Low-viscosity hydroxypropyl methylcellulose obtained by electron beam irradiation and its performance in spray drying.

Low-viscosity hydroxypropyl methylcellulose (HPMC) was obtained by electron beam irradiation, and its use as an excipient for improving the properties of spray dried pharmaceutical powders was investigated. The minimum molecular weight of HPMC which could maintain the capacity of encapsulation and powder modification was explored. As the irradiation dose was increased from 10 to 200 kGy, the molecular weight and viscosity of HPMC decreased linearly. However, its main structure and degrees of methoxy and hydroxypropyl substitution were not significantly affected. The irradiated HPMC could encapsulate particles during spray drying and, thus, modify powder properties. Furthermore, the water content of spray-dried powders with irradiated HPMC was lower than that with parent HPMC. After the spray-dried powder with irradiated HPMC was prepared into granules, their dissolution rate was also faster. However, in order to achieve high encapsulation, the molecular weight of HPMC should be ensured to be above 7.5 kDa. The designated low-viscosity HPMC obtained by electron beam irradiation is a suitable powder-modification material for use in spray drying, and it shows promise as a superior excipient in medicine, food, paint industries, among others.

Reproductive factors, genetic susceptibility and risk of type 2 diabetes: A prospective cohort study.

AIM: To explore the relationships of multiple reproductive factors with type 2 diabetes mellitus (T2DM) risk and the joint effects of reproductive factors and genetic susceptibility. METHODS: We included 262,368 women without prevalent T2DM from the UK biobank. Cox proportional hazards regression models were employed to estimate the relationships of reproductive factors with T2DM risk and the joint effects of reproductive factors and genetic susceptibility. RESULTS: During a mean follow-up of 12.2 years, 8,996 T2DM cases were identified. Early menarche (<12 years, hazard ratio (HR) 1.08 [95 % confidence interval (CI) 1.02;1.13]), late menarche (≥15 years, HR 1.11 [1.04;1.17]), early menopause (<45 years, HR 1.20 [1.12;1.29]), short reproductive lifespan (<30 years, HR 1.25 [1.16;1.35]), hysterectomy (1.31, HR [1.23;1.40]), oophorectomy (HR 1.28 [1.20;1.36]), high parity (≥4, HR 1.25 [1.17;1.34]), early age at first live birth (<20 years, HR 1.23 [1.16;1.31]), miscarriage (HR 1.13 [1.07;1.19]), stillbirth (HR 1.14 [1.03;1.27]), and ever used hormonal replacement therapy (HR 1.19 [1.14;1.24]) were related to a higher T2DM risk, while ever used oral contraceptives (HR 0.93 [0.89;0.98]) was related to a lower T2DM risk. Furthermore, women with reproductive risk factors and high genetic risk had the highest T2DM risk compared to those with low genetic risk and without reproductive risk factors. CONCLUSION: Our findings show that multiple reproductive factors are related to T2DM risk, particularly in women with high genetic risk.

Associations of exposure to organochlorine pesticides and polychlorinated biphenyls with chronic kidney disease among adults: the modifying effects of lifestyle.

Exposure to organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) has been reported to be associated with renal impairment and chronic kidney disease (CKD). Nevertheless, the research results thus far have exhibited inconsistency, and the effect of lifestyle on their association is not clear. In this study, we assessed the correlation between serum OCPs/PCBs and CKD and renal function indicators including estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) among 1721 Chinese adults. In order to further investigate the potential impact of lifestyle, we conducted joint associations of lifestyle and OCPs/PCBs on CKD. We found a negative correlation between p,p'-DDE and eGFR, while logistic regression results showed a positive correlation between PCB-153 and CKD (OR, 1.92; 95% CI, 1.21, 3.06). Quantile g-computation regression analyses showed that the association between co-exposure to OCPs/PCBs and CKD was not significant, but p,p'-DDE and PCB-153 were the main contributors to the negative and positive co-exposure effects of eGFR and CKD, respectively, which is consistent with the regression results. Participants with both relatively high PCB-153 exposure and an unhealthy lifestyle had the highest risk of CKD, in the joint association analysis. The observed associations were generally supported by the FAS-eGFR method. Our research findings suggest that exposure to OCPs/PCBs may be associated with decreased eGFR and increased prevalence of CKD in humans, and a healthy lifestyle can to some extent alleviate the adverse association between PCB-153 exposure and CKD.

Association of exposure to multiple metals with hemoglobin levels in Chinese children and adolescents.

BACKGROUND: Previous studies have linked single metal to hemoglobin levels in children and adolescents; however, studies with regards to metal mixtures are still limited. OBJECTIVE: We aimed to investigate the associations of single metal and metal mixtures with hemoglobin levels in children and adolescents. METHODS: We conducted a cross-sectional study of 2064 children and adolescents aged 6 to 19 years in Liuzhou, China in 2018. The concentrations of 15 metals in urine were determined by inductively coupled plasma mass spectrometry. Generalized linear regression and weighted quantile sum (WQS) regression were used to estimate the associations of single metal and metal mixtures with hemoglobin levels, respectively. RESULTS: The multivariable-adjusted ß-values for the highest versus the first quartiles of urinary metal concentrations were - 1.57 (95 % confidence interval [CI]: -3.01, -0.13) for chromium, -2.47 (95 % CI: -3.90, -1.05) for nickel and 1.88 (95 % CI: 0.49, 3.28) for copper. In addition, we found a significant negative association between the WQS index and hemoglobin levels (adjusted ß = -0.93, 95 % CI: -1.69, -0.19), with nickel contributing the most to the WQS index at 59.0 %. Subgroup analyses showed that exposure to urinary nickel or metal mixtures were associated with decreased hemoglobin levels in adolescents, but not in children (all Pinteration < 0.001). CONCLUSION: Among children and adolescents, urinary chromium and nickel concentrations were associated with decreased hemoglobin levels, while copper showed a positive relationship. Moreover, a negative association was observed between exposure to metal mixtures and hemoglobin levels. These findings need to be further validated in prospective studies.

Association between essential metals, adherence to healthy lifestyle behavior, and ankle-brachial index.

BACKGROUND: Ankle-brachial index (ABI) is a noninvasive diagnostic method for peripheral arterial disease (PAD) and a predictor of cardiovascular events. OBJECTIVE: The present study aimed to evaluate the association between individual or combined essential metals and ABI, as well as assess the collective impact of essential metals when coupled with healthy lifestyle on ABI. METHODS: A total of 2865 participants were recruited in Wuhan Tongji Hospital between August 2018 and March 2019. Concentrations of essential metals in urine were measured by inductively coupled plasma mass spectrometer. RESULTS: The results of general linear regression models demonstrated that after adjusting for confounding factors, there was a positive association between ABI increase and per unit increase of log 10-transformed, creatinine-corrected urinary Cr (ß (95 % CI): 0.010 (0.004, 0.016), PFDR = 0.007), Fe (ß (95 % CI): 0.010 (0.003, 0.017), PFDR = 0.018), and Co (ß (95 % CI): 0.013 (0.005, 0.021), PFDR = 0.007). The WQS regression revealed a positive relationship between the mixture of essential metals and ABI (ß (95 % CI): 0.006 (0.003, 0.010), P < 0.001), with Cr and Co contributing most to the relationship (weighted 45.48 % and 40.14 %, respectively). Compared to individuals with unfavorable lifestyle and the lowest quartile of Cr, Fe and Co, those with favorable lifestyle and the highest quartile of Cr, Fe and Co exhibited the most increase in ABI (ß (95 % CI): 0.030 (0.017, 0.044) for Cr, ß (95 % CI): 0.027 (0.013, 0.040) for Fe, and ß (95 % CI): 0.030 (0.016, 0.044) for Co). CONCLUSION: In summary, our study indicates that adequate essential metal intake together with healthy lifestyle behaviors perform crucial roles in PAD protection.

Association between hemoglobin A1c trajectory during pregnancy and adverse birth outcomes among non-gestational diabetic women.

AIMS: Previous studies have shown that higher hemoglobin A1c (HbA1c) levels within the normal range during pregnancy can increase the risk of adverse birth outcomes. However, the effects of the longitudinal HbA1c trajectory during pregnancy on adverse birth outcomes among non-gestational diabetic women are poorly characterized. We aimed to identify HbA1c trajectory during pregnancy among non-gestational diabetic women and to estimate their associations with adverse birth outcomes. METHODS: Data was extracted from the Information System of Guangdong Women and Children Hospital, China, from January 2017 to July 2022. This study involved 13,979 women who did not have gestational diabetes mellitus and underwent repeated HbA1c measurements during pregnancy. Latent mixture modeling was used to identify HbA1c trajectory groups. Logistic regression was applied to explore the associations between HbA1c trajectory groups and adverse birth outcomes, including preterm delivery, low birth weight, macrosomia, small for gestational age, and large for gestational age (LGA). RESULTS: Three HbA1c trajectory groups were identified: low-stable (range 4.0% [20 mmol/mol]-4.4% [25 mmol/mol]), moderate-stable (range 4.6% [27 mmol/mol]-5.1% [32 mmol/mol]), and elevated-increasing (range 5.0% [31 mmol/mol]-5.6% [38 mmol/mol]). Compared with the low-stable HbA1c group, the elevated-increasing group had a higher risk of preterm delivery and LGA. The adjusted OR (95% CIs) were 1.67 (1.13, 2.49) and 1.47 (1.01, 2.12) for preterm delivery and LGA, respectively. CONCLUSIONS: Among non-gestational diabetic women, the elevated-increasing HbA1c trajectory group was associated with a higher risk of preterm delivery and LGA. This finding emphasizes the importance of maintaining optimal HbA1c levels throughout pregnancy.

Associations of prenatal blood pressure trajectory and variability with child neurodevelopment at 2 years old.

BACKGROUND: The patterns of blood pressure (BP) change throughout the pregnancy were related to adverse birth outcomes. However, little is known about the long-term effect of BP change patterns on child neurodevelopment. This study aimed to explore the relationship between the BP trajectory and BP variability during pregnancy and early childhood neurodevelopment. METHOD: A total of 2797 mother-newborn pairs were derived from the Wuhan Healthy Baby Cohort Study. BP was measured during each antenatal visit, and Mental and Psychomotor Development Indexes (MDI and PDI) were assessed using the Bayley Scales of Infant Development (BSID) when the children were 2 years old. Delayed neurodevelopment was defined as scores of PDI or MDI less than - 1SD relative to the mean score of the study population. A group-based multi-trajectory model was adopted to identify multi-trajectories of systolic blood pressure (SBP) and diastolic blood pressure (DBP). Visit-to-visit BP variability was assessed by the coefficient of variation (CV), standard deviation (SD), and average real variability (ARV). Generalized linear models and multivariate logistic regressions were used to assess the associations of BP trajectories and variability with BSID scores and delayed neurodevelopment, respectively. RESULTS: Five distinct trajectories for SBP and DBP were identified, namely, "Low-increasing," "Low-stable," "Moderate-decreasing," "Moderate-increasing," and "High-stable" groups. Compared with the "Low-stable" group, the children whose mothers' BP fell into the other four groups had lower PDI scores, and mothers in the "Low-increasing," "Moderate-increasing," and "Moderate-decreasing" groups had 43% (OR: 1.43, 95% CI: 1.01, 2.03), 48% (OR: 1.48, 95% CI: 1.05, 2.08) and 45% (OR:1.45, 95% CI: 1.03, 2.04) higher risk of having offspring with delayed psychomotor neurodevelopment, respectively. High DBP variability was associated with lower BSID scores, and delayed psychomotor neurodevelopment (OR = 1.46, 95% CI: 1.10, 1.92 for DBP-SD; OR = 1.53, 95% CI: 1.16, 2.02 for DBP-CV). CONCLUSION: Our findings suggest that BP change patterns assessed by multi-trajectory and visit-to-visit variability were associated with lower BSID scores and delayed neurodevelopment. Health professionals should be aware of the influence of BP level and its oscillations during pregnancy on the risk of delayed neurodevelopment.

[Reflections on good manufacturing practice and quality control system of personalized traditional Chinese medicine preparations].

Personalized traditional Chinese medicine(TCM) preparations have entered a stage of rapid development. The key to the healthy development of this industry is to establish a sound manufacturing standard and quality control system. This paper analyzed the characteristics of personalized TCM preparations and drew reference from the quality management standards in the production of commissioned decoctions and oral pastes, on the basis of which the production quality management scheme and cautions for the safe production of personalized TCM preparations was put forward with consideration to various problems that may exist and occur in the production of such preparations. It provided references for formulating the production standards and quality management system of personalized TCM preparations. The production standards and quality control system should develop with the times. In the future, modern technologies such as big data and artificial intelligence should be employed to achieve the automated and intelligent production and establish a sound quality traceability system, online control strategy, and safety management mode of personalized TCM preparations, which will ensure the healthy development of this industry under requirement of good manufacturing practice(GMP).

[Application of microwave vacuum drying with process management in extract drying of personalized traditional Chinese medicine preparations].

Extracts are important intermediates in the production of traditional Chinese medicines preparations. The drying effect of extracts will directly affect the subsequent production process and the quality of the preparation. To meet the requirements of high drug loading, short time consumption, and simple production process of personalized traditional Chinese medicine preparations, this study explored the application of multi-program microwave vacuum drying process in the extract drying of personalized traditional Chinese medicine preparations. The influencing factors of microwave vacuum drying process were investigated for 5 excipients and 40 prescriptions. Taking the feasibility of drying, drying rate, drying time, and dried extract status as indicators, this study investigated the feeding requirements of microwave vacuum drying. With the dried extract status as the evaluation indicator, the three drying programs(A, B, and C) were compared to obtain the optimal drying condition. The experimental results showed that the optimal feeding conditions for microwave vacuum drying were material layer thickness of 2 cm and C program(a total of 7 drying processes), which solved the problem of easy scorching in microwave drying with process management. Furthermore, the preset moisture content of the dried extract in microwave drying should be 4%-5%, so that the dried extract of traditional Chinese medicine preparation had uniform quality, complete drying, and no scorching. This study lays a foundation for the application of microwave drying in the production of traditional Chinese medicine preparations, promoting the high-quality development of personalized traditional Chinese medicine preparations.

Association between functional network connectivity, retina structure and microvasculature, and visual performance in patients after thalamic stroke: An exploratory multi-modality study.

BACKGROUND AND OBJECTIVE: Neuro-ophthalmologic symptoms and retinal changes have been increasingly observed following thalamic stroke, and there is mounting evidence indicating distinct alterations occurring in the vision-related functional network. However, the intrinsic correlations between these changes are not yet fully understood. Our objective was to explore the altered patterns of functional network connectivity and retina parameters, and their correlations with visual performance in patients with thalamic stroke. METHODS: We utilized resting-state functional MRI to obtain multi-modular functional connectivity (FC), and optical coherence tomography-angiography to measure various retina parameters, such as the retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), superficial vascular complex (SVC), and deep vascular complex. Visual acuity (VA) was used as a metric for visual performance. RESULTS: We included 46 patients with first-ever unilateral thalamic stroke (mean age 59.74 ± 10.02 years, 33 males). Significant associations were found between FC of attention-to-default mode and SVC, RNFL, and GCIPL, as well as between FC of attention-to-visual and RNFL (p < .05). Both RNFL and GCIPL exhibited significant associations with FC of visual-to-visual (p < .05). Only GCIPL showed an association with VA (p = .038). Stratified analysis based on a disease duration of 6 months revealed distinct and significant linking patterns in multi-modular FC and specific retina parameters, with varying correlations with VA in each subgroup. CONCLUSION: These findings provide valuable insight into the neural basis of the associations between brain network dysfunction and impaired visual performance in patients with thalamic stroke. Our novel findings have the potential to inform future targeted and individualized therapies. However, further comprehensive studies are necessary to validate our results.

Prenatal exposure to poly- and perfluoroalkyl substances and postpartum depression in women with twin pregnancies.

BACKGROUND: Women with multiple pregnancies are vulnerable to experience postpartum depression (PPD). Emerging evidence indicates an association between poly- and perfluoroalkyl substances (PFAS) exposure and PPD in women delivering singletons. The health risks of PFAS may also be present in women delivering twins. OBJECTIVE: To estimate the impacts of prenatal PFAS exposure on the risk of PPD in women with twin pregnancies. METHODS: Our study included 150 mothers who gave birth to twins and were enrolled in the Wuhan Twin Birth Cohort. The concentrations of maternal plasma PFAS were measured in each trimester and averaged. Eight individual PFAS were included in analyses. We used Edinburgh Postnatal Depression Scale to evaluate maternal depression at early pregnancy and 1 and 6 months after childbirth. The outcome was dichotomized using a cutoff value of ≥10 for main analyses. Associations were examined using multiple informant models and modified Poisson regressions. PFAS mixture effects were estimated using quantile g-computation. RESULTS: Using quantile g-computation models, a quartile increase in the PFAS mixture during the first, second, third, and average pregnancy was significantly associated with a relative risk (RR) of 1.73 (95% CI: 1.42, 2.12), 1.54 (95% CI: 1.27, 1.84), 1.75 (95% CI: 1.49, 2.08), and 1.63 (95% CI: 1.35, 1.97) for PPD at 6 months after childbirth, respectively. The results of the single-PFAS models also indicated significant positive associations between individual PFAS and PPD at both 1 and 6 months. CONCLUSIONS: The first study of women with twin pregnancies suggests that prenatal exposure to PFAS increases PPD risk up to 6 months postpartum. Twin pregnant women should receive long-term follow-up after delivery and extensive social support.

Association between prenatal exposure to rare earth elements and the neurodevelopment of children at 24-months of age: A prospective cohort study.

The increasing consumption of rare earth elements (REEs) has resulted in a considerable risk of environmental exposure. However, the adverse effects of prenatal REEs exposure on children's neurodevelopment are not yet fully recognized. Therefore, we investigated the individual and joint effects of prenatal exposure to 13 REEs on children's neurocognitive development based on 809 mother-child pairs from a large birth cohort in Wuhan, China. Maternal urinary concentrations of 13 REEs were repeatedly measured by inductively coupled plasma mass spectrometry. Children's neurodevelopment [e.g., mental and psychomotor development index (MDI/PDI)] at 24-months was assessed using Bayley Scales of Infant Development of Chinese Revision. GEE and BKMR models were applied to estimate the individual and joint effects of prenatal REE exposure on child neurodevelopment level. After controlling for typical confounders, we observed that exposure to 9 REEs during the first trimester were significantly associated with decreased MDI scores [ßs and 95% confidence intervals (CIs) ranging from -2.24 (-3.86 âˆ¼ -0.63) to -1.44 (-2.26∼ -0.26)], and 7 REEs during third trimester were significantly associated decreased PDI scores [ß and 95% CIs ranging from -1.95 (-3.19 âˆ¼ -0.71) to -1.25 (-2.34 âˆ¼ -0.16)]. Higher quantiles of REE mixture in first and third trimester were associated with decreased MDI and PDI score. Thulium, erbium in the first trimester and cerium, lanthanum in the third trimester accounted most importance to joint effects on MDI and PDI, respectively. In conclusion, prenatal exposure to higher concentrations of REEs during the first and third trimester were negative associated with children's neurodevelopment.

Exposure to organochlorine pesticides and polychlorinated biphenyls, adherence to an ideal cardiovascular health, and arterial stiffness among Chinese adults.

This study aimed to assess the relationships between exposure to individual organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and their mixture and arterial stiffness and explore whether adherence to an ideal cardiovascular health (CVH) could mitigate these associations. The cross-sectional study enrolled 1437 Chinese adults between March and May 2019 in Wuhan, China. OCPs and PCBs concentrations were measured using solid phase extraction coupled with gas chromatography-tandem mass spectrometry. Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). CVH was determined by three behavioral and four biological metrics and categorized as ideal, intermediate, and poor CVH. We applied generalized linear model and weighted quantile sum (WQS) regression to evaluate the associations of exposure to individual OCPs or PCBs and their mixture with baPWV, respectively. We found that participants with detectable levels of heptachlor epoxide, PCB-153, and PCB-180 had higher baPWV (ß: 34.25, 95% CI 14.28-54.22; ß: 27.64, 95% CI 7.90-47.38; and ß: 30.51, 95% CI 10.68-50.35) than those with undetectable levels. In WQS regression, the mixture of OCPs and PCBs was related to a higher baPWV (ß: 24.93, 95% CI 2.70-47.15). Compared with participants with ideal CVH and undetectable OCPs or PCBs levels, those with poor CVH and detectable OCPs or PCBs levels had the highest increase in baPWV (heptachlor epoxide: ß: 147.94, 95% CI 112.52-183.55; PCB-153: ß: 150.22, 95% CI 115.40-185.04; PCB-180: ß: 147.02, 95% CI 111.66-182.38). Our findings suggested that individual OCPs, PCBs, and their mixture exposure were positively associated with arterial stiffness, and adherence to an ideal CVH may mitigate the adverse effect.

Association of prenatal essential metal exposure with newborn mitochondrial DNA copy number: Results from a birth cohort study.

Imbalance or deficiencies of essential metals can lead to oxidative stress, that can damage mitochondrial DNA (mtDNA) molecule. Knowledge on effects of exposure to essential metals and their mixture remains limited. We aimed to evaluate individual and joint associations of prenatal essential metals with neonatal mtDNA copy number. We recruited 746 mother-newborn pairs from a birth cohort study conducted in Wuhan City, China, and collected trimester-specific urine and cord blood samples. We measured the concentrations of seven urinary essential metals, include zinc (Zn), iron (Fe), selenium (Se), cobalt (Co), manganese (Mn), copper (Cu), and chromium (Cr), using inductively coupled plasma mass spectrometry, and measured cord blood mtDNA copy number using real-time quantitative polymerase chain reaction. We estimated the trimester-specific associations of individual essential metal concentrations with mtDNA copy number using a multiple informant model, and assessed their joint association using weighted quantile sum (WQS) regression. For individual essential metal, a doubling of maternal urinary Zn concentrations during the second trimester was associated with a 7.47% (95% CI: 1.17-14.17%) higher level of neonatal mtDNA copy number. For the essential metal mixture, one-unit increased in the WQS index of the essential metals mixture during the second trimester resulted in a 10.41% (95% CI: 3.04-18.30%) increase in neonatal mtDNA copy number. Our findings suggest that exposure to both Zn and essential metal mixture during the second trimester is associated with a higher neonatal mtDNA copy number. Further research should assess whether mtDNA copy number is associated with child health.

Associations of prenatal exposure to bisphenols with BMI growth trajectories in offspring within the first two years: evidence from a birth cohort study in China.

BACKGROUND: Prenatal bisphenol exposure has been reported to be associated with lower birth weight and obesity-related indicators in early childhood. These findings warrant an investigation of the relationship between prenatal bisphenol exposure and the dynamic growth of offspring. This study aimed to evaluate the relationship of maternal bisphenol concentration in urine with the body mass index (BMI) growth trajectory of children aged up to two years and to identify the critical exposure periods. METHODS: A total of 826 mother-offspring pairs were recruited from Wuhan Children's Hospital between November 2013 and March 2015. Maternal urine samples collected during the first, second, and third trimesters were analyzed for bisphenol A (BPA), bisphenol S, and bisphenol F (BPF) concentrations. Measurements of length and weight were taken at 0, 1, 3, 6, 8, 12, 18, and 24 months. Children's BMI was standardized using the World Health Organization reference, and group-based trajectory modeling was used to identify BMI growth trajectories. The associations between prenatal bisphenol exposure and BMI growth trajectory patterns were assessed using multinomial logistic regression models. RESULTS: The BMI growth trajectories of the 826 children were categorized into four patterns: low-stable (n = 134, 16.2%), low-increasing (n = 142, 17.2%), moderate-stable (n = 350, 42.4%), and moderate-increasing (n = 200, 24.2%). After adjusting for potential confounders, we observed that prenatal exposure to BPA during the second trimester [odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.09-4.43] and BPF during the third trimester (OR = 3.28, 95% CI = 1.55-6.95) at the highest quartile concentration were associated with an increased likelihood of the low-increasing BMI trajectory. Furthermore, in the subgroup analysis by infant sex, the positive association between the highest quartile of prenatal average urinary BPF concentration during the whole pregnancy and the low-increasing BMI trajectory was found only in girls (OR = 2.82, 95% CI = 1.04-7.68). CONCLUSION: Our study findings suggest that prenatal exposure to BPA and BPF (a commonly used substitute for BPA) is associated with BMI growth trajectories in offspring during the first two years, increasing the likelihood of the low-increasing pattern. Video Abstract (MP4 120033 kb).

Abdominal obesity mediates the causal relationship between depression and the risk of gallstone disease: retrospective cohort study and Mendelian randomization analyses.

OBJECTIVE: Our study aimed to explore the causal effect of depression on the risk of gallstone disease, and the mediation effects of metabolic traits. METHODS: A retrospective cohort study on Chinese elderly from the Dongfeng-Tongji cohort (including 18,141 individuals) was conducted to estimate the adverse effect of probable depression on the risk of gallstone disease. Two-sample Mendelian randomization was performed in European and East-Asian ancestries, to verify the causal relationship between major depression and gallstone disease. We further applied two-step Mendelian randomization to explore the mediation effects of metabolic traits. RESULTS: In the cohort study, probable depression was associated with an increased risk of gallstone disease within 5 years, with RR (95% CI) of 1.33 (1.12, 1.58) in multivariable regression, and 1.34 (1.11, 1.61) following propensity score weighting. Bidirectional Mendelian randomization in European ancestry revealed a positive causal effect (OR: 1.21; 95% CI: 1.07 to 1.37) of genetically predicted major depression liability on gallstone disease, based on the inverse variance weighted method. Little evidence was presented from other complementary approaches, and the analysis in East-Asian ancestry (IVW estimated OR: 1.03; 95% CI: 0.92 to 1.15). The indirect effect via waist circumference and HDL-C were 1.06 (95% CI: 1.02 to 1.10) and 1.01 (95% CI: 1.00 to 1.01) respectively, which mediated 25.8% and 3.78% of the causal relationship. CONCLUSIONS: Our study suggested a higher risk of gallstone disease in the population with probable depression, while the two-sample Mendelian randomization provided weak evidence for the causal relationship, which was moderately mediated by abdominal obesity.

The association between urinary metals/metalloids and chronic kidney disease among general adults in Wuhan, China.

The relation between exposure to single metal/metalloid and the risk of chronic kidney disease (CKD) remains unclear. We aimed to determine the single and mixed associations of 21 heavy metals/metalloids exposure and the risk of CKD. We performed a cross-sectional study that recruited 4055 participants. Multivariate logistic regression, linear regression and weighted quantile sum (WQS) regression were conducted to explore the possible effects of single and mixed metals/metalloids exposure on the risk of CKD, the risk of albuminuria and changes in the estimated glomerular filtration rate (eGFR). In single-metal models, Cu, Fe, and Zn were positively associated with increased risks of CKD (P-trend < 0.05). Compared to the lowest level, the highest quartiles of Cu (OR = 2.94; 95% CI: 1.70, 5.11; P-trend < 0.05), Fe (OR = 2.39; 95% CI: 1.42, 4.02; P-trend < 0.05), and Zn (OR = 2.35; 95% CI: 1.31, 4.24; P-trend < 0.05) were associated with an increased risk of CKD. After multi-metal adjustment, the association with the risk of CKD remained robust for Cu (P < 0.05). Weighted quantile sum regression revealed a positive association between mixed metals/metalloids and the risk of CKD, and the association was largely driven by Cu (43.7%). Specifically, the mixture of urinary metals/metalloids was positively associated with the risk of albuminuria and negatively associated with eGFR.

Associations of polychlorinated biphenyl and organochlorine pesticide exposure with hyperuricemia: modification by lifestyle factors.

Recent research has reported positive associations of exposure to polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) with hyperuricemia. However, most of these studies have primarily focused on the individual effects of PCB/OCP exposure. We aimed to explore the associations of both individual and combined PCB/OCP exposure with hyperuricemia and examine whether such associations could be modified by lifestyle factors. The cross-sectional study recruited 2032 adults between March and May 2019 in Wuhan, China. Logistic regression and weighted quantile sum (WQS) regression were applied to explore the relationship of individual and combined PCB/OCP exposure with hyperuricemia, while considering the modified effects of lifestyle factors. Of the 2032 participants, 522 (25.7%) had hyperuricemia. Compared with the non-detected group, the detected groups of PCB153 and PCB180 exhibited a positive association with hyperuricemia, with OR (95% CIs) of 1.52 (1.22, 1.91) and 1.51 (1.20, 1.90), respectively. WQS regression showed that PCB/OCP mixture was positively associated with hyperuricemia (OR: 1.31, 95% CI: 1.08, 1.58). PCB153/PCB180 exposure, combined with an unhealthy lifestyle, has a significant additive effect on hyperuricemia. Overall, PCB/OCP mixture and individual PCB153/PCB180 exposure were positively associated with hyperuricemia. Adherence to a healthy lifestyle may modify the potential negative impact of PCBs/OCPs on hyperuricemia.

Association between female-specific reproductive factors and leukocyte telomere length.

STUDY QUESTION: What are the associations between female-specific reproductive factors and leukocyte telomere length (LTL)? SUMMARY ANSWER: Early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of oral contraceptives (OCs) and hormone replacement therapy (HRT) were associated with shorter LTL. WHAT IS KNOWN ALREADY: Reproductive factors have been associated with age-related diseases, but their associations with cellular aging, as indicated by LTL, are unclear. STUDY DESIGN, SIZE, DURATION: This population-based study included 224 965 women aged 40-69 years from the UK Biobank between 2006 and 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 40-69 were included. Female-specific reproductive factors, including age at menarche, age at natural menopause, reproductive lifespan, number of live births, age at first live birth, history of stillbirth, history of miscarriage, and use of OCs and HRT were self-reported. LTL was measured using a validated polymerase chain reaction method. Multiple linear regression and restricted cubic spline models were applied to explore the association between each reproductive factor and LTL. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustment for potential confounders, early menarche (<12 years; percent change, per unit change in LTL Z score: -1.29%, 95% CI: -2.32%, -0.26%), early menopause (<45 years; percent change: -7.18%, 95% CI: -8.87%, -5.45%), short reproductive lifespan (<30 years; percent change: -6.10%, 95% CI: -8.14%, -4.01%), multiparity (percent change: -3.38%, 95% CI: -4.38%, -2.37%), early age at first live birth (<20 years; percent change: -4.46%, 95% CI: -6.00%, -2.90%), and use of OCs (percent change: -1.10%, 95% CI: -2.18%, -0.02%) and HRT (percent change: -3.72%, 95% CI: -4.63%, -2.80%) were all significantly associated with shorter LTL. However, no significant association was found for history of miscarriage and stillbirth. We observed nonlinear relationships of age at menarche, age at natural menopause, reproductive lifespan, and age at first live birth with LTL (Pnonlinear < 0.05). LIMITATIONS, REASONS FOR CAUTION: Considering that the participants were predominantly of European ethnicity, the findings may not be generalizable to women of other ethnic backgrounds. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of OCs and HRT were associated with shorter LTL, which has been linked to various chronic diseases. The accelerated shortening of telomeres may potentially contribute to the development of chronic diseases related to reproductive factors. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Natural Science Foundation of China (82003479, 82073660), Hubei Provincial Natural Science Foundation of China (2023AFB663), and the China Postdoctoral Science Foundation (2019M662646, 2020T130220). The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.

Cadmium exposure is associated with decreased muscle strength in middle-aged and older adults.

Cadmium, a toxic heavy metal, is ubiquitous in the environment. No previous research has evaluated the relationship of blood and urine cadmium levels with muscle strength measured by isokinetic knee extensor strength. This analysis included participants who were aged 50 years or older and had measurements of cadmium in blood (n = 2052) and urine (n = 811) from the National Health and Nutrition Examination Survey. Blood and urine cadmium levels were assessed by atomic absorption spectrometry and inductively coupled plasma-mass spectrometry, respectively. Isokinetic dynamometry was used to assess knee extensor strength (peak force). Linear regression models were used to examine the association between cadmium exposure and peak force, with adjustment for potential confounders. The median values (25-75th percentiles) of blood cadmium and creatinine-corrected urine cadmium were 0.50 µg/L (0.40-0.70) and 0.43 µg/g (0.27-0.71), respectively. After adjusting for potential confounders, linear dose-response relationships of peak force with blood and urine cadmium concentrations were observed in the present study. Compared to participants in the highest quartile of blood cadmium and urine cadmium, the peak force decreased by 6.99 Newton (95% CI: -21.96, 7.98) and 26.84 Newton (95% CI: -44.34, -9.34) in participants in the lowest quartiles, respectively. The observed associations were more evident among men participants. Our findings suggest that the cadmium levels have a dose response relationship with decreased muscle strength measured by isokinetic knee extensor strength in middle aged and older adults. Further longitudinal investigations are required to disentangle these complexities on this issue.