Short and long-term effects of robot-assisted therapy on upper limb motor function and activity of daily living in patients post-stroke: a meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate the effect of robot-assisted therapy (RAT) on upper limb motor control and activity function in poststroke patients compared with that of non-robotic therapy. METHODS: We searched PubMed, EMBASE, Cochrane Library, Google Scholar and Scopus. Randomized controlled trials published from 2010 to nowadays comparing the effect of RAT and control treatment on upper limb function of poststroke patients aged 18 or older were included. Researchers extracted all relevant data from the included studies, assessed the heterogeneity with inconsistency statistics (I2 statistics), evaluated the risk of bias of individual studies and performed data analysis. RESULT: Forty-six studies were included. Meta-analysis showed that the outcome of the Fugl-Meyer Upper Extremity assessment (FM-UE) (SMD = 0.20, P = 0.001) and activity function post intervention was significantly higher (SMD = 0.32, P < 0.001) in the RAT group than in the control group. Differences in outcomes of the FM-UE and activity function between the RAT group and control group were observed at the end of treatment and were not found at the follow-up. Additionally, the outcomes of the FM-UE (SMD = 0.15, P = 0.005) and activity function (SMD = 0.32, P = 0.002) were significantly different between the RAT and control groups only with a total training time of more than 15 h. Moreover, the differences in outcomes of FM-UE and activity post intervention were not significant when the arm robots were applied to patients with severe impairments (FM-UE: SMD = 0.14, P = 0.08; activity: SMD = 0.21, P = 0.06) or when patients were provided with patient-passive training (FM-UE: SMD = - 0.09, P = 0.85; activity: SMD = 0.70, P = 0.16). CONCLUSION: RAT has the significant immediate benefits for motor control and activity function of hemiparetic upper limb in patients after stroke compared with controls, but there is no evidence to support its long-term additional benefits. The superiority of RAT in improving motor control and activity function is limited by the amount of training time and the patients' active participation.

Effect of Combined Vagus Nerve Stimulation on Recovery of Upper Extremity Function in Patients with Stroke: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effectiveness of vagus nerve stimulation (VNS) combined with rehabilitation therapies in restoring upper extremity (UE) function following stroke. Data Sources A search was implemented in key databases along with hand searches of relevant papers and performed on 31 July 2021. MATERIALS AND METHODS: Only randomized controlled trials (RCTs) assessing the effect of VNS focusing on UE dysfunction in patients post-stroke were identified in this systematic review. Data were extracted independently by two authors. The study was conducted by the Preferred Reporting Items for Meta-Analyses (PRISMA) guidelines. Meta-analyses were performed when deemed feasible. RESULTS: Five RCTs involving 178 patients (VNS/C 87/91) were included. The primary outcome was the function assessment by upper UE Fugl-Meyer assessment (FMA-U). As secondary outcomes, strength was assessed with the Wolf motor function test (WMFT), the Stroke Impact Scale (SIS) and the Motor Activity Log (MAL). Meta-analysis showed a significant immediate favoring VNS-based rehabilitation (five studies) for improving upper extremity function after stroke (mean difference [MD] 3.31; 95% confidence interval [CI], 2.33-4.29; p < 0.0001,fixed-effects model), along the lines of the long-term effect (three studies) (MD = 3.13; 95% CI, 1.47--4.79; p < 0.0001,fixed-effects model). No effect was observed when compared with control groups in adverse outcomes (Risk Ratio [RR] 1.61; 95% CI, 0.65-3.99; P = 0.30). CONCLUSIONS: VNS combined with rehabilitation training may be considered as a promising intervention in UE recovery in stroke patients.

Vagus nerve stimulation promotes the M1-to-M2 transition via inhibition of TLR4/NF-κB in microglial to rescue the reperfusion injury.

OBJECTIVE: To specify the effect of vagus nerve stimulation (VNS) on microglial polarization following ischemic-reperfusion and further investigate its underlying mechanism. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into the sham, ischemic reperfusion group (IR), IR+VNS groups. VNS intervention lasting for 1 hour was administered after 30 minutes of occlusion. We analyzed the expression of Arginase 1 (Arg1), the number of M2 microglial in the peri-infarction cortex and assessed the neurological scores at the 1, 3, 7 days after reperfusion to determine the research time point. Then, we assessed polarization status of microglial, the infarct volume, neurological scores, the cellular distribution of Toll-like Receptor 4 (TLR4), the TLR4-associated pathway protein and the p-NF-κB in microglial at 3 days after reperfusion. RESULTS: We found that VNS could increase the specific marker of M2 Arg1 and upregulate the M2 microglial after reperfusion, and the increase of Arg1, M2 microglial and the neurological scores was largest at the 3 days after reperfusion. VNS treatment significantly reduced the number and percent of M1, improved the number and percent of M2 and upregulated the M2 to M1 ratio without changing the number of total microglial at the 3 days after reperfusion. Moreover, VNS reduced the infarct volume and neurological deficits. In addition, VNS significantly reduced the microglial-specific TLR4, inhibited the activated TLR4/MyD88/NF-κB pathway following ischemic-reperfusion, and ultimately suppressed the p-NF-κB in microglial. CONCLUSION: Our study revealed that VNS can promote the M1-to-M2 phenotype conversion to alleviate inflammatory response and brain injury through inhibition of TLR4/MyD88/NF-κB pathway in microglia following ischemic-reperfusion.

Vagus nerve stimulation mediates microglia M1/2 polarization via inhibition of TLR4 pathway after ischemic stroke.

Ischemic stroke is the leading cause of death and disability. Microglia are polarized toward the proinflammatory M1 phenotype and neuroprotective M2 phenotype after stroke and play an important role in the pathological process of ischemic stroke. Emerging research suggests that vagus nerve stimulation (VNS) can mediate microglia polarization after ischemic stroke and may serve as a potential treatment for ischemic stroke. However, the mechanism by which VNS mediates microglia polarization remains unclear. In this study, we aimed to investigate the underlying mechanism. Sprague-Dawley rats were randomly divided into the sham, ischemic stroke, ischemic stroke + VNS, ischemic stroke + VNS + lentivirus (LV)-TLR4 and ischemic stroke + VNS + LV-CON groups. LV was injected into the lateral ventricles of the rats 14 days before ischemic stroke surgery, and VNS was administered after 30 min of occlusion. We assessed the infarct volume, neurological scores, the TLR4/MyD88/NF-κB protein level and microglia polarization after 3 days of reperfusion. Our results revealed that VNS can promote M2 microglia polarization and inhibit M1 microglia polarization to alleviate brain injury via inhibition of the TLR4/MyD88/NF-κB pathway in microglia in the acute stage of stroke.

C1q/TNF-related protein 4 restores leptin sensitivity by downregulating NF-κB signaling and microglial activation.

OBJECTIVE: C1qTNF-related protein 4 (CTRP4) acts in the hypothalamus to modulate food intake in diet-induced obese mice and has been shown to exert an anti-inflammatory effect on macrophages. Since high-fat diet-induced microglial activation and hypothalamic inflammation impair leptin signaling and increase food intake, we aimed to explore the potential connection between the anorexigenic effect of CTRP4 and the suppression of hypothalamic inflammation in mice with DIO. METHODS: Using an adenovirus-mediated hypothalamic CTRP4 overexpression model, we investigated the impact of CTRP4 on food intake and the hypothalamic leptin signaling pathway in diet-induced obese mice. Furthermore, central and plasma proinflammatory cytokines, including TNF-α and IL-6, were measured by Western blotting and ELISA. Changes in the hypothalamic NF-κB signaling cascade and microglial activation were also examined in vivo. In addition, NF-κB signaling and proinflammatory factors were investigated in BV-2 cells after CTRP4 intervention. RESULTS: We found that food intake was decreased, while leptin signaling was significantly improved in mice with DIO after CTRP4 overexpression. Central and peripheral TNF-α and IL-6 levels were reduced by central Ad-CTRP4 administration. Hypothalamic NF-κB signaling and microglial activation were also significantly suppressed in vivo. In addition, NF-κB signaling was inhibited in BV-2 cells following CTRP4 intervention, which was consistent with the decreased production of TNF-α and IL-6. CONCLUSIONS: Our data indicate that CTRP4 reverses leptin resistance by inhibiting NF-κB-dependent microglial activation and hypothalamic inflammation.

Effect and Safety of Transcutaneous Auricular Vagus Nerve Stimulation on Recovery of Upper Limb Motor Function in Subacute Ischemic Stroke Patients: A Randomized Pilot Study.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) is regarded as a potential method for recovery in stroke. The effectiveness of taVNS in acute and subacute stroke should be further discussed as previously, only a few small-scale trials have focused on chronic stroke patients. The objective of this study is to investigate the effect and safety of taVNS on upper limb motor function in subacute ischemic stroke patients. Methods: Twenty-one subacute ischemia stroke patients with single upper limb motor function impairment were enrolled and randomly assigned to conventional rehabilitation training with real or sham taVNS, delivered for 15 consecutive days. Electrodes were fixed to the cymba conchae of the left ear with or without electrical stimulation. Conventional rehabilitation training was performed immediately after the end of real or sham taVNS by the same therapists. Baseline assessments were performed on day 0 of enrollment, and posttreatment evaluations were performed at 15 days, 4 weeks, and 12 weeks after the first intervention. The assessment included the upper limb Fugl-Meyer assessment (FMA-U), the Wolf motor function test (WMFT), the Functional Independence Measurement (FIM), and Brunnstrom stage. Heart rate (HR) and blood pressure (BP) were measured before and after each taVNS intervention. At the same time, any adverse effects were observed during the procedure. Outcomes were assessed by a blind evaluator. Results: There were no significant differences in FMA-U, WMFT, FIM, and Brunnstrom scores between the two groups at baseline (P > 0.05). At the endpoint, the FMA-U, WMFT, and FIM scores were significantly higher than before treatment (P < 0.05), and there was a significantly greater improvement of those measurements in taVNS group compared with sham-taVNS group (P < 0.05). Significant improvements in FMA-U score were found between groups at follow-up. Only one case of skin redness occurred during the study. Conclusions: This study revealed that taVNS appeared to be beneficial to the recovery of upper limb motor function in subacute ischemia stroke patients without obvious adverse effects. Trial registration. This trial is registered with ChiCTR1800019635 on 20 November 2018 (http://www.chictr.org.cn/showproj.aspx?proj=32961).

Long-term Effects of Extracorporeal Shock Wave Therapy on Poststroke Spasticity: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: The purpose of this meta-analysis was to assess the long-term effects of extracorporeal shock wave therapy (ESWT) on post-stroke spasticity. DATA SOURCES: An electronic search of EMBASE, MEDLINE, and Cochrane Central Register of Controlled Trials (CENTRAL) with hand search of relevant papers were performed on 20 June 2019. REVIEW METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the literature for randomized controlled trials of ESWT in stroke patients with spasticity. The primary outcome was the Modified Ashworth Scale (MAS) grade, and the second outcomes were the Visual Analogue Scale (VAS), range of motion (ROM) of joint, the Fugl-Meyer assessment (FMA) grade and adverse events. Two authors independently extracted data, assessed trial eligibility and risk of bias. Meta-analyses were performed using RevMan 5.3 software. RESULTS: We extracted data from 8 randomized controlled trials (301 participants). At long-term follow-up, ESWT significantly reduced MAS (Weighted Mean Difference (WMD) = -.36, 95% confidence interval (CI) = -.53 to -.19, I2 = 68%; P < .001) and VAS (WMD = -.94, 95% CI = -1.51 to -.37, I2 = 15%; P = .001), enhanced ROM (WMD = 5.97, 95% CI = 2.76 to 9.18, I2 = 0%; P < .001) and FMA (WMD = 1.26, 95% CI = .29 to 2.24, I2 = 96%; P = .01). CONCLUSIONS: ESWT showed long-term effects in relieving spasticity, while reducing pain, enhancing ROM and motor function in stroke patients.

Effects of kinesiotape on pain and disability in individuals with chronic low back pain: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE:: To explore the effects of kinesiotape on pain and disability in individuals with chronic low back pain. DATA SOURCES:: PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched for English language publications from inception to 13 February 2018. REVIEW METHODS:: This study was registered in PROSPERO (CRD42018089831). Our key search terms were ((kinesio taping) OR (kinesiotaping) OR (kinesiotape)) AND (low back pain). Randomized controlled trials evaluating the effects of kinesiotape published in English language were included in this review. The reference lists of retrieved studies and relevant reviews were also searched. Quality of the included trials was assessed according to 2015 updated Cochrane Back and Neck Review Group 13-Item criteria. RESULTS:: A total of 10 articles were included in this meta-analysis. A total of 627 participants were involved, with 317 in the kinesiotape group and 310 in the control group. The effects of kinesiotape on pain and disability were explored. While kinesiotape was not superior to placebo taping in pain reduction, either alone ( P = 0.07) or in conjunction with physical therapy ( P = 0.08), it could significantly improve disability when compared to the placebo taping ( P < 0.05). CONCLUSION:: Since kinesiotape is convenient for application, it could be used for individuals with chronic low back pain in some cases, especially when the patients could not get other physical therapy.

Comparative Efficacy of Alendronate upon Vertebral Bone Mineral Density and Fracture Rates in East Asians Versus Non-East Asians with Postmenopausal Osteoporosis: A Systematic Review and Meta-Analysis.

Bisphosphonates, such as alendronate, have become the most widely used and effective anti-resorptive therapy for postmenopausal osteoporosis. Previous genetic studies suggest that ethnicity may drive differing responses to bisphosphonate therapy in East Asians and non-East Asians. Therefore, the aim of this study was to comparatively evaluate the efficacy of alendronate upon lumbar spinal BMD and vertebral fracture rates in East Asians and non-East Asians with postmenopausal osteoporosis. MEDLINE, EMBASE, and Cochrane CENTRAL were searched for relevant randomized controlled trials (RCTs) comparing the efficacy of alendronate versus placebo (or calcium/mineral and/or Vitamin D or hormone replacement therapy) in primary postmenopausal osteoporotic women. We calculated the weighted mean differences (WMDs) for lumbar spinal BMD and the risk ratios (RRs) for vertebral fracture risk along with their respective 95% confidence intervals (CIs). From an initial set of 445 non-duplicate records, 13 full-text articles were finally included in this meta-analysis consisting of four East Asian RCTs and nine non-East Asian RCTs. Alendronate therapy displayed significant effects in improving lumbar spinal BMD in both East Asians [WMD (95% CI)=5.30 (0.32-10.29), p=0.037] and non-East Asians [WMD (95% CI)=5.73 (3.61-7.85), p=0.000]. Alendronate therapy did not display significant effects upon vertebral fracture risk in East Asians [RR (95% CI)=0.41 (0.06-2.73), p=0.358] but did display a significant effect upon lowering vertebral fracture risk in non-East Asians [RR (95% CI)=0.55 (0.42-0.72), p=0.000]. These findings suggest that ethnicity may affect the efficacy of bisphosphonate therapy in postmenopausal osteoporotic women.

Short- and long-term effects of pulmonary rehabilitation for idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

OBJECTIVE: To investigate the short- and long-term effects of pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis (IPF). DATA SOURCES: An electronic search of MEDLINE, Embase and Cochrane Central databases along with hand search of relevant papers were performed on 15 March 2018. REVIEW METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the literature for randomized controlled trials of pulmonary rehabilitation in IPF patients. The outcomes were exercise capacity and health-related quality of life. Two authors independently extracted data, assessed trial eligibility and risk of bias. Meta-analyses were performed using RevMan and STATA software. RESULTS: We extracted data from four randomized controlled trials (142 participants). At short-term follow-up, pulmonary rehabilitation significantly enhanced 6-minute walk distance (6-MWD; weighted mean difference (WMD) = 38.38, 95% confidence interval (CI) = 4.64-72.12, I2 = 60.7%; P < 0.05), reduced St. George's Respiratory Questionnaire (SGRQ)/IPF-specific SGRQ (SGRQ-I) total score (WMD = -8.40, 95% CI = -11.44 to -5.36, I2 = 0%; P < 0.00001). At long-term follow-up, pulmonary rehabilitation could not enhance 6-MWD (WMD = 17.02, 95% CI = -26.87 to 60.81, I2 = 36.3%; P = 0.43) or reduce SGRQ/SGRQ-I total score (WMD = -3.45, 95% CI = -8.55 to 1.64, I2 = 38.3%; P = 0.088). CONCLUSION: In patients with IPF, pulmonary rehabilitation showed short-term effects in enhancing exercise capacity and health-related quality of life, while it had no detectable effects at long-term follow-up.

L-PGDS Mediates Vagus Nerve Stimulation-Induced Neuroprotection in a Rat Model of Ischemic Stroke by Suppressing the Apoptotic Response.

The role of lipocalin prostaglandin D2 synthase (L-PGDS) in brain ischemia has not been fully clarified to date. Vagus nerve stimulation (VNS) protects against cerebral ischemia/reperfusion (I/R) injury, but the mechanisms involved need further exploration. This study investigated the role of L-PGDS in cerebral I/R and whether this process was involved in the mechanism of VNS-mediated neuroprotection. Male Sprague-Dawley rats were pretreated with a lentiviral vector (LV) through intracerebroventricular injection, followed by middle cerebral artery occlusion (MCAO) and VNS treatment. The expression of L-PGDS in the peri-infarct cortex was examined. The localization of L-PGDS was determined using double immunofluorescence staining. Neurologic scores, infarct volume and neuronal apoptosis were evaluated at 24 h after reperfusion. The expression of apoptosis-related molecules was measured by western blot analysis. The expression of L-PGDS in the peri-infarct cortex increased at 12 h, reached a peak at 24 h after reperfusion, and lasted up to 3 days. VNS treatment further enhanced the expression of L-PGDS following ischemic stroke. L-PGDS was mainly expressed in neurons in the peri-infarct cortex. I/R rats treated with VNS showed better neurological deficit scores, reduced infarct volume, and decreased neuronal apoptosis as indicated by the decreased levels of Bax and cleaved caspase-3 as well as increased levels of Bcl-2. Strikingly, the beneficial effects of VNS were weakened after L-PGDS down-regulation. In general, our results suggest that L-PGDS is a potential mediator of VNS-induced neuroprotection against I/R injury.

Effect of internet-based pulmonary rehabilitation on physical capacity and health-related life quality in patients with chronic obstructive pulmonary disease-a systematic review and meta-analysis.

PURPOSE: Pulmonary rehabilitation (PR) is now recognized as the most effective treatments for individuals with chronic obstructive pulmonary disease (COPD), internet-based PR arises a promising method. The aim of this study was to conduct a systematic review and meta-analysis for assessing the effect of internet-based PR programs on physical capacity and health-related quality of life in patients with COPD. MATERIALS AND METHODS: Randomized controlled trials were identified through systematically searches in PubMed, EMBASE, web of science, CENTRAL, Cochrane Library, and Google Scholar databases. RESULTS: Twelve studies (1433 patients) were included. For physical capacity, there was no significant difference between groups was found according to the 6-min walk test (6MWT) (MD10.42, 95% CI -2.92 to 23.77, p = 0.13, I2 = 0%). For the health-related quality of life, no significant difference between groups was found regarding the St George's Respiratory Questionnaire (SGRQ) (MD -0.64, 95% CI -3.52 to 2.23, p = 0.66), COPD assessment test (CAT)(MD -0.34, 95% CI -1.62 to 0.94, p = 0.60), modified Medical Research Council scale (mMRC)(MD 0.17, 95% CI -0.06 to 0.39, p = 0.15) and Chronic Respiratory Questionnaire (CRQ)(MD 1.32 95% CI -5.88 to 8.53, p = 0.72). CONCLUSIONS: This study has established the potential for delivery of PR via the internet in demonstrating non-inferiority of physical capacity and health-related quality of life (HRQoL) compared with conventional PR.IMPLICATIONS FOR REHABILITATIONLong-term rehabilitation training for patients with chronic obstructive pulmonary disease needs a more convenient and feasible way.In this study, internet-based rehabilitation showed similar effects as conventional rehabilitation on physical activity and health-related quality of life.Internet-based rehabilitation strategies would be helpful for this population.All internet-based rehabilitation strategies should be simple and sustainable.

Vagus nerve stimulation is a potential treatment for ischemic stroke.

Microglia are the brain's primary innate immune cells, and they are activated and affect pro-inflammatory phenotype or regulatory phenotype after ischemic stroke. Vagus nerve stimulation was shown to activate microglial phenotypic changes and exhibit neuroprotective effects in ischemia/reperfusion injury. In this study, we established rat models of ischemic stroke by occlusion of the middle cerebral artery and performed vagus nerve stimulation 30 minutes after modeling. We found that vagus nerve stimulation caused a shift from a pro-inflammatory phenotype to a regulatory phenotype in microglia in the ischemic penumbra. Vagus nerve stimulation decreased the levels of pro-inflammatory phenotype markers inducible nitric oxide synthase and tumor necrosis factor α and increased the expression of regulatory phenotype markers arginase 1 and transforming growth factor ß through activating α7 nicotinic acetylcholine receptor expression. Additionally, α7 nicotinic acetylcholine receptor blockade reduced the inhibition of Toll-like receptor 4/nuclear factor kappa-B pathway-associated proteins, including Toll-like receptor 4, myeloid differentiation factor 88, I kappa B alpha, and phosphorylated-I kappa B alpha, and also weakened the neuroprotective effects of vagus nerve stimulation in ischemic stroke. Vagus nerve stimulation inhibited Toll-like receptor 4/nuclear factor kappa-B expression through activating α7 nicotinic acetylcholine receptor and regulated microglial polarization after ischemic stroke, thereby playing a role in the treatment of ischemic stroke. Findings from this study confirm the mechanism underlying vagus nerve stimulation against ischemic stroke.

Running exercise improves spatial learning and memory ability and enhances angiogenesis in the cerebral cortex via endogenous nitric oxide.

BACKGROUND: The molecular mechanisms by which exercise improves brain function and capillaries in the cerebral cortex are unclear. Exercise can increase the expression of nitric oxide (NO) in the brain, and endogenous NO is thought to exert beneficial effects on proangiogenic factors, antiangiogenic factors and brain function. Therefore, we hypothesized that running exercise might improve brain function and enhance angiogenesis through endogenous NO. METHODS AND RESULTS: The following three groups of rats were administered intracerebroventricular (i.c.v.) injections before running exercise each day for 4 weeks: exercise+L-NAME group (i.c.v. L-NAME, an NO synthase blocker, dose: 1 µmol/µl and 5 µl/day; treadmill exercise, 20 min/day), exercise group (i.c.v. normal saline, 5 µl/day; treadmill exercise, 20 min/day), and sham group (i.c.v. normal saline, 5 µl/day; no treadmill exercise). Subsequently, the spatial learning and memory abilities were tested using a Morris water maze, and the nitric oxide synthase (NOS) activity in the cerebral cortex in each group of rats was measured using a method involving nitric acid reductase and metabolic chemistry. The parameters of the cortical capillaries were quantitatively investigated using an immunohistochemistry technique and stereological methods. The expression levels of proangiogenic factors (VEGF and FGF-2) and an antiangiogenic inhibitor (endostatin) in the cerebral cortex were tested using a Western blot analysis. Running exercise significantly improved the rats' spatial learning and memory abilities and increased NOS activity in the cortex. Running exercise also subsequently improved the expression of proangiogenic factors (VEGF and FGF-2) and the length, volume and surface area of capillaries and reduced the expression of antiangiogenic factors (endostatin) in the cortex. In contrast, the L-NAME treatment attenuated the effects of running exercise. CONCLUSIONS: Running exercise regulates proangiogenic factors, antiangiogenic factors and angiogenesis in the cerebral cortex via a partially NO-dependent mechanism, and influencing endogenous NO might potentially affect the exercise-related beneficial effects on cognitive ability and cortical capillaries.

Long-term intermittent fasting improves neurological function by promoting angiogenesis after cerebral ischemia via growth differentiation factor 11 signaling activation.

Intermittent fasting (IF), an alternative to caloric restriction, is a form of time restricted eating. IF conditioning has been suggested to have neuroprotective effects and potential long-term brain health benefits. But the mechanism underlying remains unclear. The present study focused on the cerebral angiogenesis effect of IF on ischemic rats. Using a rat middle cerebral artery occlusion model, we assessed neurological outcomes and various vascular parameters such as microvessel density (MVD), regional cerebral blood flow (rCBF), proliferation of endothelial cells (ECs), and functional vessels in the peri-infarct area. IF conditioning ameliorated the modified neurological severity score and adhesive removal test, increased MVD, and activated growth differentiation factor 11 (GDF11)/activin-like kinase 5 (ALK5) pathways in a time-dependent manner. In addition, long-term IF conditioning stimulated proliferation of ECs, promoted rCBF, and upregulated the total vessel surface area as well as the number of microvessel branch points through GDF11/ALK5 pathways. These data suggest that long-term IF conditioning improves neurological outcomes after cerebral ischemia, and that this positive effect is mediated partly by angiogenesis in the peri-infarct area and improvement of functional perfusion microvessels in part by activating the GDF11/ALK5 signaling pathway.

Effect of kinesiotaping on pain relief and upper limb function in stroke survivors: a systematic review and meta-analysis.

OBJECTIVES: To explore the effects of kinesiotaping in the treatment of shoulder pain and upper limb function in stroke survivors. METHODS: PubMed, EMBASE and the Cochrane Central Register of Controlled Trials were electronically and manually searched to identify relevant publications from inception to March 1, 2022. Full-text qualitative studies that explored the effects of kinesiotaping on hemiplegic shoulder pain and poststroke upper limb spasticity were included in the analysis. Data synthesis with a thematic approach was performed to generate descriptive and analytical themes. RESULTS: Nine randomized controlled trials with 253 participants were included. The meta-analysis showed that kinesiotaping significantly reduced poststroke shoulder pain (mean difference (MD) = -1.59, 95% confidence interval (CI): -3.21 to -0.02, P = 0.05), enhanced range of motion (ROM) (MD = 7.00, 95% CI: 2.3 to 11.7, P = 0.004), reduced Modified Ashworth scale (MAS) scores (MD = -0.26, 95% CI: -0.51 to -0.01, P = 0.04), and decreased the magnitude of shoulder subluxation (MD = -0.42, 95% CI: -0.76 to -0.08, P = 0.02). However, outcomes, such as the Fugl-Meyer score and Barthel index, did not differ between the kinesiotaping and control groups. CONCLUSIONS: Kinesiotaping effectively relieved shoulder pain, improved upper limb spasticity and ROM, and reduced shoulder subluxation in stroke survivors. However, the effects of kinesiotaping on upper limb function in terms of FMA-UE scores and independence in activities of daily living were not verified. High-quality RCTs designed with large sample sizes are still required in the future.

The effect of corticosteroid injection in the treatment of greater trochanter pain syndrome: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: corticosteroid injection (CSI) has been used to treat greater trochanter pain syndrome (GTPS) for many years. However, so far, the efficacy of CSI in the treatment of GTPS is still controversial. Therefore, the aim of this review is to evaluate the effectiveness of CSI in comparison with sham intervention, nature history, usual care, platelet-rich plasma (PRP), physiotherapy/exercise therapy, dry needling, or other nonsurgical treatment for improvements in pain and function in GTPS. METHODS: PubMed (Medline), Embase, Cochrane Library were searched from their inception until April 2021. Randomized controlled trails (RCTs) comparing CSI to nonsurgical treatment were included. Data on the effect of CSI on pain and function were extracted and checked by two review authors independently. The treatment effect was analyzed in the short term, medium term, and long term. RESULTS: Eight RCTs (764 patients) were included. This review suggests CSI may be superior to usual care and 'wait and see,' ESWT, but may not be superior to exercise, PRP, dry needling, and sham intervention in short-term pain or function improvement. In terms of medium-term pain or function improvement, CSI may be superior to usual care and 'wait and see,' but may not be superior to PRP. In terms of long-term pain or function improvement, CSI may be inferior to PRP and ESWT, but it may be superior to usual care and 'wait and see' at 12 months. CONCLUSIONS: Due to the small sample size and lack of sufficient clinical studies, current evidence is equivocal regarding the efficacy of CSI in the treatment of GTPS. Considering the limitations, more large-sample and high-quality RCTs are needed to prove the therapeutic effect of CSI on GTPS. TRIAL REGISTRATION: PROSPERO registration number: CRD42021247991. Registered 09 May 2021.

Efficacy and safety of electroacupuncture at auricular concha region in promoting of rehabilitation of ischemic stroke patients with upper limb motor dysfunction: A study protocol for a randomized pilot trial.

INTRODUCTION: Ischemic stroke (IS) is the one of the most severe neurological disease, survivors may live with upper limb motor dysfunction (ULMD) resulting in heavy social and economic burden. Nowadays, there are few approaches to promote the rehabilitation of ULMD. Auricular acupuncture (electroacupuncture [EA]) has long been used in the treatment of neurological disorders in China. This treatment has become an attractive treatment option due to its low cost, portability, minimal side effects, and ease of use in clinical and operational environments. However, its efficacy and safety in consciousness recovery remain to be proved. METHODS: A total of 80 IS patients with single upper limb motor function impairment will be recruited in the trial and randomized into EA or control groups. Patients in the control group will receive routine conventional treatment alone while patients in the EA group will receive EA treatment for 3 consecutive weeks based on routine conventional treatment. Baseline evaluation was carried out on day of enrollment, post-treatment evaluation was carried out 14 and 21 days after enrollment, and the 2 groups were follow-ups in 3 and 6 months after the end of the trial. The efficacy will be assessed with the changes in the upper limb Fugl-Meyer assessment, Wolf motor function test, action research arm test, active range of motion, and Barthel index. The safety of EA will be estimated by monitoring the incidence of adverse events and changes in vital signs during the study period. Analysis of feasibility will be descriptive and the change in outcome measures between groups will be analyzed using an independent sample t test. DISCUSSION: This study tried to narrow the evidence gap on the efficacy of EA at the auricular on the recovery of ULMD in patients with IS. The results of this trial will provide strong evidence for the efficacy and safety of EA of auricular concha region stimulation for IS patients.Trial registration: This trial has been registered at the Chinese Clinical Trial Registry, numbered ChiCTR2100049678.

IL-33 Deficiency Attenuates Lung Inflammation by Inducing Th17 Response and Impacting the Th17/Treg Balance in LPS-Induced ARDS Mice via Dendritic Cells.

Objectives: The characteristic pathophysiological feature of acute respiratory distress syndrome (ARDS) is a dysregulated inflammatory response. T helper 17 (Th17) cells in the lung are inflammatory cells that contribute to pulmonary inflammatory cascades. In addition, Th17/regulatory T cells (Treg cells) also play an important role in the inflammatory process. Dendritic cells (DCs) can regulate the differentiation of CD4+ T cells, including Th17 and Treg cells. Recent evidence revealed that interleukin-33 (IL-33) signaling could activate and mature DCs. Therefore, the aim of this study was to investigate the effects of IL-33 on inflammation and immunoregulation by inducing the Th17 response and influencing the Th17/Treg balance in LPS-induced ARDS. Methods: IL-33 gene knockout mice and the administration of recombinant mouse IL-33 (rmIL-33) were used to investigate the role of IL-33 and the underlying mechanisms in an LPS-induced ARDS model. Hematoxylin and eosin (H&E) staining, wet/dry (W/D) weight ratios, cell counts, and the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-17 (IL-17), and interleukin-10 (IL-10) in bronchoalveolar lavage fluid (BALF) were investigated. The levels of IL-33, orphan nuclear receptor gamma t (RORγt), and forkhead transcription factor protein 3 (FOXP3) protein in lung tissue were evaluated by Western blotting. The mRNA expression levels of IL-33 and RORγt were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Th17 and Treg cell frequencies were determined by flow cytometry. The levels of IL-6 in the supernatant in a dendritic cell culture system were examined by ELISA. Results: Increased expression of IL-33 was observed in mice with LPS-induced ARDS. IL-33 deficiency significantly inhibited inflammation and attenuated LPS-induced ARDS, whereas pretreatment with rmIL-33 aggravated pulmonary inflammatory response. Furthermore, depletion of IL-33 inhibited Th17 cells, significantly decreased RORγt mRNA and protein expression and IL-17 levels in BALF, and led to less differentiation of T cells into Th17 cells than Treg cells. Moreover, IL-33-/- DCs secreted less IL-6 and IL-23 than normal control DCs. Conclusion: IL-33 deficiency alleviated lung injury in the LPS-induced ARDS model, which was closely related to suppressing Th17 responses and regulating the Th17/Treg balance. The expansion of Th17 cells and imbalance in Th17/Treg cells may be associated with IL-6 and IL-23 secreted from IL-33-activated DCs.

Transcutaneous Auricular Vagus Nerve Stimulation Promotes White Matter Repair and Improves Dysphagia Symptoms in Cerebral Ischemia Model Rats.

Background: Clinical and animal studies have shown that transcutaneous auricular vagus nerve stimulation (ta-VNS) exerts neuroprotection following cerebral ischemia. Studies have revealed that white matter damage after ischemia is related to swallowing defects, and the degree of white matter damage is related to the severity of dysphagia. However, the effect of ta-VNS on dysphagia symptoms and white matter damage in dysphagic animals after an ischemic stroke has not been investigated. Methods: Middle cerebral artery occlusion (MCAO) rats were randomly divided into the sham, control and vagus nerve stimulation (VNS) group, which subsequently received ta-VNS for 3 weeks. The swallowing reflex was measured once weekly by electromyography (EMG). White matter remyelination, volume, angiogenesis and the inflammatory response in the white matter were assessed by electron microscopy, immunohistochemistry, stereology, enzyme-linked immunosorbent assay (ELISA) and Western blotting. Results: ta-VNS significantly increased the number of swallows within 20 s and reduced the onset latency to the first swallow. ta-VNS significantly improved remyelination but did not alleviate white matter shrinkage after MCAO. Stereology revealed that ta-VNS significantly increased the density of capillaries and increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2) expression in the white matter. ta-VNS significantly alleviated the increase inTLR4, MyD88, phosphorylated MAPK and NF-κB protein levels and suppressed the expression of the proinflammatory factors IL-1ß and TNF-α. Conclusion: These results indicated ta-VNS slightly improved dysphagia symptoms after ischemic stroke, possibly by increasing remyelination, inducing angiogenesis, and inhibiting the inflammatory response in the white matter of cerebral ischaemia model rats, implying that ta-VNS may be an effective therapeutic strategy for the treatment of dysphagia after ischemic stroke.