Trimethylamine-N-oxide promotes osteoclast differentiation and oxidative stress by activating NF-κB pathway.

BACKGROUND: Senile osteoporosis may be caused by an imbalance in intestinal flora and oxidative stress. Trimethylamine-N-oxide (TMAO), a metabolite of dietary choline dependent on gut microbes, has been found to be significantly increased in osteoporosis. However, the role of TMAO in bone loss during osteoporosis remains poorly understood. In this study, we examined the impact of TMAO on osteoclast differentiation and bone resorption in an in vitro setting. METHODS: Osteoclast differentiation was induced by incubating RAW 264.7 cells in the presence of Receptor Activator for Nuclear Factor-κB Ligand (RANKL) and macrophage-stimulating factor (M-CSF). Flow cytometry, TRAP staining assay, CCK-8, and ELISA were employed to investigate the impact of TMAO on osteoclast differentiation and bone resorption activity in vitro. For mechanistic exploration, RT-PCR and Western blotting were utilized to assess the activation of the NF-κB pathway. Additionally, protein levels of secreted cytokines and growth factors were determined using suspension array technology. RESULTS: Our findings demonstrate that TMAO enhances RANKL and M-CSF-induced osteoclast formation and bone resorption in a dose-dependent manner. Mechanistically, TMAO triggers the upregulation of the NF-κB pathway and osteoclast-related genes (NFATc1, c-Fos, NF-κB p65, Traf6, and Cathepsin K). Furthermore, TMAO markedly elevated the levels of oxidative stress and inflammatory factors. CONCLUSIONS: In conclusion, TMAO enhances RANKL and M-CSF-induced osteoclast differentiation and inflammation in RAW 264.7 cells by activating the NF-κB signaling pathway. These findings offer a new rationale for further academic and clinical research on osteoporosis treatment.

[Effect of electroacupuncture on motor function and gait in patients with post-stroke spasticity in lower limbs].

OBJECTIVE: To observe the effect on motor function, spasticity degree, muscle strength and the relevant parameters of three-dimensional gait analysis in the patients with post-stroke spasticity in the lower limbs treated with the combined therapy of electroacupuncture (EA) and muscle electricity biofeedback or the simple muscle electricity biofeedback therapy on the base of rehabilitation medicine. METHODS: A total of 60 patients with post-stroke spasticity in the lower limbs were randomized into an EA + biofeedback group, a biofeedback group and a rehabilitation group, 20 cases in each one. In the rehabilitation group, the basic rehabilitation training was provided, 45 min each time. In the biofeedback group, on the base of the treatment as the rehabilitation group, the biofeedback therapy was added, 30 min each time. In the EA + biofeedback group, besides the treatment as the biofeedback group, acupuncture was supplemented at Futu (ST 32), Liangqiu (ST 34), Zusanli (ST 36) and Fenglong (ST 40), etc, and EA was applid at Zusanli (ST 36) and Taichong (LR 3) with continuous wave and 5 Hz in frequency. In each group, the treatment was given once daily, 5 times a week, for 6 weeks totally. Separately, before and after treatment, the score of Fugle-Meyer assessment (FMA), the score of clinical spasticity index (CSI) in the lower limbs and the strength of the anterior tibial muscle on the affected side were assessed, and the spatial-temporal parameters (step frequency and steep speed) in the three-dimensional gait analysis and the kinematic parameters (maximum dorsal flexion and maximum plantar flexion of ankle joint on the affected side) were measured in the patients of three groups. RESULTS: After treatment, FMA score was increased as compared with that before treatment in all of three groups (P<0.05). FMA score in the EA + biofeedback group and the biofeedback group was higher than the rehabilitation group respectively (P<0.05). CSI score in the EA + biofeedback group and the biofeedback group was lower than that before treatment respectively (P<0.05), and lower than the rehabilitation group (P<0.05). After treatment, the step frequency and speed were all improved and the angles of maximum dorsal flexion and maximum plantar flexion of ankle joint on the affected side were all increased as compared with those before treatment in the patients of three groups separately (P<0.05). The step frequency and speed, as well as the angles of maximum dorsal flexion and maximum plantar flexion of ankle joint on the affected side in either the EA + biofeedback group or the biofeedback group were all higher than the rehabilitation group (P<0.05), and the step speed in the EA + biofeedback group was higher than the biofeedback group (P<0.05). After treatment, the strength of the anterior tibial muscle on the affected side was increased as compared with that before treatment in the patients of each group (P<0.05); and the strength of the anterior tibial muscle in the EA + biofeedback group and the biofeedback group was larger than the rehabilitation group (P<0.05). CONCLUSION: On the base of rehabilitation treatment, the combined regimen of EA and muscle electricity biofeedback therapy and the simple muscle electricity biofeedback therapy all effectively strengthen the motor functions and reduce spasticity as well as improve step frequency, step speed and the range of motion of ankle joint in the patients with post-stroke spasticity in the lower limbs. Regarding the gait improvement, the combined regimen of EA and muscle electricity biofeedback is better than the simple muscle electricity biofeedback.

Transcranial direct current stimulation improves the swallowing function in patients with cricopharyngeal muscle dysfunction following a brainstem stroke.

OBJECTIVE: This study investigated the effects of transcranial direct current stimulation (tDCS) combined with conventional swallowing training on the swallowing function in brainstem stroke patients with cricopharyngeal muscle dysfunction (CPD). METHODS: Twenty-eight brainstem stroke patients with CPD were assigned randomly to an anodal tDCS group or a sham tDCS group. The patients received anodal tDCS or sham tDCS over the bilateral oesophageal cortical area combined with simultaneous catheter balloon dilatation and conventional swallowing therapy for 20 days. Swallowing function was assessed using the functional oral intake scale (FOIS) and the functional dysphagia scale (FDS) and by measuring the pharyngoesophageal Segment Opening (PESO) before and immediately after the intervention. RESULTS: Both groups showed a significant improvement in the FDS, FOIS and PESO scores immediately after the intervention (all p < .005). However, compared with the sham stimulation group, the anodal tDCS group showed greater improvements in the FDS, FOIS and PESO scores immediately after the intervention (all p < .005). CONCLUSION: The bihemispheric anodal tDCS combined with simultaneous catheter balloon dilatation and conventional swallowing therapy effectively improves the swallowing function in patients with CPD caused by a brainstem stroke. tDCS may be an effective adjuvant therapy in CPD rehabilitation.

Effects of Tai Chi Yunshou exercise on community-based stroke patients: a cluster randomized controlled trial.

BACKGROUD: Tai Chi Chuan was used for stroke survivors with balance impairments. However, even a short-form of Tai Chi Chuan includes forms that make the exercise challenging for the stroke survivors. Tai Chi Yunshou (wave hands in the cloud) is the "mother" form and the fundamental form of all Tai Chi Chuan styles, which is considered more suitable and feasible for stroke survivors with balance impairments. So this study was designed to evaluate the effects of Tai Chi Yunshou exercise on community-based stroke patients with balance dysfunctions. METHODS: A total of 250 participants from 10 community health centers (5 per arm) were selected and randomly allocated into Tai Chi Yunshou exercise group (TC group) or a balance rehabilitation training group (control group) in an equal ratio. Participants in the TC group were received Tai Chi Yunshou exercise training five times per week for 12 weeks and those in control group were received balance rehabilitation training five times per week for 12 weeks. Outcome assessments including Berg Balance Scale (BBS), Time up to go test (TUGT), Modified Barthel Index (MBI) were measured at baseline, 4 weeks, 8 weeks, 12 weeks and followed-up 6 weeks (18 weeks), 12 weeks (24 weeks). Intention-to-treat analysis was performed. Analysis of variance of repeated measures was used to assess between-group differences. RESULTS: A total of 244 participants, 120 in the TC group and 124 in the rehabilitation group, were included in final analysis. There was no siginificant difference in Tai Chi Yunshou and balance rehabilitation training on the improvement of balance ability and mobility (P = 0.531 and P = 0.839, respectively) after adjustment for baseline. However, there was significant difference between two groups on improvement of motor funtion (P = 0.022), fear of falling (P < 0.001) and depression (P = 0.035) for the post stroke patients. No adverse events were reported during the study. CONCLUSION: Tai Chi Yunshou and balance rehabilitation training led to improved balance ability and functional mobility, and both are suitable community-based programs that may benefit for stroke recovery and community reintegration. Our data demonstrated that a 12-week Tai Chi Yunshou intervention was more effective in motor function, fear of falling and depression than balance rehabilitation training. Future studies examining the effectiveness of Tai Chi Yunahou as a balance ability improvement strategy for community-dwelling survivors of stroke are recommended. TRIAL REGISTRATION: Chinese Clinical Trail Registry: ChiCRT-TRC-13003641. Registration date: 22 August, 2013.

Electroacupuncture Inhibits Apoptosis of Peri-Ischemic Regions via Modulating p38, Extracellular Signal-Regulated Kinase (ERK1/2), and c-Jun N Terminal Kinases (JNK) in Cerebral Ischemia-Reperfusion-Injured Rats.

BACKGROUND Previous studies suggested that inhibition of apoptosis prevents the dysfunction of ischemia-reperfusion injury. In the pathogenesis of ischemia-reperfusion injury, JNK/ERK1/2 and p38 play an essential role in regulation of cell apoptosis. Electroacupuncture (EA), a form of acupuncture, has demonstrated superiority in preventing ischemia-reperfusion injury, but the underlying mechanism is unclear. In the present study, we explored the effects of electroacupuncture at Shenting (GV24) and Baihui (GV20) acupoints on focal cerebral ischemia-reperfusion (MCAO) rats, and explored whether JNK/ERK1/2- and p38-mediated cell apoptosis are involved. MATERIAL AND METHODS The rats were divided into a sham operation control group, an ischemia group, and an electroacupuncture group with acupuncture applied for 10 days (30 min per day). TTC staining was used to calculate the ischemic brain volume. TUNEL staining and transmission electron microscopy were used to detect cell apoptosis. Western blot analysis and Bio-Plex were used to detect JNK, p38, ERK1/2, Bcl-2, and Bax protein expression. RESULTS We found that electroacupuncture at day 10 significantly reduced cerebral infarction. In addition, electroacupuncture suppressed activation of JNK and p38, while enhancing the activation of ERK1/2 in the peri-ischemic regions. Consequently, the effect of electroacupuncture on these pathways resulted in the inhibition of apoptosis, which was demonstrated by TUNEL and transmission electron microscopy. We found that electroacupuncture upregulated the anti-apoptotic Bcl-2/Bax ratio in peri-ischemic regions. CONCLUSIONS Our findings suggest that inhibition of cell apoptosis via regulating multiple signaling pathways might be a mechanism whereby electroacupuncture has a positive therapeutic effect on post-stroke impairment.

Effectiveness of meditative movement on COPD: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of meditative movement (tai chi, yoga, and qigong) on COPD remained unclear. We undertook a systematic review and meta-analysis to determine the effectiveness of meditative movement on COPD patients. METHODS: We searched PubMed, Web of Science, EMBASE, and the Cochrane Center Register of Controlled Trials for relevant studies. The methods of standard meta-analysis were utilized for identifying relevant researches (until August 2017), quality appraisal, and synthesis. The primary outcomes were the 6-minute walking distance (6MWD), lung function, and dyspnea levels. RESULTS: Sixteen studies involving 1,176 COPD patients were included. When comparing with the control group, the 6MWD was significantly enhanced in the treatment group (3 months: mean difference [MD]=25.40 m, 95% CI: 16.25 to 34.54; 6 months: MD=35.75 m, 95% CI: 22.23 to 49.27), as well as functions on forced expiratory volume in 1 s (FEV1) (3 months: MD=0.1L, 95% CI: 0.02 to 0.18; 6 months: MD=0.18L, 95% CI: 0.1 to 0.26), and FEV1 % predicted (3 months: 4L, 95% CI: 2.7 to 5.31; 6 months: MD=4.8L, 95% CI: 2.56 to 7.07). Quality of life for the group doing meditative movement was better than the control group based on the Chronic Respiratory Disease Questionnaire dyspnea score (MD=0.9 units, 95% CI: 0.51 to 1.29) and fatigue score (MD=0.75 units, 95% CI: 0.42 to 1.09) and the total score (MD=1.92 units, 95% CI: 0.54 to 3.31). CONCLUSION: Meditative movement may have the potential to enhance lung function and physical activity in COPD patients. More large-scale, well-designed, multicenter, randomized controlled trials should be launched to evaluate the long-range effects of meditative movement.

Altered functional connectivity in patients with post-stroke memory impairment: A resting fMRI study.

Post-stroke memory dysfunction (PMD) is one of the most common forms of cognitive impairment among stroke survivors. However, only a limited number of studies have directly investigated the neural mechanisms associated with memory decline. The aim of the present study was to identify dynamic changes in the functional organization of the default mode network (DMN) and the dorsal attention network of patients with PMD. A total of 27 patients with PMD who experienced a stroke in the right hemisphere were enrolled in the current study, along with 27 healthy control subjects matched by age, sex, and educational level. A behavioral examination and functional magnetic resonance imaging scan were performed. The data were analyzed using an independent component analysis method. The results revealed a significantly increased functional connectivity between the DMN and prefrontal cortex (left middle/inferior frontal and left precentral gyri), temporal regions (left superior temporal gyrus), and bilateral and posterior cingulate gyri/precuneus (P<0.001). There was also a significantly decreased functional connectivity between the DMN and right middle temporal gyrus, left uvula, and right inferior parietal lobule, and between the dorsal attention network and prefrontal cortex (left precentral/inferior and right inferior/middle frontal gyri), right inferior parietal gyrus, and right insula (P<0.001). These results suggest that the stroke affected both the lesioned and contralesional hemispheres. The prefrontal cortex, temporal regions, insula, and posterior cingulate gyrus/precuneus serve a crucial role in memory processing.

WO3 Nanoparticles or Nanorods Incorporating Cs2CO3/PCBM Buffer Bilayer as Carriers Transporting Materials for Perovskite Solar Cells.

In this work, we demonstrate a novel carrier transporting combination made of tungsten trioxide (WO3) nanomaterials and Cs2CO3/PCBM buffer bilayer for the fabrication of perovskite solar cells (PSCs). Two different types of WO3, including nanoparticles and nanorods, were prepared by sol-gel process and hydrothermal method, respectively. Cs2CO3/PCBM buffer bilayer was inserted between WO3 and perovskite layers to improve charge transfer efficiency and formation of pinhole-free perovskite layer. Besides, the leakage current of the devices containing Cs2CO3/PCBM buffer bilayer was significantly suppressed. The optimized device based on WO3 nanoparticles and Cs2CO3/PCBM bilayer showed an open-circuit voltage of 0.84 V, a short-circuit current density of 20.40 mA/cm2, a fill factor of 0.61, and a power conversion efficiency of 10.49 %, which were significantly higher than those of PSCs without Cs2CO3/PCBM buffer bilayer. The results revealed that the combination of WO3 nanomaterials and Cs2CO3/PCBM bilayer provides an effective solution for improving performances of PSCs.

The effect of a therapeutic regimen of Traditional Chinese Medicine rehabilitation for post-stroke cognitive impairment: study protocol for a randomized controlled trial.

BACKGROUND: Post-stroke cognitive impairment (PSCI) lessens quality of life, restricts the rehabilitation of stroke, and increases the social and economic burden stroke imposes on patients and their families. Therefore effective treatment is of paramount importance. However, the treatment of PSCI is very limited. The primary aim of this protocol is to propose a lower cost and more effective therapy, and to confirm the long-term effectiveness of a therapeutic regimen of Traditional Chinese Medicine (TCM) rehabilitation for PSCI. METHODS/DESIGN: A prospective, multicenter, large sample, randomized controlled trial will be conducted. A total of 416 eligible patients will be recruited from seven inpatient and outpatient stroke rehabilitation units and randomly allocated into a therapeutic regimen of TCM rehabilitation group or cognitive training (CT) control group. The intervention period of both groups will last 12 weeks (30 minutes per day, five days per week). Primary and secondary outcomes will be measured at baseline, 12 weeks (at the end of the intervention), and 36 weeks (after the 24-week follow-up period). DISCUSSION: This protocol presents an objective design of a multicenter, large sample, randomized controlled trial that aims to put forward a lower cost and more effective therapy, and confirm the long-term effectiveness of a therapeutic regimen of TCM rehabilitation for PSCI through subjective and objective assessments, as well as highlight its economic advantages. TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trial Registry (identifier: ChiCTR-TRC-14004872 ) on 23 June 2014.

Evaluation of Tai Chi Yunshou exercises on community-based stroke patients with balance dysfunction: a study protocol of a cluster randomized controlled trial.

BACKGROUND: Balance dysfunction after stroke limits patients' general function and participation in daily life. Previous researches have suggested that Tai Chi exercise could offer a positive improvement in older individuals' balance function and reduce the risk of falls. But convincing evidence for the effectiveness of enhancing balance function after stroke with Tai Chi exercise is still inadequate. Considering the difficulties for stroke patients to complete the whole exercise, the current trial evaluates the benefit of Tai Chi Yunshou exercise for patients with balance dysfunction after stroke through a cluster randomization, parallel-controlled design. METHODS/DESIGN: A single-blind, cluster-randomized, parallel-controlled trial will be conducted. A total of 10 community health centers (5 per arm) will be selected and randomly allocated into Tai Chi Yunshou exercise group or balance rehabilitation training group. Each community health centers will be asked to enroll 25 eligible patients into the trial. 60 minutes per each session, 1 session per day, 5 times per week and the total training round is 12 weeks. Primary and secondary outcomes will be measured at baseline and 4-weeks, 8-weeks, 12-weeks, 6-week follow-up, 12-week follow-up after randomization. Safety and economic evaluation will also be assessed. DISCUSSION: This protocol aims to evaluate the effectiveness of Tai Chi Yunshou exercise for the balance function of patients after stroke. If the outcome is positive, this project will provide an appropriate and economic balance rehabilitation technology for community-based stroke patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-TRC-13003641. Registration date: 22 August, 2013 http://www.chictr.org/usercenter/project/listbycreater.aspx .