Enhanced Cardiomyocyte NLRP3 Inflammasome-Mediated Pyroptosis Promotes d-Galactose-Induced Cardiac Aging.

BACKGROUND: Cardiac aging represents an independent risk factor for aging-associated cardiovascular diseases. Although evidence suggests an association between NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome formation and numerous cardiovascular diseases, its role in cardiac aging remains largely unclear. METHODS AND RESULTS: The longevity of mice with wild-type and NLRP3 knockout (NLRP3-/-) genotypes was assessed, with or without d-galactose treatment. Cardiac function was evaluated using echocardiography, and cardiac histopathology was examined through hematoxylin and eosin and Masson's trichrome staining. Senescence-associated ß-galactosidase (SA-ß-gal) staining was employed to detect cardiac aging. Western blotting was used to assess aging-related proteins (p53, p21) and pyroptosis-related proteins. Additionally, dihydroethidium staining, lactate dehydrogenase release, and interleukin-1ß ELISA assays were performed, along with measurements of total superoxide dismutase and malondialdehyde levels. In vitro, H9c2 cells were exposed to d-galactose for 24 hours in the absence or presence of N-acetyl-l-cysteine (reactive oxygen species inhibitor), BAY-117082 (nuclear factor κ-light-chain enhancer of activated B cells inhibitor), MCC950 (NLRP3 inhibitor), and VX-765 (Caspase-1 inhibitor). Immunofluorescence staining was employed to detect p53, gasdermin D, and apoptosis-associated speck-like protein proteins. Intracellular reactive oxygen species levels were assessed using fluorescence microscopy and flow cytometry. Senescence-associated ß-galactosidase staining and Western blotting were also employed in vitro for the same purpose. The results showed that NLRP3 upregulation was implicated in aging and cardiovascular diseases. Inhibition of NLRP3 extended life span, mitigated the aging phenotype, improved cardiac function and blood pressure, ameliorated lipid metabolism abnormalities, inhibited pyroptosis in cardiomyocytes, and ultimately alleviated cardiac aging. In vitro, the inhibition of reactive oxygen species, nuclear factor κ-light-chain enhancer of activated B cells, NLRP3, or caspase-1 attenuated NLRP3 inflammasome-mediated pyroptosis. CONCLUSIONS: The reactive oxygen species/nuclear factor κ-light-chain enhancer of activated B cells/NLRP3 signaling pathway loop contributes to d-galactose-treated cardiomyocyte senescence and cardiac aging.

[Interaction between depression and insomnia under acupuncture treatment: a secondary analysis of a randomized controlled trial].

OBJECTIVE: To explore the interaction between emotional and insomnia symptom improvement in comorbid depression and insomnia patients treated with optimized acupuncture. METHODS: A secondary analysis was conducted on a multicenter randomized controlled trial of acupuncture treatment for comorbid depression and insomnia. One hundred and forty patients with comorbid depression and insomnia were randomly assigned to an optimized acupuncture group (70 cases, 8 cases dropped out) and a conventional acupuncture group (70 cases, 8 cases dropped out). The patients in the conventional acupuncture group were treated with acupuncture at Yintang (GV 24+), Baihui (GV 20), bilateral Hegu (LI 4) and Taichong (LR 3); the patients in the optimized acupuncture group were treated with additional acupuncture at bilateral Lieque (LU 7), Zhaohai (KI 6), and intradermal needling was applied alternately at bilateral Xinshu (BL 15) and Danshu (BL 19), Shenshu (BL 23) and Anmian (Extra). Both groups received treatments twice a week for six weeks. The Hamilton depression scale-24 (HAMD-24) and Pittsburgh sleep quality index (PSQI) scores were observed before and after treatment for both groups. Mediation analysis was used to assess the mesomeric effect of PSQI and HAMD-24 emotional factors, and latent profile analysis categorized patients into subgroups based on HAMD-24 scores, followed by between-group efficacy comparisons. RESULTS: The indirect effect of the optimized acupuncture on improving depression emotions through PSQI was 3.052 (95%CI [1.407, 4.697]), accounting for 77.5% of the total effect. Conversely, the indirect effect of improving PSQI through the optimized protocol on depression emotions was 0.479 (95%CI [0.024, 0.935]), representing 14.8% of the total effect. Latent profile analysis identified 3 categories based on emotional and insomnia symptoms, and statistically significant differences in efficacy favoring the optimized acupuncture protocol over the conventional acupuncture protocol were observed only in the subgroup with relatively mild depression and insomnia symptoms (PSQI: 95%CI [-10.98, -5.44], P<0.001; HAMD-24: 95%CI [-12.31, -3.73], P =0.001). CONCLUSION: The optimized acupuncture protocol primarily improves insomnia symptoms and further improves depression emotions. Its efficacy advantages are more evident in patients with mild symptoms compared with the conventional acupuncture protocol.

Protocol for a randomized controlled trial exploring the brain mechanism and therapeutic effect of electroacupuncture on cognitive function and sleep quality in chronic insomnia.

BACKGROUND: Insomnia is a prevalent sleep disorder that affects up to 15% of the population worldwide and is the second most common mental health issue. There is increasing interest in the effects of long-term insomnia on cognitive function. Electroacupuncture can effectively improve cognitive function and sleep quality, yet the underlying brain network mechanisms remain unclear. This study aims to explore the network regulatory mechanisms associated with enhanced cognitive function and sleep quality, providing theoretical support for the use of electroacupuncture in the clinical treatment of chronic insomnia. METHODS: This study is divided into two parts. Sixteen individuals with chronic insomnia and 16 healthy controls of similar age and gender will be recruited in Study 1 to examine the brain network topology of individuals with chronic insomnia. Study 2 will be a randomized controlled trial with 120 chronic insomnia patients divided into three groups: Group A (electroacupuncture plus placebo drug), Group B (drug plus placebo electroacupuncture), and Group C (placebo electroacupuncture plus placebo drug). Participants will be exposed to 24 treatments over an 8-week period (3 times per week) and monitored for 12 additional weeks. The primary outcome measure will be changes in brainwave data from before to after the treatment. In addition, the Wisconsin Card Sorting Test and the Pittsburgh Sleep Quality Index will be utilized as secondary outcomes to measure from before to after treatment and during the follow-up. A correlation analysis will be conducted to explore links among modifications in brainwave patterns, Wisconsin Card Sorting Test scores, and Pittsburgh Sleep Quality Index scores. Additionally, any adverse events will be strictly monitored. DISCUSSION: Electroacupuncture may represent an alternative treatment for chronic insomnia, and this trial is expected to reveal the brain mechanism by which electroacupuncture improves cognitive function and sleep quality in chronic insomnia patients. TRIAL REGISTRATION: ChiCTR2200060150 (Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 20 May 2022).

D-galactose-induced cardiac ageing: A review of model establishment and potential interventions.

Cardiovascular disease (CVD) is highly prevalent in an ageing society. The increased incidence and mortality rates of CVD are global issues endangering human health. There is an urgent requirement for understanding the aetiology and pathogenesis of CVD and developing possible interventions for preventing CVD in ageing hearts. It is necessary to select appropriate models and treatment methods. The D-galactose-induced cardiac ageing model possesses the advantages of low mortality, short time and low cost and has been increasingly used in the study of cardiovascular diseases in recent years. Therefore, understanding the latest progress in D-galactose-induced cardiac ageing is valuable. This review highlights the recent progress and potential therapeutic interventions used in D-galactose-induced cardiac ageing in recent years by providing a comprehensive summary of D-galactose-induced cardiac ageing in vivo and in vitro. This review may serve as reference literature for future research on age-related heart diseases.

Hypertension and Atrial Fibrillation: A Study on Epidemiology and Mendelian Randomization Causality.

Introduction: Hypertension (HT) and atrial fibrillation (AF) often coexist. However, the causality between these two conditions remains to be determined. Methods: We used individual participant data from the Atherosclerosis Risk in Communities (ARIC) prospective cohort with 9,474 participants. HT was ascertained at visit 1 (1987-1989), and incident AF was identified by ECGs conducted during study examinations at each visit, hospital discharge codes, and death certificates. We used the Kaplan-Meier estimate to compute the cumulative incidence of AF by the HT subgroup. Then we used Cox hazard regression model to assess the association between HT and incident AF. The causality between genetically determined HT and AF was analyzed by the two-sample Mendelian randomization (MR) based on publicly summarized genome-wide association studies (GWASs) data. Results: A total of 1,414 cases (14.9%) of AF were identified during the follow-up period (median 24.1 years). After adjusting for all covariates, the hazard ratio between the participants with HT and incident AF was 1.50 [95% confidence interval (CI) 1.29-1.73]. In the HT → AF MR analysis, we detected a causal correlation between HT and AF (OR: 1.90, 95% CI 1.18-3.04, P = 0.01) with no evidence of heterogeneity from single-nucleotide polymorphisms. Besides, the genetically determined SBP and DBP (10 mmHg) were consistently associated with a higher risk of AF. Conclusions: In the ARIC study, the incident AF increased by 50% in patients with HT. In the MR analysis, our results supported causal inference between HT and AF.

Neuroimaging mechanisms of high-frequency repetitive transcranial magnetic stimulation for treatment of amnestic mild cognitive impairment: a double-blind randomized sham-controlled trial.

Individuals with amnestic mild cognitive impairment (aMCI) have a high risk of developing Alzheimer's disease. Although repetitive transcranial magnetic stimulation (rTMS) is considered a potentially effective treatment for cognitive impairment in patients with aMCI, the neuroimaging mechanisms are poorly understood. Therefore, we performed a double-blind randomized sham-controlled trial in which rTMS was applied to the left dorsolateral prefrontal cortex of aMCI patients recruited from a community near the Third Hospital Affiliated to Sun Yat-sen University, China. Twenty-four patients with aMCI were randomly assigned to receive true rTMS (treatment group, n = 12, 6 men and 6 women; age 65.08 ± 4.89 years) or sham stimulation (sham group, n = 12, 5 men and 7 women; age 64.67 ± 4.77 years). rTMS parameters included a stimulation frequency of 10 Hz, stimulation duration of 2 seconds, stimulation interval of 8 seconds, 20 repetitions at 80% of the motor threshold, and 400 pulses per session. rTMS/sham stimulation was performed five times per week over a period of 4 consecutive weeks. Our results showed that compared with baseline, Montreal Cognitive Assessment scores were significantly increased and the value of the amplitude of low-frequency fluctuation (ALFF) was significantly increased at the end of treatment and 1 month after treatment. Compared with the sham group, the ALFF values in the right inferior frontal gyrus, triangular part of the inferior frontal gyrus, right precuneus, left angular gyrus, and right supramarginal gyrus were significantly increased, and the ALFF values in the right superior frontal gyrus were significantly decreased in the treatment group. These findings suggest that high-frequency rTMS can effectively improve cognitive function in aMCI patients and alter spontaneous brain activity in cognitive-related brain areas. This study was approved by the Ethics Committee of Shenzhen Baoan Hospital of Southern Medical University, China (approval No. BYL20190901) on September 3, 2019, and registered in the Chinese Clinical Trials Registry (registration No. ChiCTR1900028180) on December 14, 2019.

Randomized single-blind multicenter trial comparing the effects of standard and augmented acupuncture protocols on sleep quality and depressive symptoms in patients with depression.

The study was aimed to compare the effects of standard and augmented acupuncture on depressive symptoms and sleep disturbances in patients with depression. This is a randomized, single-blind, multicenter trial. 140 subjects with clinical insomnia (score of ≥ 7 on the Pittsburgh Sleep Quality Index (PSQI)) were randomized to the standard (LI4, LIV3, EX-HN3, and GV20) or augmented (LI4, LIV3, EX-HN3, GV20, LU7, and KID6, including intradermal needles for sustained treatment) acupuncture groups. Participants received two sessions weekly for six weeks. In trial, The primary outcomes were improvements in PSQI and the Hamilton Rating Scale (HAMD). Secondary outcomes were treatment credibility and adverse events. Outcomes were assessed at baseline, week 3, end of treatment, and 4-week follow-up. From the 105 randomized patients, 89 completed the trial and were included in the final analyses. Better efficacy was observed in the augmented group compared with the standard acupuncture to improve the PSQI and HAMD at week 3, end of treatment, and 4-week follow-up (all p < .05). The HAMD scores improved with time, except between end of treatment and 4-week follow-up, while in the standard group, HAMD scored improved from baseline to week 3, and stopped improving thereafter. The PSQI scores improved with time in the two groups, except between end of treatment and 4-week follow-up. Compared with the standard protocol, the augmented acupuncture protocol had a better efficacy to treat depression and to improve sleep quality of patients with depression.

Clinical study of acupuncture treatment on motor aphasia after stroke.

OBJECTIVE: To study the safety and effectiveness of the Heart-Gallbladder acupuncture treatment for motor aphasia after stroke via clinical studies. METHODS: Sixty valid patients were divided into two groups randomly with a ratio of 1:1. The treatment group was the Heart-Gallbladder acupuncture group and the control group was the conventional acupuncture group. The two groups underwent testing before and after treatments, which included: the Aphasia Battery of Chinese (ABC), the Chinese functional communication profile (CFCP), and the Boston diagnostic aphasia examination (BDAE). RESULTS: All the BDAE, CFCP and ABC results showed a significant difference between the two groups after treatment (P< 0.05), indicating that the Heart-Gallbladder acupuncture treatment for motor aphasia after stroke can reduce the degree of aphasia and improve patients' daily communication skills more than the conventional acupuncture treatment. The Heart-Gallbladder acupuncture treatment is better than the conventional acupuncture treatments for motor aphasia after stroke, with significantly improved scores for fluency, repetition, naming, and reading. CONCLUSIONS: Both the Heart-Gallbladder acupuncture and the conventional acupuncture are effective in the treatment of motor aphasia after stroke. Nevertheless, when compared to the conventional acupuncture, the Heart-Gallbladder acupuncture had better efficacy and it is safe as well.

Validity of the "streitberger" needle in a chinese population with acupuncture: a randomized, single-blinded, and crossover pilot study.

We studied the validity of a "Streitberger" needle as a valid approach in a Chinese population with experience of acupuncture. Volunteers were recruited from students of the School of Acupuncture and Moxibustion, Guangzhou University of Chinese Medicine. Sixty students receiving education in acupuncture theory and experience in practical acupuncture were tested in study determining whether needling with the placebo needle felt any different from conventional acupuncture. Outcomes included measures of penetration sensation, VAS ratings, and Deqi sensation questionnaire. As a result, needle penetration, VAS ratings for either needle and Deqi sensation were not significantly different between two kinds of needles. Our findings show that the use of "Streitberger" needle is credible in a Chinese population with acupuncture experience.