LncRNA NPTN-IT1-201 Ameliorates Depressive-like Behavior by Targeting miR-142-5p and Regulating Inflammation and Apoptosis via BDNF.

OBJECTIVE: Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are widely expressed in the brain and are associated with the development of neurological and neurodegenerative diseases. However, their roles and molecular mechanisms in major depressive disorder (MDD) remain largely unknown. This study aimed to identify lncRNAs and miRNAs involved in the development of MDD and elucidate their molecular mechanisms. METHODS: Transcriptome and bioinformatic analyses were performed to identify miRNAs and lncRNAs related to MDD. C57 mice were subjected to chronic unpredictable mild stress (CUMS) to establish a depression model. Lentiviruses containing either lncRNA NPTN-IT1-201 or miR-142-5p were microinjected into the hippocampal region of these mice. Behavioral tests including the sucrose preference test (SPT), tail suspension test (TST), and forced swim test (FST) were conducted to evaluate depressive-like behaviors. RESULTS: The results revealed that overexpression of lncRNA NPTN-IT1-201 or inhibition of miR-142-5p significantly ameliorated depressive-like behaviors in CUMS-treated mice. Dual-luciferase reporter assays confirmed interactions between miR-142-5p with both brain-derived neurotrophic factor (BDNF) and NPTN-IT1-201. ELISA analysis revealed significant alterations in relevant biomarkers in the blood samples of MDD patients compared to healthy controls. Histological analyses, including HE and Nissl staining, showed marked structural changes in brain tissues following CUMS treatment, which were partially reversed by lncRNA NPTN-IT1-201 overexpression or miR-142-5p inhibition. Immunofluorescence imaging demonstrated significant differences in the levels of BAX, Bcl2, p65, Iba1 among different treatment groups. TUNEL assays confirmed reduced apoptosis in brain tissues following these interventions. Western blotting showed the significant differences in BDNF, BAX, and Bcl2 protein levels among different treatment groups. CONCLUSION: NPTN-IT1-201 regulates inflammation and apoptosis in MDD by targeting BDNF via miR-142-5p, making it a potential therapeutic target for MDD.

Exercise-Induced Oxygen Desaturation Increases Arterial Stiffness in Patients with COPD During the 6WMT.

Objective: Given the established impact of exercise in reducing arterial stiffness and the potential for intermittent hypoxia to induce its elevation, this study aims to understand how oxygen desaturation during exercise affects arterial stiffness in individuals with COPD. Methods: We enrolled patients with stable COPD from China-Japan Friendship Hospital from November 2022 to June 2023. The 6-minute walk test (6-MWT) was performed with continuous blood oxygen saturation (SpO2) monitoring in these patients. The patients were classified into three groups: non-exercise induced desaturation (EID), mild-EID and severe-EID, according to the changes in SpO2 during the 6-MWT. The Cardio-Ankle Vascular Index (CAVI) and the change in CAVI (ΔCAVI, calculated as CAVI before 6MWT minus CAVI after the 6MWT) were measured before and immediately after the 6MWT to assess the acute effects of exercise on arterial stiffness. GOLD Stage, pulmonary function, and other functional outcomes were also measured in this study. Results: A total of 37 patients with stable COPD underwent evaluation for changes in CAVI (ΔCAVI) before and after the 6-MWT. Stratification based on revealed three subgroups: non-EID (n=12), mild-EID (n=15), and severe-EID (n=10). The ΔCAVI values was -0.53 (-0.95 to -0.31) in non-EID group, -0.20 (-1.45 to 0.50) in mild-EID group, 0.6 (0.08 to 0.73) in severe-EID group. Parametric tests indicated significant differences in ΔCAVI among EID groups (p = 0.005). Pairwise comparisons demonstrated significant distinctions between mild-EID and severe-EID groups, as well as between non-EID and severe-EID groups (p = 0.048 and p = 0.003, respectively). Multivariable analysis, adjusting for age, sex, GOLD stage, diffusion capacity, and blood pressure, identified severe-EID as an independent factor associated with ΔCAVI (B = 1.118, p = 0.038). Conclusion: Patients with COPD and severe-EID may experience worsening arterial stiffness even during short periods of exercise.

Developing and validating prediction models for severe exacerbations and readmissions in patients hospitalised for COPD exacerbation (SERCO) in China: a prospective observational study.

BACKGROUND: There is a lack of individualised prediction models for patients hospitalised with chronic obstructive pulmonary disease (COPD) for clinical practice. We developed and validated prediction models of severe exacerbations and readmissions in patients hospitalised for COPD exacerbation (SERCO). METHODS: Data were obtained from the Acute Exacerbations of Chronic Obstructive Pulmonary Disease Inpatient Registry study (NCT02657525) in China. Cause-specific hazard models were used to estimate coefficients. C-statistic was used to evaluate the discrimination. Slope and intercept were used to evaluate the calibration and used for model adjustment. Models were validated internally by 10-fold cross-validation and externally using data from different regions. Risk-stratified scoring scales and nomograms were provided. The discrimination ability of the SERCO model was compared with the exacerbation history in the previous year. RESULTS: Two sets with 2196 and 1869 patients from different geographical regions were used for model development and external validation. The 12-month severe exacerbations cumulative incidence rates were 11.55% (95% CI 10.06% to 13.16%) in development cohorts and 12.30% (95% CI 10.67% to 14.05%) in validation cohorts. The COPD-specific readmission incidence rates were 11.31% (95% CI 9.83% to 12.91%) and 12.26% (95% CI 10.63% to 14.02%), respectively. Demographic characteristics, medical history, comorbidities, drug usage, Global Initiative for Chronic Obstructive Lung Disease stage and interactions were included as predictors. C-indexes for severe exacerbations were 77.3 (95% CI 70.7 to 83.9), 76.5 (95% CI 72.6 to 80.4) and 74.7 (95% CI 71.2 to 78.2) at 1, 6 and 12 months. The corresponding values for readmissions were 77.1 (95% CI 70.1 to 84.0), 76.3 (95% CI 72.3 to 80.4) and 74.5 (95% CI 71.0 to 78.0). The SERCO model was consistently discriminative and accurate with C-indexes in the derivation and internal validation groups. In external validation, the C-indexes were relatively lower at 60-70 levels. The SERCO model discriminated outcomes better than prior severe exacerbation history. The slope and intercept after adjustment showed close agreement between predicted and observed risks. However, in external validation, the models may overestimate the risk in higher-risk groups. The model-driven risk groups showed significant disparities in prognosis. CONCLUSION: The SERCO model provides individual predictions for severe exacerbation and COPD-specific readmission risk, which enables identifying high-risk patients and implementing personalised preventive intervention for patients with COPD.

Efficacy and safety of a music-therapy facilitated pulmonary telerehabilitation program in COPD patients: the COPDMELODY study protocol.

Despite considerable evidence for the benefit in chronic obstructive pulmonary disease (COPD), the implementation of pulmonary rehabilitation (PR) is insufficient. However, music therapy may help address this gap due to its unique benefits. Therefore, we aimed to develop a music-therapy facilitated pulmonary telerehabilitation program based on rhythm-guided walking, singing, and objective telemonitoring. A supervised, parallel-group, single-blinded, randomized controlled clinical trial will be conducted, including 75 patients with COPD anticipated to be randomized in a 1:1:1 ratio into three groups. The intervention groups will receive a 12-week remotely monitored rehabilitation program, while the usual care group will not receive any rehabilitation interventions. Of the two intervention groups, the multi-module music therapy group will contain rhythm-guided walking and singing training, while the rhythm-guided walking group will only include music tempo-guided walking. The primary outcome is the distance of the incremental shuttle walking test. Secondary outcomes include respiratory muscle function, spirometry, lower extremity function, symptoms, quality of life, anxiety and depression levels, physical activity level, training adherence, and safety measurements. The results of this study can contribute to develop and evaluate a home-based music-facilitated rehabilitation program, which has the potential to act as a supplement and/or substitute (according to the needs) for traditional center-based PR in patients with stable COPD. Clinical trial registration: https://classic.clinicaltrials.gov/, NCT05832814.

Sociodemographic correlates with prevalence of comorbidities in patients with chronic obstructive pulmonary disease: a study from a Chinese National Survey.

Background: An increase in the prevalence of comorbidities has been reported in patients with chronic obstructive pulmonary disease (COPD). However, contemporary estimates of the overall prevalence of the sociodemographic correlates of COPD comorbidities are scarce and inconsistent in China. This study aimed to investigate the prevalence of sociodemographic correlates of comorbidities in patients with COPD across China. Methods: This was a cross-sectional study. We used data from the Enjoying Breathing Program between May 2020 and April 2022. Participants with COPD from 17 provinces (or equivalent) were included. Comorbidity clusters were stratified based on the number of comorbidities per person. Univariable and multivariable analyses were used to determine the sociodemographic associations of patients with COPD with specific clusters of comorbidities after adjusting for age, sex, and other prespecified covariates. Tetrachoric correlation analyses were performed to determine the associations between specific comorbidities. Findings: A total of 3913 participants with COPD were included, of whom 1744 (44.7%) had at least one comorbidity; 25.4% had one comorbid disease, 12.9% had two, and 6.4% had three or more concurrent diseases. The most common comorbidities were hypertension (17.8%), asthma (9.9%), bronchiectasis (8.2%), diabetes (8.2%), and coronary artery disease (7.7%). In the logistic regression models adjusted for a broad set of factors, patients with COPD residing in the east region of China and having health insurance experienced a decreased likelihood of comorbidities (from OR = 0.70 [95% confidence interval [CI], 0.53-0.93] to OR = 0.50 [95% CI, 0.25-0.99]). However, patients over 80 years had increased risk (OR 1.43 [95% CI 1.01-2.03]), as did those in all Modified Medical Research Council (mMRC) grade categories (grade 1: OR = 1.30 [95% CI, 1.02-1.65]; grade 2: OR = 1.39 [95% CI, 1.07-1.8]; grade 3: OR = 1.67 [95% CI, 1.23-2.26]; and grade 4: OR = 1.81 [95% CI, 1.00-3.28]) and in Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 classification (OR = 1.30 [95% CI, 1.03-1.65]) relative to their respective references. The associations observed in these subgroups were consistent regardless of the number of comorbidities per person. Tetrachoric correlations demonstrated negative associations in pairwise comparisons of the top five comorbidities, ranging from -0.03 to -0.31 (p < 0.001 in all groups). Interpretation: In China, comorbidities are highly prevalent among patients with COPD, with older age, higher mMRC grade, and lung function decline being the major risk factors. Studies with larger sample sizes are required to elucidate the complex mechanisms underlying COPD comorbidities. Funding: This study was funded by CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-049 and 2022-I2M-C&T-B-107).

Influence of a diet and/or exercise intervention on long-term mortality and vascular complications in people with impaired glucose tolerance: Da Qing Diabetes Prevention Outcome study.

AIM: We aimed to investigate the long-term influence of a diet and/or exercise intervention on long-term mortality and cardiovascular disease (CVD) events. METHODS: The Da Qing Diabetes Prevention Study had 576 participants with impaired glucose tolerance (IGT) randomized to diet-only, exercise-only and diet-plus-exercise intervention group and control group. The participants underwent lifestyle interventions for 6 years. The subsequent Da Qing Diabetes Prevention Outcome Study was a prospective cohort study to follow-up the participants for up to 24 years after the end of 6-year intervention. In total, 540 participants completed the follow-up, while 36 subjects lost in follow-up. Cox proportional hazards analysis was applied to assess the influence of lifestyle interventions on targeted outcomes. RESULTS: Compared with controls, the diet-only intervention in people with IGT was significantly associated with a reduced risk of all-cause death [hazard ratio (HR) 0.77, 95% confidence interval (CI) (0.61-0.97)], CVD death [HR 0.67, 95% CI (0.46-0.97)] and CVD events [HR 0.72, 95% CI (0.54-0.96)]. The diet-plus-exercise intervention was significantly associated with a decreased risk of all-cause death [HR 0.64, 95% CI (0.48-0.84)], CVD death [HR 0.54, 95% CI (0.30-0.97)] and CVD events [HR 0.68, 95% CI (0.52-0.90)]. Unexpectedly, the exercise-only intervention was not significantly associated with the reduction of any of these outcomes, although there was a consistent trend towards reduction. CONCLUSIONS: A diet-only intervention and a diet-plus-exercise intervention in people with IGT were significantly associated with a reduced risk of all-cause death, CVD death and CVD events, while an exercise-only intervention was not. It suggests that diet-related interventions may have a potentially more reliable influence on long-term vascular complications and mortality.

Integrated analysis of transcriptome and metabolome reveals the regulatory mechanism of largemouth bass (Micropterus salmoides) in response to Nocardia seriolae infection.

Nocardia seriolae is a severe bacterial pathogen that has seriously affected the development of aquaculture industry. Largemouth bass (Micropterus salmoides) is a commercially significant freshwater fish that suffers a variety of environmental threats, including bacterial pathogens. However, the immune responses and metabolic alterations of largemouth bass to N. seriolae infection remain largely unclear. We discovered that N. seriolae caused pathological alterations in largemouth bass and shifted the transcript of immune-related and apoptotic genes in head kidney after infection. To answer the aforementioned question, a combined transcriptome and metabolome analysis was employed to explore the alterations in genes, metabolites, and metabolic pathways in largemouth bass following bacterial infection. A total of 3579 genes and 1929 metabolites are significant differentially changed in the head kidney post infection. In response to N. seriolae infection, host modifies the PI3K-Akt signaling pathway, TCA cycle, glycolysis, and amino acid metabolism. The integrated analysis of transcriptome and metabolome suggested that with the arginine metabolism pathway as the core, multiple biomarkers (arg gene, arginine) are involved in the antibacterial and immune functions of largemouth bass. Thus, we hypothesized that arginine plays a crucial role in the immune responses of largemouth bass against N. seriolae infection, and increasing arginine levels suitably is beneficial for the host against bacterial infection. Our results shed light on the regulatory mechanism of largemouth bass resistance to N. seriolae infection and contributed to the development of more effective N. seriolae resistance strategies.