The causal relationship between sleep disturbances and the risk of frailty: a two-sample Mendelian randomization study.

OBJECTIVE: Adequate sleep is closely related to people's health. However, with increasing age, the quality of sleep worsens. At the same time, among elderly individuals, frailty is also a disturbing factor, which makes elderly individuals more vulnerable to negative factors. To explore the relationship between the two, we conducted this study. METHODS: In this paper, independent genetic variations related to insomnia, sleep duration and daytime sleepiness were selected as IVs, and related genetic tools were used to search published genome-wide association studies for a two-sample Mendelian randomization (TSMR) analysis. The inverse-variance weighted (IVW) method was used as the main Mendelian randomization analysis method. Cochran's Q test was used to test heterogeneity, MR‒Egger was used to test horizontal pleiotropy, and the MR-PRESSO test was used to remove outliers. RESULTS: According to our research, insomnia (OR = 1.10, 95% CI 1.03-1.17, P = 2.59e-97), long sleep duration (OR = 0.66, 95% CI 0.37-1.17, P = 0.02), short sleep duration (OR = 1.30, 95% CI 1.22-1.38, P = 2.23e-17) and daytime sleepiness (OR = 1.49, 95% CI 1.25-1.77, P = 0.96e-4) had a bidirectional causal relationship with frailty. CONCLUSIONS: Our research showed that there is a causal relationship between sleep disturbances and frailty. This result was obtained by a TSMR analysis, which involves the use of genetic variation as an IV to determine causal relationships between exposure and outcome. Future TSMR studies should include a larger sample for analysis.

Changes in frailty and depressive symptoms among middle-aged and older Chinese people: a nationwide cohort study.

BACKGROUND AND AIMS: The older people bears a severe burden of disease due to frailty and depressive symptoms, however, the results of association between the two in the older Chinese people have been conflicting. Therefore, this study aimed to investigate the developmental trajectories and interactions of frailty and depressive symptoms in the Chinese middle-aged and older adults. METHODS: The study used four waves of data from 2011, 2013, 2015 and 2018 in the China Health and Retirement Longitudinal Study (CHARLS) database, focused on middle-aged and older people ≥ 45 years of age, and analyzed using latent growth models and cross-lagged models. RESULTS: The parallel latent growth model showed that the initial level of depressive symptoms had a significant positive predictive effect on the initial level of frailty. The rate of change in depressive symptoms significantly positively predicted the rate of change in frailty. The initial level of frailty had a significant positive predictive effect on the initial level of depressive symptoms, but a significant negative predictive effect on the rate of change in depressive symptoms. The rate of change in frailty had a significant positive predictive effect on the rate of change in depressive symptoms. The results of the cross-lagged analysis indicated a bidirectional causal association between frailty and depressive symptoms in the total sample population. Results for the total sample population grouped by age and gender were consistent with the total sample. CONCLUSIONS: This study recommends advancing the age of concern for frailty and depressive symptoms to middle-aged adults. Both men and women need early screening and intervention for frailty and depressive symptoms to promote healthy aging.

The prevalence and influencing factors of frailty in patients with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: To investigate the prevalence and influencing factors of frailty and pre-frailty in chronic kidney disease (CKD) patients and thereby provide a scientific basis for effective avoidance of frailty in patients with CKD. METHODS: PubMed, EMBASE, Web of Science, EBSCO, Cochrane Library, CNKI, VIP, CBMdisc, and Wanfang databases were searched for relevant studies published till December 31, 2021. The summary results were described as odds ratios (ORs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs). A meta-analysis was performed using StataSE12.0. RESULTS: Fifteen published studies, which enrolled a total of 3294 CKD patients, met the inclusion criteria. The combined prevalence of frailty in CKD patients was 38.1% (95% CI 29.7-46.5%) and pre-frailty was 37.9% (95% CI 32.7-43.1%). The main factors influencing frailty in CKD patients were age (SMD 0.524, 95% CI 0.326-0.723), diastolic blood pressure (SMD - 0.294, 95% CI - 0.518 to - 0.071), body mass index (BMI) (SMD - 0.267, 95% CI - 0.471 to - 0.064), grip strength (SMD - 0.929, 95% CI - 1.233 to - 0.626), hemoglobin level (SMD - 0.346, 95% CI - 0.448 to - 0.243), serum albumin level (SMD - 0.533, 95% CI - 0.655 to - 0.411), Charlson Comorbidity Index (SMD 0.421, 95% CI 0.150-0.692), multiple medications (SMD 0.625, 95% CI 0.354-0.895), Mini-Mental State Examination (MMSE) score (SMD - 0.563, 95% CI - 0.846 to - 0.280), and female (OR 2.391, 95% CI 1.236-4.627). CONCLUSION: Frailty is common in CKD patients. The prevalence of frailty among CKD patients was related to age, diastolic blood pressure, BMI, grip strength, hemoglobin and serum albumin levels, Charlson Comorbidity Index, multiple medications, MMSE score, and female.

Age-standardized incidence, prevalence, and mortality rates of autoimmune diseases in women of childbearing age from 1990 to 2019.

AIM: To estimate the age-standardized incidence, prevalence, and mortality rates of autoimmune diseases including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), asthma, and psoriasis in women of childbearing age from 1990 to 2019, and to further analyze their changing trends, at global, regional, and national levels. METHODS: Women of childbearing age was defined as 15-49 years old. The estimates and 95% uncertainty intervals (UIs) for case number of RA, IBD, MS, T1DM, asthma and psoriasis in seven age groups (15-19, 20-24, 25-29, 30-34, 35-39, 40-44, 45-49 years) were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Age standardization by direct method was adopted to estimate the age-standardized incidence, prevalence, and mortality rates of these autoimmune diseases in women of childbearing age. Joinpoint regression analysis was utilized to analyze the changing trends of estimated age-standardized incidence, prevalence, and mortality rates from 1990 to 2019 by calculating the average annual percentage change (AAPC) and its 95% confidence intervals (CIs). RESULTS: In 2019, the estimated global age-standardized incidence, prevalence, and mortality rates of RA in women of childbearing age was 17.13 (95% UI: 12.39 to 22.60), 215.86 (95% UI: 179.04 to 259.70), and 0.06 (95% UI: 0.04 to 0.08); of IBD was 5.85 (95% UI: 4.72 to 7.12), 63.54 (95% UI: 53.50 to 74.37), and 0.11 (95% UI: 0.08 to 0.13); of MS was 1.63 (95% UI: 1.05 to 2.28), 28.74 (95% UI: 23.80 to 34.46), and 0.17 (95% UI: 0.14 to 0.27); of T1DM was 6.22 (95% UI: 2.75 to 11.50), 290.51 (95% UI: 221.39 to 370.19), and 0.63 (95% UI: 0.48 to 0.78); of asthma was 291.14 (95% UI: 157.06 to 468.78), 2796.25 (95%UI: 1987.07 to 3842.97), and 1.42 (95% UI: 1.12 to 1.75), respectively. The estimated global age-standardized incidence and prevalence rates of psoriasis in women of childbearing age was 58.68 (95% UI: 51.04 to 66.85) and 477.20 (95% UI: 440.30 to 515.76). Highest disease burden generally exists in Region of the Americas and European Region. From 1990 to 2019, the estimated global age-standardized incidence and prevalence rates of RA (AAPC: 0.18, 95% CI: 0.11 to 0.24; AAPC: 0.24, 95% CI: 0.18 to 0.30) and T1DM (AAPC: 1.47, 95% CI: 1.40 to 1.54; AAPC: 0.83, 95% CI: 0.79 to 0.88) in women of childbearing age showed significantly increasing trends whereas those of IBD (AAPC: -0.76, 95% CI: -0.80 to -0.73; AAPC: -0.65, 95% CI: -0.70 to -0.60), MS (AAPC: -0.20, 95% CI: -0.23 to -0.16; AAPC: -0.25, 95% CI: -0.26 to -0.23), asthma (AAPC: -0.53, 95% CI: -0.60 to -0.47; AAPC: -0.74, 95% CI: -0.81 to -0.68), and psoriasis (AAPC: -0.83, 95% CI: -0.85 to -0.82; AAPC: -0.99, 95% CI: -1.02 to -0.96) showed significantly decreasing trends. Favorably, the estimated global age-standardized mortality rate of RA (AAPC: -1.32, 95% CI: -1.63 to -1.01), IBD (AAPC: -0.95, 95% CI: -1.06 to -0.84), MS (AAPC: -0.96, 95% CI: -1.12 to -0.80), T1DM (AAPC: -1.05, 95% CI: -1.21 to -0.89), and asthma (AAPC: -2.27, 95% CI: -2.34 to -2.19) in women of childbearing age all declined. The changing trends of estimated age-standardized incidence, prevalence, and mortality rates varied significantly across 204 countries and territories. CONCLUSIONS: Our study provides an accurate estimation on the age-standardization of disease indicators of autoimmune diseases in women of childbearing age. There are remarkable disparities in the incidence, prevalence, and mortality burden related to autoimmune diseases in women of childbearing age, as well as their changing trends across the world, suggesting that each individual government should establish flexible health policies and make reasonable source allocation to address different needs for autoimmune diseases in this population.

Bidirectional causal relationship between depression and frailty: a univariate and multivariate Mendelian randomisation study.

BACKGROUND: cumulative evidence from cohort studies suggested that there were inconsistent conclusions as to whether there was a bidirectional association between depression and frailty. Therefore, this study used a bidirectional two-sample Mendelian randomisation (MR) study to investigate the causal relationship between depression and frailty. METHODS: we performed univariate and multivariate bidirectional MR analyses to assess the causal association between depression and frailty. Independent genetic variants associated with depression and frailty were selected as instrumental variables. Inverse variance weighted (IVW), MR-Egger, weighted median and weighted mode were mainly used in univariate MR analysis. Multivariate MR (MVMR) analyses used multivariable inverse variance-weighted methods to individually and jointly adjust for three potential confounders, body mass index (BMI), age at menarche (AAM) and waist-to-hip ratio (WHR, adjusted for BMI). RESULTS: univariate MR analysis showed a positive causal relationship between depression and risk of frailty (IVW, odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.23-1.37, P = 6.54E-22). Causal relationship between frailty and risk of depression (IVW, OR = 1.69, 95% CI = 1.33-2.16, P = 2.09E-05). MVMR analysis revealed that the bidirectional causal association between depression and frailty remained after adjusting for three potential confounders, BMI, AAM and WHR (adjusted for BMI), individually and in combination. CONCLUSIONS: our findings supported a causal relationship between genetically predicted depression and frailty in both directions.

[Effects of moxibustion on acupoints at "opening" time on testicular tissue apoptosis in aging rats].

OBJECTIVE: To observe the effect of "lingguibafa" moxibustion at "opening" time on the level of superoxide dismutase(SOD), malondialdehyde(MDA), the protein expressions of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in aging model rats. METHODS: SD rats were randomly divided into blank control, model and lingguibafa groups, with 8 rats in each group. The aging model was established by daily intraperitoneal injection of D-galactose (500 mg/kg) for 42 consecutive days. After successful modeling, moxibustion intervention was applied at"lingguibafa" acupoints, 3 moxa-cone for each acupoint, once a day for 28 consecutive days. The contents of SOD and MDA in serum were detected by ELISA. Morphological changes of testicular tissue and the number of Leydig cells were observed after HE staining. Apoptosis rate of testicular cells was detected by TUNEL staining. The protein expression levels of Bcl-2 and Bax in testis were detected by Western blot. RESULTS: Compared with the blank control group, the SOD content in the serum, the number of testicular Leydig cells, the expression level of Bcl-2 protein in testis were significantly decreased (P<0.01) in the model group, while the MDA content in the serum, the apoptosis rate of testicular cells and the expression level of Bax protein in testis were significantly increased (P<0.01). Compared with the model group, the SOD content in serum, the number of testicular Leydig cells, the Bcl-2 protein expression in testis were significantly increased (P<0.01), while the MDA content in serum, the apoptosis rate of testicular cells, the expression level of Bax protein in testis were significantly decreased(P<0.01) in the lingguibafa group. CONCLUSION: Moxibustion on acupoints at "opening" time can delay testicular aging, and the mechanism may be related to balancing the metabolism of free radicals, reducing oxidative damage, and inhibiting the apoptosis of testicular cells.

Influencing factors of self-disclosure and its impact on quality of life in patients with systemic lupus erythematosus.

BACKGROUND: Self-disclosure may enhance positive illness perceptions, whereas patients with systemic lupus erythematosus (SLE) always facing negative illness perceptions due to multiple reasons, so elucidation of factors affecting self-disclosure may facilitate the development of quality of life. METHODS: A total of 161 hospitalized patients with SLE were recruited. Scales on demographic and clinical characteristics, self-disclosure, psychosocial status (e.g. Social Support Rating Scale - SSRS) and quality of life were used to collect related information from clients. Univariate analysis was performed by Kruskal-Wallis rank-sum test or chi-square test, and multivariate analysis by ordinal logistic regression. RESULTS: Social support, drinking, depression and cause of hospitalization were found to be influencing factors of self-disclosure. Multiple logistic regression analyses revealed that the significant and independent factors associated with self-disclosure in patients with SLE were social support, drinking and depression. Domains of LupusQoL, except physical health and fatigue, were positively correlated with self-disclosure. CONCLUSIONS: With the increase of social support, the level of self-disclosure become worse, drinking, depression and cause of hospitalization are risk factors for it. Moreover, the level of self-disclosure is positively related to the LupusQoL. Medical staff should formulate effective measures according to the results to improve self-disclosure in patients with SLE and promote their quality of life.

The mediating effect of psychological resilience on empathy and professional identity of Chinese nursing students: A structural equation model analysis.

BACKGROUND: Previous studies have shown that empathy has a positive impact on the professional identity of nursing students. And developing psychological resilience can improve the professional identity of nursing students. However, studies investigating the mechanism of the relationship between empathy and psychological resilience on professional identity remain few. PURPOSE: Among Chinese nursing students, we sought to determine whether psychological resilience mediates the association between empathy and professional identity. METHODS: A total of 495 undergraduate and postgraduate nursing students in a medical university nursing college in Hefei were investigated by demographic data questionnaire, nursing students' empathy scale, nursing students' professional identity questionnaire, and psychological resilience questionnaire. Structural equation modeling was used to analyze the mediating effect of psychological resilience between empathy and the professional identity of nursing students. RESULTS: The total score of professional identity of nursing students was 57.07 ± 10.38. Psychological resilience (r = 0.316, P < 0.01) and professional identity (r = 0.313, P < 0.01) both had positive correlations with empathy, respectively. Additionally, there was a strong correlation between psychological resilience and professional identity (r = 0.488, P < 0.01). Empathy had an indirect effect on professional identity through psychological resilience, with a direct effect of 0.256 and an indirect effect of 0.145, and the indirect effect accounted for 36.16 % of the total effect. CONCLUSION: Nursing educators should pay attention to the cultivation of empathy ability and psychological resilience to enhance nursing students' professional identity.

The impact of distress disclosure and anxiety on the association between social support and quality of life among Chinese women with systemic lupus erythematosus.

The evidence on the relationship between social support and quality of life in female systemic lupus erythematosus (SLE) patients is complex. The purpose of this study was to explore the impacts of distress disclosure and anxiety on the association between social support and quality of life among Chinese women with SLE. A cross-sectional study was conducted, and 237 samples were obtained. Measures included demographic characteristics, Lupus Quality of Life (LupusQoL), social support rate scale (SSRS), distress disclosure index (DDI), and self-rating anxiety scale (SAS). Descriptive statistics, correlation analysis, and moderated mediating effect analysis were carried out. The LupusQoL was negatively correlated with age, systemic lupus erythematosus disease activity index (SLEDAI), DDI, and SAS. SSRS had a positive predictive effect on the LupusQoL, while SLEDAI and DDI had the opposite effect. SAS had a negative predictive effect on the LupusQoL. There were interactive effects of SAS and DDI on LupusQoL. In the moderated mediation model, SAS played moderating effect in the role of DDI on LupusQoL; the DDI of female patients with SLE played a partial mediator role, the mediation effect was 0.19, and the mediation effect ratio was 33.3%. In conclusion, to pay attention to the QOL, we should consider the mediator role of distress disclosure and the moderating role of anxiety.

Causal Relationship Between Sleep Traits and Risk of Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study.

A correlation between sleep and systemic lupus erythematosus (SLE) has been observed in a number of prior investigations. However, little is known regarding the potential causative relationship between them. In this study, we selected genetic instruments for sleep traits from pooled data from published genome-wide association studies (GWAS). Independent genetic variants associated with six sleep-related traits (chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, and daytime sleepiness) were selected as instrumental variables. A two-sample Mendelian randomization (TSMR) study was first conducted to assess the causal relationship between sleep traits and SLE (7219 cases versus 15,991 controls). The reverse MR analysis was then used to infer the causal relationship between SLE and sleep traits. Inverse variance weighted (IVW), MR Egger, Weighted median, and Weighted mode were applied to perform the primary MR analysis. MR Egger regression and the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test were used to detect horizontal pleiotropy, and Cochran's Q was used to detect heterogeneity. In studies of the effect of sleep traits on SLE risk, the IVW method demonstrated no causal relationship between chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, daytime sleepiness and SLE risk. The remaining three methods agreed with the results of IVW. In studies of the effect of SLE on the risk of sleep traits, neither IVW, MR Egger, Weighted median, nor Weighted mode methods provided evidence of a causal relationship between SLE and the risk of sleep traits. Overall, our study found no evidence of a bidirectional causal relationship between genetically predicted sleep traits and SLE.

Association Between Sleep Traits and Rheumatoid Arthritis: A Mendelian Randomization Study.

Currently, the causal association between sleep disorders and rheumatoid arthritis (RA) has been poorly understood. In this two-sample Mendelian randomization (TSMR) study, we tried to explore whether sleep disorders are causally associated with RA. Seven sleep-related traits were chosen from the published Genome-Wide Association Study (GWAS): short sleep duration, frequent insomnia, any insomnia, sleep duration, getting up, morningness (early-to-bed/up habit), and snoring, 27, 53, 57, 57, 70, 274, and 42 individual single-nucleotide polymorphisms (SNPs) (P < 5 × 10-8) were obtained as instrumental variables (IVs) for these sleep-related traits. Outcome variables were obtained from a public GWAS study that included 14,361 cases and 43,923 European Ancestry controls. The causal relationship between sleep disturbances and RA risk were evaluated by a two-sample Mendelian randomization (MR) analysis using inverse variance weighted (IVW), MR-Egger regression, weighted median, and weight mode methods. MR-Egger Regression and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) were used to test for horizontal pleomorphism and outliers. There was no evidence of a link between RA and frequent insomnia (IVW, odds ratio (OR): 0.99; 95% interval (CI): 0.84-1.16; P = 0.858), any insomnia (IVW, OR: 1.09; 95% CI: 0.85-1.42; P = 0.489), sleep duration (IVW, OR: 0.65, 95% CI: 0.38-1.10, P = 0.269), getting up (IVW, OR: 0.56, 95% CI: 0.13-2.46, P = 0.442), morningness (IVW, OR: 2.59; 95% CI: 0.73-9.16; P = 0.142), or snoring (IVW, OR: 0.95; 95% CI: 0.68-1.33; P = 0.757). Short sleep duration (6h) had a causal effect on RA, as supported by IVW and weighted median (OR: 1.47, 95% CI: 1.12-1.94, P = 0.006; OR: 1.43, 95%CI:1.01-2.05, P = 0.047). Sensitivity analysis showed that the results were stable. Our findings imply that short sleep duration is causally linked to an increased risk of RA. Therefore, sleep length should be considered in disease models, and physicians should advise people to avoid short sleep duration practices to lower the risk of RA.

Choroideremia Is a Systemic Disease With Lymphocyte Crystals and Plasma Lipid and RBC Membrane Abnormalities.

PURPOSE: Photoreceptor neuronal degenerations are common, incurable causes of human blindness affecting 1 in 2000 patients worldwide. Only half of all patients are associated with known mutations in over 250 disease genes, prompting our research program to identify the remaining new genes. Most retinal degenerations are restricted to the retina, but photoreceptor degenerations can also be found in a wide variety of systemic diseases. We identified an X-linked family from Sri Lanka with a severe choroidal degeneration and postulated a new disease entity. Because of phenotypic overlaps with Bietti's crystalline dystrophy, which was recently found to have systemic features, we hypothesized that a systemic disease may be present in this new disease as well. METHODS: For phenotyping, we performed detailed eye exams with in vivo retinal imaging by optical coherence tomography. For genotyping, we performed whole exome sequencing, followed by Sanger sequencing confirmations and cosegregation. Systemic investigations included electron microscopy studies of peripheral blood cells in patients and in normal controls and detailed fatty acid profiles (both plasma and red blood cell [RBC] membranes). Fatty acid levels were compared to normal controls, and only values two standard deviations above or below normal controls were further evaluated. RESULTS: The family segregated a REP1 mutation, suggesting choroideremia (CHM). We then found crystals in peripheral blood lymphocytes and discovered significant plasma fatty acid abnormalities and RBC membrane abnormalities (i.e., elevated plasmalogens). To replicate our discoveries, we expanded the cohort to nine CHM patients, genotyped them for REP1 mutations, and found the same abnormalities (crystals and fatty acid abnormalities) in all patients. CONCLUSIONS: Previously, CHM was thought to be restricted to the retina. We show, to our knowledge for the first time, that CHM is a systemic condition with prominent crystals in lymphocytes and significant fatty acid abnormalities.