Elucidating the distinctive regulatory effects and mechanisms of active compounds in Salvia miltiorrhiza Bunge via network pharmacology: Unveiling their roles in the modulation of platelet activation and thrombus formation.

Salvia miltiorrhiza Bunge. (DS), as an important traditional Chinese medicine (TCM), has a long history of usage for promoting blood circulation and removing blood stasis. Modern studies have shown that the chemical components of DS have many biological activities such as cardiovascular protection, anti-arrhythmia, anti-atherosclerosis, improvement of microcirculation, protection of myocardium, inhibition and removal of platelet aggregation. Nevertheless, the action mechanism of DS as well its active compounds on platelet activation has not been fully uncovered. This study aimed to find out the potential targets and mechanisms of DS in the modulation of platelet activation and thrombosis, using network pharmacology and biological experimental. These compounds with anti-thrombotic activity in DS, cryptotanshinone (CPT), isoeugenol (ISO) and tanshinone IIA (TSA), together with the corresponding targets being Src, Akt and RhoA are screened by network pharmacology. We confirmed that ISO, CPT and TSA dose-dependently inhibited platelet activation in vitro, mainly by inhibiting agonist-induced clot retraction, aggregation and P-selectin and ATP release. The western blot findings indicated that ISO, CPT, and TSA led to reduced levels of p-Akt and p-ERK in activated platelets. Additionally, ISO and TSA were observed to decrease p-cSrc expression while increasing RhoA expression. ISO, CPT, and TSA demonstrated a potential to restrict the advancement of carotid arterial thrombosis in vivo. We confirm that ISO, CPT and TSA are the key anti-thrombotic active compounds in DS. These active compounds exhibit unique inhibitory effects on platelet activation and thrombus formation by modulating the Akt/ERK and cSrc/RhoA signaling pathways.

Tetrahedral Framework Nucleic Acids Inhibit Muscular Mitochondria-Mediated Apoptosis and Ameliorate Muscle Atrophy in Sarcopenia.

Sarcopenia is known as age-related muscle atrophy, which influences over a quarter of the elderly population worldwide. It is characterized by a progressive decline in muscle mass, strength, and performance. To date, clinical treatments in sarcopenia are limited to rehabilitative interventions and dietary supplements. Tetrahedral framework nucleic acids (tFNAs) represent a novel kind of DNA-based nanomaterial with superior antiapoptosis capacity in cells, tissues, organs, and systems. In our study, the therapeutic effect of tFNAs treatment on sarcopenia was evaluated both in vivo and in vitro. Results from muscular biophysiological characteristics demonstrated significant improvement in muscle function and endurance in the aged mouse model, and histologic examinations also showed beneficial morphological changes in muscle fibers. In vitro, DEX-induced sarcopenic myotube atrophy was also ameliorated through the inhibition of mitochondria-mediated cell apoptosis. Collectively, tFNAs treatment might serve as an alternative option to deal with sarcopenia in the near future.

Platelet-rich plasma treatment for talar cartilage repair: a systematic review and meta-analysis.

PURPOSE: To systematically review the studies regarding to the safety, efficacy and application methods of PRP in promoting the talar cartilage repair. METHODS: A systematic review was performed by searching PubMed, Web of Science, OVID and EMBASE to identify studies that compared the clinical efficacy of PRP for talar cartilage repair. Main outcome was the American Orthopedic Foot and Ankle Society (AOFAS) score for function and Visual Analog Scale (VAS) for pain was the second outcome. RESULTS: A total of 10 studies were included in this systematic review, including 4 randomized controlled trials, 1 controlled trial, 3 case series and 2 cohort studies. Four RCTs were analyzed using meta-analysis. For all outcomes, statistical results favored PRP group (AOFAS: MD = 7.84; 95% CI= [-0.13, 15.80], I2 = 83%, P < 0.01; VAS: MD = 1.86; 95% CI= [0.68, 3.04], I2 = 85%, P < 0.01). There were almost no reports of adverse events related to PRP intervention. Subgroup analysis showed that whether PRP was used alone or combined with other treatments could result in high heterogeneity but no more specific factors were identified to contribute to this. CONCLUSION: PRP is safe and effective for talar cartilage repair. In addition to the standardization of PRP preparation and application, it is necessary to distinguish the effects of PRP used alone or in combination with other treatments. In PRP studies, surgical treatment of talar cartilage repair remains the mainstream. The regulation of PRP in surgical applications are worth exploring. The most relative component is the mesenchymal stem cell because it is the only exposed chondrocyte precursor in the articular cavity whether it is microfracture or cell transplantation. TRIAL REGISTRATION: The study was registered in the PROSPERO International prospective register of systematic reviews (CRD42022360183).

[Effect of pulsed electromagnetic fields on mesenchymal stem cell-derived exosomes in inhibiting chondrocyte apoptosis].

The study aims to explore the effect of mesenchymal stem cells-derived exosomes (MSCs-Exo) on staurosporine (STS)-induced chondrocyte apoptosis before and after exposure to pulsed electromagnetic field (PEMF) at different frequencies. The AMSCs were extracted from the epididymal fat of healthy rats before and after exposure to the PEMF at 1 mT amplitude and a frequency of 15, 45, and 75 Hz, respectively, in an incubator. MSCs-Exo was extracted and identified. Exosomes were labeled with DiO fluorescent dye, and then co-cultured with STS-induced chondrocytes for 24 h. Cellular uptake of MSC-Exo, apoptosis, and the protein and mRNA expression of aggrecan, caspase-3 and collagenⅡA in chondrocytes were observed. The study demonstrated that the exposure of 75 Hz PEMF was superior to 15 and 45 Hz PEMF in enhancing the effect of exosomes in alleviating chondrocyte apoptosis and promoting cell matrix synthesis. This study lays a foundation for the regulatory mechanism of PEMF stimulation on MSCs-Exo in inhibiting chondrocyte apoptosis, and opens up a new direction for the prevention and treatment of osteoarthritis.

Conservative treatment of partial-thickness rotator cuff tears and tendinopathy with platelet-rich plasma: A systematic review and meta-analysis.

OBJECTIVE: To assess the effect of platelet-rich plasma as a conservative therapy in individuals with partial-thickness rotator cuff tears or tendinopathy on pain, and function. DATA SOURCES: Embase, MEDLINE, CENTRAL, Web of Science, CINAHL, PEDro, and the grey literature (to 31 March 2021). METHODS: Randomized controlled trials in English that reported short-term (6 ± 1 months), or long-term (⩾1 year) outcomes (shoulder pain or function) were conducted. Two independent reviewers screened the literature, completed the assessment of the Cochrane's risk of bias and extracted the data. Mean difference or standardized mean difference was used for continuous data. Heterogeneity was identified with I2 test. RESULTS: A total of 11 studies were eligible, and nine studies (n = 629) were included in this meta-analysis, that showed statistically significant short-term effects of platelet-rich plasma on pain relief (MD = -1.56; 95% CI -2.82 to -0.30), Constant-Murley score (MD = 16.48; 95% CI 12.57 to 20.40), and Shoulder Pain and Disability Index (MD = -18.78; 95% CI -36.55 to -1.02). Nonetheless, no long-term effect was observed on pain and function, except Constant-Murley score (MD = 24.30; 95% CI 23.27 to 25.33). The results of minimal important difference reached the minimal clinically important difference, except American Shoulder and Elbow Surgeons. For subgroup analysis, differences of pain relief were statistically significant in platelet-rich plasma-treated groups with double centrifugation, single injection, and post-injection rehabilitation. CONCLUSION: Our results suggested platelet-rich plasma had positive effects on pain relief and functional improvement for partial-thickness rotator cuff tears and rotator cuff tendinopathy, although the effects may not last for a long time.

Exoskeleton-assisted walking improves pulmonary function and walking parameters among individuals with spinal cord injury: a randomized controlled pilot study.

BACKGROUND: Exoskeleton-assisted walking (EAW) is expected to improve the gait of spinal cord injury (SCI) individuals. However, few studies reported the changes of pulmonary function (PF) parameters after EAW trainings. Hence, we aimed to explore the effect of EAW on PF parameters, 6-min walk test (6MWT) and lower extremity motor score (LEMS) in individuals with SCI and to compare those with conventional trainings. METHODS: In this prospective, single-center, single-blinded randomized controlled pilot study, 18 SCI participants were randomized into the EAW group (n = 9) and conventional group (n = 9) and received 16 sessions of 50-60 min training (4 days/week, 4 weeks). Pulmonary function parameters consisting of the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flow (FEF), peak expiratory flow, and maximal voluntary ventilation, 6MWT with assisted devices and LEMS were reported pre- and post-training. RESULTS: Values of FVC (p = 0.041), predicted FVC% (p = 0.012) and FEV1 (p = 0.013) were significantly greater in EAW group (FVC: 3.8 ± 1.1 L; FVC% pred = 94.1 ± 24.5%; FEV1: 3.5 ± 1.0 L) compared with conventional group (FVC: 2.8 ± 0.8 L; FVC% pred = 65.4 ± 17.6%; FEV1: 2.4 ± 0.6 L) after training. Participants in EAW group completed 6MWT with median 17.3 m while wearing the exoskeleton. There was no difference in LEMS and no adverse event. CONCLUSIONS: The current results suggest that EAW has potential benefits to facilitate PF parameters among individuals with lower thoracic neurological level of SCI compared with conventional trainings. Additionally, robotic exoskeleton helped walking. TRIAL REGISTRATION: Registered on 22 May 2020 at Chinese Clinical Trial Registry (ChiCTR2000033166). http://www.chictr.org.cn/edit.aspx?pid=53920&htm=4 .

The safety and feasibility of a new rehabilitation robotic exoskeleton for assisting individuals with lower extremity motor complete lesions following spinal cord injury (SCI): an observational study.

STUDY DESIGN: A pre-post observational study. OBJECTIVES: To evaluate the safety and feasibility of a new rehabilitation robotic device for assisting individuals with lower extremity motor complete lesions following spinal cord injury (SCI). SETTING: Three hospitals in Sichuan Province, China. METHODS: Individuals aged 15-75 years with an SCI between vertebrae six (T6) and lumbar 1 (L1) and complete motor paralysis participated in an exoskeletal-assisted walking (EAW) programme (2 weeks, 5 days/week, 30 min/day). Data were collected pre-, mid- (week 1) and post-intervention (week 2). RESULTS: Twenty-eight individuals (mean age = 41.3, 71% males) participated in the EAW programme. The distance walked during the 6-min walking test (6MWT) increased relative to that at baseline, during week 1 (13.0 ± 5.3 m) and week 2 (16.2 ± 5.3 m) when wearing the exoskeleton. The walking speed during the 10-m walking test (10MWT) increased from 0.039 ± 0.016 to 0.045 ± 0.016 m/s. The Hoffer walking ability grade, the Spinal Cord Independence Measure (SCIM), and the Walking Index for SCI II (WISCI II) changed after 2 weeks of EAW. No improvement in lower extremity motor score (LEMS) was observed. The rates of adverse events and serious adverse events were 21% and 4%, respectively. CONCLUSIONS: The EAW programme with the new robotic exoskeleton provided potential meaningful improvements in mobility for individuals with SCI and had few adverse events.

Pulsed electromagnetic field improves subchondral bone microstructure in knee osteoarthritis rats through a Wnt/ß-catenin signaling-associated mechanism.

Pulsed electromagnetic field (PEMF) is often used for management of osteoarthritis (OA). The aim of the study was to determine whether PEMF can successfully improve subchondral bone microstructure through a Wnt/ß-catenin signaling-associated pathway in rats with knee OA induced by low-dose monosodium iodoacetate (MIA). Seventy-two 12-week-old male Sprague-Dawley rats were randomly assigned to three groups: OA (n = 24), PEMF (n = 24), and Control (n = 24). OA was induced (OA and PEMF groups) by injecting 0.2 mg MIA in rats' right knee joint. The control rats received a single sterile saline injection in the right knee. Rats in the PEMF group were exposed to daily 2 h PEMF exposure with 75 Hz, 1.6 mT for 4 weeks. After 4 weeks, micro-computed tomography (micro-CT), real-time PCR, and immunohistochemistry staining were performed. The PEMF group increased bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and suppressed bone surface/bone volume (BS/BV) and trabecular separation (Tb.Sp) levels in micro-CT analysis. Real-time PCR analysis showed that PEMF promoted tibial subchondral bone's gene expressions of Wnt3a, ß-catenin, and OPG, but did not alter LRP5 and RANKL mRNA levels. Similar results involved tibial subchondral bone's protein expressions that were observed in immunohistochemistry staining. These results suggest that PEMF preserved the structural integrity of subchondral bone in knee OA rats by promoting the activation of Wnt/ß-catenin signaling and OPG/RANKL/RANK signaling. Bioelectromagnetics. 39:89-97, 2018. © 2017 Wiley Periodicals, Inc.

Effects of pulsed electromagnetic fields on postmenopausal osteoporosis.

Postmenopausal osteoporosis (PMOP) is considered to be a well-defined subject that has caused high morbidity and mortality. In elderly women diagnosed with PMOP, low bone mass and fragile bone strength have been proven to significantly increase risk of fragility fractures. Currently, various anabolic and anti-resorptive therapies have been employed in an attempt to retain healthy bone mass and strength. Pulsed electromagnetic fields (PEMFs), first applied in treating patients with delayed fracture healing and nonunions, may turn out to be another potential and effective therapy for PMOP. PEMFs can enhance osteoblastogenesis and inhibit osteoclastogenesis, thus contributing to an increase in bone mass and strength. However, accurate mechanisms of the positive effects of PEMFs on PMOP remain to be further elucidated. This review attempts to summarize recent advances of PEMFs in treating PMOP based on clinical trials, and animal and cellular studies. Possible mechanisms are also introduced, and the future possibility of application of PEMFs on PMOP are further explored and discussed. Bioelectromagnetics. 38:406-424, 2017. © 2017 Wiley Periodicals, Inc.

Pulsed electromagnetic field at different stages of knee osteoarthritis in rats induced by low-dose monosodium iodoacetate: Effect on subchondral trabecular bone microarchitecture and cartilage degradation.

The aim of the study was to investigate the efficacy of pre-emptive, early, and delayed pulsed electromagnetic field (PEMF) treatment on cartilage and subchondral trabecular bone in knee osteoarthritis (OA) rats induced by low-dose monosodium iodoacetate (MIA). Seventy-five 12-week-old male Sprague-Dawley rats were assigned to five groups: OA (n = 30), pre-emptive PEMF (n = 10), early PEMF (n = 10), delayed PEMF (n = 10), and control (n = 15). Osteoarthritis was induced by injecting 0.2 mg MIA in rat's right knee joint. Control rats received a single sterile saline injection in the right knee. Male rats received pre-emptive (n = 10, day 0-end of week 4), early (n = 10, end of week 4-end of week 8), or delayed (n = 10, end of week 8-end of week 12) PEMF treatment (75 Hz, 1.6 mT). After 4, 8, and 12 weeks, rats were sacrificed at each time point and right knees were harvested. After sacrifice, micro-computed tomography, histology, and biomarker analyses were performed. We found pre-emptive PEMF treatment preserved subchondral trabecular bone microarchitecture and prevented subchondral bone loss in MIA-induced OA rat model. Early and delayed PEMF treatment maintained subchondral trabeculae. PEMF treatment increased bone and cartilage formation, and decreased bone and cartilage resorption. Pre-emptive and early PEMF treatment had moderate effects on cartilage degradation. Time point of treatment initiation is crucial for treating OA. PEMF might become a potential biophysical treatment modality for osteoarthritis. Bioelectromagnetics. 38:227-238, 2017. © 2016 Wiley Periodicals, Inc.

Effects of whole-body vibration on neuromuscular performance in individuals with spinal cord injury: a systematic review.

OBJECTIVE: To examine the effects of whole-body vibration on neuromuscular performance in people with spinal cord injury and evaluate the safe and effective vibration protocols. METHODS: PubMed, EMBASE, CINAHL and PEDro were mainly searched for English literatures. Other data sources were ClinicalTrials.gov , Current Controlled Trials and reference lists of all relevant articles. The PEDro scale was used to evaluate the methodological quality, and the Oxford Centre for Evidence-based Medicine level of evidence was used to assess the level of evidence. Basic information and whole-body vibration protocols were extracted by two independent researchers. Any disagreements were resolved by the third researcher. RESULTS: Of the eight included studies involving 94 individuals with spinal cord injury and 24 able-bodied participants, six of them reported beneficial effects of whole-body vibration on muscle activation and the other two on muscle spasticity. Based on the reviewed studies, an intermittent mode of whole-body vibration (frequency: 10-50 Hz; amplitude: 0.6-4 mm) is less likely to cause adverse events when applying to spinal cord injury subjects standing on platform (knees flexed at 10°-40°). CONCLUSIONS: The strength of evidence is insufficient in supporting the benefits of whole-body vibration on neuromuscular performance in individuals with spinal cord injury. The intermittent vibration (frequency: 10-50 Hz; amplitude: 0.6-4 mm; knee flexion: 10°-40°) may be the possible effective range and have good compliance.

Effects of whole body vibration on pulmonary function, functional exercise capacity and quality of life in people with chronic obstructive pulmonary disease: a systematic review.

OBJECTIVE: To examine the effect of whole-body vibration in enhancing pulmonary function, functional exercise capacity and quality of life in people with chronic obstructive pulmonary disease and examine its safety. METHOD: Randomized controlled trials examining the effects of whole body vibration among people with chronic obstructive pulmonary disease were identified by two independent researchers. Articles were excluded if they were studies on people with other primary diagnosis, abstracts published in the conferences or books. PEDro scale was used to assess the methodological quality of the selected studies. We evaluated the level of evidence by using the GRADE approach. The results were extracted by two researchers and confirmed by the third researcher if disagreement existed. DATA SOURCE: Sources included Cochrane Central Register of Controlled Trials, PubMed, CINAHL, EMBASE, PEDro, AMED, PsycINFO, ClinicalTrials.gov, Current Controlled Trials and reference lists of all relevant articles. RESULT: Four studies involving 206 participants were included in this systematic review. Methodological quality was rated as good for two studies. No great benefits on pulmonary function were found in whole body vibration treatment group. Two studies showed that quality of life was improved in people with chronic obstructive pulmonary disease. Whole body vibration led to significant improvements in functional exercise capacity measured with six minutes walking test. Nearly no adverse events were observed. CONCLUSION: Whole body vibration may improve functional exercise capacity and quality of life in people with chronic obstructive pulmonary disease. There was insufficient evidence to prove the effects of whole body vibration on pulmonary function.

The Influence of Exercise on Cancer Risk, the Tumor Microenvironment and the Treatment of Cancer.

There are several modifiable factors that can be targeted to prevent and manage the occurrence and progression of cancer, and maintaining adequate exercise is a crucial one. Regular physical exercise has been shown to be a beneficial strategy in preventing cancer, potentially amplifying the effectiveness of established cancer therapies, alleviating certain cancer-related symptoms, and possibly mitigating side effects resulting from treatment. Nevertheless, the exact mechanisms by which exercise affects tumors, especially its impact on the tumor microenvironment (TME), remain uncertain. This review aims to present an overview of the beneficial effects of exercise in the context of cancer management, followed by a summary of the exercise parameters, especially exercise intensity, that need to be considered when prescribing exercise for cancer patients. Finally, we discuss the influence of exercise on the TME, including its effects on crucial immune cells (e.g., T cells, macrophages, neutrophils, natural killer cells, myeloid-derived suppressor cells, B cells), intratumor angiogenesis, and cancer metabolism. This comprehensive review provides up-to-date scientific evidence on the effects of exercise training on cancer and offers guidance to clinicians for the development of safe and feasible exercise training programs for cancer patients in clinical practice.

Effect of postoperative exercise training on physical function and quality of life of lung cancer patients with chronic obstructive pulmonary disease: A randomized controlled trial.

BACKGROUND: Postoperative rehabilitation programs consisting of exercise training are considered effective for unselected lung cancer patients. However, whether postoperative exercise is beneficial to lung cancer patients comorbid with chronic obstructive pulmonary disease remains unknown. METHODS: Eighty-four patients diagnosed with both lung cancer and chronic obstructive pulmonary disease were randomized into the exercise group and control group. Both groups were given standard postoperative rehabilitation for 1 week. After that, oxygen therapy (if needed) and nebulization were given to the control group, while patients in the exercise group started to participate in exercise programs on the basis of receiving oxygen therapy and nebulization as in the control group. The exercise programs consisted of 24 training sessions. RESULTS: In both groups, the functional status and the results of the pulmonary function test decreased from baseline to the endpoint. However, after surgery and the intervention program, both the maximal oxygen consumption in the cardiopulmonary exercise test and walking distance in the 6-minute walk test in the exercise group were significantly better than those in the control group [15.5 (±1.4) mL/kg/min vs 13.1 (±1.3) mL/kg/min, P = 0.016; 437.4 (±48.6) m vs 381.7 (±40.5) m, P = 0.040]. Force vital capacity and forced expiratory volume in the first second in the exercise group were better than those in the control group, but the differences were not statistically significant [1798.1 (±298.9) mL vs 1664.0 (±329.7) mL, P = 0.254; 1155.7 (±174.3) mL vs 967.4 (±219.4) mL, P = 0.497]. The decline in the standard score of the QLQ-C30 (V3.0) was smaller in the exercise group, but the difference did not meet a statistically significant level [61.7 (±5.7) vs 58.4 (±9.3), P = 0.318]. CONCLUSION: This study demonstrates that a short-term postoperative exercise training program can facilitate the recovery of functional capacity in lung cancer patients with comorbidities of chronic obstructive pulmonary disease.

Pulsed electromagnetic fields on postmenopausal osteoporosis in Southwest China: a randomized, active-controlled clinical trial.

A randomized, active-controlled clinical trial was conducted to examine the effect of pulsed electromagnetic fields (PEMFs) on women with postmenopausal osteoporosis (PMO) in southwest China. Forty-four participants were randomly assigned to receive alendronate or one course of PEMFs treatment. The primary endpoint was the mean percentage change in bone mineral density of the lumbar spine (BMDL), and secondary endpoints were the mean percentage changes in left proximal femur bone mineral density (BMDF), serum 25OH vitamin D3 (25(OH)D) concentrations, total lower-extremity manual muscle test (LE MMT) score, and Berg Balance Scale (BBS) score. The BMDL, BMDF, total LE MMT score and BBS score were recorded at baseline, 5, 12, and 24 weeks. Serum concentrations of 25(OH)D were measured at baseline and 5 weeks. Using a mixed linear model, there was no significant treatment difference between the two groups in the BMDL, BMDF, total LE MMT score, and BBS score (P ≥ 0.05). For 25(OH)D concentrations, the effects were also comparable between the two groups (P ≥ 0.05) with the Mann-Whitney's U-test. These results suggested that a course of PEMFs treatment with specific parameters was as effective as alendronate in treating PMO within 24 weeks.

A comparison of different physical stimulation combined with platelet-rich plasma for the treatment of knee osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Platelet-rich plasma (PRP) contains various growth factors and inflammatory regulators, which can effectively reduce inflammation in joints and promote tissue repair. Multiple studies have proved its effectiveness in the treatment of knee osteoarthritis (KOA). Low-intensity focused ultrasound (LIFU) and transcutaneous electrical nerve stimulation (TENS) are non-invasive and safe physical therapy methods for KOA. This study is the first to propose the treatment of KOA with physical stimulation after PRP treatment, and to observe the clinical efficacy of the treatment method. METHODS: This is a protocol paper that outlines a randomized controlled trial, patients will be assigned randomly to the PRP group, PRP+LIFU group, PRP+TENS group, and PRP+LIFU combined TENS group. The patients will be followed at 12-week and 24-week time points to evaluate the primary and secondary outcomes of the study. The primary outcome is the VAS pain score. Secondary outcomes include Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and International Knee Documentation Committee scores (IKDC). After baseline examination, all patients will sign a written informed consent for study participation after a full explanation of the treatment protocol. We have planned a total of 120 patients (30 patients per group). DISCUSSION: The objective of this clinical trial is to evaluate the effect of different physical stimulation after PRP treatment for KOA. The data will be published after the completion of the study. TRIAL REGISTRATION: This study has been registered with the Chinese Clinical Trials Registry. REGISTRATION NUMBER: ChiCTR2200065119 (registered date: 10/28/2022).

Assistance level quantification-based human-robot interaction space reshaping for rehabilitation training.

Stroke has become a major disease that seriously threatens human health due to its high incidence and disability rates. Most patients undergo upper limb motor dysfunction after stroke, which significantly impairs the ability of stroke survivors in their activities of daily living (ADL). Robots provide an optional solution for stroke rehabilitation by attending therapy in the hospital and the community, however, the rehabilitation robot still has difficulty in providing needed assistance interactively like human clinicians in conventional therapy. For safe and rehabilitation training, a human-robot interaction space reshaping method was proposed based on the recovery states of patients. According to different recovery states, we designed seven experimental protocols suitable for distinguishing rehabilitation training sessions. To achieve assist-as-needed (AAN) control, a PSO-SVM classification model and an LSTM-KF regression model were introduced to recognize the motor ability of patients with electromyography (EMG) and kinematic data, and a region controller for interaction space shaping was studied. Ten groups of offline and online experiments and corresponding data processing were conducted, and the machine learning and AAN control results were presented, which ensured the effective and the safe upper limb rehabilitation training. To discuss the human-robot interaction in different training stages and sessions, we defined a quantified assistance level index that characterizes the rehabilitation needs by considering the engagement of the patients and had the potential to apply in clinical upper limb rehabilitation training.

Exoskeleton-Assisted Walking for Pulmonary and Exercise Performances of SCI Individuals.

OBJECTIVE: To determine whether exoskeleton-assisted walking (EAW) improves pulmonary ventilation function, motor function and related body structure, and activities equivalently as the conventional exercise program for people with spinal cord injury (SCI). METHODS: Forty participants (7 females and 33 males; age 37.1±12.0 years) with thoracic SCI were randomized into two groups and undertook 16 sessions of 50-60 min training (4 days/week). Participants in the EAW group received EAW trainings, such as assisted standing, walking, and climbing the stairs. The control group received a conventional exercise program. Outcomes were measured at baseline and upon completion of treatment. RESULTS: After trainings, the EAW group improved more than the control group in the forced vital capacity (FVC, 0.53 L [0.01-1.06 L]), predicted FVC% (19.59 [6.63-32.54]) and forced expiratory volume in 1s (0.61 L [0.15-1.07 L]), basic activities of daily living (BADL) (19.75 [10.88-28.62]), and distal femoral cartilage. Participants in the EAW group completed 6-minute walk test with median 17.3 meters while wearing the exoskeleton. There was no difference in trunk and lower extremity motor function, bone mineral density, and adverse events ( P > 0.05). CONCLUSION: In people with lower thoracic neurological level of SCI, EAW training has potential benefits to facilitate pulmonary ventilation function, walking, BADL and thickness of cartilage comparing to a conventional excise program. SIGNIFICANCE: This study provided more evidence for using EAW in clinic, and partly proved EAW had equivalent effects as conventional exercise program, which may combine with conventional exercise program for reducing burden of therapists in the future.

Mesenchymal stromal cell-based therapy for cartilage regeneration in knee osteoarthritis.

Osteoarthritis, as a degenerative disease, is a common problem and results in high socioeconomic costs and rates of disability. The most commonly affected joint is the knee and characterized by progressive destruction of articular cartilage, loss of extracellular matrix, and progressive inflammation. Mesenchymal stromal cell (MSC)-based therapy has been explored as a new regenerative treatment for knee osteoarthritis in recent years. However, the detailed functions of MSC-based therapy and related mechanism, especially of cartilage regeneration, have not been explained. Hence, this review summarized how to choose, authenticate, and culture different origins of MSCs and derived exosomes. Moreover, clinical application and the latest mechanistical findings of MSC-based therapy in cartilage regeneration were also demonstrated.

The Effect of Different Frequencies of Pulsed Electromagnetic Fields on Cartilage Repair of Adipose Mesenchymal Stem Cell-Derived Exosomes in Osteoarthritis.

BACKGROUND: The intra-articular injection of mesenchymal stem cell (MSC)-derived exosomes has already been proved to reverse osteoarthritic cartilage degeneration. Pulsed electromagnetic field (PEMF) has been found to regulate the biogenic function of MSCs. However, the effect of PEMF on MSC-derived exosomes has not yet been characterized. The aim of this study was to elucidate the regulatory role of different frequencies of PEMF in promoting the osteoarthritic cartilage regeneration of MSC-derived exosomes. METHODS: The adipose tissue-derived MSCs (AMSCs) were extracted from the epididymal fat of healthy rats and further exposed to the PEMF at 1 mT amplitude and a frequency of 15, 45, and 75 Hz, respectively, in an incubator. The chondrocytes were treated with interlukin-1ß (IL-1ß) and the regenerative effect of co-culturing with PEMF-exposed AMSC-derived exosomes was assessed via Western blot, quantitative polymerase chain reaction, and ELISA assays. A rat model of osteoarthritis was established by anterior cruciate ligament transection (ACLT) surgery and received 4 times intra-articular injection of PEMF-exposed AMSC-derived exosomes once a week. After 8 weeks, the knee joint specimens of rats were collected for micro-computed tomography and histologic analyses. RESULTS: PEMF-exposed AMSC-derived exosomes could be endocytosed with IL-1ß-induced chondrocytes. Compared with the AMSC-derived exosomes alone, the PEMF-exposed AMSC-derived exosomes substantially suppressed the inflammation and extracellular matrix degeneration of IL-1ß-induced chondrocytes as shown by higher expression of transcripts and proteins of COL2A1, SOX9, and ACAN and lower expression of MMP13 and caspase-1. Of these, the 75-Hz PEMF presented a more significant inhibitive effect than the 15-Hz and 45-Hz PEMFs. Furthermore, the intra-articular injection of 75-Hz PEMF-exposed exosomes could obviously increase the number of tibial epiphyseal trabeculae, lead to a remarkable decrease in Osteoarthritis Research Society International score, and upregulate the COL2A1 and ACAN protein level of the degenerated cartilage. CONCLUSION: The present study demonstrated that PEMF stimulation could effectively promote the regeneration effects of AMSC-derived exosomes on osteoarthritic cartilage. Compared with other frequency parameters, the PEMF at a frequency of 75 Hz showed a superior positive effect on AMSC-derived exosomes in suppressing the IL-1ß-induced chondrocyte inflammation and extracellular matrix catabolism, as well as the osteoarthritic cartilage degeneration.