Experimental Evaluation of Performance of a Low-Initial-Viscosity Gel Flooding System.

In order to effectively adjust reservoir heterogeneity and further exploit the remaining oil, a new type of low-viscosity gel was prepared by adding a regulating agent, retarder, and reinforcing agent on the basis of a polymer + Cr3+ crosslinking system. The new gel has the advantages of low initial viscosity, a slow gel formation rate, and high strength after gel formation. The effectiveness of the gel was verified through three-layer core displacement experiments, and the injection scheme was optimized by changing the slug combination of the polymer and the gel. The results showed that the gel can effectively block the high-permeability layer and adjust reservoir heterogeneity. An injection of 0.1 pore volume (PV) low-initial-viscosity gel can improve oil recovery by 5.10%. By changing the slug combination of the gel and polymer, oil recovery was further increased by 3.12% when using an injection of 0.07 PV low-initial-viscosity gel +0.2 PV high-concentration polymer +0.05 PV low-initial-viscosity gel +0.5 PV high-concentration polymer.

Magnifying image-enhanced endoscopy-only mode boosted early cancer diagnostic efficiency: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Magnifying image-enhanced endoscopy (MIEE) is an advanced endoscopy with image enhancement and magnification used in preoperative examination. However, its impact on the detection rate is unknown. METHODS: We conducted an open-label, randomized, parallel (1:1:1), controlled trial in 6 hospitals in China. Patients were recruited between February 14, 2022 and July 30, 2022. Eligible patients were aged ≥18 years and undergoing gastroscopy in outpatient departments. Participants were randomly assigned to the MIEE-only mode (o-MIEE) group, white-light endoscopy-only mode (o-WLE) group, and MIEE when necessary mode (n-MIEE) group (initial WLE followed by switching to another endoscope with MIEE if necessary). Biopsy sampling of suspicious lesions of the lesser curvature of the gastric antrum was performed. Primary and secondary aims were to compare detection rates and positive predictive value (PPV) of early cancer and precancerous lesions in these 3 modes, respectively. RESULTS: A total of 5100 recruited patients were randomly assigned to the o-MIEE (n = 1700), o-WLE (n = 1700), and n-MIEE (n = 1700) groups. In the o-MIEE, o-WLE, and n-MIEE groups, 29 (1.51%; 95% confidence interval [CI], 1.05-2.16), 4 (.21%; 95% CI, .08-.54), and 8 (.43%; 95% CI, .22-.85) early cancers were found, respectively (P < .001). The PPV for early cancer was higher in the o-MIEE group compared with the o-WLE and n-MIEE groups (63.04%, 33.33%, and 38.1%, respectively; P = .062). The same trend was seen for precancerous lesions (36.67%, 10.00%, and 21.74%, respectively). CONCLUSIONS: The o-MIEE mode resulted in a significant improvement in diagnosing early upper GI cancer and precancerous lesions; thus, it could be used for opportunistic screening. (Clinical trial registration number: ChiCTR2200064174.).

Associations of daytime napping and nighttime sleep quality with depressive symptoms in older Chinese: the Guangzhou biobank cohort study.

BACKGROUND: Poor sleep quality has been linked to depression in older adults, but results of the association between daytime napping and depression remains limited and conflicting. Moreover, whether the association of daytime napping with depression varies by nighttime sleep quality is unclear. Hence, we examined the associations of daytime napping and nighttime sleep quality with depressive symptoms in older Chinese. METHODS: A total of 16,786 participants aged ≥50 from the Guangzhou Biobank Cohort Study second-round examination (2008-2012) were included in this cross-sectional study. Geriatric Depression Scale (GDS-15), Pittsburgh Sleep Quality Index (PSQI), napping and demographic data were collected by face-to-face interview using a computerized questionnaire. Logistic regression was used to calculate odds ratio (OR) of depressive symptoms for napping and sleep quality. RESULTS: The prevalence of depressive symptoms (GDS score > 5) and poor global sleep quality (PSQI score ≥ 6) was 5.3 and 31.9%, respectively. Compared to non-nappers, nappers showed significantly higher odds of depressive symptoms, with OR (95% confidence interval (CI)) being 1.28 (1.11-1.49). The odds of depressive symptoms for daytime napping varied by nighttime sleep quality (P for interaction = 0.04). In good-quality sleepers, compared to non-nappers, nappers had significantly higher odds of depressive symptoms, with OR (95% CI) being 1.57 (1.23-2.01), whereas no association was found in poor-quality sleepers (OR = 1.13, 0.94-1.36). CONCLUSION: Napping was associated with higher odds of depressive symptoms in older people, and the association was stronger in good-quality sleepers.

Brain-derived neurotrophic factor gene variants and obesity in former smokers.

OBJECTIVE: From genome-wide association studies, brain-derived neurotrophic factor (BDNF) locus on chromosome 11 was the only SNP associated with both smoking and body mass index (BMI) in European, African and Asian population. This study aims to explore the unique genetic predisposition to obesity in former smokers by examining the effects of BDNF on BMI and waist circumference (WC). METHODS: The study design is case-control study with a cohort validation in supplementary. We included 15,072 ethnic Chinese participants in the Guangzhou Biobank Cohort Study (GBCS) with data of four BDNF SNPs related to both BMI and smoking behavior. We used baseline smoke exposure data in 2003-2007 and follow-up outcomes of general obesity (by BMI) and central obesity (WC) in 2008-2012. Odds ratios (ORs) and 95% confidence intervals (CIs) for general obesity and central obesity associated with these SNPs were derived from logistic regression. RESULTS: Of 15,072 participants (3169 men and 11,903 women), 1664 (11.0%) had general and 7868 (52.2%) had central obesity. In 1233 former smokers, the rs6265 GG, versus AA, genotype was associated with higher risks of general obesity (OR = 1.79, 95% CI = 1.06-3.01) and central obesity (OR = 2.08, 95% CI = 1.47-2.92) after adjustment. These associations were not significant in never or current smokers. In former heavy (≥20 cigarettes/day) smokers, the rs6265 GG genotype showed a higher odds for general obesity (OR = 2.15, 95% CI = 1.05-4.40), while no association was found in former light (1-9 cigarettes/day) smokers. Similar results were found for the association of rs6265 with central obesity and for the associations of other two BDNF SNPs (rs4923457 and rs11030104) with both general and central obesity. CONCLUSIONS: We firstly identified the genetic predisposition (BDNF SNPs) to general and central obesity in former smokers, particularly in former heavy smokers. The different associations of the SNPs for general/central obesity in different smoke exposure groups may be related to the competitive performance of the sites and epigenetic modification, which needs further study.

Higher total white blood cell and neutrophil counts are associated with an increased risk of fatal stroke occurrence: the Guangzhou biobank cohort study.

BACKGROUND: Chronic inflammatory diseases are linked to an increased risk of stroke events. The white blood cell (WBC) count is a common marker of the inflammatory response. However, it is unclear whether the WBC count, its subpopulations and their dynamic changes are related to the risk of fatal stroke in relatively healthy elderly population. METHODS: In total, 27,811 participants without a stroke history at baseline were included and followed up for a mean of 11.5 (standard deviation = 2.3) years. After review of available records, 503 stroke deaths (ischaemic 227, haemorrhagic 172 and unclassified 104) were recorded. Cox proportional hazards regression was used to assess the associations between the WBC count, its subpopulations and their dynamic changes (two-phase examination from baseline to the 1st follow-up) and the risk of fatal all stroke, fatal ischaemic stroke and fatal haemorrhagic stroke. RESULTS: (i) Regarding the WBC count in relation to the risk of fatal stroke, restricted cubic splines showed an atypically U-curved association between the WBC count and the risk of fatal all stroke occurrence. Compared with those in the lowest WBC count quartile (< 5.3*10^9/L), the participants with the highest WBC count (> 7.2*10^9/L) had a 53 and 67% increased risk for fatal all stroke (adjusted hazard ratio [aHR] = 1.53, 95% confidence interval (CI) 1.16-2.02, P = 0.003) and fatal haemorrhagic stroke (aHR = 1.67, 95% CI 1.10-2.67, P = 0.03), respectively; compared with those in the lowest quartile (< 3.0*10^9/L), the participants with the highest NEUT count (> 4.5*10^9/L) had a 45 and 65% increased risk for fatal all stroke (aHR = 1.45, 95% CI 1.10-1.89, P = 0.008) and fatal ischaemic stroke (aHR = 1.65, 95%CI 1.10-2.47 P = 0.02), respectively. With the additional adjustment for C-reactive protein, the same results as those for all stroke and ischaemic stroke, but not haemorrhagic stroke, were obtained for the WBC count (4 ~ 10*10^9/L) and the NEUT count (the NEUT counts in the top 1% and bottom 1% at baseline were excluded). (ii) Regarding dynamic changes in the WBC count in relation to the risk of fatal stroke, compared with the stable group (- 25% ~ 25%, dynamic changes from two phases of examination (baseline, from September 1st, 2003 to February 28th, 2008; 1st follow-up, from March 31st 2008 to December 31st 2012)), the groups with a 25% increase in the WBC count and NEUT count respectively had a 60% (aHR = 1.60, 95% CI 1.07-2.40, P = 0.02) and 45% (aHR = 1.45, 95% CI1.02-2.05, P = 0.04) increased risk of fatal all stroke occurrence. CONCLUSIONS: The WBC count, especially the NEUT count, was associated with an increased risk of fatal all stroke occurrence. Longitudinal changes in the WBC count and NEUT count increase in excess of 25% were also associated with an increased risk of fatal all stroke occurrence in the elderly population.

Genetic scores for BMI related to metabolically unhealthy obesity in an older Chinese population.

OBJECTIVE: In this study, a genetic risk score (GRS) for the body mass index (BMI) tested and built using a large sample of Chinese individuals aged at least 50 years in southern China. We collected information regarding the participants' weights at 20 years of age and middle age and tested the BMI-GRS effect modes. METHODS: This study involved a prospective study design. The genetic data of the participants in from the Guangzhou Biobank Cohort Study and selected BMI-related single-nucleotide polymorphisms (SNPs) were used to establish the GRS. RESULTS: We included 13 597 participants with 12 SNPs. After adjusting for covariates, the high-GRS group was 36% (95% CI: 25%-48%) and 34% (95% CI: 23%-47%) more likely of being overweight at baseline and follow-up, respectively, and 56% (95% CI: 34%-82%) and 49% (95% CI: 29%-72%) more likely of being obese at baseline and follow-up, respectively, compared with the low-GRS group (P-value for all trends <.05). The RRs for the incidences of metabolically healthy and unhealthy obese (MHO and MUO, respectively) individuals in the high-GRS group were 0.94 (95% CI: 0.65-1.35) and 1.28 (95% CI: 1.00-1.63), respectively. CONCLUSION: High-GRS participants were more likely to be overweight/obese at baseline and follow-up, and this relationship exhibited a dose-response relationship. The GRS was also associated with MUO.

Age at menarche and cardiovascular risk factors using Mendelian randomization in the Guangzhou Biobank Cohort Study.

Observational studies show earlier age at menarche associated with higher risk of cardiovascular disease although these studies could be confounded by childhood obesity or childhood socioeconomic position. We tested the hypothesis that earlier age at menarche is associated with poorer cardiovascular risk factors using a Mendelian randomization design. We conducted a Mendelian randomization study in a large Southern Chinese cohort, the Guangzhou Biobank Cohort Study (n=12,279), to clarify the causal role of menarche in cardiovascular disease risk factors including blood pressure, lipids, fasting glucose, adiposity and type 2 diabetes. A genetic allele score was obtained from single nucleotide polymorphisms associated with age at menarche using stepwise regression and with cross validation. Estimates of the association of age at menarche with cardiovascular disease risk factors were obtained using two stage least squares regression. Height was included as a positive control outcome. The F-statistic for the allele score (rs17268785, rs1859345, rs2090409, rs4452860 and rs4946651) was 19.9. Older age at menarche was associated with lower glucose (-0.39mmol/L per year older menarche, 95% confidence interval (CI) -0.78 to -0.001) but not clearly with any other cardiovascular risk factors. Older age at menarche was also associated with taller height. Age at menarche did not appear to affect cardiovascular disease risk factors except for glucose in an inverse manner. However, these results need to be confirmed in larger Mendelian randomization studies.

Childhood secondhand smoke exposure and pregnancy loss in never smokers: the Guangzhou Biobank Cohort Study.

OBJECTIVE: Studies of secondhand smoke (SHS) exposure especially childhood SHS exposure and pregnancy loss are limited. We used baseline data of the Guangzhou Biobank Cohort Study (GBCS) to examine the association of childhood SHS exposure with a history of pregnancy loss. METHODS: Never smoking women aged 50 years or above in GBCS from 2003 to 2008 were included. Propensity score matching (PSM) was used to control for confounding. Negative binomial regression and logistic regression were used to examine the association of childhood SHS, assessed by number of smokers in childhood household and frequency of exposure, with past pregnancy loss. RESULTS: Of 19 562 women, 56.7% (11 096) had SHS exposure during childhood. In negative binomial regression, after adjusting for age, education, past occupational dust exposure, past home fuel exposure, oral contraceptive, adulthood SHS exposure, age at first pregnancy and age at first menarche, compared to non-exposure, the incidence rate ratio of one more pregnancy loss was 1.20 (95% CI1.05 to 1.37) in those who lived with ≥2 smokers in the same household, and 1.14 (95% CI 1.04 to 1.25) in those exposed ≥5 times/week. After similar adjustment, logistic regression showed that the OR of pregnancy loss ≥2 times (versus 0 to 1 time) was 1.25 (95% CI 1.00 to 1.57) and 1.20 (95% CI 1.03 to 1.40) for high density (≥2 smokers in the same household) and frequency (≥5 times/week) of childhood exposure, respectively. CONCLUSIONS: Childhood SHS exposure was associated with higher risks of pregnancy loss in middle-aged and older Chinese women.

Genetically predicted 17beta-estradiol, cognitive function and depressive symptoms in women: A Mendelian randomization in the Guangzhou Biobank Cohort Study.

OBJECTIVE: The role of estrogen in cognitive function and depressive symptoms is controversial due to discrepancies between results from randomized controlled trials (RCT) and observational studies. Mendelian randomization analysis may provide further insights concerning the role of estrogen in these outcomes as it assesses the effect of lifelong endogenous exposure but is less vulnerable to confounding than observational studies. METHOD: We used separate sample instrumental variable analysis to estimate the association of log 17ß estradiol with cognitive function (Delayed 10 word recall, and Mini Mental State Examination (MMSE)) and depressive symptoms (Geriatric Depression Scale (GDS)) in older Chinese women of the Guangzhou Biobank Cohort Study (GBCS, n=3086). The estimate was derived based on the Wald estimator, the ratio of the association of genetic determinants (rs1008805 and rs2175898) of log 17ß-estradiol with cognitive function and depressive symptoms in GBCS and the association of log 17ß-estradiol with genetic determinants in the sample of young women in Hong Kong (n=236). RESULTS: Genetically predicted 17ß-estradiol was not associated with delayed 10-word recall (0.42 words per log increase in 17ß-estradiol (pmol/L), 95% confidence interval (CI) -0.49 to 1.34) MMSE (0.39 per log increase in 17ß-estradiol (pmol/L), 95% CI -0.87 to 1.65) or GDS (0.24 per log increase in 17ß-estradiol (pmol/L), 95% CI -0.57 to 1.05). CONCLUSION: These results were largely consistent with evidence from RCTs and did not show any beneficial effect of estrogen on cognitive function and depressive symptoms. However, larger Mendelian randomization analyses are needed to identify any minor effects.

Stress across the life course and depression in a rapidly developing population: the Guangzhou Biobank Cohort Study.

OBJECTIVE: The objective of this study was to examine the role of stress across the life course in the development of depression among older adults in a non-Western developing setting. METHODS: Multivariable linear and multinomial logistic regression were used in cross-sectional analyses of 9729 Chinese participants (mean age 60.2 years) from phase 3 of the Guangzhou Biobank Cohort Study (2006-2008) to investigate the association of childhood adversities and adulthood stressors with depression. RESULTS: Childhood adversities were associated with mild depression (odds ratio (OR) 1.78, 95% confidence interval (CI) 1.58, 2.02) and moderate-to-severe depression (OR 2.30, 95% CI 1.68, 3.15), adjusted for age, sex, education and childhood socio-economic status. Past-year adulthood stressors were also associated with mild depression (OR 1.96, 95% CI 1.54, 2.02) and moderate-to-severe depression (OR 3.55, 95% CI 2.21, 5.68), adjusting additionally for occupation and income. Adulthood stressors were more strongly associated with depressive symptoms among individuals with a history of childhood adversities. CONCLUSIONS: Childhood adversities and adulthood stressors were independently associated with an increased risk of depression among older ambulatory adults, although adulthood stressors were more strongly associated with depression following exposure to childhood adversities. This is consistent with evidence from Western settings in which the social context of risk and protective factors for depression may differ and implies that the role of stress in the aetiology of depression is not context specific.

Evaluation of Moderate Alcohol Use With QT Interval and Heart Rate Using Mendelian Randomization Analysis Among Older Southern Chinese Men in the Guangzhou Biobank Cohort Study.

Western observational studies show that moderate alcohol use is associated with lower cardiovascular disease (CVD) risk, but these associations may be confounded by the healthier attributes of moderate users in these settings. Mendelian randomization analysis may help to ascertain the causal effect of moderate alcohol use on specific factors related to CVD and thereby clarify the role of alcohol. We used Mendelian randomization analysis with the aldehyde dehydrogenase 2 gene (ALDH2) as an instrumental variable to examine the association of alcohol units (10 g of ethanol) per day with heart rate-corrected QT interval and heart rate assessed from electrocardiogram among 4,588 older southern Chinese men in the Guangzhou Biobank Cohort Study (2003-2008). The F statistic was 77 for ALDH2 on alcohol use, suggesting little weak-instrument bias. Instrumental variable analysis showed that alcohol units were not associated with the corrected QT interval, with ß = 1.04 (95% confidence interval: -0.61, 2.70) milliseconds, but they were associated with increased heart rate, with ß = 0.98 (95% confidence interval: 0.04, 1.92) beat per minute. This study suggests that moderate alcohol use in men is not beneficial for heart function via QT interval or heart rate but could be detrimental. Future studies using specific cardiovascular outcomes may elucidate how alcohol affects different aspects of the cardiovascular system and, hence, the overall effects of alcohol on CVD can be estimated.

Smoking and nasopharyngeal carcinoma mortality: a cohort study of 101,823 adults in Guangzhou, China.

BACKGROUND: Nasopharyngeal carcinoma (NPC), also known as Cantonese cancer, is rare worldwide, but has particularly high incidence in North Africa and Southeast Asia, especially in Guangdong, China, such as Guangzhou. Tobacco causes head and neck cancers, but nasopharyngeal carcinoma is not included as causally related to smoking in the 2014 United States Surgeon General's report. Prospective evidence remains limited. We used Guangzhou Occupational Cohort data to conduct the first and robust prospective study on smoking and NPC mortality in an NPC high-risk region. METHODS: Information on demographic characteristics and smoking status was collected through occupational health examinations in factories and driver examination stations from March 1988 to December 1992. Vital status and causes of deaths were retrieved until the end of 1999. Cox proportional hazard model was used to assess the association of smoking with NPC mortality. RESULTS: Of 101,823 subjects included for the present analysis, 34 NPC deaths occurred during the average 7.3 years of follow up. The mean age (standard deviation) of the subjects was 41 (5.7) years. Compared with never smokers, the hazard ratio (HR) of NPC mortality was 2.95 (95% confidence interval 1.01-8.68; p=0.048) for daily smokers and 4.03 (1.29-12.58; p=0.016) for smokers with more than 10 pack-years of cumulative consumption, after adjusting for age, sex, education, drinking status, occupation and cohort status and accounting for smoking-drinking interaction. The risk of NPC mortality increased significantly with cigarettes per day (p for trend=0.01) and number of pack-years (p for trend=0.02). CONCLUSIONS: In this first and largest cohort in a high NPC risk region, smoking was associated with higher NPC mortality. The findings have shown statistically significant dose-response trend between smoking amount and smoking cumulative consumption and the risk of NPC mortality, but due to the small event number, further studies with larger sample size are needed to confirm the findings in the present study. Our results support that smoking is one of the risk factors likely to be causally associated with NPC mortality.

Association of sleep duration and napping with stroke mortality in older Chinese: A 14-year prospective cohort study of the Guangzhou Biobank Cohort study.

STUDY OBJECTIVE: Evidence regarding the association of short sleep duration and napping with stroke remains limited and controversial. We examined the association of sleep duration and napping with risk of stroke mortality in an older Chinese cohort. METHODS: Sleep duration and daytime napping were assessed by face-to-face interview during 2003-2008. Information of causes of death until April 30, 2021 was collected via record linkage with the Death Registry. Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Of 27,254 participants aged average 62.0 (standard deviation = 7.1) years, 818 stroke deaths occurred within 388,798 person-years (mean = 14.3 years) of follow-up. A U-shaped relation between sleep duration and risk of stroke mortality was observed. Participants with short (≤5 h/day) or long sleep duration (≥9 h/day) showed higher risks of total stroke mortality, with adjusted HRs (95% CIs) being 1.27 (1.01-1.59) and 1.37 (1.07-1.75), respectively. However, non-significant association of short or long sleep duration with hemorrhagic or ischemic stroke mortality was found. The associations of short and long sleep duration with total stroke mortality were more pronounced in those with hypertension (P for interaction with hypertension = 0.01), with HRs (95% CIs) being 1.37 (1.04-1.82) and 1.77 (1.33-2.36), respectively. No association between napping and risk of stroke mortality was found. CONCLUSIONS: Both short and long sleep duration, but not daytime napping, were associated with higher risk of stroke mortality. Public health messages to encourage good sleep hygiene may be important, especially for people with hypertension.

Association of Salt Intake with Muscle Strength and Physical Performance in Middle-Aged to Older Chinese: The Guangzhou Biobank Cohort Study.

Older people have higher amounts of sodium accumulation in skeletal muscles than younger people, indicating the possible role of salt intake on muscular and physical function. This large population-based cross-sectional study examined the association of salt intake with muscle strength and physical performance in 4867 participants with an average age of 60.4 (standard deviation = 7.7) years. Information on salt intake was collected from self-reports. Absolute and relative grip strength (AGS and RGS), timed up-and-go test (TUGT), and falls were considered the indicators of muscle strength and physical performance. Linear and logistic regression were used to examine the associations of salt intake with AGS, RGS, TUGT score, and falls, adjusting for demographic and lifestyle factors, body mass index, self-rated health, and self-reported hypertension. Higher salt intake was independently associated with lower grip strength and a higher TUGT score. Versus light salt intake, the adjusted ß (95% confidence interval (CI)) of AGSmax, RGSmax, and TUGT scores in those with salty taste were -0.53 (-0.97, -0.08) kg, -0.04 (-0.06, -0.02) kg per kg/m2, and 0.08 (0.02, 0.14) s, respectively. A non-significant association was found between salt intake and falls. In sex-stratification analysis, the association remained in women but became non-significant in men. Our results suggest that avoiding high-salt diets may play a role in preserving muscle strength and physical function in the elderly, especially in women.

Parity and incident type 2 diabetes in older Chinese women: Guangzhou Biobank Cohort Study.

This study examined the association between parity and incident type 2 diabetes in older Chinese women and estimated the mediation effect of adiposity indicators. A total of 11,473 women without diabetes at baseline from 2003 to 2008 were followed up until 2012. We used Cox proportional hazards regression to assess the association between parity and incident type 2 diabetes, and mediation analysis to estimate the mediation effect of adiposity indicators. Compared to women with one parity, the hazard ratio (HR) (95% confidence interval (CI)) for incident type 2 diabetes was 0.85 (0.44-1.63), 1.20 (1.11-1.30), 1.28 (1.16-1.41) and 1.27 (1.14-1.42) for women with parity of 0, 2, 3, and ≥ 4, respectively. The proportion of indirect effect (95% CI) mediated by body mass index, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio and body fat percentage was 26.5% (19.2-52.2%), 54.5% (39.4-108.7%), 25.1% (18.2-49.1%), 35.9% (25.6-74.1%), 50.3% (36.5-98.6%) and 15.1% (- 66.4 to 112.3%), respectively. Compared to women with one parity, women with multiparity (≥ 2) had a higher risk of incident type 2 diabetes and up to half of the association was mediated by abdominal obesity.

Influence of Surface Ligand Density and Particle Size on the Penetration of the Blood-Brain Barrier by Porous Silicon Nanoparticles.

Overcoming the blood-brain barrier (BBB) remains a significant challenge with regard to drug delivery to the brain. By incorporating targeting ligands, and by carefully adjusting particle sizes, nanocarriers can be customized to improve drug delivery. Among these targeting ligands, transferrin stands out due to the high expression level of its receptor (i.e., transferrin receptor) on the BBB. Porous silicon nanoparticles (pSiNPs) are a promising drug nanocarrier to the brain due to their biodegradability, biocompatibility, and exceptional drug-loading capacity. However, an in-depth understanding of the optimal nanoparticle size and transferrin surface density, in order to maximize BBB penetration, is still lacking. To address this gap, a diverse library of pSiNPs was synthesized using bifunctional poly(ethylene glycol) linkers with methoxy or/and carboxyl terminal groups. These variations allowed us to explore different transferrin surface densities in addition to particle sizes. The effects of these parameters on the cellular association, uptake, and transcytosis in immortalized human brain microvascular endothelial cells (hCMEC/D3) were investigated using multiple in vitro systems of increasing degrees of complexity. These systems included the following: a 2D cell culture, a static Transwell model, and a dynamic BBB-on-a-chip model. Our results revealed the significant impact of both the ligand surface density and size of pSiNPs on their ability to penetrate the BBB, wherein intermediate-level transferrin densities and smaller pSiNPs exhibited the highest BBB transportation efficiency in vitro. Moreover, notable discrepancies emerged between the tested in vitro assays, further emphasizing the necessity of using more physiologically relevant assays, such as a microfluidic BBB-on-a-chip model, for nanocarrier testing and evaluation.

Obesity indicators as mediators of the association between age at menopause and blood pressure values.

Having a later age at menopause is associated with having a higher blood pressure (BP) value, but the mediation pathways remain unclear. We quantitatively examined the mediation effects of various obesity indicators using baseline data from phase 4 of the Guangzhou Biobank Cohort Study. The product of coefficients approach and bootstrapping procedures were used to assess the mediation effects of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) on the association between age at menopause and BP values. Age, education, occupation, family income, smoking, drinking, diet, physical activity, age at menarche, number of births, fasting glucose, triglycerides, and high-density lipoprotein cholesterol were adjusted as covariates. Of 5429 women with natural menopause, the mean age and menopausal age were 60.0 (standard deviation = 5.8) and 50.3 (3.1) years, respectively. The prevalence of hypertension was 29.6%. In women with a menopausal age of ≥50 years, BMI, WC, WHR and WHtR showed significant mediation effects on the positive association between menopausal age and BP. The adjusted proportion (95% confidence interval) of the mediation effects for those variables were 26.04% (10.40-116.82%), 25.92% (10.19-108.57%), 14.11% (3.59-62.78%), and 23.17% (8.70-95.81%), respectively, for systolic BP values and 22.59% (10.72-53.60%), 20.67% (9.83-49.31%), 9.21% (2.73-23.92%), and 17.19% (7.56-41.31%) for diastolic BP values. In women with a menopausal age of <50 years, no significant association between age at menopause and systolic/diastolic BP values was found. In conclusion, obesity indicators showed significant mediating effects on the association between having a later age at menopause and having a higher BP value. Further longitudinal studies with detailed and accurate measurements of metabolic changes after menopause and sufficient follow-up are warranted to confirm these results. We demonstrated obesity indicators showed significant mediating effects on the association between later age at menopause (≥50 years) and higher BP.

[A study on the relationship between hearing impairment and blood pressure and hypertension in workers occupationally exposed to noise].

OBJECTIVE: To study the correlation between noise and blood pressure and/or hypertension, and its age characteristic. METHODS: The pure tone audiometric and blood pressure examinations were performed in 14537 workers from 157 factories. Hearing impairment was used as a surrogate indicator of cumulated noise exposure. The associations of hearing impairment and duration of noise exposure with blood pressure and hypertension were analyzed respectively after age and gender stratification. RESULTS: Most of the objects were males (81.2%), younger than 35 years old (77.8%), and the duration of exposure to noise was less than 5 years (73.6%). The prevalence of hearing impairment in males was significantly higher than that in males, and increased with age and duration of noise exposure. Only in males with age younger than 35 years old, the systolic and diastolic blood pressures of subjects with sensorineural hearing loss significantly enhanced, and the diastolic blood pressure and prevalence of hypertension increased with duration of noise exposure. The risk of hypertension in males with sensorineural hearing loss significantly increased, the odds ratios in subjects with age younger than 35 years old and with age older than 35 years old were 3.0 (95%CI: 1.5 ∼ 6.1) and 2.1 (95%CI: 1.2 ∼ 3.4), respectively. CONCLUSION: The severe hearing impairment induced by noise was associated with hypertension. It is suggested that people should pay attention to the effects of noise on hypertension in young workers.

Association of Hand Grip Strength with Mild Cognitive Impairment in Middle-Aged and Older People in Guangzhou Biobank Cohort Study.

Background: Lower hand grip strength has been linked to cognitive impairment, but studies in older Chinese are limited. We examined the association of hand grip strength with cognitive function in a large sample of older Chinese. Methods: 6806 participants aged 50+ years from the Guangzhou Biobank Cohort Study (GBCS) were included. Relative grip strength was calculated by absolute handgrip strength divided by the body mass index (BMI). Cognitive function was assessed using the Delayed Word Recall Test (DWRT, from 0 to 10) and the Mini Mental State Examination (MMSE, from 0 to 30), with higher scores indicating better cognition. Results: After adjusting for multiple potential confounders, lower absolute grip strength and relative grip strength were significantly associated with lower DWRT (all p < 0.05) in all participants. No significant interaction effects between sex and handgrip strength on cognitive impairment were found (p from 0.27 to 0.87). No significant association between handgrip strength and total MMSE scores was found in the total sample or by sex (p from 0.06 to 0.50). Regarding the individual components of MMSE, lower absolute and relative grip strength were significantly associated with lower scores of the recall memory performance in all participants (p from 0.003 to 0.04). Conclusion: We have shown for the first time a positive association of grip strength with recall memory performance, but not general cognitive function in older people, which warrants further investigation.

Low-Carbohydrate Diets and Mortality in Older Asian People: A 15-Year Follow-Up from a Prospective Cohort Study.

The long-term effects of a low-carbohydrate diet (LCD) on mortality, accounting for the quality and source of the carbohydrate, are unclear. Hence, we examined the associations of LCDs with all-cause and cause-specific mortality in a prospective cohort study. A total of 20,206 participants (13.8% diabetes) aged 50+ years were included. Overall, vegetable-based and meat-based LCD scores were calculated based on the percentage of energy as total and subtypes of carbohydrates, fat, and protein. Cox regression analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). During 294,848 person-years of follow-up, 4624 deaths occurred, including 3661 and 963 deaths in participants without and with diabetes, respectively. In all participants, overall LCD score was not associated with all-cause and cause-specific mortality, after multivariable adjustment. However, for the highest versus the lowest quartiles of vegetable-based LCD, the adjusted HRs (95%CIs) of all-cause and CVD mortality were 1.16 (1.05-1.27) and 1.39 (1.19-1.62), respectively. The corresponding values for highest versus lowest quartiles of meat-based LCD for all-cause and CVD mortality were 0.89 (0.81-0.97) and 0.81 (0.70-0.93), respectively. Similar associations were found in participants without diabetes. In patients with diabetes, the adjusted HR (95%CI) of CVD mortality for the highest versus the lowest quartiles of vegetable-based LCD was 1.54 (1.11-2.14). Although there were no significant associations with overall LCD score, we found that the vegetable-based LCD score was positively, whereas the meat-based LCD score was negatively, associated with all-cause and CVD mortality in older Asian people.