Pulsed electromagnetic fields potentiate bone marrow mesenchymal stem cell chondrogenesis by regulating the Wnt/ß-catenin signaling pathway.

BACKGROUND: Pulsed electromagnetic fields (PEMFs) show promise as a treatment for knee osteoarthritis (KOA) by reducing inflammation and promoting chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). PURPOSE: To identify the efficacy window of PEMFs to induce BMSCs chondrogenic differentiation and explore the cellular mechanism under chondrogenesis of BMSCs in regular and inflammatory microenvironments. METHODS: BMSCs were exposed to PEMFs (75 Hz, 1.6/2/3/3.8 mT) for 7 and 14 days. The histology, proliferation, migration and chondrogenesis of BMSCs were assessed to identify the optimal parameters. Using these optimal parameters, transcriptome analysis was performed to identify target genes and signaling pathways, validated through immunohistochemical assays, western blotting, and qRT-PCR, with or without the presence of IL-1ß. The therapeutic effects of PEMFs and the effective cellular signaling pathways were evaluated in vivo. RESULTS: BMSCs treated with 3 mT PEMFs showed the optimal chondrogenesis on day 7, indicated by increased expression of ACAN, COL2A, and SOX9, and decreased levels of MMP3 and MMP13 at both transcriptional and protein levels. The advantages of 3 mT PEMFs diminished in the 14-day culture groups. Transcriptome analysis identified sFRP3 as a key molecule targeted by PEMF treatment, which competitively inhibited Wnt/ß-catenin signaling, regardless of IL-1ß presence or duration of exposure. This inhibition of the Wnt/ß-catenin pathway was also confirmed in a KOA mouse model following PEMF exposure. CONCLUSIONS: PEMFs at 75 Hz and 3 mT are optimal in inducing early-stage chondrogenic differentiation of BMSCs. The induction and chondroprotective effects of PEMFs are mediated by sFRP3 and Wnt/ß-catenin signaling, irrespective of inflammatory conditions.

Pulsed Electromagnetic Fields Combined With Adipose-Derived Stem Cells Protect Ischemic Myocardium by Regulating miR-20a-5p/E2F1/p73 Signaling.

Myocardial infarction (MI) is a serious threat to human health. Although monotherapy with pulsed electromagnetic fields (PEMFs) or adipose-derived stem cells (ADSCs) has been reported to have positive effect on the treatment of MI, a satisfactory outcome has not yet been achieved. In recent years, combination therapy has attracted widespread interest. Herein, we explored the synergistic therapeutic effect of combination therapy with PEMFs and ADSCs on MI and found that the combination of PEMFs and ADSCs effectively reduced infarct size, inhibited cardiomyocyte apoptosis and protected the cardiac function in mice with MI. In addition, bioinformatics analysis and RT-qPCR showed that the combination therapy could affect apoptosis by regulating the expression of miR-20a-5p. A dual-luciferase reporter gene assay also confirmed that the miR-20a-5p could target E2F transcription factor 1 (E2F1) and inhibit cardiomyocyte apoptosis by regulating the E2F1/p73 signaling pathway. Therefore, our study systematically demonstrated the effectiveness of combination therapy on the inhibition of cardiomyocyte apoptosis by regulating the miR-20a-5p/E2F1/p73 signaling pathway in mice with MI. Thus, our study underscored the effectiveness of the combination of PEMFs and ADSCs and identified miR-20a-5p as a promising therapeutic target for the treatment of MI in the future.

Triglyceride glucose index combined with body mass index and its 4-year change with the risk of hypertension in middle-aged and older Chinese: A prospective cohort study.

BACKGROUND AND AIM: To explore the association of triglyceride glucose index-body mass index (TyG-BMI) and its dynamic changes with the risk of hypertension among middle-aged and older Chinese adults based on a large-sample prospective cohort study. METHODS AND RESULTS: Participants over 45 years old and without a history of hypertension were included from the China Health and Retirement Longitudinal Study registry. Data were collected in 2011 and followed up in 2015. TyG index and TyG-BMI were calculated as ln (triglyceride∗glucose/2) and TyG index∗BMI, respectively. We performed multivariate logistic regression analysis to identify the relationship between the TyG index, TyG-BMI and their dynamic change and the risk of hypertension. In the analyses, 3885 participants were included. After 4 years of follow-up, 1705 (43.89 %) patients developed hypertension. Logistic regression analysis revealed that after adjustments for all potential confounding factors, the highest tertile of baseline TyG index, baseline TyG-BMI, and the dynamic change in TyG-BMI were each associated with higher hypertension incidence than the lowest tertile: OR,1.38, 95 % CI, 1.17-1.63, OR,1.28, 95 % CI, 1.06-1.56, and OR, 1.26, 95 % CI, 1.07-1.48, respectively, whereas TyG index change was not. Moreover, the risk of hypertension increased with increasing levels of baseline TyG index (P for trend < 0.001), baseline TyG-BMI (P for trend = 0.013), and the dynamic change in TyG-BMI (P for trend = 0.006). CONCLUSIONS: The baseline TyG index, baseline TyG-BMI, and the dynamic changes in TyG-BMI were significantly and positively associated with the risk of hypertension in Chinese adults older than 45 years.

The efficacy of exercise training for improving body composition in patients with breast cancer: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To evaluate the efficacy of exercise in improving body composition in patients with breast cancer; the effects of exercise on weight and BMI were evaluated as secondary outcomes. DATA SOURCES: Cochrane Library, EMBASE, PubMed and Web of Science were searched for randomized controlled trials published in English from database inception to 29 November 2023. METHODS: The effects of exercise on body composition in patients with breast cancer were explored. After separately extracting the data, two reviewers assessed the overall quality of the evidence as well as the methodological quality of the included studies. RESULTS: Fourteen studies with 1241 participants were included, of which 12 studies were eligible for meta-analysis. Exercise significantly reduced body fat (mean difference [MD], -0.33; 95% CI, -0.37 to -0.29; P < 0.00001) and increased lean mass (MD, 0.42; 95% CI, 0.34 to 0.49; P < 0.00001) in patients with breast cancer. Further, exercise intervention was associated with increased BMI of patients with breast cancer (MD, 0.03; 95% CI, 0.01 to 0.06; P = 0.01), while no significant difference in weight was detected between the exercise and the non-exercise groups. Subgroup analysis results showed that only resistance exercise reduced fat mass (MD, -0.22; 95% CI, -0.27 to -0.16; P < 0.00001). CONCLUSIONS: Exercise effectively improves body composition in patients with breast cancer. Clinicians should encourage patients to engage in exercise and develop optimized exercise prescriptions.

Effectiveness of Rehabilitation Interventions in Individuals With Emerging Virtual Respiratory Tract Infectious Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: Assessing rehabilitation effectiveness for persistent symptoms post-infection with emerging viral respiratory diseases. DATA SOURCES: Systematic review of seven databases (MEDLINE, EMBASE, Cochrane Library, PEDro, MedRxiv, CNKI, Wanfang) until 30 December 2023. REVIEW METHODS: Evaluated 101 studies (9593 participants) on respiratory function, exercise capacity, and quality of life. Methodological quality was assessed using the Cochrane Collaboration's Risk of Bias tool for randomized controlled trials (RCTs), the Newcastle-Ottawa Scale (NOS) for observational studies and non-RCTs, and the NIH Quality Assessment Tools for before-after studies. RESULTS: The most common rehabilitation program combined breathing exercises with aerobic exercise or strength training. Rehabilitation interventions significantly enhanced respiratory function, as evidenced by improvements on the Borg Scale (MD, -1.85; 95% CI, -3.00 to -0.70, low certainty), the mMRC Dyspnea Scale (MD, -0.45; 95% CI, -0.72 to -0.18, low certainty), and the Multidimensional Dyspnoea-12 Scale (MD, -4.64; 95% CI, -6.54 to -2.74, moderate certainty). Exercise capacity also improved, demonstrated by results from the Six-Minute Walk Test (MD, 38.18; 95% CI, 25.33-51.03, moderate certainty) and the Sit-to-Stand Test (MD, 3.04; 95% CI, 1.07-5.01, low certainty). CONCLUSION: Rehabilitation interventions are promising for survivors of viral respiratory diseases, yet gaps in research remain. Future investigations should focus on personalizing rehabilitation efforts, utilizing remote technology-assisted programs, improving research quality, and identifying specific subgroups for customized rehabilitation strategies to achieve the best outcomes for survivors.

Prognostic value of the systemic inflammatory index (SII) and systemic inflammatory response index (SIRI) in patients with traumatic spinal cord injury.

PURPOSE: The overwhelming inflammatory response plays a critical role in the secondary injury cascade of traumatic spinal cord injury (tSCI). The systemic immune inflammatory index (SII) and systemic inflammatory response index (SIRI) are two novel inflammatory biomarkers. The SII was calculated based on lymphocyte, neutrophil, and platelet counts, while the SIRI was calculated based on lymphocyte, neutrophil, and monocyte counts. Their prognostic value in patients with tSCI remains unclear. METHODS: Patients with tSCI admitted within 24 h of trauma were retrospectively and consecutively enrolled. Peripheral blood samples were collected on admission. The primary outcome was American Spinal Injury Association Impairment Scale (AIS) grade conversion at discharge. Multivariable logistic regression analysis was performed to determine the relationship between SII and SIRI and AIS grade conversion. We performed receiver operating characteristic curve (ROC) analysis to assess the discriminative ability of SII, and SIRI in predicting AIS grade conversion. RESULTS: Among 280 included patients, 77 (27.5%) had improved AIS grade conversion at discharge. After adjustment for confounders, SII was independently associated with AIS grade conversion (per SD, odds ratio [OR], 0.68; 95% confidence interval [CI] 0.47-0.98, p = 0.040), while the association between SIRI and AIS grade conversion was insignificant (per 1 SD, OR, 0.77; 95% CI 0.55-1.08, p = 0.130). The ROC analysis revealed that the SII had the best predictive value for AIS grade conversion (area under curve: 0.608, 95% CI 0.536-0.678). CONCLUSIONS: Increased SII was independently associated with a decreased likelihood of improved AIS grade conversion.

Development and validation of a novel screening tool for deep vein thrombosis in patients with spinal cord injury: A five-year cross-sectional study.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: Deep vein thrombosis (DVT) presents a significant risk of complication in patients with spinal cord injury (SCI), necessitating accurate screening methods. While the Caprini Risk Assessment Model (Caprini RAM) has seen extensive use for DVT screening, its efficacy remains under scrutiny. SETTING: First Affiliated Hospital of China University of Science and Technology. METHODS: We created and evaluated three nomograms for their effectiveness in DVT screening. Model 1 incorporated variables such as age, D-dimer level, red blood cell (RBC) counts, platelet counts, presence of type 2 diabetes mellitus, high blood pressure, mode and level of injury, degree of impairments, and Caprini scores. Model 2 was derived from Caprini scores alone, and Model 3 focused on independent risk factors. We assessed these models using the area under the curve (AUC) of the receiver operating characteristic (ROC), calibration curves, and decision curve analysis (DCA), employing bootstrap resampling tests (500 iterations) to determine their accuracy, discriminative ability, and clinical utility. Internal validation was performed on a separate cohort. Nomogram was established with well-fitted calibration curves for model 1, 2 and 3(AUC = 0.808, 0.751 and 0.797; 95%CI = 0.76-0.86, 0.70-0.80 and 0.75-0.84; respectively), indicating model 1 outperformed the others in prediction DVT risk, followed by model 3 and 2. These findings were consistent in the validation cohort, with DCA further corroborating our conclusions. CONCLUSION: A nomogram integrating clinical data with Caprini RAM provides a superior option for DVT screening in SCI patients within rehabilitation settings, outperforming Caprini RAM.

Telehealth-Supported Exercise or Physical Activity Programs for Knee Osteoarthritis: Systematic Review and Meta-Analysis.

BACKGROUND: The integration of telehealth-supported programs in chronic disease management has become increasingly common. However, its effectiveness for individuals with knee osteoarthritis (KOA) remains unclear. OBJECTIVE: This study aimed to assess the effectiveness of telehealth-supported exercise or physical activity programs for individuals with KOA. METHODS: A comprehensive literature search encompassing Embase, MEDLINE, CENTRAL, Web of Science, PubMed, Scopus, PEDro, GreyNet, and medRxiv from inception to September 2023 was conducted to identify randomized controlled trials comparing telehealth-supported exercise or physical activity programs to a control condition for KOA. Data were extracted and qualitatively synthesized across eligible studies, and a meta-analysis was performed to evaluate the effects. The study was reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020. RESULTS: In total, 23 studies met eligibility criteria, with 20 included in the meta-analysis. Results showed that telehealth-supported exercise or physical activity programs reduced pain (g=-0.39; 95% CI -0.67 to -0.11; P<.001), improved physical activity (g=0.13; 95% CI 0.03-0.23; P=.01), and enhanced physical function (g=-0.51; 95% CI -0.98 to -0.05; P=.03). Moreover, significant improvements in quality of life (g=0.25; 95% CI 0.14-0.36; P<.001), self-efficacy for pain (g=0.72; 95% CI 0.53-0.91; P<.001), and global improvement (odds ratio 2.69, 95% CI 1.41-5.15; P<.001) were observed. However, self-efficacy for physical function (g=0.14; 95% CI -0.26 to 0.53; P=.50) showed insignificant improvements. Subgroup analyses based on the World Health Organization classification of digital health (pain: χ22=6.5; P=.04 and physical function: χ22=6.4; P=.04), the type of teletechnology in the intervention group (pain: χ24=4.8; P=.31 and function: χ24=13.0; P=.01), and active or inactive controls (pain: χ21=5.3; P=.02 and physical function: χ21=3.4; P=.07) showed significant subgroup differences. CONCLUSIONS: Telehealth-supported exercise or physical activity programs might reduce knee pain and improve physical activity, physical function, quality of life, self-efficacy, and global improvement in individuals with KOA. Future research should consider longer implementation durations and assess the feasibility of incorporating wearables and standardized components into large-scale interventions to evaluate the effects. TRIAL REGISTRATION: PROSPERO CRD42022359658; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=359658.

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.

Regulation of cholesterol homeostasis in osteoporosis mechanisms and therapeutics.

Osteoporosis is a metabolic bone disease that affects hundreds of millions of people worldwide and is characterized by excessive loss of bone protein and mineral content. The incidence and mortality of osteoporosis increase with age, creating a significant medical and economic burden globally. The importance of cholesterol levels has been reported in the development of diseases including osteoporosis. It is important to note that key enzymes and molecules involved in cholesterol homeostasis are closely related to bone formation. Excessive cholesterol may cause osteoporosis, cholesterol and its metabolites affect bone homeostasis by regulating the proliferation and stimulation of osteoblasts and osteoclasts. Therefore, antagonism of elevated cholesterol levels may be a potential strategy to prevent osteoporosis. There is sufficient evidence to support the use of bisphosphonates and statin drugs for osteoporosis in the clinic. Therefore, in view of the aggravation of the aging problem, we summarize the intracellular mechanism of cholesterol homeostasis and its relationship with osteoporosis (including cholesterol and cholesterol oxidation products (COPs) in osteoporosis). Furthermore, the current clinical cholesterol-lowering drugs for osteoporosis were also summarized, as are new and promising therapies (cell-based therapies (e.g., stem cells) and biomaterial-delivered target drug therapies for osteoporosis as well).

Monocyte to high-density lipoprotein ratio is associated with mortality in patients with coronary artery diseases.

BACKGROUND: Whether the monocyte to high-density lipoprotein ratio (MHR) is associated with the prognosis of coronary artery disease (CAD) is inconclusive. METHODS: Patients with CAD were enrolled and their data were collected. Blood was sampled within 24 h after admission. Multivariate Cox regression analysis was performed to determine the relationship between the MHR and all-cause mortality as well as complications during hospitalization. RESULTS: We included 5371 patients in our cohort study. Among them, 114 (2.12%) patients died in hospital. MHR was independently associated with all-cause mortality (hazard ratio [HR], 1.81; 95% confidence interval [CI] 1.35, 2.42), cardiovascular mortality (1.69; 1.17, 2.45) and non-cardiovascular mortality (2.04; 1.27, 3.28). This association was only observed in patients with hypertension (P for interaction = 0.003). Patients with higher MHR levels also have a higher risk of complications, including infection, pneumonia, electrolyte disturbance, gastrointestinal bleeding, multiple organ dysfunction syndrome, and disturbance of consciousness. The receiver operating characteristic (ROC) analysis showed that the MHR had higher prognostic values than monocytes and high-density lipoprotein. CONCLUSION: MHR was an independent predictor of all-cause mortality and in-hospital complications in patients with CAD, especially in patients with hypertension.

Effects of home-based cardiac telerehabilitation programs in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: Recent advances in telecommunications technology have raised the possibility of telehealth intervention delivering cardiac telerehabilitation, which may provide the efficacy of health services in patients after percutaneous coronary intervention (PCI). This study aimed to investigate the effects of home-based cardiac telerehabilitation (HBCTR) in patients undergoing PCI. METHODS: We performed a comprehensive search of the following electronic databases: PubMed, Cochrane Central, Web of Science, Embase, CNKI, and WANFANG. For the prespecified outcomes, the primary outcomes were results of physical function (the six-minute walking test, 6MWT) and quality of life (QoL) of the participants. The secondary outcomes were results of (1) blood pressure; (2) full lipid profile (3) reliable assessment of anxiety and depression in patients. RESULTS: All studies were conducted between 2013 and 2022, and a total of 5 articles could be included in the quantitative meta-analysis. The results showed that there was a statistically significant difference between the HBCTR intervention group and the control group in 6WMT (MD 16.59, 95%CI 7.13 to 26.06, P = 0.0006), but there was no difference in QoL (SMD - 0.25, 95%CI - 1.63 to 1.13, P = 0.73). According to the fixed effects model, there was a statistically significant difference between the HBCTR group versus the control group (MD - 2.88, 95%CI - 5.19 to - 0.57, P = 0.01), but not in diastolic blood pressure. Likewise, significant improvements of triglycerides and in low-density lipoprotein cholesterol were observed in HBTCR groups, but no significant differences were observed regarding total cholesterol and high-density lipoprotein cholesterol. CONCLUSION: This systematic review and meta-analysis have proven that the HBCTR is one of the promisingly effective cardiac rehabilitation strategies that improve cardiorespiratory fitness and reduce cardiovascular disease risk factors. With the continuous improvement of the telerehabilitation network, it is expected to serve in clinical.

MiR-30 Family: A Novel Avenue for Treating Bone and Joint Diseases?

Bone and joint diseases are a group of clinically heterogeneous diseases characterized by various bone strength disorders, bone structural defects and bone mass abnormalities. Common bone diseases include osteoporosis, skeletal dysplasia, and osteosarcoma, and common joint diseases include osteoarthritis, rheumatoid arthritis, and degenerative disc disease. all of them lead to high medical costs. The miR-30 family consists of a total of 5 members: miR-30a, miR-30b, miR-30c, miR-30d and miR-30e. Accumulating evidence has indicated that the miR-30 family may be involved in the occurrence and development of bone and joint diseases. For example, miR-30a is highly expressed in blood samples of osteoporosis patients, miR-30a/b increases in cartilage tissue of osteoarthritis patients, and lower expression of miR-30c is associated with higher malignance and shorter survival time of osteosarcoma. Mechanistically, by targeting crucial transcription factors (RUNX2, SOX9, beclin-1, etc.), the miR-30 family regulates some critical pathways of bone homeostasis (Wnt/ß-Catenin, mTOR, PI3K/AKT, etc.). In view of the distinct actions of the miR-30 family on bone metabolism, we hypothesize that the miR-30 family may be a new remedy for the clinical treatment and prevention of some bone and joint diseases.

Effectiveness of robotic-assisted gait training on cardiopulmonary fitness and exercise capacity for incomplete spinal cord injury: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To determine the effects of robotic-assisted gait training on cardiopulmonary fitness and exercise capacity for people with incomplete spinal cord injury. METHODS: PubMed, Embase, Web of Science, PEDro, CENTRAL and CINAHL were searched from inception until September 4, 2022. Randomized controlled trials that evaluated the effects of robotic-assisted gait training on cardiopulmonary fitness and exercise capacity for individuals with incomplete spinal cord injury were selected. Mean differences (MD) with 95% confidence interval (CI) were calculated. The methodological quality was evaluated by the Cochrane Risk of Bias 2.0 tool. Subgroup analyses were conducted according to the time since injury. RESULTS: In total 19 studies involving 770 patients were eligible for analysis. Individuals with acute incomplete spinal cord injury in robotic-assisted gait training groups showed significantly greater improvements in 6-minute walking test (MD 53.32; 95% CI 33.49 to 73.15; P < 0.001), lower extremity motor scale (MD 5.22; 95% CI 3.63 to 6.80; P < 0.001) and walking index for spinal cord injury II (MD 3.18; 95% CI 1.34 to 5.02; P < 0.001). Robotic-assisted gait training improved peak oxygen consumption to a greater degree for chronic incomplete spinal cord injury patients (MD 4.90; 95% CI 0.96 to 8.84; P = 0.01). CONCLUSION: Robot-assisted gait training may be a feasible and effective intervention in terms of cardiopulmonary fitness and exercise capacity for individuals with incomplete spinal cord injury.

Association between neutrophil percentage-to-albumin ratio and pneumonia in patients with traumatic spinal cord injury.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To investigate the association between neutrophil percentage-to-albumin ratio (NPAR) and pneumonia in patients with SCI. SETTING: Department of Rehabilitation Medicine Center, West China Hospital, Sichuan University. METHODS: SCI patients admitted to West China Hospital within 24 h of injury were consecutively enrolled. Blood samples were collected on admission. Pneumonia was diagnosed based on chest radiography and clinician records of patient symptoms and laboratory tests. Multivariable logistic regression analysis was performed to determine the relationship between NPAR and pneumonia. Receiver operating characteristic (ROC) curves were generated to assess the predictive value of NPAR. RESULTS: A total of 264 SCI patients were included, of whom 65 (24.6%) developed pneumonia. NPAR was positively correlated with pneumonia (OR 2.66, 95% CI, 1.06-6.71, p = 0.038). Patients in the upper NPAR tertile (2.35-3.71) had a higher risk of pneumonia than patients in the lower tertile (1.66-2.12) after adjustment for potential confounders (OR 2.55, 95% CI, 1.05-6.19, p = 0.039). The risk of pneumonia increased stepwise across NPAR tertiles (p for trend = 0.031). The optimal cutoff value of NPAR for predicting pneumonia was 2.17 with a sensitivity of 0.82 and a specificity of 0.50. There was a significant interaction between NPAR and neurological level of injury (p for interaction = 0.034), with no significant association between NPAR and pneumonia in patients with cervical SCI. CONCLUSIONS: A higher NPAR was independently associated with higher risk of pneumonia in a dose-dependent manner in patients with non-cervical SCI.

Evaluation of the effect of physical therapy on pain and dysfunction of knee osteoarthritis based on fNIRS: a randomized controlled trial protocol.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic musculoskeletal disease that can cause joint pain and dysfunction, affecting the quality of life of patients. Nonsurgical treatment is the conventional treatment of KOA, among which physical therapy is widely used because of its simplicity, convenience and effectiveness. The functional biomarker will add to the clinical fidelity and diagnostic accuracy. Therefore, our study chose a more objective evaluation indicator, functional near-infrared spectroscopy (fNIRS), to identify between healthy people and KOA patients, and to detect the pain change before and after treatment of KOA patients. METHODS: The study will be conducted in the Rehabilitation Medical Center of West China Hospital of Sichuan University and divided into 2 stages. In the first stage, we will compare and determine the differences in baseline data between healthy volunteers and KOA patients. In the second stage, 72 KOA patients will be randomly divided into two groups: the drug therapy group (DT) and the combination therapy group (CT) for 10 treatments. Outcome measures will be measured at baseline and on the 5th and 10th days after the intervention, including the numerical rating scale (NRS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), pain catastrophizing scale (PCS), the association of pain severity with task-state functional connectivity fNIRS and association of pain severity with task-activated fNIRS. DISCUSSION: By analyzing the fNIRS data of healthy volunteers and KOA patients, our study will be determined whether fNIRS can be used as a new indicator to reflect the severity of pain in KOA patients. Subsequently, the same fNIRS data for KOA patients before and after the intervention will be collected to provide an accurate evaluation criterion for the effect of physical therapy on KOA. TRIAL REGISTRATION: The study was registered on the Chinese Registry website (registered in ChiCTR.org with the identifiers ChiCTR2200064175 and 29/09/2022).

CD44 promotes angiogenesis in myocardial infarction through regulating plasma exosome uptake and further enhancing FGFR2 signaling transduction.

BACKGROUND: Since angiogenesis occurs as the pathological process following myocardial infarction to alleviate ischemia, therapeutic angiogenesis has been proposed to be a cardioprotective strategy. CD44 has been implicated in endothelial cell functions and its role has been well established in angiogenesis for years. Although recent studies indicate the close correlation between CD44 and exosome, as well as the two being implicated in myocardial ischemia pathological processes, the effect and the underlying mechanism of CD44 and its regulated plasma exosome in pathological angiogenesis post-myocardial infarction have not been fully elucidated. METHODS: In this study, we used CD44 knockout mice to study the in vivo impacts of CD44 on ischemic angiogenesis in myocardial infarction. Mouse cardiac function was measured by echocardiography, histological changes were observed by Evans Blue and TTC-double staining and Masson's trichrome staining, and molecular changes were detected by immunofluorescence. In the in vitro study, CD44 knockout HUVECs were generated and CD44 inhibitor was used to study the mechanism of CD44 on angiogenesis. We performed the immunoprecipitation, proximity ligation assay, and super-resolution imaging to study the mechanistic regulation of FGFR2 signaling transduction by CD44. Importantly, we also isolated plasma exosomes from myocardial infarction model mice and studied the effect of plasma exosomes on the activation of the FGFR2 signaling pathway and the related phenotypic alterations, including exosomes uptake and angiogenic function in primary mouse microvascular endothelial cells, and further discovered the regulation mechanism of exosomal miRNAs. RESULTS: We observed that the expression of CD44 in the border zone of the infarcted heart was tightly related to pathological angiogenesis following myocardial ischemia. The depletion of CD44 impaired angiogenesis and impacts biogenesis and proangiogenic function of plasma exosomes. Subsequently, we found that CD44 mediated the activation of the FGFR2 signaling pathway as well as the caveolin 1-dependent uptake of exosomes in vascular endothelial cells. Most importantly, the proangiogenic therapeutic effect of plasma exosomal miRNAs depended upon the participation of CD44/FGFR2 signaling transduction in vascular endothelial cells. CONCLUSION: CD44 and its regulated plasma exosomes have crucial potent angiogenic activity. Our studies elucidate that CD44 plays a key role in plasma exosomal miRNA-enhanced angiogenic FGFR2 singling transduction and ischemic angiogenesis in the early stage of myocardial infarction.

HK2: a potential regulator of osteoarthritis via glycolytic and non-glycolytic pathways.

Osteoarthritis (OA) is an age-related chronic degenerative joint disease where the main characteristics include progressive degeneration of cartilage, varying degrees of synovitis, and periarticular osteogenesis. However, the underlying factors involved in OA pathogenesis remain elusive which has resulted in poor clinical treatment effect. Recently, glucose metabolism changes provide a new perspective on the pathogenesis of OA. Under the stimulation of external environment, the metabolic pathway of chondrocytes tends to change from oxidative phosphorylation (OXPHOS) to aerobic glycolysis. Previous studies have demonstrated that glycolysis of synovial tissue is increased in OA. The hexokinase (HK) is the first rate limiting enzyme in aerobic glycolysis, participating and catalyzing the main pathway of glucose utilization. An isoform of HKs, HK2 is considered to be a key regulator of glucose metabolism, promotes the transformation of glycolysis from OXPHOS to aerobic glycolysis. Moreover, the expression level of HK2 in OA synovial tissue (FLS) was higher than that in control group, which indicated the potential therapeutic effect of HK2 in OA. However, there is no summary to help us understand the potential therapeutic role of glucose metabolism in OA. Therefore, this review focuses on the properties of HK2 and existing research concerning HK2 and OA. We also highlight the potential role and mechanism of HK2 in OA. Video abstract.

What conservative interventions can improve the long-term quality of life, depression, and anxiety of individuals with stable COPD? A systematic review and meta-analysis.

PURPOSE: Many conservative interventions are used in the management of stable chronic obstructive pulmonary disease (COPD). It could be helpful for the prescribers to know what the evidence suggests about the effects of these interventions on the long-term quality of life (QoL), depression, and anxiety. This study aimed to summarize the rationale for the use of conservative interventions to improve the long-term QoL, depression, and anxiety in patients with stable COPD. METHODS: The MEDLINE, Embase, Cochrane Library, and Web of Science databases were searched from database inception to December 2019. Randomized clinical trials (RCTs) investigating the long-term effects of conservative interventions on three parameters, including QoL, depression, and anxiety in patients with COPD were eligible for further analysis. To improve methodological rigor, only RCTs examining these parameters as primary outcomes were included. The standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated using random effects models. Quality of evidence was rated using the updated version of Van Tulder's criteria. RESULTS: Thirty-eight RCTs were identified. Regarding long-term depression, there was moderate evidence supporting cognitive behavioral therapy compared with usual care in patients with COPD; regarding the long-term QoL of patients with COPD, there was limited evidence supporting walking programs, supplementary sugarcane bagasse dietary fiber, roflumilast, and tiotropium. CONCLUSIONS: Cognitive behavioral therapy is effective in alleviating the long-term depression of patients with COPD. Evidence for other interventions was insufficient, making it difficult to draw conclusions in terms of their effectiveness on the long-term QoL, depression, and anxiety.

Oculopharyngodistal myopathy with CGG repeat expansions in GIPC1: the first report from southwestern China.

Oculopharyngodistal myopathy (OPDM) is a rare adult-onset hereditary muscular disease characterized by slowly progressive ptosis, external ophthalmoplegia and weakness of the facial, pharyngeal and distal limb muscles. Recently, CGG repeat expansion mutations in three genes, LRP12, GIPC1 and NOTCH2NLC, have been identified as causative factors for OPDM. Here, we report clinicopathologically typical familial OPDM patients from southwestern China. CGG repeat expansions in GIPC1 were detected in two OPDM-affected individuals. Our study was the first GIPC1-OPDM report from southwestern China, further confirming expanded GGC repeats in GIPC1 as the cause of OPDM.