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.

Tryptophan metabolism as bridge between gut microbiota and brain in chronic social defeat stress-induced depression mice.

Backgrounds: Gut microbiota plays a critical role in the onset and development of depression, but the underlying molecular mechanisms are unclear. This study was conducted to explore the relationships between gut microbiota and host's metabolism in depression. Methods: Chronic social defeat stress (CSDS) model of depression was established using C57BL/6 male mice. Fecal samples were collected from CSDS group and control group to measure gut microbiota and microbial metabolites. Meanwhile, tryptophan metabolism-related metabolites in hippocampus were also analyzed. Results: CSDS successfully induced depressive-like behaviors in CSDS group. The 24 differential bacterial taxa between the two groups were identified, and 14 (60.87%) differential bacterial taxa belonged to phylum Firmicutes. Functional analysis showed that tryptophan metabolism was significantly affected in CSDS mice. Meanwhile, 120 differential microbial metabolites were identified, and two key tryptophan metabolism-related metabolites (tryptophan and 5-hydroxytryptophan (5-HTP)) were significantly decreased in feces of CSDS mice. The correlation analysis found the significant relationships between tryptophan and differential bacterial taxa under Firmicutes, especially genus Lactobacillus (r=0.801, p=0.0002). In addition, the significantly decreased 5-hydroxytryptamine (5-HT) in hippocampus of depressed mice was also observed. Conclusions: Our results showed that tryptophan metabolism might have an important role in the crosstalk between gut microbioa and brain in depression, and phylum Firmicutes, especially genus Lactobacillus, might be involved in the onset of depression through regulating tryptophan metabolism.

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.

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.

Stress-induced myelin damage in the hippocampal formation in a rat model of depression.

BACKGROUND: According to previous studies, myelin damage may be involved in the occurrence of depression. However, to date, no study has quantitatively investigated the changes in myelinated fibers and myelin sheaths in the hippocampal formation (HF) and hippocampal subfields in the context of depression. METHODS: Male Sprague-Dawley (SD) rats (aged 4-5 weeks) were evenly divided into the control group and chronic unpredictable stress (CUS) group. Behavioral tests were performed, and then changes in myelinated fibers and myelin ultrastructure in hippocampal subfields in depression model rats were investigated using modern stereological methods and transmission electron microscopy techniques. RESULTS: After a four-week CUS protocol, CUS rats showed depressive-like and anxiety-like behaviors. The total length and total volume of myelinated fibers were reduced in the CA1 region and DG in the CUS group compared with the control group. The total volumes of myelin sheaths and axons in the CA1 region but not in the DG were significantly lower in the CUS group than in the control group. The decrease in the total length of myelinated nerve fibers in the CA1 region in CUS rats was mainly due to a decrease in the length of myelinated fibers with a myelin sheath thickness of 0.15 µm-0.20 µm. LIMITATIONS: The exact relationship between the degeneration of myelin sheaths and depression-like, anxiety-like behaviors needs to be further investigated. CONCLUSIONS: CUS induces depression- and anxiety-like behaviors, and the demyelination in the CA1 region induced by 4 weeks of CUS might be an important structural basis for these behaviors.

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.

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.

Effects of 4-month running exercise on the spatial learning ability and white matter volume and microvessels of middle-aged female and male rats.

Age-related degeneration of microvessels is known to occur in white matter, and exercise training can enhance brain function and promote cerebral blood flow. However, the effects of exercise training on microvessels in aged white matter are unknown. Forty-one middle-aged male and female Sprague-Dawley rats were randomly divided into a sedentary group and an exercised group. The rats in the exercised group were made to run on treadmills for 4 months. The spatial learning capacities of all groups were then assessed with the Morris water maze. White matter and its microvessels were investigated using immunohistological techniques and stereological methods. In the exercised group, females but not males, showed improved performance over time in the Morris water maze. In females but not males, the exercised rats showed significantly increased white matter volume compared with that of sedentary rats. The total length of microvessels in the white matter in the exercised group was significantly increased compared with that in the sedentary group in both males and females, but the total volume and total surface area of microvessels in the white matter did not differ significantly between the sedentary and exercised rats. Regular treadmill exercise had protective effects on spatial learning capacity, white matter volume, and the total length of microvessels in the white matter in middle-aged female rats and on the total length of microvessels in the white matter in middle-aged male rats. The results obtained might increase our understanding of the mechanisms by which exercise delays brain aging.

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.

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.

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.

Combined effectiveness of extracorporeal radial shockwave therapy and ultrasound-guided trigger point injection of lidocaine in upper trapezius myofascial pain syndrome.

OBJECTIVE: Myofascial pain syndrome (MPS) is a major musculoskeletal problem and a leading cause of disability worldwide. Extracorporeal shockwave therapy (ESWT) and trigger point injection (TPI) have shown positive results for MPS but no previous study has investigated the combined effects of radial shockwave and trigger point injection of lidocaine for upper trapezius myofascial pain syndrome. METHOD: For this purpose, forty-five participants were randomly divided into shockwave (n = 15), shockwave with ultrasound-guided trigger point injection (combined; n = 15), and control (standard care; n = 15) groups. Participants were assessed at baseline, one week and four weeks by using the visual analog scale, neck disability index, electromyography, infrared thermography, and sonoelastography. RESULTS: Compared with control group, both shockwave and combined groups showed a statistically significant reduction in pain (P<0.01), functional disability (P<0.01), skin temperature (P<0.01), and elastic stiffness, with greater reduction in the combined group (P<0.01) than shockwave group (P<0.05) at four weeks. However, no significant difference was found in electrical activity between the groups (P>0.05). The combined group also showed significant differences in pain (P<0.05) and elastic stiffness (P<0.01) compared with shockwave group at four weeks. CONCLUSION: Our study revealed that extracorporeal radial shockwave therapy combined with trigger point injection of lidocaine was more effective for decreasing pain and elastic stiffness in upper trapezius myofascial pain syndrome at four weeks.

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.

Cardiac Rehabilitation Programs for Chronic Heart Disease: A Bayesian Network Meta-analysis.

BACKGROUND: Cardiac rehabilitation is a medically supervised program after coronary events that involves exercise and dietary modification. We evaluated the comparative benefits and harms of cardiac rehabilitation strategies via a network meta-analysis. METHODS: We followed a pre-specified protocol (PROSPERO: CRD42018094998). We searched Embase, MEDLINE, and Cochrane Central Register of Randomized Trials databases for randomized controlled trials that evaluated cardiac rehabilitation vs a second form of rehabilitation or standard/usual care in adults after myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, or angiography. Risk of bias and evidence quality was evaluated using the Cochrane tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. Pairwise and Bayesian network meta-analyses were performed for 11 clinical outcomes. RESULTS: We included 134 randomized controlled trials involving 62,322 participants. Compared with standard care, exercise-only cardiac rehabilitation reduced the odds of cardiovascular mortality (odds ratio [OR], 0.70; 95% credibility interval [CrI], 0.51-0.96; moderate-quality evidence), major adverse cardiovascular events (OR, 0.57; 95% CrI, 0.40-0.78; low-quality evidence), nonfatal myocardial infarction (OR, 0.71; 95% CrI, 0.54-0.93; moderate-quality evidence), all-cause hospitalization (OR, 0.74; 95% CrI, 0.54-0.98; moderate-quality evidence), and cardiovascular hospitalization (OR, 0.69; 95% CrI, 0.51-0.88; moderate-quality evidence). Exercise-only cardiac rehabilitation was associated with lower cardiovascular hospitalization risk relative to cardiac rehabilitation without exercise (OR, 0.68; 95% CrI, 0.48-0.97; moderate-quality evidence). CONCLUSIONS: Cardiac rehabilitation programs containing exercise might provide broader cardiovascular benefits compared with those without exercise.

Long-Term Running Exercise Delays Age-Related Changes in White Matter in Rats.

Running exercise, one of the strategies to protect brain function, has positive effects on neurons and synapses in the cortex and hippocampus. However, white matter, as an important structure of the brain, is often overlooked, and the effects of long-term running exercise on white matter are unknown. Here, 14-month-old male Sprague-Dawley (SD) rats were divided into a middle-aged control group (18-month-old control group), an old control group (28-month-old control group), and a long-term runner group (28-month-old runner group). The rats in the runner group underwent a 14-month running exercise regime. Spatial learning ability was tested using the Morris water maze, and white matter volume, myelinated fiber parameters, total mature oligodendrocyte number, and white matter capillary parameters were investigated using stereological methods. The levels of growth factors related to nerve growth and vascular growth in peripheral blood and the level of neurite outgrowth inhibitor-A (Nogo-A) in white matter were measured using an enzyme-linked immunosorbent assay (ELISA). The present results indicated that long-term running exercise effectively delayed the age-related decline in spatial learning ability and the atrophy of white matter by protecting against age-related changes in myelinated fibers and oligodendrocytes in the white matter. Moreover, long-term running exercise prevented age-related changes in capillaries within white matter, which might be related to the protective effects of long-term exercise on aged white matter.

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).

Exercise-induced Nitric Oxide Contributes to Spatial Memory and Hippocampal Capillaries in Rats.

Exercise has been argued to improve cognitive function in both humans and rodents. Angiogenesis significantly contributes to brain health, including cognition. The hippocampus is a crucial brain region for cognitive function. However, studies quantifying the capillary changes in the hippocampus after running exercise are lacking. Moreover, the molecular details underlying the effects of running exercise remain poorly understood. We show that endogenous nitric oxide contributes to the beneficial effects of running exercise on cognition and hippocampal capillaries. Four weeks of running exercise significantly improved spatial memory ability and increased the number of capillaries in the cornu ammonis 1 subfield and dentate gyrus of Sprague-Dawley rats. Running exercise also significantly increased nitric oxide synthase activity and nitric oxide content in the rat hippocampus. After blocking the synthesis of endogenous nitric oxide by lateral ventricular injection of NG-nitro-L-arginine methyl ester, a nonspecific nitric oxide synthase inhibitor, the protective effect of running exercise on spatial memory was eliminated. The protective effect of running exercise on angiogenesis in the cornu ammonis 1 subfield and dentate gyrus of rats was also absent after nitric oxide synthase inhibition. Therefore, during running excise, endogenous nitric oxide may contribute to regulating spatial memory ability and angiogenesis in cornu ammonis 1 subfield and dentate gyrus of the hippocampus.

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.

Nonsurgical medical treatment in the management of pain due to lumbar disc prolapse: A network meta-analysis.

BACKGROUND: Evaluate the comparative effectiveness of treatment strategies for patients with pain due to lumbar disc prolapse (LDP). METHODS: PubMed, EMBASE, and the Cochrane Database were searched through September 2017. Randomized controlled trials on LDP reporting on pain intensity and/or global pain effects which compared included treatments head-to-head, against placebo, and/or against conventional care were included. Study data were independently double-extracted and data on patient traits and outcomes were collected. Risk of bias was assessed using the Cochrane risk of bias tool. Separate Bayesian network meta-analyses were undertaken to synthesize direct and indirect, short-term and long-term outcomes, summarized as odds ratios (OR) or weighted mean differences (WMD) with 95% credible intervals (CI) as well as surface under the cumulative ranking curve (SUCRA) values. RESULTS: 58 studies in global effects and 74 studies in pain intensity analysis were included. Thirty-eight (65.5%) of these studies reported a possible elevated risk of bias. Autonomic drugs and transforminal epidural steroid injections (TESIs) had the highest SUCRA scores at short-term follow up (86.7 and 83.5 respectively), while Cytokines/Immunomodulators and TESI had the highest SUCRA values at long-term-follow-up in the global effect's analysis (86.6 and 80.9 respectively). Caudal steroid injections and TESIs had the highest SUCRA scores at short-term follow up (79.4 and 75.9 respectively), while at long-term follow-up biological agents and manipulation had the highest SUCRA scores (86.4 and 68.5 respectively) for pain intensity. Some treatments had few studies and/or no associated placebo-controlled trials. Studies often did not report on co-interventions, systematically differed, and reported an overall elevated risk of bias. CONCLUSION: No treatment stands out as superior when compared on multiple outcomes and time periods but TESIs show promise as an effective short-term treatment. High quality studies are needed to confirm many nodes of this network meta-analysis.

Changes in white matter and the effects of fluoxetine on such changes in the CUS rat model of depression.

OBJECTIVE: To explore the pathogenesis of depression and the possible mechanism of the effects of selective serotonin reuptake inhibitors (SSRIs) on the myelinated fibers and myelin sheaths in the white matter during the antidepressant action of fluoxetine. METHODS: In this study, Sprague Dawley (SD) rats were divided into a Control group, a group treated with CUS and no drugs (CUS/Standard group) and a group treated with CUS and fluoxetine (CUS/FLX group). The CUS/FLX group was treated with fluoxetine at dose of 5 mg/kg for 21 days. The white matter volume, the myelinated fiber parameters and the myelin sheath volume in the white matter were calculated from transmission electron microscope images through unbiased stereological methods. RESULTS: The total volume and total length of myelinated fibers;and mean volume of white matter of the CUS/Standard group were significantly decreased compared to values from the control group (p = 0.025, p = 0.007, p = 0.000), whereas no significant differences in these stereological parameters were found between the CUS/Standard and CUS/FLX groups (p > 0.05). CONCLUSIONS: Fluoxetine successfully treated depression-like behavior but had no effects on the white matter or its component myelinated fibers in the CUS rat model of depression.