Causality between sleep traits and the risk of frailty: a Mendelian randomization study.

Background: Research based on observation has demonstrated a relationship between sleep traits and frailty; however, it remains uncertain if this correlation indicates causation. The purpose of this study was to look at the causal relationship that exists between frailty and sleep traits. Method: Using summaries from a genome-wide association study of self-reported sleep features and frailty index, we performed a bidirectional Mendelian randomization (MR) analysis. Examining the causal relationships between seven sleep-related traits and frailty was the goal. The major method used to calculate effect estimates was the inverse-variance weighted method, supplemented by the weighted median and MR-Egger approaches. The study investigated pleiotropy and heterogeneity using several methodologies, such as the MR-Egger intercept, the MR-PRESSO approach, and the Cochran's Q test. We took multivariate Mendelian randomization and genetic correlations between related traits to enhance the confidence of the results. Furthermore, we used MRlap to correct for any estimation bias due to sample overlap. Results: Insomnia, napping during the day, and sleep apnea syndrome exhibited a positive connection with the frailty index in forward MR analysis. Conversely, there is a negative link between getting up in the morning, snoring and sleep duration with the frailty index. During the reverse MR analysis, the frailty index exhibited a positive correlation with insomnia, napping during the day, and sleep apnea syndrome, while demonstrating a negative correlation with sleep duration. There was no direct correlation between snoring, chronotype, and frailty. In MVMR analyses, the causal effect of sleep characteristics on frailty indices remained consistent after adjusting for potential confounders including BMI, smoking, and triglycerides. Conclusion: The findings of our investigation yield novel evidence that substantiates the notion of a bidirectional causal connection between sleep traits and frailty. Through the optimization of sleep, it is potentially feasible to hinder, postpone, or even reverse the state of frailty, and we proposed relevant interventions.

Effect of "needle sensation" and the real-time changes in autonomic nervous system activity during acupuncture analgesia.

Introduction: Acupuncture analgesia (AA) is widely used in clinical practice. The autonomic nervous system (ANS) may be an important pathway for acupuncture signal transduction. However, real-time changes in autonomic function during AA and the effect of "needle sensation" remain unclear. Methods: We established a human pain model in healthy adults and randomly assigned 128 participants to the model, sham acupuncture, and acupuncture groups in a 1:1:2 ratio. Heart rate variability (HRV), including total power (TP), low-frequency power (LF), high-frequency power (HF), ratio of LF to HF (LF/HF), standard deviation of the normal-normal intervals (SDNN), and root mean square of successive interval differences (RMSSD), were used to assess autonomic function. The visual analog scale (VAS) and efficiency were used to assess the analgesic effect of acupuncture. The Massachusetts General Hospital acupuncture sensation scale (MASS) was used to indicate the intensity of the needle sensation. Anxiety levels were also measured. Finally, the correlation of MASS with HRV, VAS, and anxiety levels was analyzed. Results: VAS decreased after 10 min of needling and 5 min after needle withdrawal in the acupuncture group compared with those in the model group (p = 0.038, p = 0.020). The efficacy rates were 82.0, 50.0, and 61.3% in the acupuncture, model, and sham groups, respectively. These represent significant differences between the acupuncture group and the model and sham acupuncture groups (p < 0.001 in each case). No differences were observed between the model and sham acupuncture groups. HF, TP, SDNN, and RMSSD were all increased in the acupuncture group compared with those in the model group (p = 0.045, p = 0.041, p = 0.002, p = 0.006, respectively). No differences were observed in the sham acupuncture group compared to the model group (p = 0.632, p = 0.542, p = 0.093, p = 0.222, respectively). The LF and LF/HF did not differ among all three groups. A positive correlation was observed between MASS and RMSSD2, LF2, RMSSD4, TP4, VAS5, and anxiety levels. Conclusion: AA was associated with enhanced vagal activity. The intensity of needle sensation was positively correlated with vagal and sympathetic nerve activities. Acupuncture is an effective means of regulating autonomic function, and needle sensation may be an important modulator.

Cardiovascular disease treatment using traditional Chinese medicine：Mitochondria as the Achilles' heel.

Cardiovascular disease (CVD), involving the pathological alteration of the heart or blood vessels, is one of the main causes of disability and death worldwide, with an estimated 18.6 million deaths per year. CVDs are caused by a variety of risk factors, including inflammation, hyperglycemia, hyperlipidemia, and increased oxidative stress. Mitochondria, the hub of ATP production and the main generator of reactive oxygen species (ROS), are linked to multiple cellular signaling pathways that regulate the progression of CVD and therefore are recognized as an essential target for CVD management. Initial treatment of CVD generally focuses on diet and lifestyle interventions; proper drugs or surgery can prolong or save the patient's life. Traditional Chinese medicine (TCM), a holistic medical care system with an over 2500-year history, has been proven to be efficient in curing CVD and other illnesses, with a strengthening effect on the body. However, the mechanisms underlying TCM alleviation of CVD remain elusive. Recent studies have recognized that TCM can alleviate cardiovascular disease by manipulating the quality and function of mitochondria. This review systematically summarizes the association of mitochondria with cardiovascular risk factors, and the relationships between mitochondrial dysfunction and CVD progression. We will investigate the research progress of managing cardiovascular disease by TCM and cover widely used TCMs that target mitochondria for the treatment of cardiovascular disease.

Gut microbiota may be involved in Alzheimer's disease pathology by dysregulating pyrimidine metabolism in APP/PS1 mice.

Introduction: Alzheimer's disease (AD) is the most common form of dementia worldwide. The biological mechanisms underlying the pathogenesis of AD aren't completely clear. Studies have shown that the gut microbiota could be associated with AD pathogenesis; however, the pathways involved still need to be investigated. Aims: To explore the possible pathways of the involvement of gut microbiota in AD pathogenesis through metabolites and to identify new AD biomarkers. Methods: Seven-month-old APP/PS1 mice were used as AD models. The Morris water maze test was used to examine learning and memory ability. 16S rRNA gene sequencing and widely targeted metabolomics were used to identify the gut microbiota composition and fecal metabolic profile, respectively, followed by a combined analysis of microbiomics and metabolomics. Results: Impaired learning abilities were observed in APP/PS1 mice. Statistically significant changes in the gut microbiota were detected, including a reduction in ß-diversity, a higher ratio of Firmicutes/Bacteroidota, and multiple differential bacteria. Statistically significant changes in fecal metabolism were also detected, with 40 differential fecal metabolites and perturbations in the pyrimidine metabolism. Approximately 40% of the differential fecal metabolites were markedly associated with the gut microbiota, and the top two bacteria associated with the most differential metabolites were Bacillus firmus and Rikenella. Deoxycytidine, which causes changes in the pyrimidine metabolic pathway, was significantly correlated with Clostridium sp. Culture-27. Conclusions: Gut microbiota may be involved in the pathological processes associated with cognitive impairment in AD by dysregulating pyrimidine metabolism. B. firmus, Rikenella, Clostridium sp. Culture-27, and deoxyuridine may be important biological markers for AD. Our findings provide new insights into the host-microbe crosstalk in AD pathology and contribute to the discovery of diagnostic markers and therapeutic targets for AD.

Multi-center study for acupuncture combined with Chinese medicine in the treatment of chronic spontaneous urticaria based on the theory of taking shu-stream points when the disease is aggravated.

Chronic spontaneous urticaria (CSU) is a common dermatologic disease that seriously affects patient quality of life. The choice of therapy to control the disease and prevent its recurrence has always presented a difficult clinical issue. Previous studies have shown that traditional Chinese medicine is a safe and effective treatment for CSU. Recently, the temporal rhythms of CSU, a disease characterized by intermittent flares of active disease and periods of little or no disease, have attracted the attention of traditional Chinese medicine researchers. We designed a multicenter, randomized, controlled study to evaluate the efficacy and safety of combining a Chinese herbal formulation with acupuncture using shu-stream acupoints applied on the corresponding time meridians during disease exacerbations. We plan to recruit 111 outpatients with CSU aged 18 to 65 years. Participants will be randomized to 1 of the 3 groups: group A, which will be given basic acupuncture and the herbal formulation dangui yinzi; group B, which will be given danggui yinzi and shu-stream acupuncture; and a control group, which will be given danggui yinzi alone. Patients will be treated for 4 weeks and followed for 8 additional weeks. Investigators will evaluate the following parameters: the symptoms and side effects of treatment, quality of life (using the chronic urticaria quality of life questionnaire), and overall patient condition. Each week, patients will also complete the measurement of 7-day urticarial activity score. This is the first use of a combination of shu-stream acupoints and Chinese herbal medicine in the treatment of CSU. If successful, it will prove to be a simple, inexpensive, treatment strategy for solving a difficult clinical problem.

[Effect of electro-acupuncture on metabolites in the cerebral cortex of ulcerative colitis rats based on Pi/Wei-brain related theory].

OBJECTIVE: To study the effect of electro-acupuncture (EA) at points along Foot Yangming Channel on metabolite of ulcerative colitis (UC) rats' cerebral cortex and to identify key metabolites by referring to Pi/Wei-brain related theory in Chinese medicine (CM). METHODS: The UC rat model was set up by dextran sulfate sodium (DSS) method. Male SD rats were randomly divided into the model group and the EA group, 13 in each group. Another 13 rats were recruited as the blank control group. Rats in the blank control group and the model group received no EA. EA was performed at Zusanli (ST36), Shangjuxu (ST37), and Tianshu (ST25) for 5 days by using disperse-dense wave. Then all rats were sacrificed. Their recto-colon and the ileocecal junction were pathomorphologically observed by light microscope and transmission electron microscope (TEM). Cerebral cortexes were extracted. Water-soluble and lipid-soluble brain tissue metabolites were respectively extracted for metabolic research using 1H nuclear magnetic resonance (1H-NMR). RESULTS: EA could obviously improve the general condition of UC model rats, decrease the value of DAI, reduce the infiltration of inflammatory cells in the intestinal tract, stabilize structures such as mitochondria, endoplasmic reticulum and so on (P <0.05). 1HNMR analysis showed that in the model group, contents of glutamic acid, cholesterol, very low density lipoproein (VLDL) in the pallium obviously decreased, while alanine and low density lipoprotein (LDL) significantly increased. After EA, levels of lactic acid, glutamic acid, total cholesterol (TC), and VLDL all increased, and levels of alanine and LDL decreased. All indices were approximate to those of the blank control group. CONCLUSION: EA at Foot Yangming channel was found to have some effect on metabolites in the brain tissue of UC model rats, which had specific metabonomic material basis and mechanism based on the Pi/Wei-brain related theory.

[Effect of electroacupuncture intervention on enteric microecology in ulcerative colitis rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on enteric microbial populations in ulcerative colitis (UC) model rats, so as to study its mechanisms underlying improving UC. METHODS: Thirty-nine male SD rats were randomly divided into control group, model group and EA group (n = 13 in each group). The UC model was established by intragstric perfusion of 4% dextran sodiumaqueous solution (DSS), once daily for 7 days. EA (15-25 Hz, 0.1 mA) was applied to bilateral "Tianshu" (ST 25), "Zusanli" (ST 36) and "Shangjuxu" (ST 37) for 10 min, once daily for 5 days. Disease Activity Index (DAI) including body weight and stool blood state was used to evaluate the animals' conditions. The rats' excrement was collected to detect the abundance and diversity of bacterial populations by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). RESULTS: In comparison with the control group, the animals' DAI score and enteric Clostridium bifermentans content were significantly increased (P < 0.05), and the abundance and diversity of bacterial populations, and contents of enteric Lachnospiraceae bacterium and Lactobacillus sp. were considerably down-regulated in the model group (P < 0.05, P < 0.01). Compared with the model group, the DAI score and enteric Clostridium bifermentans content were significantly lowered, and the abundance and diversity of bacterial populations, and contents of enteric Lachnospiraceae bacterium and Lactobacillus sp. were notably increased in the EA group (P < 0.05, P < 0.01). CONCLUSION: EA can improve DAI and the abundance and diversity of enteric bacterial microbiota in UC rats, which may be related to its protective effect on enteric microecology in UC.