Background: Cathepsin C (Cat C) functions as a central coordinator for activation of many serine proteases in inflammatory cells. It has been recognized that Cat C is responsible for neutrophil recruitment and production of chemokines and cytokines in many inflammatory diseases. However, Cat C expression and its functional role in the brain under normal conditions or in neuroinflammatory processes remain unclear. Our previous study showed that Cat C promoted the progress of brain demyelination in cuprizone-treated mice. The present study further investigated the Cat C expression and activity in lipopolysaccharide (LPS)-induced neuroinflammation in vivo and in vitro. Methods: C57BL/6 J mice were intraperitoneally injected with either 0.9% saline or lipopolysaccharide (LPS, 5 mg/kg). Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to analyze microglial activation, TNF-α, IL-1β, IL-6, iNOS mRNAs expressions and cellular localization of Cat C in the brain. Nitrite assay was used to examine microglial activation in vitro; RT-PCR and ELISA were used to determine the expression and release of Cat C. Cat C activity was analyzed by cellular Cat C assay kit. Data were evaluated for statistical significance with paired t test. Results: Cat C was predominantly expressed in hippocampal CA2 neurons in C57BL/6 J mice under normal conditions. Six hours after LPS injection, Cat C expression was detected in cerebral cortical neurons; whereas, twenty-four hours later, Cat C expression was captured in activated microglial cells throughout the entire brain. The duration of induced Cat C expression in neurons and in microglial cells was ten days and three days, respectively. In vitro, LPS, IL-1β and IL-6 treatments increased microglial Cat C expression in a dose-dependent manner and upregulated Cat C secretion and its activity. Conclusions: Taken together, these data indicate that LPS and proinflammatory cytokines IL-1β, IL-6 induce the expression, release and upregulate enzymatic activity of Cat C in microglial cells. Further investigation is required to determine the functional role of Cat C in the progression of neuroinflammation, which may have implications for therapeutics for the prevention of neuroinflammation-involved neurological disorders in the future.

Aims: The monocyte to high‐density lipoprotein cholesterol ratio (MHR) has emerged as a novel inflammatory biomarker of atherosclerotic cardiovascular disease. However, it has not yet been identified whether MHR can predict the long‐term prognosis of ischemic stroke. We aimed to investigate the associations of MHR levels with clinical outcomes in patients with ischemic stroke or transient ischemic attack (TIA) at 3 months and 1 year.Methods: We derived data from the Third China National Stroke Registry (CNSR‐III). Enrolled patients were divided into four groups by quartiles of MHR. Multivariable Cox regression for all‐cause death and stroke recurrence and logistic regression for the poor functional outcome (modified Rankin Scale score 3–6) were used.Results: Among 13,865 enrolled patients, the median MHR was 0.39 (interquartile range, 0.27–0.53). After adjustment for conventional confounding factors, the MHR level in quartile 4 was associated with an increased risk of all‐cause death (hazard ratio [HR], 1.45; 95% confidence interval [CI], 1.10–1.90), and poor functional outcome (odd ratio [OR], 1.47; 95% CI, 1.22–1.76), but not with stroke recurrence (HR, 1.02; 95% CI, 0.85–1.21) at 1 year follow‐up, compared with MHR level in quartile 1. Similar results were observed for outcomes at 3 months. The addition of MHR to a basic model including conventional factors improved predictive ability for all‐cause death and poor functional outcome validated by the C‐statistic and net reclassification index (all p < 0.05).Conclusions: Elevated MHR can independently predict all‐cause death and poor functional outcome in patients with ischemic stroke or TIA.

Background Continuous theta burst stimulation (cTBS) is a much more rapid protocol than low-frequency repetitive transcranial magnetic stimulation (rTMS), but no clinical trial has yet investigated the efficacy and mechanisms of cTBS for the treatment of generalized anxiety disorder. The purpose of this study was to compare the clinical effects and α oscillations induced by cTBS versus 1 Hz rTMS as predictors of response, and to assess the underlying mechanisms of the therapeutic effects of cTBS in patients with generalized anxiety disorder. Methods We randomly allocated 120 patients with generalized anxiety disorder to receive cTBS (n = 41), 1 Hz rTMS (n = 40) or sham cTBS (n = 39) over the right dorsolateral prefrontal cortex; we also included healthy controls (n = 30) to compare neurophysiological data. We analyzed changes in Hamilton Anxiety Rating Scale scores and α oscillations (frequency and power) at baseline, post-treatment and 1-month follow-up. Results After 20 sessions of treatment, patients’ anxiety had improved and α power had increased in the cTBS and 1 Hz rTMS groups. However, at 1-month follow-up the cTBS group had significantly more responders and remitters, and higher α oscillations than the 1 Hz rTMS group (post hoc analysis: cTBS > rTMS > sham). At baseline, α frequency was inversely correlated with psychological symptom scores on the Hamilton Anxiety Rating Scale (r = −0.613, p < 0.001); post-treatment, this correlation was present only in the cTBS group (r = −0.685, p < 0.001). Limitations Electroencephalography data were limited to the α band. Conclusion Our findings provide evidence for the clinical use of cTBS, a novel brain stimulation protocol. Its therapeutic effects may be the result of increasing α frequency, thereby improving the psychological symptoms of generalized anxiety disorder.

Introduction: Tai Chi standing meditation (Zhan Zhuang, also called pile standing) is characterized by meditation, deep breathing, and mental focus based on theories of traditional Chinese medicine. The purpose of the present study was to explore prefrontal cortical hemodynamics and the functional network organization associated with Tai Chi standing meditation by using functional near-infrared spectroscopy (fNIRS).Methods: Twenty-four channel fNIRS signals were recorded from 24 male Tai Chi Quan practitioners (54.71 ± 8.04 years) while standing at rest and standing during Tai Chi meditation. The general linear model and the SPM method were used to analyze the fNIRS signals. Pearson correlation was calculated to determine the functional connectivity between the prefrontal cortical sub-regions. The small world properties of the FC networks were then further analyzed based on graph theory.Results: During Tai Chi standing meditation, significantly higher concentrations of oxygenated hemoglobin were observed in bilateral dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), frontal eye field (FEF), and pre-motor cortex (PMC) compared with the values measured during standing rest (p < 0.05). Simultaneously, significant decreases in deoxygenated hemoglobin concentration were observed in left VLPFC, right PMC and DLPFC during Tai Chi standing meditation than during standing rest (p < 0.05). Functional connectivity between the left and right PFC was also significantly stronger during the Tai Chi standing meditation (p < 0.05). The functional brain networks exhibited small-world architecture, and more network hubs located in DLPFC and VLPFC were identified during Tai Chi standing meditation than during standing rest.Discussion: These findings suggest that Tai Chi standing meditation introduces significant changes in the cortical blood flow and the brain functional network organization.