[The impacts of outpatient vs inpatient holistic management based on exercise training on cardiac rehabilitation efficacy among patients with chronic heart failure].

Objective: To evaluate the impacts of outpatient vs inpatient exercise training (ET) on cardiac rehabilitation efficacy among patients with chronic heart failure (CHF). Methods: Thirty six patients who were diagnosed with CHF in Beijing Rehabilitation Hospital from September 2015 to September 2018, were randomly divided into three groups: control group (n=12), outpatient ET group (n=12) and inpatient ET group (n=12). Patients in control group were treated with conventional cardiac rehabilitation without ET, patients in outpatient and inpatient ET groups were treated with holistic cardiac rehabilitation with the core of ET according to individualized exercise prescription based on cardiopulmonary exercise testing (CPET). Exercise intensity of cycle ergometer was Δ50% power above anaerobic threshold (AT), 30 min/d, 5 d/week, for 12 weeks. General information, CPET parameters, echocardiogram, 6 minute walking distance (6MWD) and quality of life (QoL) score of three groups of patients before and after treatment were recorded. Results: All patients in 3 groups finished symptom-limited CPET and patients in ET groups finished 12 weeks - ET safely without complications. Before treatment, there were no significant differences in CPET parameters, echocardiogram results, 6MWD and QoL score among 3 groups (P>0.05). After treatment, AT (ml/min, ml/(min·kg), %pred), peak oxygen uptake (VO2) (ml/min, ml/(min·kg), %pred), peak oxygen pulse(ml/beat), peak workload(W/min, %pred), left ventricular ejection fraction (LVEF) and 6MWD of patients in outpatient and inpatient ET groups were significantly higher than those of patients in control group (P<0.05), QoL score of patients in outpatient and inpatient ET groups was lower than that of patients in control group(P<0.05). To be noted, there were no obvious differences in CPET indexes, echocardiogram results, 6MWD and QoL score in patients between outpatient ET group and inpatient ET group (P>0.05). For patients in control group, there were no significant differences in above parameters before and after treatment (P>0.05). AT(ml/min, ml/(min·kg)), Peak VO2 (ml/min, ml/(min·kg), %pred), peak oxygen pulse(ml/beat, %pred), peak workload(W/min, %pred), LVEF and 6MWD of patients in outpatient and inpatient ET groups were significantly higher than those before treatment (P<0.05), QoL score of patients in outpatient and inpatient ET groups after treatment was significantly lower than that before treatment (P<0.05). Conclusion: Outpatient ET can improve the cardiopulmonary function, exercise tolerance and QoL of CHF patients, which has no significant difference compared with inpatient ET, indicating that outpatient cardiac rehabilitation, as an effective rehabilitation mode, is deserved to be applied widely.

Curcumin Ameliorates White Matter Injury after Ischemic Stroke by Inhibiting Microglia/Macrophage Pyroptosis through NF-κB Suppression and NLRP3 Inflammasome Inhibition.

NLRP3 inflammasome-mediated pyroptosis is a proinflammatory programmed cell death pathway, which plays a vital role in functional outcomes after stroke. We previously described the beneficial effects of curcumin against stroke-induced neuronal damage through modulating microglial polarization. However, the impact of curcumin on microglial pyroptosis remains unknown. Here, stroke was modeled in mice by middle cerebral artery occlusion (MCAO) for 60 minutes and treated with curcumin (150 mg/kg) intraperitoneally immediately after reperfusion, followed by daily administrations for 7 days. Curcumin ameliorated white matter (WM) lesions and brain tissue loss 21 days poststroke and improved sensorimotor function 3, 10, and 21 days after stroke. Furthermore, curcumin significantly reduced the number of gasdermin D+ (GSDMD+) Iba1+ and caspase-1+Iba1+ microglia/macrophage 21 days after stroke. In vitro, lipopolysaccharide (LPS) with ATP treatment was used to induce pyroptosis in primary microglia. Western blot revealed a decrease in pyroptosis-related proteins, e.g., GSDMD-N, cleaved caspase-1, NLRP3, IL-1ß, and IL-18, following in vitro or in vivo curcumin treatment. Mechanistically, both in vivo and in vitro studies confirmed that curcumin inhibited the activation of the NF-κB pathway. NLRP3 knocked down by siRNA transfection markedly increased the inhibitory effects of curcumin on microglial pyroptosis and proinflammatory responses, both in vitro and in vivo. Furthermore, stereotaxic microinjection of AAV-based NLRP3 shRNA significantly improved sensorimotor function and reduced WM lesion following curcumin treatment in MCAO mice. Our study suggested that curcumin reduced stroke-induced WM damage, improved functional outcomes, and attenuated microglial pyroptosis, at least partially, through suppression of the NF-κB/NLRP3 signaling pathway, further supporting curcumin as a potential therapeutic drug for stroke.

Baicalein ameliorates ischemic brain damage through suppressing proinflammatory microglia polarization via inhibiting the TLR4/NF-κB and STAT1 pathway.

Microglial polarization mediated neuroinflammation plays an important role in the pathological process of stroke. The aim of this study is to determine whether baicalein indirectly ameliorates neuronal injury through modulating microglial polarization after stroke and if so, then by what mechanism. The effects of baicalein on microglial polarization were revealed through the middle cerebral artery occlusion mouse model (MCAO, n = 6), the lipopolysaccharide (LPS) + interferon-γ (IFN-γ) and oxygen-glucose deprivation (OGD) induced neuroinflammatory microglia model (BV2, n = 3), respectively. Mice were treated with baicalein (100 mg/kg, i.g.) after reperfusion, and followed by daily administrations for 3 days. Results showed that the infarct volumes at 3 d in vehicle and baicalein-treated MCAO mice were 91.18 ± 4.02% and 55.36 ± 4.10%. Baicalein improved sensorimotor functions (p < 0.01) after MCAO. Real-time PCR revealed that baicalein decreased proinflammatory markers expression (p < 0.05), while elevated the anti-inflammatory markers (p < 0.05) in vivo and in vitro. Both western blot and immunofluorescent staining further confirmed that baicalein reduced proinflammatory marker CD16 levels (p < 0.01) and enhanced anti-inflammatory marker CD206 or Arg-1 levels (p < 0.05). Notably, baicalein suppressed the release of proinflammatory cytokines (p < 0.05) and nitric oxide (NO, p < 0.001). Mechanistically, baicalein prevented increases in TLR4 protein levels (p < 0.001), the phosphorylation of IKBα and p65 (p < 0.01), and the nuclear translocation of NF-κB p65 (p < 0.05). The NF-κB inhibitor, BAY 11-7085, enhanced the inhibitory effect of baicalein on the proinflammatory microglial polarization. Baicalein also inhibited the phosphorylation of signal transducer and activator of transcription 1 (STAT1, p < 0.001). A microglia-neuron co-culture system revealed that baicalein driven neuroprotection against OGD induced neuronal damage through modulating microglial polarization (p < 0.05). Baicalein indirectly ameliorates neuronal injury after stroke by polarizing microglia toward the anti-inflammatory phenotype via inhibition of the TLR4/NF-κB pathway and down-regulation of phosphorylated STAT1, suggesting that baicalein might serve a potential therapy for stroke.

Respiratory muscle endurance training with normocapnic hyperpnoea for patients with chronic spinal cord injury: A pilot short-term randomized controlled trial.

OBJECTIVE: To investigate the effects of normocapnic hyperpnoea training on pulmonary function and patient-reported outcomes in chronic spinal cord injury. DESIGN: Single-centre randomized controlled trial. PATIENTS: Eighteen patients with spinal cord injury > 24 months post-injury and without regular respiratory muscle training prior to the study were included prospectively. METHODS: Patients were randomly assigned to either normocapnic hyperpnoea or control groups. The normocapnic hyperpnoea group patients performed training 15-20 min per day, 5 times a week for 4 weeks. The patients hyperventilated through partial re-breathing of ventilated air. The control group received no respiratory muscle training. Other rehabilitative programmes were performed identically in both groups. Lung function testing was performed in the sitting position prior to and after the study. Patient-reported outcomes were assessed using the Patient Health Questionnaire-9, St George's Respiratory Questionnaire, Chronic Obstructive Pulmonary Disease Assessment Test and Borg scores. RESULTS: Significant differences were found in the improvement ratio between the normocapnic hyperpnoea and control groups for all investigated parameters, except total lung capacity and diffusing capacity of the lung for carbon monoxide. CONCLUSION: Normocapnic hyperpnoea training may reduce the incidence of respiratory symptoms, improve pulmonary function and quality of life, and reduce depression in patients with chronic spinal cord injury, regardless of their neurological level of injury, even at more than 24 months after injury.