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Objective: This study aims to explore how Grem1 regulates the differentiation and signaling activity of mandibular bone marrow mesenchymal stem cells (MBMSCs), affecting their osteogenic differentiation capacity and participating in the pathophysiological mechanism of postmenopausal mandibular osteoporosis. Materials and methods: A postmenopausal osteoporosis (POP) rat model was constructed via bilateral ovariectomy. Techniques such as Western Blot (WB) and Real-Time Quantitative PCR (RT-qPCR) were employed to determine changes in Grem1 expression in MBMSCs of postmenopausal rats and its effect on osteogenic differentiation. Plasmids for Grem1 overexpression and siRNA for Grem1 knockdown were transfected into MBMSCs, and WB was used to assess the regulatory role of Grem1 on MBMSCs osteogenic differentiation. Results: Grem1 expression was significantly elevated in the MBMSCs and mandibular tissues of POP rats, accompanied by inhibited osteogenic differentiation. Grem1 levels were inversely proportional to osteogenic capacity and BMP/Smad1/5 signaling activity. BMP-2 alleviated Grem1's inhibitory effects on the BMP/Smad1/5 pathway, influencing MBMSCs' osteogenic differentiation. Upregulating Grem1 in MBMSCs suppressed BMP/Smad1/5 pathway activity and osteogenic differentiation, while Grem1 knockdown restored these processes in the OVX group. Conclusion: Grem1 reduces osteogenic capacity in mandibular POP rats by inhibiting the BMP/Smad1/5 signaling pathway. Targeting Grem1 or enhancing BMP/Smad1/5 signaling activity may improve mandibular bone health in osteoporosis patients.

Abstract Peripheral immune cells play a vital role in the development of Parkinson’s disease (PD). However, their cytokine and chemokine secretion functions remain unclear. Therefore, we aimed to explore the cytokine and chemokine secretion functions of specific immune cell subtypes in drug-naïve patients with PD at different ages of onset. We included 10 early-onset and 10 late-onset patients with PD and age-matched healthy controls (HCs). We used mass cytometry to select specific immune cell subsets and evaluate intracellular cytokine and chemokine expression. Statistical tests included t-tests, analysis of variance, bivariate correlation analysis, and linear regression analysis. Compared with HCs, patients with PD exhibited significantly decreased intracellular pro-inflammatory cytokines and chemokines in selected clusters (e.g., tumor necrosis factor (TNF)-α, interleukin (IL)−8, IL-1β, and CC-chemokine ligand (CCL)17). Specific cytokines and cell clusters were associated with clinical symptoms. TNF-α played an important role in cognitive impairment. Intracellular TNF-α levels in the naïve CD8+ T-cell cluster C16 (CD57− naïve CD8+ T) and natural killer (NK) cell cluster C32 (CD57− CD28− NK) were negatively correlated with Montreal Cognitive Assessment scores. The C16 cluster affected cognitive function and motor symptoms. Increased TNF-α and decreased interferon-γ expression in C16 correlated with increased Unified Parkinson’s Disease Rating Scale III scores in patients with PD. In summary, we developed a more detailed cytokine and chemokine map of peripheral specific CD8+ T cell and NK cell subsets, which revealed disrupted secretory function in patients with PD and provided unique clues for further mechanistic exploration.

Abstract Background Mindfulness-based cognitive therapy (MBCT) is a promising alternative treatment for generalized anxiety disorder (GAD). The objective of this study was to examine whether the efficacy of group MBCT adapted for treating GAD (MBCT-A) was noninferior to group cognitive behavioural therapy (CBT) designed to treat GAD (CBT-A), which was considered one of first-line treatments for GAD patients. We also explored the efficacy of MBCT-A in symptomatic GAD patients compared with CBT-A for a variety of outcomes of anxiety symptoms, as well as depressive symptoms, overall illness severity, quality of life and mindfulness. Methods This was a randomized, controlled, noninferiority trial with two arms involving symptomatic GAD patients. Adult patients with GAD (n = 138) were randomized to MBCT-A or CBT-A in addition to treatment as usual (TAU). The primary outcome was the anxiety response rate assessed at 8 weeks after treatment as measured using the Hamilton Anxiety Scale (HAMA). Secondary outcomes included anxiety remission rates, scores on the HAMA, the state-trait anxiety inventory (STAI), the Hamilton Depression Scale (HAMD), the Severity Subscale of the Clinical Global Impression Scale (CGI-S), and the 12-item Short-Form Health Survey (SF-12), as well as mindfulness, which was measured by the Five Facet Mindfulness Questionnaire (FFMQ). Assessments were performed at baseline, 8 weeks after treatment, and 3 months after treatment. Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed for primary analyses. The χ2 test and separate two-way mixed ANOVAs were used for the secondary analyses. Results ITT and PP analyses showed noninferiority of MBCT-A compared with CBT-A for response rate [ITT rate difference = 7.25% (95% CI: -8.16, 22.65); PP rate difference = 5.85% (95% CI: − 7.83, 19.53)]. The anxiety remission rate, overall illness severity and mindfulness were significantly different between the two groups at 8 weeks. There were no significant differences between the two groups at the 3-month follow-up. No severe adverse events were identified. Conclusions Our data indicate that MBCT-A was noninferior to CBT-A in reducing anxiety symptoms in GAD patients. Both interventions appeared to be effective for long-term benefits. Trial registration Registered at chictr.org.cn (registration number: ChiCTR1800019150 , registration date: 27/10/2018).

Abstract Recent evidence suggests that innate and adaptive immunity play a crucial role in Parkinson’s disease (PD). However, studies regarding specific immune cell classification in the peripheral blood in PD remain lacking. Therefore, we aimed to explore the different immune status in patients with PD at different ages of onset. We included 22 patients; among them were 10 who had early-onset PD (EOPD) and 12 had late-onset PD (LOPD) and 10 young healthy controls (YHCs) and 8 elder HCs (EHCs). Mass cytometry staining technology was used to perform accurate immunotyping of cell populations in the peripheral blood. Motor symptoms and cognitive function were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) III score and Mini-mental State Examination (MMSE) score, respectively. T test and ANOVA statistical analysis were performed on the frequency of annotated cell population. Linear regression model was used to analyze the correlation between clusters and clinical symptoms. We characterized 60 cell clusters and discovered that the immune signature of PD consists of cluster changes, including decreased effector CD8+ T cells, lower cytotoxicity natural killer (NK) cells and increased activated monocytes in PD patients. In summary, we found that CD8+ T cells, NK cells, and monocytes were associated with PD. Furthermore, there may be some differences in the immune status of patients with EOPD and LOPD, suggesting differences in the pathogenesis between these groups.

BackgroundParkinson's disease (PD) and dystonia are closely related in terms of pathophysiology and clinical manifestations, but their common genetic characteristics remain unclear. Some genome-wide association studies (GWASs) and replication studies have revealed correlations between single nucleotide polymorphisms (SNPs) of the ARSG, BDNF, NALCN, OR4X2, KIAA1715, and OR4B1 genes and dystonia. This study was conducted to assess the association between these genetic loci and PD in a population from Eastern China.MethodsWe genotyped the SNPs (rs11655081 of ARSG; rs6265 of BDNF; rs61973742, rs1338051, rs9518384, and rs9518385 of NALCN; rs67863238 of OR4X2; rs10930717 of KIAA1715; and rs35875350 of OR4B1) in a cohort of 474 patients with PD and 439 healthy controls from East China. To determine the genotypes of these SNPs, we used an Agena MassARRAY Typer 4.0. Odds ratios (ORs) and 95% CIs were computed to evaluate the correlations between these SNPs and the risk of PD.ResultsThere were significant differences in the genotype distribution (OR = 0.649, 95% CI = 0.478–0.880) and minor allele frequency (MAF) (OR = 0.703, 95% CI = 0.533–0.929) of SNP rs61973742 (NALCN) between patients with PD and healthy controls. A significant difference was detected in the genotype distribution of rs11655081 (ARSG) (OR = 1.486, 95% CI = 1.080–2.045).ConclusionSingle nucleotide polymorphisms rs11655081 (ARSG) and rs61973742 (NALCN) may be associated with PD. The C allele of rs11655081 may increase the risk of PD, whereas the G allele of rs61973742 may be a protective factor.

Purpose: To investigate health behaviours and family function in stroke survivors, and evaluate the relationships among them. Methods: Patients who were diagnosed with stroke before and went back to neurology clinic between August 2011 and February 2012 in a tertiary hospital in Guangzhou, China were recruited for this study. Patients that were discharged and living at home for at least two months were asked to complete Family Assessment Device (FAD) and Health Promoting Lifestyle Profile, version II (HPLP-II) questionnaires. Individual items were scored between 1 and 4 points, and survey scores were compared and analysed using Pearson's correlations. Results: The mean overall FAD family function score was 2.18 ± 0.25 points, with lower scores observed for problem solving and role function factors, and higher scores for communication, affection involvement, and behaviour control. The mean overall HPLP-II health behaviour score was 2.27 ± 0.36 points, with the highest score for the nutrition factor, and the lowest score for the exercise factor. The total score of family function negatively correlated with health behaviours (r = −0.535, p