Immunity-and-matrix-regulatory cells enhance cartilage regeneration for meniscus injuries: a phase I dose-escalation trial.

Immunity-and-matrix-regulatory cells (IMRCs) derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix, which could be mass-produced with stable biological properties. Despite resemblance to mesenchymal stem cells (MSCs) in terms of self-renew and tri-lineage differentiation, the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined. Here, we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury. Following injection into the knees of rabbits with meniscal injury, IMRCs enhanced endogenous fibrocartilage regeneration. In the dose-escalating phase I clinical trial (NCT03839238) with eighteen patients recruited, we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting. Furthermore, the effective results of magnetic resonance imaging (MRI) of meniscus repair and knee functional scores suggested that 5 × 107 cells are optimal for meniscus injury treatment. In summary, we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury. Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.

Efficacy and safety of ultra-short wave diathermy on COVID-19 pneumonia: a pioneering study.

Background: The ultra-short wave diathermy (USWD) is widely used to ameliorate inflammation of bacterial pneumonia, however, for COVID-19 pneumonia, USWD still needs to be verified. This study aimed to investigate the efficacy and safety of USWD in COVID-19 pneumonia patients. Methods: This was a single-center, evaluator-blinded, randomized controlled trial. Moderate and severe COVID-19 patients were recruited between 18 February and 20 April 2020. Participants were randomly allocated to receive USWD + standard medical treatment (USWD group) or standard medical treatment alone (control group). The negative conversion rate of SARS-CoV-2 and Systemic Inflammatory Response Scale (SIRS) on days 7, 14, 21, and 28 were assessed as primary outcomes. Secondary outcomes included time to clinical recovery, the 7-point ordinal scale, and adverse events. Results: Fifty patients were randomized (USWD, 25; control, 25), which included 22 males (44.0%) and 28 females (56.0%) with a mean (SD) age of 53 ± 10.69. The rates of SARS-CoV-2 negative conversion on day 7 (p = 0.066), day 14 (p = 0.239), day 21 (p = 0.269), and day 28 (p = 0.490) were insignificant. However, systemic inflammation by SIRS was ameliorated with significance on day 7 (p = 0.030), day 14 (p = 0.002), day 21 (p = 0.003), and day 28 (p = 0.011). Time to clinical recovery (USWD 36.84 ± 9.93 vs. control 43.56 ± 12.15, p = 0.037) was significantly shortened with a between-group difference of 6.72 ± 3.14 days. 7-point ordinal scale on days 21 and 28 showed significance (p = 0.002, 0.003), whereas the difference on days 7 and 14 was insignificant (p = 0.524, 0.108). In addition, artificial intelligence-assisted CT analysis showed a greater decrease in the infection volume in the USWD group, without significant between-group differences. No treatment-associated adverse events or worsening of pulmonary fibrosis were observed in either group. Conclusion: Among patients with moderate and severe COVID-19 pneumonia, USWD added to standard medical treatment could ameliorate systemic inflammation and shorten the duration of hospitalization without causing any adverse effects.Clinical Trial Registration: chictr.org.cn, identifier ChiCTR2000029972.

Efficacy of orthotic support in mitigating low back pain and disability in low back pain sufferers.

BACKGROUND: Low back pain (LBP) is a prevalent disabling ailment that affects people all over the world. A wide variety of orthotic designs, ranging from lumbosacral corsets to rigid thermoplastic thoraco-lumbosacral orthosis are used for managing LBP. OBJECTIVE: Explore and summarize quality literature on the efficacy of orthotic devices in the management of LBP. METHODS: A systematic review and meta-analysis of the literature on the efficacy of orthosis in low back pain management conducted using electronic databases. Studies utilizing orthotic management alone or combined with other therapies for 2 weeks or above were included. A meta-analysis was performed on primary and secondary variables using Mean difference (MD), Inverse variance (IV), and fixed effect model with 95% CI, Physiotherapy Evidence Database (PEDro) scale, Cochrane Risk of Bias 2 (RoB2) tool were used to assess the quality of evidence and the risk bias. RESULTS: Out of 14671 studies, only 13 Randomized Controlled Trials (RCT) were deemed eligible for inclusion in this study, all level 1 evidence. We found that orthotics could significantly mitigate LBP (P-value < 0.00001). Similarly, a significant reeducation in LBP-associated disability was observed after orthotic intervention (P-value 0.004). CONCLUSION: Lumber orthosis plays a significant role in LBP and associated disability mitigations in sufferers of LBP.

Constraint-Induced Movement Therapy Combined With Botulinum Toxin for Post-stroke Spasticity: A Systematic Review and Meta-Analysis.

Stroke is considered one of the main causes of adult disability and the second most serious cause of death worldwide. The combination of botulinum toxin type A (BTX) with rehabilitation techniques such as modified constraint-induced movement therapy (mCIMT) has emerged as a highly efficient intervention for stroke patients to start synchronized motor function along with spasticity reduction. The current systematic review and meta-analysis were conducted in order to evaluate the available literature about the safety and efficacy of constraint-induced movement therapy (CIMT) combined with BTX in stroke patients with upper limb spasticity. Searches were conducted on WoS (Web of Science), Ovid, EBSCO-ASC&BSC, and PubMed for identifying relevant literature published from 2000-2020. Randomized Controlled Trials (RCTs) and Quasi-experimental studies were considered for inclusion. Rayyan (systematic review tool) QCRI (Qatar Computing Research Institute) was used for independent screening of the studies by two reviewers. For risk of bias and study quality assessment, Cochrane risk of bias tool (RoB 2) and Physiotherapy Evidence Database (PEDro) scales were used. Cochrane review manager was used to carry out the meta-analyses of the included studies. The search resulted in a total of 13065 references, of which 4967 were duplicates. After the title, abstract and full-text screening, two RCTs were deemed eligible for inclusion. Both the RCTs scored 8 on PEDro and were level evidence. The studies were heterogeneous. The findings of this meta-analysis in all the three joints post-stroke spasticity assessed on modified Ashworth scale (MAS) at four weeks post-injection aren't statistically significant (elbow P-value 0.74, wrist P-value 0.57, fingers P-value 0.42), however, according to one of the included studies the therapeutic efficacy of the combination of BTX-mCIMT injection assessed at four weeks post-injection in wrist and finger flexors was promising.  The effectiveness of BTX-CIMT combination over conventional therapy (CT) for improving post-stroke spasticity still needs to be explored with long-term, multicenter rigorously designed RCTs having a good sample size. However, the BTX-CIMT combination is promising for enhancing motor function recovery and improving activities of daily living (ADLs).

Human spinal GABA neurons alleviate spasticity and improve locomotion in rats with spinal cord injury.

Spinal cord injury (SCI) often results in spasticity. There is currently no effective therapy for spasticity. Here, we describe a method to efficiently differentiate human pluripotent stem cells from spinal GABA neurons. After transplantation into the injured rat spinal cord, the DREADD (designer receptors exclusively activated by designer drug)-expressing spinal progenitors differentiate into GABA neurons, mitigating spasticity-like response of the rat hindlimbs and locomotion deficits in 3 months. Administering clozapine-N-oxide, which activates the grafted GABA neurons, further alleviates spasticity-like response, suggesting an integration of grafted GABA neurons into the local neural circuit. These results highlight the therapeutic potential of the spinal GABA neurons for SCI.

Temporal expression profiles of lncRNA and mRNA in human embryonic stem cell-derived motor neurons during differentiation.

BACKGROUND: Human embryonic stem cells (hESC) have been an invaluable research tool to study motor neuron development and disorders. However, transcriptional regulation of multiple temporal stages from ESCs to spinal motor neurons (MNs) has not yet been fully elucidated. Thus, the goals of this study were to profile the time-course expression patterns of lncRNAs during MN differentiation of ESCs and to clarify the potential mechanisms of the lncRNAs that are related to MN differentiation. METHODS: We utilized our previous protocol which can harvest motor neuron in more than 90% purity from hESCs. Then, differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) during MN differentiation were identified through RNA sequencing. Bioinformatic analyses were performed to assess potential biological functions of genes. We also performed qRT-PCR to validate the DElncRNAs and DEmRNAs. RESULTS: A total of 441 lncRNAs and 1,068 mRNAs at day 6, 443 and 1,175 at day 12, and 338 lncRNAs and 68 mRNAs at day 18 were differentially expressed compared with day 0. Bioinformatic analyses identified that several key regulatory genes including POU5F1, TDGF1, SOX17, LEFTY2 and ZSCAN10, which involved in the regulation of embryonic development. We also predicted 283 target genes of DElncRNAs, in which 6 mRNAs were differentially expressed. Significant fold changes in lncRNAs (NCAM1-AS) and mRNAs (HOXA3) were confirmed by qRT-PCR. Then, through predicted overlapped miRNA verification, we constructed a lncRNA NCAM1-AS-miRNA-HOXA3 network.

Scaling the Need, Benefits, and Risks Associated with COVID-19 Acute and Postacute Care Rehabilitation: A Review.

Coronavirus is an RNA virus, which attacks the respiratory system causing complications including severe respiratory distress and pneumonia and many other symptoms. Recently, a novel coronavirus (COVID-19) outbreak emerged in Wuhan, which caused a significant number of infections in China and resulted in a global pandemic. The main aim of this study is to review and summarize the evidence regarding the supportive role of physical rehabilitation techniques in managing COVID-19-associated pneumonia. In this review, we also emphasize the use of rehabilitation techniques in the management of pneumonia in COVID-19-infected patients. Based on the evidence presented, we conclude that certain physical rehabilitation techniques and modalities could be of great support in the management of COVID-19-associated pneumonia. The safety of staff and patients when applying rehabilitation intervention requires attention. The combination of physical rehabilitation and medical treatment would result in improved treatment outcomes, faster recovery, and shorter hospital stay. Many rehabilitation techniques are safe and feasible and can be easily incorporated into the management protocol of COVID-19 victims. Decisions of early rehabilitation induction should be based on the patient's medical condition and tolerability.