Hyperuricemia and coronary heart disease: The mediating role of blood pressure and thrombospondin 3.

BACKGROUND & AIMS: Although hyperuricemia is a known risk factor for coronary heart disease (CHD), little is known about the role of blood pressure in mediating this association. The purpose of this study is to investigate the role of blood pressure-related indicators and Thrombospondin 3 (THBS3) in the association between hyperuricemia and CHD. METHODS AND RESULTS: Our observational epidemiology study included 593 CHD cases and 760 controls from a residential stable sample. We also chose 43 new CHD patients and 43 controls to test the expression levels of THBS3 using ELISA kits. We used logistic regression models and mediating effect analysis to investigate the relationships between hyperuricemia and CHD, as well as the mediating role of blood pressure-related indicators and THBS3. In the general population (OR: 2.001 [95% CI: 1.528-2.622]), male population (OR: 1.591 [95% CI: 1.119-2.262]), and female population (OR: 2.813 [95% CI: 1.836-4.310]), hyperuricemia is an independent risk factor for CHD. In general, average systolic blood pressure (SBP) and average pulse pressure difference (PPD) mediated 3.35% and 4.59%, respectively, of the association between hyperuricemia and CHD, and 6.60% and 6.60% in women. However, in the male population, we have not yet found that blood pressure-related indicators had a significant mediating effect. Meanwhile, we found that THBS3 mediated 19.23% of the association between hyperuricemia and CHD. CONCLUSIONS: Average SBP, PPD, and THBS3 all play a role in the association of hyperuricemia and CHD. In the female population, similar mediating results in blood pressure-related indicators were observed.

Association between polyfluoroalkyl substances exposure and sex steroids in adolescents: The mediating role of serum albumin.

BACKGROUND: Polyfluoroalkyl substances (PFASs) are an emerging class of contaminants with endocrine disrupting hazards. The impact of PFASs exposure on sex steroids remain inconclusive. METHODS: This study used data from the 2013-2016 National Health and Nutrition Examination Survey (NHANES), including 525 adolescents aged 12-19. We explored the association between serum PFASs and sex steroids using multiple linear regression, weighted quantified sum (WQS) regression, and Bayesian kernel machine regression (BKMR). Mediation analyses were performed to assess whether serum albumin mediates the effects of PFASs on sex steroids. RESULTS: Single exposure to perfluorohexane sulfonic acid (PFHxS) or n-perfluorooctanoic acid (n-PFOA) was found to be inversely associated with sex hormone binding protein (SHBG) after adjustment for confounders. Results from both the WQS and BKMR models showed that mixed exposure to the five PFASs was negatively associated with SHBG and testosterone (TT) in all adolescents, while only in the WQS model, the mixed exposure to PFASs was negatively correlated with E2 and FAI in boys and negatively correlated with TT and SHBG in girls. Serum albumin was found to possibly mediate 9.7 % of the association between mixed PFAS exposure and TT, and 9.7 % of the association between mixed PFAS exposure and SHBG. CONCLUSION: Our study demonstrates a negative association between mixed exposure to PFASs and adolescent TT and SHBG levels, and suggests that albumin may merit further study as a potential target for PFAS harm reduction.

Intravenous Patient-Controlled Analgesia Versus Oral Opioid to Maintain Analgesia for Severe Cancer Pain: A Randomized Phase II Trial.

BACKGROUND: Optimal analgesic maintenance for severe cancer pain is unknown. This study evaluated the efficacy and safety of intravenous patient-controlled analgesia (IPCA) with continuous infusion plus rescue dose or bolus-only dose versus conventional oral extended-release morphine as a background dose with normal-release morphine as a rescue dose to maintain analgesia in patients with severe cancer pain after successful opioid titration. METHODS: Patients with persistent severe cancer pain (≥7 at rest on the 11-point numeric rating scale [NRS]) were randomly assigned to 1 of 3 treatment arms: (A1) IPCA hydromorphone with bolus-only dose where dosage was 10% to 20% of the total equianalgesic over the previous 24 hours (TEOP24H) administered as needed, (A2) IPCA hydromorphone with continuous infusion where dose per hour was the TEOP24H divided by 24 and bolus dosage for breakthrough pain was 10% to 20% of the TEOP24H, and (B) oral extended-release morphine based on TEOP24H/2 × 75% (because of incomplete cross-tolerance) every 12 hours plus normal-release morphine based on TEOP24H × 10% to 20% for breakthrough pain. After randomization, patients underwent IPCA hydromorphone titration for 24 hours to achieve pain control before beginning their assigned treatment. The primary endpoint was NRS over days 1 to 3. RESULTS: A total of 95 patients from 9 oncology study sites underwent randomization: 30 into arm A1, 32 into arm A2, and 33 into arm B. Arm B produced a significantly higher NRS over days 1 to 3 compared with arm A1 or A2 (P<.001). Daily NRS from day 1 to day 6 and patient satisfaction scores on day 3 and day 6 were worse in arm B. Median equivalent-morphine consumption increase was significantly lower in A1 (P=.024) among the 3 arms. No severe adverse event occurred in any arm. CONCLUSIONS: Compared with oral morphine maintenance, IPCA hydromorphone for analgesia maintenance improves control of severe cancer pain after successful titration. Furthermore, IPCA hydromorphone without continuous infusion may consume less opioid.

Comparing Patient-Controlled Analgesia Versus Non-PCA Hydromorphone Titration for Severe Cancer Pain: A Randomized Phase III Trial.

BACKGROUND: Opioid titration is necessary to achieve rapid, safe pain relief. Medication can be administered via patient-controlled analgesia (PCA) or by a healthcare provider (non-PCA). We evaluated the efficacy of intravenous PCA versus non-PCA hydromorphone titration for severe cancer pain (≥7 at rest on the 11-point numeric rating scale [NRS]). PATIENTS AND METHODS: Patients with severe cancer pain were randomized 1:1 to PCA or non-PCA titration, stratified by opioid-tolerant or opioid-naïve status. The PCA pump was set to no continuous dose, with a hydromorphone bolus dose 10% to 20% of the total previous 24-hour equianalgesic (for opioid-tolerant patients) or 0.5 mg (for opioid-naïve patients). For the non-PCA group, the initial hydromorphone bolus dose was identical to that in the PCA group, with the subsequent dose increased by 50% to 100% (for NRS unchanged or increased) or repeated at the current dose (for NRS 4-6). Hydromorphone delivery was initiated every 15 minutes (for NRS ≥4) or as needed (for NRS ≤3). The primary endpoint was time to successful titration (TST; time from first hydromorphone dose to first occurrence of NRS ≤3 in 2 consecutive 15-minute intervals). RESULTS: Among 214 patients (PCA, n=106; non-PCA, n=108), median TSTs (95% CI) were 0.50 hours (0.25-0.50) and 0.79 hours (0.50-1.42) for the PCA and non-PCA groups, respectively (hazard ratio [HR], 1.64; 95% CI, 1.23-2.17; P=.001). TSTs in opioid-tolerant patients were 0.50 hours (0.25-0.75) and 1.00 hours (0.50-2.00) for the PCA and non-PCA groups, respectively (HR, 1.92; 95% CI, 1.32-2.78; P=.003); in opioid-naive patients, TST was not significantly different for the PCA versus non-PCA groups (HR, 1.35; 95% CI, 0.88-2.04; P=.162). Pain score (median NRS; interquartile range) over 24 hours was significantly lower in the PCA group (2.80; 2.15-3.22) than in the non-PCA group (3.00; 2.47-3.53; P=.020). PCA administration produces significantly higher patient satisfaction with pain control than non-PCA administration (P<.001). CONCLUSIONS: Intravenous hydromorphone titration for severe cancer pain was achieved more effectively with PCA than with non-PCA administration.

Associations between meteorological variation and rupture of intracranial aneurysm in Fujian, China: A 5-year multicenter study.

OBJECTIVE: By exploring the exposure-response relationships between meteorological factors and rupture of intracranial aneurysm (IA) to reveal the influence of meteorological variation on IA rupture under the specific climate in Fujian, China. METHOD: 7515 cases of IA rupture from several municipal medical institutions in Fujian Province as well as local meteorological data during the same period were collected from 2013 to 2017. Poisson regression and Spearman correlation analysis were applied to explore the distribution characteristics of IA rupture and how it is associated with meteorological parameters. Poisson generalized additive model was established to further analyze the exposure-response relationships between meteorological factors and IA rupture, and its hysteresis effects. RESULT: The IA rupture exhibited a negative correlation with temperature (rs = -0.323, 95% CI: -0.539 ~ -0.068) and a positive correlation with atmospheric pressure (rs = 0.397, 95% CI: 0.152-0.597) or pressure difference (rs = 0.296, 95% CI: 0.038-0.517), 21.05 â„ƒ and 1000.14 hPa were the risk thresholds for the onset ascribed to variation in temperature and atmospheric pressure, respectively. Temperature and atmospheric pressure also exerted hysteresis effects on IA rupture. Cold will increase the rupture risk in the subsequent 1-3 days, and high pressure will raise the morbidity in the next 1-2 days. Besides, drastic variations in temperature and atmospheric pressure were also associated with the higher risk of IA rupture in the next 2 days and 1 day, respectively. CONCLUSION: Temperature and atmospheric pressure have a negative and positive correlation with IA rupture in Fujian, China, respectively. Variation in temperature and atmospheric pressure exert different degrees of hysteresis effects on IA rupture.

Region-specific air pollutants and meteorological parameters influence COVID-19: A study from mainland China.

Coronavirus disease 2019 (COVID-19) was first detected in December 2019 in Wuhan, China, with 11,669,259 positive cases and 539,906 deaths globally as of July 8, 2020. The objective of the present study was to determine whether meteorological parameters and air quality affect the transmission of COVID-19, analogous to SARS. We captured data from 29 provinces, including numbers of COVID-19 cases, meteorological parameters, air quality and population flow data, between Jan 21, 2020 and Apr 3, 2020. To evaluate the transmissibility of COVID-19, the basic reproductive ratio (R0) was calculated with the maximum likelihood "removal" method, which is based on chain-binomial model, and the association between COVID-19 and air pollutants or meteorological parameters was estimated by correlation analyses. The mean estimated value of R0 was 1.79 ± 0.31 in 29 provinces, ranging from 1.08 to 2.45. The correlation between R0 and the mean relative humidity was positive, with coefficient of 0.370. In provinces with high flow, indicators such as carbon monoxide (CO) and 24-h average concentration of carbon monoxide (CO_24 h) were positively correlated with R0, while nitrogen dioxide (NO2), 24-h average concentration of nitrogen dioxide (NO2_24 h) and daily maximum temperature were inversely correlated to R0, with coefficients of 0.644, 0.661, -0.636, -0.657, -0.645, respectively. In provinces with medium flow, only the weather factors were correlated with R0, including mean/maximum/minimum air pressure and mean wind speed, with coefficients of -0.697, -0.697, -0.697 and -0.841, respectively. There was no correlation with R0 and meteorological parameters or air pollutants in provinces with low flow. Our findings suggest that higher ambient CO concentration is a risk factor for increased transmissibility of the novel coronavirus, while higher temperature and air pressure, and efficient ventilation reduce its transmissibility. The effect of meteorological parameters and air pollutants varies in different regions, and requires that these issues be considered in future modeling disease transmissibility.

Influence of miR-520e-mediated MAPK signalling pathway on HBV replication and regulation of hepatocellular carcinoma cells via targeting EphA2.

We determined the role of miR-520e in the replication of hepatitis B virus (HBV) and the growth of hepatocellular carcinoma (HCC) cells. MiR-520e and EPH receptor A2 (EphA2) in HBV-positive HCC tissues and cells were detected, and we studied the impact of miR-520e and the EphA2 receptor in cellular and murine HBV replication models. We find that MiR-520e was upregulated and EphA2 was downregulated in HBV-positive HCC tissues and cells. MiR-520e was decreased in Huh7-X and HepG2-X cells in which HBx was stably expressed, but was dose-dependently elevated after interfering with HBx. Additionally, miR-520e mimic and si-EphA2 groups were reduced in association with increases in HBV DNA content, HBsAg and HBeAg levels, cell proliferation and were enhanced in the expressions of EphA2, p-p38MAPK/p38MAPK, phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2)/ERK1/2 and cell apoptosis. Furthermore, si-EphA2 reversed the promotion effect of miR-520e inhibitor on HBV replication and tumour cell growth. Upregulating miR-520e in rAAV8-1.3HBV-infected mouse resulted in reduced EphA2 in liver tissues and HBV DNA content in serum. We find that MiR-520e was decreased in HBV-positive HCC, while overexpression of miR-520e blocked p38MAPK and ERK1/2 signalling pathways by an inhibitory effect on EphA2 and ultimately reduced HBV replication and inhibited tumour cell growth. These data indicate a role for miR-520e in the regulation of HBV replication.

Association of circular RNAs and environmental risk factors with coronary heart disease.

BACKGROUND: Coronary heart disease (CHD) is a complex disease caused by multi-factors and a major threat to human health. Circular RNAs (circRNAs) have critical roles in various biological processes and diseases. This study explores the independent role of circRNAs and their interaction with environmental factors in CHD. METHODS: A case-control study was conducted from March 2015 to September 2017 in Fuzhou, China. A total of 585 CHD patients and 585 gender- and age-matched healthy controls were enrolled. Questionnaire survey, health examination and molecular biology laboratory testing were conducted. Microarray technology and quantitative real-time polymerase chain reaction (PCR) were used to profile the expression levels of circRNAs. The area under the curve (AUC) of the receiver operating characteristic (ROC) was used to determine the diagnostic cut-offs. Multivariate logistic regression and multiplicative analysis were used to analyse the effects of environmental factors and hsa_circ_0008507, hsa_circ_0001946, hsa_circ_0000284 and hsa_circ_0125589 on CHD. RESULTS: The expression profile of circRNAs showed that 3423 circRNAs were differentially expressed at P < 0.05, but none pass multiple testing correction. qRT-PCR further confirmed the expression levels of hsa_circ_0008507, hsa_circ_0001946 and hsa_circ_0000284 in peripheral blood leukocytes in CHD cases were higher than those in non-CHD subjects (All p < 0.05). Hsa_circ_0008507 (OR = 1.29; 95% CI: 1.11-1.50), hsa_circ_0001946 (OR = 1.20; 95% CI: 1.01-1.42) and hsa_circ_0000284 (OR = 2.05; 95% CI: 1.32-3.19) were independent risk factors for CHD after controlling other common environmental risk factors. The AUC for hsa_circ_0008507, hsa_circ_0001946 and hsa_circ_0000284 was 0.75, 0.71 and 0.68, respectively. Compared with non-smoking individuals with low hsa_circ_0008507 expression, the smokers with high hsa_circ_0008507 expression showed the highest magnitude of OR in CHD risk. Additionally, a statistically significant multiplicative interaction was found between hsa_circ_0008507 and smoking for CHD. CONCLUSIONS: Hsa_circ_0008507, hsa_circ_0001946 and hsa_circ_0000284 were closely related to the occurrence and development of CHD. The combination of smoking and high hsa_circ_0008507 expression causes the occurrence and development of CHD.

[Interaction between long noncoding RNA and environmental factors on coronary heart disease].

OBJECTIVE: To investigate the role of leukocyte long noncoding RNA(lncRNA) and environmental factors on coronary heart disease(CHD). METHODS: A case-control study was conducted in a hospital in Fuzhou City by using stratified random sampling method during March 2015 and December 2017. The related surveys included questionnaire investigation, physical examination and laboratory detection. And real-time fluorescence quantitative PCR was used to detect the expression of lncRNA(NR_027032, NR_047116 and NR_104181) in case group and control group. Multivariate Logistic regression models and crossover analysis were used to analyze the interaction and association of environmental factors and lncRNA on CHD. RESULTS: Wilcoxon rank sum test indicated that: The expression levels of NR_027032, NR_047116 and NR_104181 in CHD were lower than those in control group, the difference was statistically significant(P<0.05). Multivariate Logistic regression analysis showed that the low expression of NR_027032, NR_047116 and NR_104181 may increase the risk of CHD. Crossover analysis showed that the risk of CHD was 19.053 times(95% CI 5.159-70.361) in the presence of overweight and low expression of NR_047116 than that in the normal condition. And the additive model between the two groups was statistically significant(U=1.999, P=0.046). The evaluation indexes were S=0.598, AP=10.070 and RERI=0.629. CONCLUSION: CHD is the result of environmental factors and genetic factors. The association and additive effect of NR_047116 low expression and overweight may increase the risk of CHD.

Relationship of cardiovascular disease risk factors and noncoding RNAs with hypertension: a case-control study.

BACKGROUND: The present study sought to explore the relationship of common cardiovascular disease risk factors and noncoding RNAs with essential hypertension (EH). METHODS: A total of 402 EH patients and 402 gender- and age-frequency matched healthy controls were enrolled in this study. Each participant received a questionnaire survey, physical examination and laboratory tests. Quantitative real-time polymerase chain reaction (qPCR) was performed to assess relative expression levels of six noncoding RNAs (NR_027032, NR_034083, NR_104181, miR-126, miR-143 and miR-145) in peripheral blood leucocytes. Multiple logistic regression analysis was used to estimate the risk of having EH between hypertensive and non-hypertensive patients. RESULTS: Analysis showed that participants with anxiety, high body mass index, abdominal obesity and family history of hypertension had higher risk for EH, whereas those with bland diet and occupational physical activities had lower risk for EH. qPCR assays showed that NR_027032 (P = 0.015) and NR_034083 (P = 0.004) were significantly reduced in EH patients compared with controls, whereas NR_104181 (P = 0.007), miR-143 (P = 0.005) and miR-145 (P = 0.015) were significantly elevated. After controlling the cardiovascular risk factors, multivariate analysis showed that lower expression levels of NR_034083 and higher expression levels of NR_104181 and miR-143 were risk factors for EH. CONCLUSIONS: EH is a result of environmental and epigenetic factors. Strikingly, NR_034083, NR_104181 and miR-143 may be correlated with the risk for EH development; therefore, epigenetic markers could be used to measure hypertension levels to help elucidate the pathogenesis of EH.

[Measurement invariance of sub-health questionnaire in doctor and nurse].

OBJECTIVE: To examine the measurement invariance of sub-health questionnaire in doctor and nurse, and compare their sub-health status. METHODS: Totally 1832 doctors and nurses were selected by multi-stage stratified cluster random sampling method and investigated with a sub-health questionnaire. Measurement invariance between two groups was tested by multiple group confirmatory factor analysis. RESULTS: The test of measurement invariance for the one-factor model showed that the subhealth questionnaire met the criteria for measurement invariance( ΔCFI < 0. 01). The level of strict invariance( equal factor loadings, intercepts, and residual variances between groups) was achieved. When the latent means were compared, differences between groups were not statistically significant( the latent means of the dimensions were0. 029, 0. 050, 0. 054 and 0. 010, respectively, and the P value were 0. 385, 0. 168, 0. 092 and 0. 753, respectively). CONCLUSION: The sub-health questionnaire has the universal applicability to the medical staff.

Hypomethylation of the Angiotensin II Type I Receptor (AGTR1) Gene Along with Environmental Factors Increases the Risk for Essential Hypertension.

OBJECTIVES: The present study aimed to evaluate the hypertension status of community residents, analyze environmental and epigenetic factors, and propose prevention measures for hypertension. METHODS: In our study, different methylation levels were distinguished utilizing melting temperature (Tm) values in both the case and the control group. Multiple logistic regression analysis was used to estimate the risk of having essential hypertension (EH) between hypertensive and nonhypertensive participants. A receiver-operating characteristic curve was used to analyze Tm cutoff levels of methylation. RESULTS: The average DNA Tm was 71.784 with a standard deviation of 0.210. The Tm value of community residents (Fujian, China) was inversely correlated with systolic and diastolic blood pressure. Student t test analysis showed a clear separation in Tm expression levels between the hypertensive and the control group (p < 0.05). The Tm value was lower in the hypertension group than in the normotensive group. Multivariate regression analysis showed that high levels of DNA methylation were a protective factor in hypertension with adjustment of demographic and environmental factors, whereas when the Tm value increased by 0.1 units, the risk of hypertension was reduced by 0.652 times. Patients that smoked and consumed an irregular diet demonstrated a lower degree of methylation in the presence of hypertension. CONCLUSIONS: DNA methylation affects the risk for the development of hypertension; therefore, epigenetic markers could be used to measure hypertension levels to help elucidate the pathogenesis of EH.

[A study of sub-healthy status of community residents and its relevant factors in Fuzhou City].

OBJECTIVE: To evaluate the sub-healthy status of community residents and its main relevant factors. METHODS: The proportional stratified random sampling was selected to take the sample of 5000 community residents from two communities in Fujian province. The sub-healthy status and its main influence factors were measured with the method of physical examination and questionnaire. RESULTS: The women, the oldest group (≥60 years old) and the divorce/widowed group were found to have the higher scores of sub-health status than others (P <0. 05). Multivariate analysis showed that female, age, education level and irregular eating were the main risk factors for the three dimensions of sub-health status. Divorced or widowed statue was unfavorable factors for physical and psychological sub-health status. Quit smoking was found to be significant risk factor for psychological and social sub-health status. Body mass index (BMI) was related to physical sub-health status, alone. While physical exercise was the main protective factor for sub-health status. CONCLUSION: Improving behavioral habits, maintaining stable family, maintaining normal BMI may be important to prevent sub-health status among community residents.

[Status of job burnout and its influential factors in seafarers].

OBJECTIVE: To investigate the status of job burnout and its main influential factors in seafarers and to provide a scientific basis for ensuring the physical and psychological health of seafarers and increasing their working performance. METHODS: A total of 1027 seafarers, who underwent physical examination at Fujian International Travel Health Care Center from January to June, 2013, and left and entered China through the Fujian port, were selected. The status of job burnout was investigated using a job burnout scale. A total of 1027 questionnaires were sent out, and 989 valid ones (96.30%) were returned. RESULTS: The scores of emotional exhaustion and cynicism were the highest in the youngest age group (<30 years), divorced or widowed group, or those with a monthly income per person over 10,000 yuan (P < 0.05). The score of reduced personal accomplishment was the highest in seafarers with a degree of junior high school or less or those with a monthly income per person of 3 000-6 000 yuan (P < 0.05). The highest scores of emotional exhaustion and cynicism were also seen in seafarers with the highest frequency of overtime working, high occupational stress, less than 6 hours' sleep per day, or poor sleep quality (P < 0.05). The highest score of reduced personal accomplishment was also seen in seafarers with the latest sail time lasting for more than six months, low occupational stress, or good sleep quality (P < 0.05). Multivariate analysis showed that poor sleep quality and occupational stress were the main risk factors for job burnout in seafarers, while physical exercise was a protective factor. CONCLUSION: Job burnout among seafarers is influenced by many factors. Therefore, measures should be taken by relevant administrative departments and seafarers themselves to reduce the incidence of job burnout.

Bayesian estimation of the measurement of interactions in epidemiological studies.

Background: Interaction identification is important in epidemiological studies and can be detected by including a product term in the model. However, as Rothman noted, a product term in exponential models may be regarded as multiplicative rather than additive to better reflect biological interactions. Currently, the additive interaction is largely measured by the relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and the synergy index (S), and confidence intervals are developed via frequentist approaches. However, few studies have focused on the same issue from a Bayesian perspective. The present study aims to provide a Bayesian view of the estimation and credible intervals of the additive interaction measures. Methods: Bayesian logistic regression was employed, and estimates and credible intervals were calculated from posterior samples of the RERI, AP and S. Since Bayesian inference depends only on posterior samples, it is very easy to apply this method to preventive factors. The validity of the proposed method was verified by comparing the Bayesian method with the delta and bootstrap approaches in simulation studies with example data. Results: In all the simulation studies, the Bayesian estimates were very close to the corresponding true values. Due to the skewness of the interaction measures, compared with the confidence intervals of the delta method, the credible intervals of the Bayesian approach were more balanced and matched the nominal 95% level. Compared with the bootstrap method, the Bayesian method appeared to be a competitive alternative and fared better when small sample sizes were used. Conclusions: The proposed Bayesian method is a competitive alternative to other methods. This approach can assist epidemiologists in detecting additive-scale interactions.

Prevalence, genetic and clinical characteristics in first-degree relatives of patients with familial cerebral cavernous malformations in China.

OBJECTIVE: This study aims to investigate the prevalence of familial cerebral cavernous malformations (FCCMs) in first-degree relatives (FDRs) using familial screening, to describe the distribution of initial symptoms, lesion count on cranial MRI and pathogenic gene in patients. METHODS: Patients with multiple CCMs who enrolled from the Treatments and Outcomes of Untreated Cerebral Cavernous Malformations in China database were considered as probands and FDRs were recruited. Cranial MRI was performed to screen the CCMs lesions, and whole-exome sequencing was performed to identify CCM mutations. MRI and genetic screening were combined to diagnose FCCM in FDRs, and the results were presented as prevalence and 95% CIs. The Kaplan-Meier (KM) method was used to calculate the cumulative incidence of FCCM. RESULTS: 33 (76.74%) of the 43 families (110 FDRs) were identified as FCCM (85 FDRs). Receiver operating characteristic analysis revealed three lesions on T2-weighted imaging (T2WI) were the strong indicator for distinguishing probands with FCCM (sensitivity, 87.10%; specificity, 87.50%). Of the 85 FDRs, 31 were diagnosed with FCCM, resulting in a prevalence of 36.5% (26.2%-46.7%). In families with FCCMs, the mutation rates for CCM1, CCM2 and CCM3 were 45.45%, 21.21% and 9.09%, respectively. Furthermore, 53.13% of patients were asymptomatic, 17.19% were intracranial haemorrhage and 9.38% were epilepsy. The mean age of symptom onset analysed by KM was 46.67 (40.56-52.78) years. CONCLUSION: Based on MRI and genetic analysis, the prevalence of CCMs in the FDRs of families with FCCMs in China was 36.5%. Genetic counselling and MRI screening are recommended for FDRs in patients with more than three CCM lesions on T2WI.

Plasmonic metasurface enhanced by nanobumps for label-free biosensing of lung tumor markers in serum.

Plasmonic metasurface biosensing has excellent potential in label-free detection of tumor biomarkers. In general, a variety of plasmonic metasurface nanofabrication leads to various degree of metallic surface roughness. However, the metasurface roughness effects on plasmonic sensing of tumor markers have been barely reported. Here we fabricate high-roughness (HR) gold nanohole metasurfaces with nanobumps and investigate their biosensing in comparison with the low-roughness (LR) counterparts. The HR metasurfaces demonstrate the surface sensitivity of multilayer polyelectrolyte molecules, which is 57.0% higher than the LR ones. The HR metasurfaces also illuminate higher immunoassay sensitivity to multiple lung cancer biomarkers, including carcinoembryonic antigen, neuron-specific enolase and cytokeratin fragment 21-1. The highest increasement of tumor marker sensitivity is up to 71.4%. The biosensing enhancement is attributed to the introduction of gold nanobumps on metasurfaces, which provides more hot-spot regions, higher localized near-field intensity and better optical impedance matching. Furthermore, the biosensing of HR metasurfaces effectively covers the threshold values of tumor markers for early lung cancer diagnosis, and is used for the detection of clinical serum samples. The testing deviation is less than 4% compared with commercial immunoassay, which implies promising applications on medical examinations. Our research provides a scientific guide to surface roughness engineering for plasmonic metasensing in the future point-of-care testing.

Label-free plasmonic metasensing of PSA and exosomes in serum for rapid high-sensitivity diagnosis of early prostate cancer.

Prostate-specific antigen (PSA) test is widely used to diagnose early prostate cancer (PCa). Its low sensitivity, especially in the gray zone, usually incurs overtreatment or missed diagnosis. As an emerging tumor marker, exosomes have attracted great interest in non-invasive diagnosis of PCa. However, the quick direct detection of exosomes in serum is still a big challenge for convenient screening of early PCa due to their high-degree heterogeneity and complexity. Here we develop the label-free biosensors based on wafer-scale plasmonic metasurfaces, and establish a flexible spectral methodology of exosomes profiling, which facilitates their identification and quantification in serum. We combine the metasurfaces functionalized by anti-PSA and anti-CD63, respectively, and build a portable immunoassay system to detect serum PSA and exosomes simultaneously within 20 min. Our scheme can discriminate early PCa from benign prostatic hyperplasia with a diagnostic sensitivity of 92.3%, which is much higher that of 58.3% for conventional PSA tests. The receiver operating characteristic analysis in clinical trials demonstrates significant PCa distinguishing capability with an area under the curve up to 99.4%. Our work provides a rapid and powerful approach for precise diagnosis of early PCa, and will inspire more exosomes metasensing studies for other early cancer screening.

Life-course fertility and multimorbidity among middle-aged and elderly women in China: Evidence from China health and retirement longitudinal study.

Background: Multimorbidity has become an important public health problem in China, especially among middle-aged and elderly women. Few studies have been reported on the association between multimorbidity and female fertility, which is an important stage in the life course. This study aimed to explore the association between multimorbidity and fertility history among middle-aged and elderly women in China. Methods: Data from 10,182 middle-aged and elderly female participants in the China Health and Retirement Longitudinal Study (CHARLS) in 2018 were used in this study. Multimorbidity was defined as the presence of at least two or more chronic conditions. Logistic regression analysis, negative binomial regression analysis, and restrictive cubic splines (RCSs) were used to analyze the relationship between female fertility history and multimorbidity or the number of chronic conditions. Multivariable linear regression was used to analyze the relationship between female fertility history and multimorbidity pattern factor scores. Results: The results of this study showed that high parity and early childbearing were significantly associated with an increased risk of multimorbidity and an increased number of chronic conditions among middle-aged and elderly women in China. Late childbearing was significantly associated with reduced risk of multimorbidity and lessened diseases. Parity and age of first childbirth were significantly correlated with the odds of multimorbidity. The association between fertility history and multimorbidity was found to be influenced by age and urban-rural dual structure. Women with high parity tend to have higher factor scores of cardiac-metabolic, visceral-arthritic, and respiratory-psychiatric patterns. Women with early childbearing tended to have higher factor scores of the visceral-arthritic pattern and those with late childbearing tended to have lower factor scores of the cardiac-metabolic pattern. Conclusion: Fertility history has a significant effect on multimorbidity in the middle and later lives of Chinese women. This study is of great importance for reducing the prevalence of multimorbidity among Chinese women through their life course and promoting health during their middle and later lives.

Prognostic factors affecting the ruptured intracranial aneurysms: A 9-year multicenter study in Fujian, China.

BACKGROUND: A multicenter retrospective study was conducted to explore the factors affecting short-term prognosis and long-term outcomes of intracranial aneurysms (IA) rupture. Further, the prognosis prediction model was constructed based on survival analysis, contributing to the development of prevention strategies for aneurysmal subarachnoid hemorrhage. METHODS: Data of 1280 patients with IA rupture were gathered between 2014 and 2022 in Fujian, China. Logistic regression was implemented to study the short-term prognostic factors of IA rupture. Survival analysis of 911 patients among them was performed to explore the long-term outcome status by Cox risk assessment. Nomogram prognosis models were constructed using R software. RESULTS: The findings displayed that blood type O (OR = 1.79; P = 0.019), high systolic pressure (OR = 1.01; P < 0.001), Glasgow Coma score (GCS) 9-12 (OR = 2.73; P = 0.022), GCS < 9 (OR = 3.222; P = 0.006), diabetes (OR = 2.044; P = 0.040), and high white blood cell count (OR = 1.059, P = 0.040) were core influencing factors for poor short-term prognosis. Survival analysis revealed that age > 60 years (HR = 2.87; P = 0.001), hypertension (HR = 1.95; P = 0.001), conservative (HR = 6.89; P < 0.001) and endovascular treatment (HR = 2.20; P = 0.001), multiple ruptured IAs (HR = 2.37; P = 0.01), Fisher 3 (HR = 1.68; P = 0.09), Fisher 4 (HR = 2.75; P = 0.001), and Hunt-Hess 3 (HR = 0.55; P = 0.05) were the major risk factors for terrible long-term outcomes. CONCLUSIONS: People over 60 years with characteristics of type O blood, high systolic pressure, diabetes, high white blood cell count, and onset GCS < 12 will have more complications and a worse short-term prognosis. Those aged > 60 years with hypertension, conservative and endovascular treatment, multiple ruptured IAs, Fisher ≥ 3 and Hunt-Hess 3 have a greater risk of poor long-term prognosis.