Use of the traditional Chinese medicine "compound healthy ear agent" to protect against age-related hearing loss in mice: A proteomics study.

Background: Previous studies have shown that the traditional Chinese medicine (TCM) called "compound healthy ear agent" (CHEA) had anti-apoptosis effects in cochlear hair cells and spiral ganglion neurons, and could protect mice hearing against presbycusis or age-related hearing loss (AHL), as well as aminoglycoside antibiotic-induced ototoxicity. Because its mechanisms of action are still unclear, we investigated the mechanism of action of CHEA against AHL in mice using proteomics techniques. Methods: Eighteen C57BL/6J mice at 1 month of age were randomly divided into three groups: (A) drinking water until 2 months of age, K2M); (B) drinking water until 7 months of age to induce AHL, K7M; (C) drinking water containing CHEA daily until 7 months of age as treatment group, Z7M. At 2 or 7 months mice were sacrificed and their cochleae were removed for proteomics analysis. Results: The numbers of proteins with a false discovery rate (FDR) < 1% were respectively 5873 for qualitative and 5492 for quantitative statistics. The numbers of proteins with differential enrichment at least 1.5-fold (p < 0.05) were respectively 351 for K7M vs K2M groups, 52 for Z7M vs K7M groups, 264 for Z7M vs K2M groups. The differentially expressed proteins in the Z7M group were involved in synaptic molecular transmission, energy metabolism, immune response, antioxidant defenses, and anti-apoptosis. Conclusion: The TCM CHEA played a protective role against AHL in mice by regulating the expression of specific proteins and genes in cochlear hair cells and spiral ganglion neurons. Besides the pathways expected to be involved (antioxidant and anti-apoptosis), proteins related to immune response is a new finding of the present study.

A Continuous Volatility Forecasting Model Based on Neural Differential Equations and Scale-Similarity.

Volatility forecasting is a problem in finance that attracts the attention of both academia and industry. While existing approaches typically utilize a discrete-time latent process that governs the volatility to forecast its future level, volatility is considered to evolve continuously, which makes discrete-time modeling inevitably lose some critical information about the evolution of volatility. In this article, a novel neural-network-based model, Continuous Volatility Forecasting Model, CVFM is proposed to tackle this problem. First, CVFM introduces a continuous-time latent process, whose evolution is modeled with neural differential equations (NDEs), to govern volatility, which effectively captures the continuous evolutionary behavior of volatility in a data-driven way. Second, a scale-similarity-based mechanism is designed to calibrate the evolution equation of the latent process with real-world observations in the absence of high-frequency data. CVFM is tested on six real-world stock index datasets. The main experimental results show that CVFM can significantly outperform existing models in terms of both forecasting accuracy and high-volatility recognition.

Phenylalanine-Arginine-ß-Naphthylamide Enhances the Photobactericidal Effect of Methylene Blue on Pseudomonas aeruginosa.

Objective: To investigate the effectiveness, dosing sequence, concentration, and mechanism of antimicrobial photodynamic inactivation (aPDI) using methylene blue (MB) plus phenylalanine-arginine-ß-naphthylamide (PAßN) against Pseudomonas aeruginosa. Methods: P. aeruginosa bacterial suspension was incubated with MB for different times (5-240 min), and then, 10 J/cm2 red light was irradiated. The efflux pump inhibitor (EPI) PAßN (10-100 µg/mL) was combined with MB (1-20 µM) in different sequences (PAßN-first, PAßN+MB, PAßN-after). Colony-forming units were then determined by serial dilution. Results: Using MB 10 µM plus 10 J/cm2, the killing effect of MB-aPDI on P. aeruginosa increased first and then decreased with longer incubation time. The killing effect of MB+PAßN-aPDI on P. aeruginosa was better than that of MB-aPDI (p < 0.05) by up to 2 logs. PAßN-first had the best killing effect, whereas PAßN-after had the worst killing effect. The killing effect increased with PAßN concentration and at 100 µg/mL reached 5.1 logs. Conclusions: The EPI PAßN enhanced the bactericidal effect of MB-aPDI on P. aeruginosa, especially when added before MB. It is proposed that MB is a substrate of the resistance-nodulation-division family efflux pump.

Cell transplantation therapies for spinal cord injury focusing on bone marrow mesenchymal stem cells: Advances and challenges.

Spinal cord injury (SCI) is a devastating condition with complex pathological mechanisms that lead to sensory, motor, and autonomic dysfunction below the site of injury. To date, no effective therapy is available for the treatment of SCI. Recently, bone marrow-derived mesenchymal stem cells (BMMSCs) have been considered to be the most promising source for cellular therapies following SCI. The objective of the present review is to summarize the most recent insights into the cellular and molecular mechanism using BMMSC therapy to treat SCI. In this work, we review the specific mechanism of BMMSCs in SCI repair mainly from the following aspects: Neuroprotection, axon sprouting and/or regeneration, myelin regeneration, inhibitory microenvironments, glial scar formation, immunomodulation, and angiogenesis. Additionally, we summarize the latest evidence on the application of BMMSCs in clinical trials and further discuss the challenges and future directions for stem cell therapy in SCI models.

Bone marrow mesenchymal stem cells and exercise restore motor function following spinal cord injury by activating PI3K/AKT/mTOR pathway.

Although many therapeutic interventions have shown promise in treating spinal cord injury, focusing on a single aspect of repair cannot achieve successful and functional regeneration in patients following spinal cord injury . In this study, we applied a combinatorial approach for treating spinal cord injury involving neuroprotection and rehabilitation, exploiting cell transplantation and functional sensorimotor training to promote nerve regeneration and functional recovery. Here, we used a mouse model of thoracic contusive spinal cord injury to investigate whether the combination of bone marrow mesenchymal stem cell transplantation and exercise training has a synergistic effect on functional restoration. Locomotor function was evaluated by the Basso Mouse Scale, horizontal ladder test, and footprint analysis. Magnetic resonance imaging, histological examination, transmission electron microscopy observation, immunofluorescence staining, and western blotting were performed 8 weeks after spinal cord injury to further explore the potential mechanism behind the synergistic repair effect. In vivo, the combination of bone marrow mesenchymal stem cell transplantation and exercise showed a better therapeutic effect on motor function than the single treatments. Further investigations revealed that the combination of bone marrow mesenchymal stem cell transplantation and exercise markedly reduced fibrotic scar tissue, protected neurons, and promoted axon and myelin protection. Additionally, the synergistic effects of bone marrow mesenchymal stem cell transplantation and exercise on spinal cord injury recovery occurred via the PI3K/AKT/mTOR pathway. In vitro, experimental evidence from the PC12 cell line and primary cortical neuron culture also demonstrated that blocking of the PI3K/AKT/mTOR pathway would aggravate neuronal damage. Thus, bone marrow mesenchymal stem cell transplantation combined with exercise training can effectively restore motor function after spinal cord injury by activating the PI3K/AKT/mTOR pathway.

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.

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.

Enhanced effect of combining bone marrow mesenchymal stem cells (BMMSCs) and pulsed electromagnetic fields (PEMF) to promote recovery after spinal cord injury in mice.

Spinal cord injury (SCI) is a destructive traumatic disease of the central nervous system without satisfying therapy efficiency. Bone marrow mesenchymal stem cells (BMMSCs) therapy promotes the neurotrophic factors' secretion and axonal regeneration, thereby promoting recovery of SCI. Pulsed electromagnetic fields (PEMF) therapy has been proven to promote neural growth and regeneration. Both BMMSCs and PEMF have shown curative effects for SCI; PEMF can further promote stem cell differentiation. Thus, we explored the combined effects of BMMSCs and PEMF and the potential interaction between these two therapies in SCI. Compared with the SCI control, BMMSCs, and PEMF groups, the combinational therapy displayed the best therapeutic effect. Combinational therapy increased the expression levels of nutritional factors including brain-derived neurotrophic factor (BDNF), nerve growth factors (NGF) and vascular endothelial growth factor (VEGF), enhanced neuron preservation (NeuN and NF-200), and increased axonal growth (MBP and myelin sheath). Additionally, PEMF promoted the expression levels of BDNF and VEGF in BMMSCs via Wnt/ß-catenin signaling pathway. In summary, the combined therapy of BMMSCs and PEMF displayed a more satisfactory effect than BMMSCs and PEMF therapy alone, indicating a promising application of combined therapy for the therapy of SCI.

Effects of Curcumin-mediated photodynamic therapy on autophagy and epithelial-mesenchymal transition of lung cancer cells.

BACKGROUND: This study aimed to investigated whether Curcumin-mediated PDT can suppress EMT in lung cancer cells, and explore the roles of autophagy in the process of regulating EMT. METHODS: Lung cancer cell viability was assessed by CCK-8 assay. The expression of epithelial marker and mesenchymal markers, the conversion of LC3-I to LC3-II and the levels of p62 and beclin1 in A549 and SPCA1 cells were measured by Western blotting assay. The Wound healing and Transwell assays were used to detect the migration and invasion abilities of the A549 and SPCA1 cells. Autophagosome formation was detected via observing the colocalization of Lamp-2 with LC3 in A549 cells, and the autophagy ultrastructure was observed by TEM. RESULTS: Curcumin-PDT inhibited EMT, migration and invasion and induced autophagy in lung cancer cells. Curcumin-PDT induced autophagy was involved in the process of PDT inhibiting EMT, but it presented a promoting effect of EMT in lung cancer cells. Curcumin-PDT combined with CQ further inhibited EMT, invasion and migration of lung cancer cells. CONCLUSIONS: The role of PDT-induced autophagy in the regulation of EMT was determined to be a promoting effect in lung cancer. Therefore, Curcumin-mediated PDT combined with autophagy inhibitor further suppressed EMT of lung cancer cells, and may represent a potential strategy against invasion and migration of lung cancer.

Non-invasive Vagus Nerve Stimulation in Cerebral Stroke: Current Status and Future Perspectives.

Stroke poses a serious threat to human health and burdens both society and the healthcare system. Standard rehabilitative therapies may not be effective in improving functions after stroke, so alternative strategies are needed. The FDA has approved vagus nerve stimulation (VNS) for the treatment of epilepsy, migraines, and depression. Recent studies have demonstrated that VNS can facilitate the benefits of rehabilitation interventions. VNS coupled with upper limb rehabilitation enhances the recovery of upper limb function in patients with chronic stroke. However, its invasive nature limits its clinical application. Researchers have developed a non-invasive method to stimulate the vagus nerve (non-invasive vagus nerve stimulation, nVNS). It has been suggested that nVNS coupled with rehabilitation could be a promising alternative for improving muscle function in chronic stroke patients. In this article, we review the current researches in preclinical and clinical studies as well as the potential applications of nVNS in stroke. We summarize the parameters, advantages, potential mechanisms, and adverse effects of current nVNS applications, as well as the future challenges and directions for nVNS in cerebral stroke treatment. These studies indicate that nVNS has promising efficacy in reducing stroke volume and attenuating neurological deficits in ischemic stroke models. While more basic and clinical research is required to fully understand its mechanisms of efficacy, especially Phase III trials with a large number of patients, these data suggest that nVNS can be applied easily not only as a possible secondary prophylactic treatment in chronic cerebral stroke, but also as a promising adjunctive treatment in acute cerebral stroke in the near future.

Efficacy of pulsed electromagnetic field on pain and physical function in patients with low back pain: A systematic review and meta-analysis.

OBJECTIVE: To assess the effectiveness of pulsed electromagnetic field (PEMF) on pain and physical function in patients with low back pain. DATA SOURCES: A search of PubMed, Embase, Cochrane Library, and Web of Science was conducted up to December 2021. METHODS: We included randomized controlled trials that investigated the effectiveness of PEMF in patients with low back pain. The primary outcome was pain intensity and the secondary outcome was physical function, both were evaluated by assessment scales. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated for the summary statistics analysis. The registration number of this systematic review in PROSPERO is CRD42020213829. RESULTS: Fourteen trials involving 618 participants were included. The PEMF treatment showed more significant pain alleviation than placebo or other therapy alone in patients with low back pain (SMD = -1.01, 95% CI -1.42 to -0.6, P < 0.001, I2 = 31%; SMD = -0.36, 95% CI -0.62 to -0.11, P = 0.005, I2 = 37%, respectively.) In addition, a significant difference in pain alleviation was observed in patients with chronic low back pain (SMD = -0.6, 95%CI - 0.94 to -0.25, p < 0.001, I2 = 67%), whereas no significant difference was observed in patients with acute low back pain (SMD = -0.46, 95%CI - 0.99 to 0.07, p = 0.09, I2 = 0%). PEMF did not improve physical function compared with the control treatment (SMD = -0.45, 95% CI - 0.98 to 0.07, p = 0.09, I2 = 86%). CONCLUSION: PEMF is beneficial for alleviating pain in patients with chronic low back pain despite having no advantage in improving physical function.

Reference values and the Z-score values of tricuspid annular plane systolic excursion in Chinese children.

To establish age-specific and body surface area (BSA)-specific reference values of Tricuspid Annular Plane Systolic Excursion (TAPSE) for children under 15 years old in China. A retrospective study was conducted in Children's Hospital Attached to the Capital Institute of Pediatrics. A total of 702 cases were included in this research to establish reference values of TAPSE in Chinese children. SPSS 25.0 (IBM) was used for data analysis. Lambda-mu-sigma method was used to calculate and construct the age-specific and BSA-specific percentiles and Z-score curves of TAPSE. The mean value of TAPSE increased with age and BSA from 0 to 15 years in a nonlinear way and reached the adult threshold (17 mm) until 1 year old. There was no difference between genders. TAPSE values increased with age and BSA in Chinese children aged between 0 and 15 years and there was no difference between boys and girls. A prospective, multicenter cohort study from different parts of China is supposed to be conducted in the future to reflect the whole spectrum of TAPSE in Chinese children.

Comparison of the Effects of Constraint-Induced Movement Therapy and Unconstraint Exercise on Oxidative Stress and Limb Function-A Study on Human Patients and Rats with Cerebral Infarction.

Most conventional post-stroke rehabilitation treatments do not involve imposed constraints of the unaffected limb. In contrast, Constraint-Induced Movement Therapy (CIMT) is comprised of massed task practice with the affected limb and constraint of the unaffected limb. CIMT is a promising rehabilitation technique used for motor recovery of affected limbs after stroke, but its effectiveness and mechanism are not fully understood. We compared the effects of the two exercise modes on limb function post-stroke in animal models and human subjects, and investigated whether oxidative stress response was involved in regulating the effects. We first conducted a randomized controlled trial (RCT), in which 84 subjects with cerebral infarction were assigned to dose-matched constraint-induced movement therapy (CIMT), or unconstraint exercise (UE), or conventional rehabilitation treatment. Motor functions of the limb are primary outcomes of the RCT measured using Brief Fugl-Meyer upper extremity score (FMA-UE), Ashworth score, and Barthel scale. Psychological influence of CIMT and UE was also examined using Self-Rating Depression Scale (SDS). Next, we investigated the effects of CIMT and UE in rats undergoing middle cerebral artery occlusion and reperfusion (MCAO/R). Motor function, infarct volume, and pathohistological changes were investigated by mNSS, MRI, and histological studies. The role of Keap1-Nrf2-ARE was investigated using qRT-PCR, Western blot, immunochemistry, immunofluorescence, and ELISA experiments. In RCT, patients taking CIMT had a higher score in FMA-UE, Barthel index, and SDS, and a lower score in modified Ashworth, compared to those taking UE. In rats receiving CIMT, motor function was increased, and infarct volume was decreased compared to those receiving UE. The expression of Keap1 protein and mRNA in the peri-infarct tissue was decreased, and Nrf2 and ARE protein and mRNA were increased in rats receiving CIMT compared with UE. Nrf2 agonist t-BHQ increased the benefits of CIMT. In conclusion, CIMT is more effective than UE in improving upper limb motor function, reducing muscle spasm in patients with cerebral infarction compared to UE, but patients receiving CIMT may feel depressed. Moreover, both CIMT and UE are beneficial to limb function recovery and limit the infarct expansion in MCAO/R rats, but CIMT was more effective than UE. Oxidative stress reaction has an essential role in regulating the CIMT induced benefits.

Combination of Electroacupuncture and Constraint-Induced Movement Therapy Enhances Functional Recovery After Ischemic Stroke in Rats.

Both electroacupuncture and constraint-induced movement therapy have been reported to produce therapeutic effects on the recovery of ischemic stroke. The combined use of these two therapies is not rare clinically, although its effectiveness is not yet clear. We aimed to evaluate the efficacy of the combination of electroacupuncture and constraint-induced movement therapy in ischemic stroke rats, and to explore the potential molecular mechanisms. Ischemic stroke rat models were established by middle cerebral artery occlusion. Then, the rats were assigned to receive one of the following interventions: sole electroacupuncture, sole constraint-induced movement therapy, the combination of both therapies, and no treatment. Functional recovery was assessed with the beam balance test and rotarod test. The infarct volume of the brain and the expression of the molecules Nogo-A, P75NTR, NGF, BDNF, and VEGF in the brain tissue were investigated. The results demonstrated that the combination of the two therapies significantly improved neurological functional recovery in ischemic stroke rats compared to each therapy alone (P < 0.01). We also observed a significant decrease in infarct volume in rats receiving the combined treatment. Nogo-A and P75NTR were downregulated and NGF, BDNF, and VEGF were upregulated in the combined treatment rats compared to the control rats. In conclusion, the combination of electroacupuncture and constraint-induced movement therapy enhanced functional recovery after ischemic stroke in rats, and it is a promising treatment strategy in the rehabilitation of stroke. The anti-Nogo-A effect of electroacupuncture may explain its good compatibility with CIMT in ischemic stroke rats.

Curcumin-mediated Photodynamic Therapy Inhibits the Phenotypic Transformation, Migration, and Foaming of Oxidized Low-density Lipoprotein-treated Vascular Smooth Muscle Cells by Promoting Autophagy.

ABSTRACT: Vascular smooth muscle cells (VSMCs) are becoming a hot spot and target of atherosclerosis research. This study aimed to observe the specific effects of curcumin (CUR)-mediated photodynamic therapy (CUR-PDT) on oxidized low-density lipoprotein (ox-LDL)-treated VSMCs and confirm whether these effects are mediated by autophagy. In this study, the mouse aortic smooth muscle cell line and A7r5 cell lines were used for parallel experiments. VSMC viability was evaluated by Cell Counting Kit-8 assay. VSMCs were treated with ox-LDL to establish a model of atherosclerosis in vitro. The autophagy level and the expression of proteins related to phenotypic transformation were detected by western blotting. The migration ability of the cells was detected by using transwell assay. The presence of intracellular lipid droplets was detected by Oil Red O staining. The results showed that VSMCs transformed from the contraction phenotype to the synthetic phenotype when stimulated by ox-LDL, during which autophagy was inhibited. However, CUR-PDT treatment significantly promoted the level of autophagy and inhibited the process of phenotypic transformation induced by ox-LDL. In addition, ox-LDL significantly promoted VSMC migration and increased the number of lipid droplets, whereas CUR-PDT treatment significantly reduced the ox-LDL-induced increase in the migration ability of, and lipid droplet numbers in, VSMCs. When the VSMCs were pretreated with the autophagy inhibitor 3-methyladenine for 24 hours, the effects of CUR-PDT were reversed. Therefore, our study indicated that CUR-PDT can inhibit the phenotypic transformation, migration, and foaming of ox-LDL-treated VSMCs by inducing autophagy.

Effects of hyperbaric oxygen therapy on patients with spinal cord injury: A systematic review and meta-analysis of Randomized Controlled Trials.

BACKGROUND: The effects of hyperbaric oxygen therapy (HBO) for spinal cord injury (SCI) are controversial. OBJECTIVE: The purpose of this study was to evaluate the effects of HBO therapy on motor function, sensory function, and psychology after SCI. METHOD: We searched the following databases: Medline, Embase, PubMed, Ovid, Cochrane library, China National Knowledge Infrastructure (CNKI), Wan Fang, and VIP up to May 2020. We included Randomized Controlled Trials (RCTs) which investigated patients with SCI received HBO during hospitalization. Motor function, sensory function, and psychology status were measured by commonly used scales including American Spinal Injury Association (ASIA) motor score, Modified Barthel Index (MBI), ASIA sensory score, Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA). We performed a meta-analysis by calculating mean difference (MD) to determine the effect of HBO on three levels of function on patients with SCI. We evaluated heterogeneity by I2 test, and I2> 50% was significant. RESULTS: A total of 1746 studies were identified initially, and 11 studies were included, involving 875 participants. HBO therapy significantly improved the ASIA motor score (MD 15.84, 95% CI 9.04 to 22.64, I2= 87%). Six trails suggested that HBO therapy statistically promoted ASIA sensory score (MD 66.30, 95% CI 53.44 to 79.16, I2= 95%). The other four trails suggested that HBO therapy statistically increased the light touch score (MD 9.27, 95% CI 3.89 to 14.65, I2= 91%) and needling score (MD 10.01, 95% CI 8.60 to 11.43, I2= 95%), respectively. HBO therapy was implicated in the significant improvement of MBI (MD 13.80, 95% CI 10.65 to 16.94, I2= 0%). HBO therapy also decreased the HAMA (MD -2.37, 95% CI -2.72 to -2.02, I2= 0%) and HAMD (MD -3.74, 95% CI -5.82 to -1.65, I2= 90%). CONCLUSIONS: HBO therapy may improve motor function, sensory function and psychology after SCI compared to conventional treatments. More high-quality, large sample size RCTs are needed to support these perspectives.

Antimicrobial photodynamic therapy for oral Candida infection in adult AIDS patients: A pilot clinical trial.

BACKGROUND: Antimicrobial photodynamic therapy (aPDT) using methylene blue (MB) plus potassium iodide (KI) has been shown to be effective in killing Candida albicans in many in vitro and in vivo studies, however, there are limited reports of clinical investigations. This study aimed to explore the clinical application of aPDT with MB plus KI for the treatment of oral infection caused by C. albicans in adult acquired immune deficiency syndrome (AIDS) patients. METHODS: A total of 21 adult AIDS patients with C. albicans oral candidiasis were divided into two groups according to MB concentration and received two consecutive aPDT treatments. Immediately before and after the aPDT treatments, C. albicans yeast isolates were recovered to measure the colony-forming units per mL (CFU/mL), biofilm formation, and to analyze the 25S rDNA genotype. Patients were assessed for the clinical recovery of oral lesions and improvement of symptoms. RESULTS: The Log10 CFU/mL of C. albicans decreased significantly after the second aPDT but not the first aPDT. There was no significant difference between the two MB concentrations. Both aPDT protocols decreased the oral lesions and clinical symptoms with no significant difference after 2-fraction aPDT. The biofilm formation of C. albicans isolates did not change before and after aPDT. The killing efficiency of 2-fraction-aPDT was not associated with either biofilm formation or 25S rDNA genotype. CONCLUSIONS: Two-fraction-aPDT with MB plus KI could reduce the number of viable C. albicans fungal cells and improve the clinical symptoms of oral candidiasis in adult AIDS patients, regardless of the biofilm formation or 25S rDNA genotype of infected C. albicans isolates.

Stem Cell Therapy for Spinal Cord Injury.

Traumatic spinal cord injury (SCI) results in direct and indirect damage to neural tissues, which results in motor and sensory dysfunction, dystonia, and pathological reflex that ultimately lead to paraplegia or tetraplegia. A loss of cells, axon regeneration failure, and time-sensitive pathophysiology make tissue repair difficult. Despite various medical developments, there are currently no effective regenerative treatments. Stem cell therapy is a promising treatment for SCI due to its multiple targets and reactivity benefits. The present review focuses on SCI stem cell therapy, including bone marrow mesenchymal stem cells, umbilical mesenchymal stem cells, adipose-derived mesenchymal stem cells, neural stem cells, neural progenitor cells, embryonic stem cells, induced pluripotent stem cells, and extracellular vesicles. Each cell type targets certain features of SCI pathology and shows therapeutic effects via cell replacement, nutritional support, scaffolds, and immunomodulation mechanisms. However, many preclinical studies and a growing number of clinical trials found that single-cell treatments had only limited benefits for SCI. SCI damage is multifaceted, and there is a growing consensus that a combined treatment is needed.

Physical Therapist Management of COVID-19 in the Intensive Care Unit: The West China Hospital Experience.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has dominated the attention of health care systems globally since January 2020. Various health disciplines, including physical therapists, are still exploring the best way to manage this new disease. The role and involvement of physical therapists in the management of COVID-19 are not yet well defined and are limited in many hospitals. This article reports a physical therapy service specially commissioned by the Health Commission of Sichuan Province to manage COVID-19 during patients' stay in the intensive care unit (ICU) at the Public Health Clinical Center of Chengdu in China. METHODS: Patients diagnosed with COVID-19 were classified into 4 categories under a directive from the National Health Commission of the People's Republic of China. Patients in the "severe" and "critical" categories were admitted to the ICU irrespective of mechanical ventilation was required. Between January 31, 2020, and March 8, 2020, a cohort of 16 patients was admitted to the ICU at the Public Health Clinical Center of Chengdu. The median (minimum to maximum) hospital and ICU stays for these patients were 27 (11-46) and 15 (6-38) days, respectively. Medical management included antiviral, immunoregulation, and supportive treatment of associated comorbidities. Physical therapist interventions included body positioning, airway clearance techniques, oscillatory positive end-expiratory pressure, inspiratory muscle training, and mobility exercises. All patients had at least 1 comorbidity. Three of the 16 patients required mechanical ventilation and were excluded for outcome measures that required understanding of verbal instructions. In the remaining 13 patients, respiratory outcomes-including the Borg Dyspnea Scale, peak expiratory flow rate, Pao2/Fio2 ratio, maximal inspiratory pressure, strength outcomes, Medical Research Council Sum Score, and functional outcomes (including the Physical Function in Intensive Care Test score, De Morton Mobility Index, and Modified Barthel Index)-were measured on the first day the patient received the physical therapist intervention and at discharge. RESULTS: At discharge from the ICU, while most outcome measures were near normal for the majority of the patients, 61% and 31% of these patients had peak expiratory flow rate and maximal inspiratory pressure, respectively, below 80% of the predicted value and 46% had De Morton Mobility Index values below the normative value. CONCLUSION: The respiratory and physical functions of some patients remained poor at ICU discharge, suggesting that long-term rehabilitation may be required for these patients. IMPACT: Our experience in the management of patients with COVID-19 has revealed that physical therapist intervention is safe and appears to be associated with an improvement in respiratory and physical function in patients with COVID-19 in the ICU.