Development of Integrin-Facilitated Bispecific Aptamer Chimeras for Membrane Protein Degradation.

The emergence of lysosome-targeting chimeras (LYTACs), which represents a promising strategy for membrane protein degradation based on lysosomal pathways, has attracted much attention in disease intervention and treatment. However, the expression level of commonly used lysosome-targeting receptors (LTRs) varies in different cell lines, thus limiting the broad applications of LYTACs. To overcome this difficulty, we herein report the development of integrin α3ß1 (ITGA3B1)-facilitated bispecific aptamer chimeras (ITGBACs) as a platform for the degradation of membrane proteins. ITGBACs consist of two aptamers, one targeting ITGA3B1 and another binding to the membrane-associated protein of interest (POI), effectively transporting the POI into lysosomes for degradation. Our findings demonstrate that ITGBACs effectively eliminate pathological membrane proteins, such as CD71 and PTK7, inducing significant cell-cycle arrest and apoptosis and markedly inhibiting tumor growth in tumor-bearing mice models. Therefore, this work provides a novel and versatile membrane protein degradation platform, offering a promising targeted therapy based on tumor-specific LTRs.

Tributyltin-induced oxidative stress causes developmental damage in the cardiovascular system of zebrafish (Danio rerio).

Tributyltin (TBT) can be used as an antifouling agent with anticorrosive, antiseptic and antifungal properties and is widely used in wood preservation and ship painting. However, it has recently been found that TBT can be harmful to aquatic organisms. In this study, to gain insight into the effects of TBT with respect to the development of the cardiovascular system in zebrafish embryos, zebrafish embryos were exposed to different concentrations of TBT solutions (0.2 µg/L, 1 µg/L, and 2 µg/L) at 2 h post-fertilization (hpf) TBT exposure resulted in decreased hatchability and heart rate, deformed features such as pericardial edema, yolk sac edema, and spinal curvature in zebrafish embryos, and impaired heart development. Expression of cardiac development-related genes (vmhc, myh6, nkx2.5, tbx5a, gata4, tbx2b, nppa) is dysregulated. Transgenic zebrafish Tg (fli1: EGFP) were used to explore the effects of TBT exposure on vascular development. It was found that TBT exposure could lead to impaired development of intersegmental vessels (ISVs), common cardinal vein (CCV), subintestinal vessels (SIVs) and cerebrovascular. The expression of vascular endothelial growth factor (VEGF) signaling pathway-related genes (flt1, flt4, kdr, vegfa) was downregulated. Biochemical indices showed that ROS and MDA levels were significantly elevated and that SOD and CAT activities were significantly reduced. The expression of key genes for prostacyclin synthesis (pla2, ptgs2a, ptgs2b, ptgis, ptgs1) is abnormal. Therefore, it is possible that oxidative stress induced by TBT exposure leads to the blockage of arachidonic acid (AA) production in zebrafish embryos, which affects prostacyclin synthesis and consequently the normal development of the heart and blood vessels in zebrafish embryos.

Associations of serum uric acid with hypertension status, stages, phenotypes and progressions among Chinese middle-aged and elderly.

BACKGROUND AND AIMS: No consensus has been reached on the association between serum uric acid (SUA) and hypertension. This study aimed to investigate the associations between SUA and hypertension, including its status, stages, phenotypes and progressions, among middle-aged and older Chinese. METHODS AND RESULTS: Data were obtained from the China Health and Retirement Longitudinal Study 2011-2015. Binary logistic regression was used to evaluate the association between SUA and hypertension status. Multinomial logistic regression was used to explore the associations of SUA with hypertension stages, phenotypes and hypertension status progressions. Models were adjusted for potential confounders and stratified by sex. A total of 7931 individuals aged ≥45 years were included, with 39.16 % of hypertension. Significant associations were found of SUA with stage2 and above hypertension (quartile 4 [Q4] vs quartile 1 [Q1]: odds ratio 1.78, 95 % confidence interval 1.31-2.42, P < 0.001), and systolic diastolic hypertension (SDH) (Q4 vs Q1: 1.53, 1.14-2.06, P = 0.005). In sex stratification, significant associations were found between SUA and stage2 and above hypertension and SDH only for men. Moreover, higher quartiles of baseline SUA showed increased risks of maintained hypertension from 2011 to 2015 (Q3 vs Q1: 1.23, 1.03-1.48, P = 0.024; Q4 vs Q1: 1.73, 1.43-2.10, P < 0.001). CONCLUSION: Higher SUA was associated with hypertension and maintained hypertension among Chinese middle-aged and elderly. Sex-specific associations of SUA with hypertension stages and phenotypes were observed. Regular measurement of SUA in clinical practice may indicate hypertension and its progression, particularly among men.

Prevalence of childhood hypertension and associated factors in Zhejiang Province: a cross-sectional analysis based on random forest model and logistic regression.

With childhood hypertension emerging as a global public health concern, understanding its associated factors is crucial. This study investigated the prevalence and associated factors of hypertension among Chinese children. This cross-sectional investigation was conducted in Pinghu, Zhejiang province, involving 2,373 children aged 8-14 years from 12 schools. Anthropometric measurements were taken by trained staff. Blood pressure (BP) was measured in three separate occasions, with an interval of at least two weeks. Childhood hypertension was defined as systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) ≥ age-, sex-, and height-specific 95th percentile, across all three visits. A self-administered questionnaire was utilized to collect demographic, socioeconomic, health behavioral, and parental information at the first visit of BP measurement. Random forest (RF) and multivariable logistic regression model were used collectively to identify associated factors. Additionally, population attributable fractions (PAFs) were calculated. The prevalence of childhood hypertension was 5.0% (95% confidence interval [CI]: 4.1-5.9%). Children with body mass index (BMI) ≥ 85th percentile were grouped into abnormal weight, and those with waist circumference (WC) > 90th percentile were sorted into central obesity. Normal weight with central obesity (NWCO, adjusted odds ratio [aOR] = 5.04, 95% CI: 1.96-12.98), abnormal weight with no central obesity (AWNCO, aOR = 4.60, 95% CI: 2.57-8.21), and abnormal weight with central obesity (AWCO, aOR = 9.94, 95% CI: 6.06-16.32) were associated with an increased risk of childhood hypertension. Childhood hypertension was attributable to AWCO mostly (PAF: 0.64, 95% CI: 0.50-0.75), followed by AWNCO (PAF: 0.34, 95% CI: 0.19-0.51), and NWCO (PAF: 0.13, 95% CI: 0.03-0.30). Our results indicated that obesity phenotype is associated with childhood hypertension, and the role of weight management could serve as potential target for intervention.

Paternal and maternal exposures to adverse childhood experiences and spontaneous fetal loss: a nationwide cross-sectional analysis.

BACKGROUND: Adverse childhood experiences (ACEs) might be associated with maternal spontaneous fetal loss, while evidence among Chinese population is limited. This study aims to explore the associations of adverse childhood experiences (ACEs) among women and their spouses with the risk of spontaneous abortion and stillbirth. METHOD: Data were from the China Health and Retirement Longitudinal Study (CHARLS) 2014 survey. ACEs were categorized into intra-familial ACEs and extra-familial ACEs. The associations of maternal and paternal ACEs with women's history of spontaneous abortion and stillbirth were investigated by logistic regression. RESULTS: 7,742 women were included with 9.05% and 2.47% experiencing at least one spontaneous abortion or stillbirth, respectively. Women exposed to 2, 3, and ≥ 4 ACEs were at significantly higher odds of spontaneous abortion, with adjusted odds ratios (ORs) of 1.52 (95% [CI, Confidence Interval] 1.10-2.10), 1.50 (95% CI 1.07-2.09) and 1.68 (95% CI 1.21-2.32), respectively. A significant association between ≥ 4 maternal intra-familial ACEs and stillbirth (OR 2.23, 95% CI 1.12-4.42) was also revealed. Furthermore, paternal exposures to 3 and ≥ 4 overall ACEs were significantly associated with their wives' history of spontaneous abortion, with adjusted ORs of 1.81 (95% CI 1.01-3.26) and 1.83 (95% CI 1.03-3.25), respectively. CONCLUSION: Both maternal and paternal ACEs were associated with spontaneous abortion, and potential mediators might need to be considered to further explore impacts of maternal and paternal ACEs on maternal reproductive health.

Aptamer-Based Targeted Delivery of Functional Nucleic Acids.

Functional nucleic acid (NA)-based drugs have a broad range of applications since they allow the alteration and control of gene/protein expression patterns in cells. In principle, functional NAs need to be transported precisely and efficiently to target cells to guarantee both functionality and safety. Owing to their negative charges, it is difficult for natural NAs to cross the cell membrane composed of lipid bilayer and enter targeted cells. Worse still, the delivery of undirected functional NAs to nontargeted healthy cells and/or tissues would induce unpredictable adverse effects. Therefore, the precisely targeted delivery of functional NAs to specific cells/organs, particularly in extrahepatic sites, is required. Since aptamers can bind to various proteins on the cell surface with high specificity and selectivity, they can serve as the molecular recognition units to accurately bind target cells and subsequently enable the efficient delivery of cargo. In this perspective, we summarize the original, proof-of-concept aptamer-based strategies for the targeted delivery of functional NAs. A few specific examples are then discussed, followed by our perspectives on some of the challenges and opportunities that lie ahead.

Status and transition of normal-weight central obesity and the risk of cardiovascular diseases: A population-based cohort study in China.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) has become a growing public health concern. Normal weight central obesity (NWCO) has emerged as a potential risk factor for cardiometabolic dysregulation. To date, the association between NWCO and new-onset CVDs remains unclear. We aimed to evaluate the associations of NWCO and its longitudinal transitions with cardiovascular risks in middle-aged and older Chinese. METHODS AND RESULTS: Data were from the China Health and Retirement Longitudinal Study 2011-2018. NWCO was defined as the combination of a body mass index (BMI) of <24.0 kg/m2 and a waist circumference (WC) of >85 cm in males or >80 cm in females. CVDs included heart diseases and stroke. Cause-specific hazard models and subdistribution hazard models with all-cause death as the competing event were applied. In 2011, 9856 participants without prior CVDs were included, of whom 1814 developed CVDs during a 7-year follow-up. Compared to normal weight and non-central obesity (NWNCO), NWCO was significantly associated with new-onset CVDs, with cause-specific hazard ratios (cHRs) and 95% confidence intervals (CIs) of 1.21 (1.04-1.41) for heart diseases and 1.40 (1.11-1.76) for stroke. From 2011 to 2013, 571 NWNCO participants developed NWCO who subsequently demonstrated a 45% higher risk of CVDs than those with maintained NWNCO. CONCLUSION: NWCO and transition from NWNCO to NWCO are associated with higher risks of CVDs. Identification and prevention of NWCO may be useful in the management of CVDs.

Adverse childhood experiences and handgrip strength among middle-aged and older adults: a cross-sectional study in China.

BACKGROUND: Evidence on the association between adverse childhood experiences (ACEs) and handgrip strength (HGS) in later life was limited and inconclusive. We aimed to explore the impact of ACEs on HGS among middle-aged and older Chinese adults. METHODS: We conducted a cross-sectional study with data extracted from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative survey with respondents recruited from 450 villages/urban communities of 28 provinces. Participants aged 45 years or older were drawn from the CHARLS 2014 life history survey and the 2015 health survey. Twelve ACE indicators before the age of 17 years were collected. HGS was measured with a dynamometer and the maximum value of HGS obtained from both hands was used in the analyses. Low muscle strength (LMS) was defined according to the recommendation of European Working Group on Sarcopenia in Older People (EWGSOP). Multivariate linear and logistic regression models were constructed to evaluate the association of ACEs with continuous HGS and LMS, with adjustment for age, sex, marital status, ethnicity, area of residence, smoking and drinking status, body mass index, hypertension, dyslipidaemia, diabetes mellitus, cardiovascular disease, arthritis, hip fracture, and memory-related disease. RESULTS: Of the 7209 eligible participants, 2258 (31.3%) had experienced three or more ACEs. Compared to individuals without ACEs, exposure to ≥ 3 ACEs was negatively associated with continuous HGS in kilogram (ß = -0.93, 95% CI: -1.37, -0.49) and positively associated with the risk of LMS (OR = 1.34, 95% CI: 1.12, 1.61). Such associations were consistently found both in men and women who had experienced three or more ACEs. Significant dose-response relationship between the number of ACEs and outcomes was also observed in the overall population and different sex groups. CONCLUSION: Exposure to ACEs was associated with lower HGS and increased risk of LMS among middle-aged and older Chinese adults, indicating the importance of intervention in individuals with experience of ACEs in order to mitigate its detrimental impact on HGS and promote healthy ageing.

A carbon dot doped lanthanide coordination polymer nanocomposite as the ratiometric fluorescent probe for the sensitive detection of alkaline phosphatase activity.

The development of sensitive methods for alkaline phosphatase (ALP) activity analysis is an important analytical topic. Based on the stimulus-responsive lanthanide coordination polymer, a simple ratiometric fluorescence sensing strategy was proposed to detect ALP activity. A carbon dot (CD) doped fluorescent supramolecular lanthanide coordination polymer (CDs@Tb-GMP) was prepared with Tb3+ and the ligand guanine single nucleotide (GMP). To construct a ratiometric fluorescence biosensor, the fluorescence of Tb-GMP was used as a response signal, and the fluorescence of CDs was used as a reference signal due to its good stability. When excited at 290 nm, the polymer network Tb-GMP emits characteristic fluorescence at 545 nm, while the CDs encapsulated in the polymer network emit fluorescence at 370 nm. After adding ALP to the system, the substrate GMP can be hydrolyzed by ALP, resulting in the destruction of the polymer network. Accordingly, the fluorescence of Tb-GMP significantly decreased, while the fluorescence of CDs slightly increased due to their release from the polymer network. By comparing the relationship between the fluorescence intensity ratio of the two signals and the concentration of ALP, sensitive detection of ALP could be achieved with the linear range from 0.5 to 80 U L-1 and a detection limit of 0.13 U L-1. Furthermore, the proposed ratiometric sensing system was applied to the detection of ALP in human serum samples with desirable results, indicating potential application in clinical diagnosis.

Molecular Engineering-Based Aptamer-Drug Conjugates with Accurate Tunability of Drug Ratios for Drug Combination Targeted Cancer Therapy.

Polytherapy (or drug combination cancer therapy (DCCT)), targeting multiple mechanisms associated with tumor proliferation, can efficiently maximize therapeutic efficacy, decrease drug dosage, and reduce drug resistance. However, most DCCT strategies cannot coordinate the specific delivery of a drug combination in an accurately tuned ratio into cancer cells. To address these limitations, the present work reports the engineering of circular bivalent aptamer-drug conjugates (cb-ApDCs). The cb-ApDCs exhibit high stability, specific recognition, excellent cellular uptake, and esterase-triggered release. Furthermore, the drug ratios in cb-ApDCs can be tuned for an enhanced synergistic effect without the need for complex chemistry. Therefore, cb-ApDCs provide a promising platform for the development of DCCT strategies for different drug combinations and ratios.

Empowering Exosomes with Aptamers for Precision Theranostics.

As information messengers for cell-to-cell communication, exosomes, typically small membrane vesicles (30-150 nm), play an imperative role in the physiological and pathological processes of living systems. Accumulating studies have demonstrated that exosomes are potential biological candidates for theranostics, including liquid biopsy-based diagnosis and drug delivery. However, their clinical applications are hindered by several issues, especially their unspecific detection and insufficient targeting ability. How to upgrade the accuracy of exosome-based theranostics is being widely explored. Aptamers, benefitting from their admirable characteristics, are used as excellent molecular recognition elements to empower exosomes for precision theranostics. With high affinity against targets and easy site-specific modification, aptamers can be incorporated with platforms for the specific detection of exosomes, thus providing opportunities for advancing disease diagnostics. Furthermore, aptamers can be tailored and functionalized on exosomes to enable targeted therapeutics. Herein, this review emphasizes the empowering of exosomes by aptamers for precision theranostics. A brief introduction of exosomes and aptamers is provided, followed by a discussion of recent progress in aptamer-based exosome detection for disease diagnosis, and the emerging applications of aptamer-functionalized exosomes for targeted therapeutics. Finally, current challenges and opportunities in this research field are presented.

Meeting the Canadian 24-Hour Movement Guidelines and physical-mental comorbidity among Chinese children and adolescents: Prevalence, associations, and the population impacts.

OBJECTIVES: To examine the association between meeting the Canadian 24-Hour Movement Guidelines and physical-mental comorbidity among children and adolescents in a cross-sectional study. METHODS: A total of 21,061 students aged 11-17 years from Zhejiang Province, China was recruited in the study. We examined the coexistence of five specific physical illnesses - hypertension, high myopia, dental caries, scoliosis, and obesity - with mental illness, specifically depressive symptoms. Generalized linear mixed models were performed to assess the association between overall and specific combinations of movement guidelines and physical-mental comorbidity, presented by odds ratio (OR) and 95% confidence interval (CI). Population attributable fraction (PAF) was calculated to estimate the preventable proportion of comorbid cases via meeting all three movement recommendations. RESULTS: Of the included participants, 19.3% had physical-mental comorbidity. There were 3.8% and 17.0% meeting all three and none of the recommendations, respectively. Meeting at least one recommendation, except for moderate-to-vigorous physical activity recommendation only, was associated with a lower risk of physical-mental comorbidity, with ORs (95% CIs) ranging from 0.72 (0.66-0.79) to 0.40 (0.31-0.51). Meeting more recommendations was associated with decreased comorbid risks, and the association was stronger in 4th-6th graders. The association between specific combinations of recommendations and comorbid risks showed differences by gender and grade. Of the comorbid cases, 42.1% were attributed to not adhering to all three recommendations, and the PAFs varied from 27.4% to 55.7% across different genders and grades. CONCLUSION: Adherence to the 24-h movement guidelines was associated with lower risks of physical-mental comorbidity among children and adolescents.

Lifetime cumulative effect of reproductive factors on ischaemic heart disease in a prospective cohort.

OBJECTIVE: This study aimed to examine the association between lifetime oestrogen exposure and ischaemic heart disease (IHD), based on the hypothesis that higher lifetime oestrogen exposure is linked to lower cardiovascular risk. METHODS: In 2004-2008, lifetime cumulative exposure to reproductive factors was assessed among postmenopausal females from the China Kadoorie Biobank using reproductive lifespan (RLS), endogenous oestrogen exposure (EEE) and total oestrogen exposure (TEE). EEE was calculated by subtracting pregnancy-related and contraceptive use duration from RLS, while TEE by adding up the same components except for lactation. Incident IHD during follow-up (2004-2015) was identified. Stratified Cox proportional hazards models estimated the HRs and 95% CIs of IHD for RLS, EEE and TEE. RESULTS: Among 118 855 postmenopausal females, 13 162 (11.1%) developed IHD during a median follow-up of 8.9 years. The IHD incidence rates were 13.0, 12.1, 12.5, 13.8 per 1000 person-years for RLS Q1-Q4, 15.8, 12.6, 11.3, 12.1 per 1000 person-years for EEE Q1-Q4 and 13.7, 12.3, 12.2, 13.4 per 1000 person-years for TEE Q1-Q4. The highest quartile (Q4) of RLS and TEE were associated with lower risks of IHD (adjusted HR (aHR) 0.95, 95% CI 0.91 to 1.00 and 0.92, 95% CI 0.88 to 0.97, respectively) compared with the lowest quartile (Q1). Longer EEE showed progressively lower risks of incident IHD (aHR 0.93, 95% CI 0.88 to 0.97; 0.88, 95% CI 0.84 to 0.93; 0.87, 95% CI 0.83 to 0.92 for Q2-Q4 vs Q1). CONCLUSIONS: Longer RLS, TEE and EEE were associated with lower risks of IHD among Chinese postmenopausal females.

Socioeconomic disparities in the association of age at first live birth with incident stroke among Chinese parous women: A prospective cohort study.

Background: Stroke has become a significant public health issue in China. Although studies have shown that women's age at first live birth (AFLB) might be associated with incident stroke, there is limited evidence on this relationship among Chinese parous women. Likewise, the nature of this association across urban-rural socioeconomic status (SES) has yet to be explored. In this prospective study, we sought to investigate the associations of women's AFLB with the risk of incident stroke and its subtypes (ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage) and to explore the differences of these associations as well as the population-level impacts across SES classes. Methods: We used data on 290 932 Chinese parous women from the China Kadoorie Biobank who were recruited in the baseline survey between 2004 and 2008 and followed up until 2015. We used latent class analysis to identify urban-rural SES classes and Cox proportional hazard regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for AFLB's association with incident stroke. We then calculated population attributable fraction (PAF) to demonstrate the population-level impact of later AFLB on stroke. Results: Around 8.9% of parous women developed stroke after AFLB. Compared with women with AFLB <22 years, those with older AFLB had a higher risk of total stroke, with fully adjusted HRs (95% CI) of 1.71 (95% CI = 1.65-1.77) for 22-24 years and 3.37 (95% CI = 3.24-3.51) for ≥25 years. The associations of AFLB with ischaemic stroke were stronger among rural-low-SES participants. We found the highest PAFs of ischaemic stroke (60.1%; 95% CI = 46.2-70.3) associated with later AFLB for urban-high-SES individuals. Conclusions: Older AFLB was associated with higher risks of incident stroke and its subtypes among Chinese parous women, with stronger associations between AFLB and ischaemic stroke among rural-low-SES participants. Targeted medical advice for pregnant women of different ages could have long-term benefits for stroke prevention.

Temporal trends and projections in the global burden of neck pain: findings from the Global Burden of Disease Study 2019.

ABSTRACT: Data were obtained from the Global Burden of Disease study 2019. Joinpoint regression model was used to analyze the temporal trends from 1990 to 2019 of neck pain burden, focusing on age-standardized incidence rates, age-standardized prevalence rates, and age-standardized years lived with disability (YLDs) rates at the global, regional, and national levels. The age-period-cohort analysis was used to estimate the effects of age (5-99 years), period (1990-2019), and cohort (1893-2012) at the global, regional, and national levels. Future projections for the global burden of neck pain from 2020 to 2044 were estimated using the nordpred age-period-cohort model. From 1990 to 2019, the global incidence, prevalence cases, and YLDs counts of neck pain have increased by 71.89%, 98.21%, and 78.17%, respectively. The joinpoint analysis indicated significant shifts in the global trends of age-standardized neck pain burden, which varied across regions and nations. The age-period-cohort model indicated that the neck pain burden was predominantly concentrated in middle-aged and older age, with period and cohort effects showing minimal variation from 1990 to 2019. Compared with 2019, the incident cases, prevalent cases, and YLDs counts of neck pain were projected to increase by 134%, 142%, and 140% by 2044. The global burden of neck pain has persisted at a relatively elevated level from 1990 to 2019, with projections indicating a continuing upward trend. Future research is urgently needed to better understand the predictors and clinical course of neck pain and to enhance prevention and management strategies.

The global and regional prevalence of restless legs syndrome among adults: A systematic review and modelling analysis.

Background: Restless legs syndrome (RLS) is a prevalent neuro-sensory disorder that impairs quality of life. In this systematic review and modelling study, we estimated the global and regional prevalence of RLS and its associated factors. Methods: We searched PubMed, Embase, and Medline for population-based studies on RLS prevalence published up to 12 November 2023. The included studies reported prevalence using the International Restless Leg Syndrome Study Group's (IRLSSG) minimal diagnostic criteria without limitations on frequency, duration, or severity. We applied a multilevel multivariable mixed-effects meta-regression to generate the age-specific and sex-specific prevalence of RLS for high socio-demographic index (H-SDI) and low and middle socio-demographic index (LM-SDI) regions. We pooled odds ratios (ORs) for RLS associated factors using random-effects models. Finally, we derived the regional prevalence and cases of RLS based on an associated factor-based model. Results: From 52 articles across 23 countries, the global RLS prevalence in 2019 was estimated to be 7.12% (95% confidence interval (CI) = 5.15-9.76) among adults 20-79 years of age, equating to 356.07 million (95% CI = 257.61-488.09) affected individuals. Prevalence was similar in H-SDI (7.29%; 95% CI = 5.04-10.41) and LM-SDI (7.10%; 95% CI = 5.16-9.70) regions, with the majority of cases in LM-SDI countries (323.06 million; 90.73%). Europe had the highest (7.60%; 95% CI = 5.44-10.52) and Africa the lowest regional prevalence (6.48%; 95% CI = 4.70-8.87). The Western Pacific Region, meanwhile, had the most cases (111.91 million; 95% CI = 80.93-153.42). Factors positively associated with RLS included advanced age (OR = 1.13; 95% CI = 1.04-1.24), smoking (OR = 1.46; 95% CI = 1.29-1.64), depression (OR = 1.71; 95% CI = 1.26-2.32), and diabetes (OR = 1.54; 95% CI = 1.19-1.97). Conclusions: A considerable global burden of RLS exists. Effective strategies are needed to increase awareness and optimise resource allocation to address this often-overlooked condition. High-quality epidemiological investigations employing standardised and rigorous criteria for RLS are essential for addressing RLS burden more effectively. Registration: PROSPERO: CRD42020161860.

Dose-Response Associations of Internet Use Time and Internet Addiction With Depressive Symptoms Among Chinese Children and Adolescents: Cross-Sectional Study.

Background: Children's lives are increasingly mediated by digital technologies, yet evidence regarding the associations between internet use and depression is far from comprehensive and remains unclear. Objective: This study aimed to investigate the dose-response association between internet use, including use time and addiction behaviors, and depressive symptoms among children and adolescents in Zhejiang Province. Methods: Data were collected from a school-based health survey China Common Disease and Risk Factor Surveillance Among Students, encompassing 21,336 students in Zhejiang Province. The daily internet use time, internet addiction (IA) behaviors, and depressive symptoms were assessed with questionnaires. Logistic regression models were used to explore the associations of internet use time and IA behaviors with depressive symptoms among children and adolescents. Restricted cubic spline curves were used to determine the dose-response associations. Results: A total of 6225 (29.2%) students had depressive symptoms. Compared to those reporting no internet use, boys using the internet for >2 hours/day (odds ratio [OR] 1.53, 95% CI 1.34-1.74) and girls using internet for 1.1-2 hours/day (OR 1.22, 95% CI 1.06-1.39) and >2 hours/day (OR 1.70, 95% CI 1.50-1.93) were at higher risks of depressive symptoms. A significant J-shaped association was identified between internet use time and depressive symptoms among children and adolescents, especially in boys and primary school students (nonlinear P values were .006, .003, and <.001, respectively). Increased IA behaviors were associated with a higher odd of depressive symptoms (1 IA behavior: OR 2.01, 95% CI 1.83-2.21; 2 IA behaviors: 2.91, 95% CI 2.57-3.29; and ≥3 IA behaviors: 4.72, 95% CI 4.26-5.22). A positive nonlinear association between the number of IA behaviors and depressive symptoms was found in total population, girls, and primary school students (nonlinear P values were .02, .002, .007, respectively). Conclusions: Findings suggested that excessive internet use time and IA behaviors were significantly associated with an increased risk of depressive symptoms, highlighting the importance of interventions to regulate and educate about adequate internet use during childhood and adolescence.

Combined associations of general obesity and central obesity with hypertension stages and phenotypes among children and adolescents in Zhejiang, China.

General and central obesity are suggested to be associated with elevated blood pressure (BP), whereas few studies have investigated their combined associations with hypertension in children. This study aimed to assess the associations of combinations of general obesity and central obesity with hypertension in Chinese children, including its stages and phenotypes. A total of 5430 children aged 7-17 years in Zhejiang Province were enrolled. General obesity was evaluated by body mass index (BMI), while central obesity was by waist circumference (WC). Then all children were sorted into three mutually exclusive groups: normal weight with or with no central obesity (NW), abnormal weight with no central obesity (AWNCO), and abnormal weight with central obesity (AWCO). Hypertension was defined as either a systolic or diastolic BP ≥ 95th percentile, and further classified into stage 1 hypertension, stage 2 hypertension, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic diastolic hypertension (SDH). Logistic regression was used. AWNCO and AWCO were associated with stage 1 hypertension (AWNCO, odds ratio [OR] = 1.94, 95% confidence interval [CI]: 1.59-2.37; AWCO, 2.67, 2.20-3.25), stage 2 hypertension (AWNCO, 2.35, 1.33-4.13; AWCO, 4.53, 2.79-7.37), ISH (AWNCO, 2.50, 1.96-3.18; AWCO, 3.95, 3.15-4.95), and SDH (AWNCO, 2.48, 1.75-3.52; AWCO, 2.78, 1.94-3.99). Children with AWCO were more likely to have stage 1 and stage 2 hypertension, as well as ISH and SDH. The combined measurement of general and central obesity is suggested as an appropriate screening tool for hypertension among children and adolescents.

Associations between adverse childhood experiences and diabetes among middle-aged and older Chinese: a social-ecological perspective.

OBJECTIVES: This study examined the associations between adverse childhood experiences (ACEs) and diabetes within a social-ecological framework, incorporating personal and environmental unfavorable conditions during childhood from family, school, and community contexts. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study (2014 life history survey and 2015 survey), including 9,179 participants aged ≥45 years. ACEs were collected through self-report questionnaires, and participants were categorized based on the number of distinct ACEs experienced (0, 1, 2, 3, or ≥4 ACEs). Diabetes was defined by biomarkers, self-reported diagnosis, and treatment status. Logistic regression was conducted to explore the associations between ACEs and diabetes. Subgroup analyses were conducted by gender, age, and obesity status. RESULTS: Compared with participants without ACEs, those exposed to any ACE (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.01 to 1.40), 3 ACEs (OR, 1.32; 95% CI, 1.07 to 1.62) and ≥4 ACEs (OR, 1.29; 95% CI, 1.07 to 1.56) had an increased risk of diabetes. For each additional ACE, the risk of diabetes increased by about 5%. Regarding the source of ACEs, those originating from the family (OR, 1.23; 95% CI, 1.08 to 1.41) were associated with diabetes. In terms of specific ACE types, family members with substance abuse (OR, 1.23; 95% CI, 1.01 to 1.52), emotional abuse (OR, 1.28; 95% CI, 1.12 to 1.46), and poor parental relationship (OR, 1.25; 95% CI, 1.09 to 1.43) were associated with diabetes. CONCLUSIONS: ACEs, particularly those originating from the family, were associated with diabetes. Interventions aimed at preventing and mitigating ACEs are essential for the early prevention of diabetes.