structural distribution of the common factors, the measurement indicators were effectively concentrated in their respective dimensions, showing that the extracted common factors effectively matched the conceptual dimensions assumed in the above theoretical model. See To measure whether the scale elements of this questionnaire and the concepts in the theoretical model hypotheses can match one another, in this study, efforts were made to attempt to preliminarily test the samples through exploratory factor analysis. Firstly, a factor analysis suitability test was conducted, and the results showed that the KMO value was 0.938 and the value of Bartlett's test of sphericity was 21,236.6 (p < 0.001), showing that the survey data had good construct validity as a whole; then, the AVE and The confirmatory factor analysis can effectively confirm the quality of fitting between each scale dimension and the data, and if the quality is good, it means that the scale has good reliability and validity; therefore, in this study, the reliability and validity were further tested through the confirmatory factor analysis. The results showed that in terms of reliability, the factor loadings of the observed variables under the four latent variables were greater than the specified threshold of 0.5 , the CroTo further verify the research hypotheses, measure the relationships between the three dimensions, and examine model fitting, in this paper, the goodness of fit of the model was tested using AMOS 23.0 software. Generally, when the parsimonious fit indices  are >0.5 , it meanAfter fitting, the detailed results of the empirical analysis of the model are shown in According to Common mediating effect testing methods include stepwise regression, Sobel test, difference coefficient test, and bootstrap method. Among them, the bootstrap method does not only allow variables to contain measurement errors but also can include all data information and reduce the loss of information, playing a unique role in mediating effect testing. Therefore, the bootstrap method was adopted in this study to analyze the significance of the mediating effect. It was estimated using the bootstrapping procedure of Amos 23.0 with 1,000 times of resampling at the 95% confidence interval and based on the maximum likelihood method. Generally, when the absolute value of Z is ≥1.96 or when neither the bias-corrected confidence interval nor the percentile confidence interval contains 0 at the 95% confidence level, it means that the indirect effect is significant. According to the results, the indirect effect of government support through institutional support on the rehabilitation effects of disabled children is 0.289 with a z-score of 12.565, which is >1.96, and its bias-corrected and percentile confidence intervals do not contain 0, showing a significant mediating effect of institutional support in the path of “government support—institutional support—rehabilitation effects,” playing a partial mediating role. The indirect effect of family support through institutional support on the rehabilitation effects of disabled children is 0.066 with a z-score of 6, which is >1.96, and its bias-corrected and percentile confidence intervals do not contain 0, showing a significant mediating effect of institutional support in the path of “family support—institutional support—rehabilitation effects,” playing a partial mediating role. Therefore, research hypothesis H4 holds.According to the results of the total effect analysis, the total effects of family support and government support on institutional support are consistent with the direct effects thereof, and government support, institutional support, and family support have significant positive, diversified, and non-equilibrium effects on promoting the rehabilitation of disabled children, among which, the promotion effect of institutional support is the largest, followed by government support, and the promotion effect of family support is the smallest. Specifically, the total effect of government support on the rehabilitation effects of disabled children is 0.407, mainly consisting of the direct effect of “government support—rehabilitation effects” (0.118) and the indirect effect of “government support—institutional support—rehabilitation effects” (0.289), separately accounting for 28.99 and 71.01%. The effect of institutional support on the rehabilitation effects of disabled children is a single direct effect, with a total effect of 0.455. The total effect of family support on the rehabilitation effects of disabled children is 0.285, including the direct effect of “family support—rehabilitation effects” (0.219) and the indirect effect of “family support—institutional support—rehabilitation effects” (0.066), accounting for 76.84 and 23.16% of the total effect of family support, respectively.In this study, based on the survey data on 1,698 disabled children in 243 designated rehabilitation institutions in Hu'nan Province, the structural equation modeling and the bootstrap method are adopted to study the influence paths and effects of government support, institutional support, and family support on the rehabilitation effects of disabled children. The results show that:U-shaped development trend with the increase of age, and the preferential aspect of the system needs to be strengthened. Of course, it is worth stating that there is a large difference in the proportion of rural and non-rural samples in this study. When the 1,698 survey samples were counted, it was found that there were only 411 children with disabilities from urban household registration, accounting for only 24.2% of the sample, while there were as many as 1,287 children with disabilities from rural household registration, accounting for 75.8% of the sample. This situation seems unreasonable, but in fact it is relatively consistent with the current distribution of children with disabilities by household registration in China. The occurrence of disability is caused by the combined effects of multiple factors such as natural conditions, medical and health care, living habits, and safety accidents. Due to natural factors such as inbred marriage, excessive fluoride content in drinking water, and lack of iodine in natural environment, rural communities are more prominent than urban communities; medical and health conditions such as medical conditions, disease prevention conditions, and the degree of medical and health knowledge diffusion, rural communities are worse than urban communities; alcohol and smoking among pregnant women, non-medical examination of pregnant women, wrong medication and drug stimulation during pregnancy, and accidents during delivery, rural communities are more than urban communities; consumption of junk food and Expired food, lack of nutrients, inadequate nutrition, improper nutritional mix and other life habits are more prominent in rural communities than in urban communities; traffic accidents, medical accidents, accidental injuries, carbon monoxide poisoning, drug poisoning, pesticide moderate, food poisoning and other life safety accidents are more likely in rural communities than in urban communities. These factors contribute to the fact that there are many more children with disabilities in rural than in urban areas. Therefore, in this study, after in-depth interviews and questionnaires in the rehabilitation institutions, the sample was mostly composed of rural children with disabilities.The inclusive welfare effect of the rehabilitation assistance system for disabled children has emerged, and disabled children receiving free rehabilitation in the designated institutions achieved good rehabilitation results as a whole, however, disabled children of different age groups have significant generational differences in the rehabilitation effects, the rehabilitation effects of disabled children have an inverted Government support, institutional support, and family support all have significant and direct positive effects on the rehabilitation effects of disabled children. The richer the support resources available from the government, rehabilitation institutions, and families, the better the rehabilitation effects of disabled children. However, it is worth noting that the government is the leader, organizer, guide, and securer of the social support system for disabled children, and especially after the issuance of the rehabilitation assistance system for disabled children, the government is supposed to have a stronger direct influence on the rehabilitation of disabled children, however, in the table, the direct effect of government support on the rehabilitation effects of disabled children is significantly lower than that of institutional support and family support, which, to some extent, highlights that in promoting the rehabilitation of disabled children, the government still has certain shortcomings in system development rules, cooperation among departments, and public opinion publicity, lacks direct contact with disabled children and their families, and ignores the actual ideas of the demand side, leading to serious supply and demand deviation . FurtherInstitutional support plays a partial mediating role between government support, family support, and disabled children's rehabilitation effects. Not only can government support and family support directly influence the rehabilitation effects of disabled children, but they can also indirectly influence the rehabilitation effects through institutional support, which effectively compensates for the loss of their direct effects and enables the three to initially form close interconnection. In the previous project-based social support system for the rehabilitation of disabled children, different subjects had clear boundaries, were disconnected and isolated, and input support resources for the rehabilitation of disabled children in a single linear manner . The aboGovernment support, institutional support, and family support have non-equilibrium effects in promoting the rehabilitation effects of disabled children, among which, institutional support has the largest promoting effect on the rehabilitation effects of disabled children, followed by government support, and family support has the smallest promoting effect. The above results show that with the vigorous advancement of the rehabilitation of disabled children, the welfare effect of the rehabilitation assistance system for disabled children has emerged, the social support system for the rehabilitation assistance of disabled children is experiencing structural, social and kernel changes, the support from the subjects has evolved from the traditional closed and disconnected one-way resource support to the open, coordinated, and interactive multi-support, the delivery of resources between the subjects and the object has gradually evolved from the inherent “sending—receiving” single linear relationship to “sending—receiving—feedback—sending” two-way relationship, and a comprehensive and efficient interactive support system is gradually forming to advance the rehabilitation of disabled children, with families as the foundation, institutions as the main body, and the government as the core. However, it cannot be ignored that the sum of the total effects of government support and family support on the rehabilitation effects of disabled children is slightly greater than the total effect of institutional support on the rehabilitation effects of disabled children, which is slightly deviated from what Eskow and Nuri revealed about the effect of government support and Thomas revealed about the effect of family support , 56, 57.Based on the above, to further improve the rehabilitation effects of disabled children and promote the effective implementation of the rehabilitation assistance system, the following suggestions are hereby given:In terms of further improving government support, it is important to increase support efforts and enhance the scientificity, effectiveness, and specificity of the support content. Specifically, efforts should be made to: (a) Firstly, strengthen the survey on the willingness of the demand side, enhance the specificity of system content revision, effectively distinguish the structure of rehabilitation needs of children of different ages, stages, and types of disabilities, sort out the total number of demanders for rehabilitation services, the number and percentage of demanders for various types of rehabilitation services, the types and percentage of services required by different disability classes, etc., and promote the transformation of inclusive rehabilitation to inclusive and targeted rehabilitation; (b) Secondly, strengthen the comprehensive cooperation and coordination among financial, health, human resources and social security, education, civil affairs, safety supervision, publicity, development and reform, and justice departments with DPFs as the core, to integrate administrative resources, form policy synergy, effectively ensure the effective connection among different welfare policies, jointly protect the rehabilitation rights and interests of disabled children, and reduce the heavy rehabilitation burden on disabled children and their families; and (c) Thirdly, strengthen the publicity and public opinion support of the system, and fully use internet self-media and the offline publicity channels of local governments at different levels in an organized, planned, and step-by-step manner to improve the clear awareness of the system among families of disabled children and society's care for and attention to disabled children.In terms of further improving institutional support, it is important to optimize the comprehensive conditions of rehabilitation institutions and comprehensively enhance their rehabilitation treatment capacities. Specifically, efforts should be made to: (a) Firstly, raise the access threshold for designated rehabilitation institutions, strengthen the daily assessment of rehabilitation institutions, strictly eliminate unqualified institutions, urge rehabilitation institutions to independently optimize their environment and upgrade their rehabilitation equipment, and ensure the professional quality, completeness, and adaptability of the external environment such as sites, equipment, and space available from designated rehabilitation institutions; (b) Secondly, strengthen the specialization of rehabilitation personnel, build a new model of joint cultivation by universities and institutions, promote daily training in rehabilitation knowledge, and comprehensively enhance the comprehensive quality and abilities of rehabilitation personnel; (c) Thirdly, build a shared network of rehabilitation institutions, strengthen the sharing and connection of rehabilitation institutions, actively promote and popularize new rehabilitation techniques at home and abroad, and improve rehabilitation techniques and levels; and (d) Fourthly, promote the refined development of institutional rehabilitation departments, expand the service content of rehabilitation institutions, and urge institutions to comprehensively provide various scientific rehabilitation programs such as physical therapy, occupational therapy, speech therapy, hydrotherapy, prosthetics and orthotics, music therapy, psychotherapy, and social therapy.In terms of improving family support, it is important to comprehensively increase family support through multiple channels. Specifically, efforts should be made to: (a) Firstly, comprehensively and effectively ensure the effective distribution of subsidies for low-income households, subsidies for people with disabilities, medical reimbursement funds, and special funds for the rehabilitation of disabled children, guide social financial assistance for families in difficulty, vigorously develop public welfare positions suitable for families with disabled children, and enhance the economic resilience of families with disabled children; (b) Secondly, improve the rehabilitation knowledge of other family members through multiple channels, provide targeted guidance on rehabilitation training, parent-child activities, daily maintenance of assistive devices, and other basic knowledge for families with different types of disabled children, and urge families to conduct daily and standardized basic rehabilitation activities; and (c) Thirdly, build a psychological aid system for parents, guide them to understand their children's disabilities objectively and scientifically, improve their confidence in treatment, and teach them basic knowledge of psychological guidance, so as to provide daily psychological counseling to disabled children and reduce the internal inferiority complex, loneliness, and social disengagement feeling of disabled children.It is important to improve the social support system for the rehabilitation of disabled children, strengthen the effective connection between the subjects and between the subjects and object of social support, and build a comprehensive and efficient interactive support system with families as the foundation, institutions as the main body, and the government as the core. Specifically, efforts should be made to: (a) Firstly, strengthen the government's support for institutions, introduce reasonable and scientific preferential policies, change the funding method of allocating rehabilitation funds annually, reduce the survival pressure on rehabilitation institutions, and regularly conduct institution assessment and rehabilitation guidance, to effectively guarantee the service level and quality of rehabilitation institutions; (b) Secondly, strengthen the feedback on family needs to rehabilitation institutions, highlight families' supervision over institutions, and urge rehabilitation institutions to reasonably use rehabilitation funds, expand rehabilitation services, and provide accurate training in rehabilitation; and (c) Thirdly, completely break the traditional inherent “sending—receiving” linear delivery relationship between the subjects and the object, strengthen the forms of the demand side's expression of will through multiple channels, strengthen the connection channels between the subjects and the object, and create a regular “sending—receiving—feedback—sending” benign support relationship.This study also has some limitations. Firstly, in terms of assessing the implementation effect of the system, because the rehabilitation assistance system for children with disabilities is a typical new thing, involving various fields such as rehabilitation medicine, sociology, and management, there is no mature method for assessing the implementation effect of the rehabilitation assistance system for children with disabilities in the academic field. As a result, the assessment of the effect of the implementation of the rehabilitation assistance system for children with disabilities is based only on the fundamental goal of the implementation of the rehabilitation assistance system for children with disabilities, and the effect of the rehabilitation of children with disabilities is selected as a direct variable to assess the effect of the implementation of the system, which may miss some information. The system is a macroscopic and systematic concept, and its implementation effects need to be measured from multiple dimensions. Therefore, in future studies on the implementation effects of the rehabilitation assistance system for children with disabilities, it is necessary to consider other indicators such as system coverage, accessibility, and equality, while taking into account the rehabilitation effects of children with disabilities. Secondly, in terms of the study population, the analysis was mainly conducted on a unified sample of urban children with disabilities and rural children with disabilities, and the differences in the implementation effects of rehabilitation assistance systems for children with disabilities by household registration were not explored in depth. The spatial heterogeneity and uniqueness of China's rehabilitation problems are determined by its vast territory and unbalanced development between urban and rural areas. Therefore, future studies should further refine the scope of the study to investigate the implementation effects of the rehabilitation assistance system for children with disabilities in rural and urban areas separately, and reveal and analyze the differences.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the study of human participants in accordance with the local legislation and institutional requirements. Written informed consent from the participants was not required to participate in this study in accordance with the national legislation and the institutional requirements.ZG: conceptualization, investigation, writing the original manuscript, revising the manuscript, and administration. HZ: conceptualization, investigation, writing the original manuscript, and revising the manuscript. HT: methodology, investigation, and writing the original manuscript. All authors contributed to the article and approved the submitted version.