Synergistic impact of co-exposures to whole blood metals on chronic kidney disease in general US adults: a cross­sectional study of the National Health and Nutrition Examination Survey 2011-2020.

The impact of exposure to metals on chronic kidney disease (CKD) has only been investigated in two-way or single metal interactions in previous studies. We investigated the associations between five single metals in blood and their mixed exposure and CKD by using the machine learning approach. Relevant data were extracted from the National Health and Nutrition Examination Survey (NHANES 2011-2020), and the level of five metals in blood detected by inductively coupled plasma mass spectrometry was considered as exposures, namely, cadmium (Cd), lead (Pb), total mercury (Hg), manganese (Mn), and selenium (Se). The correlations between individual metal and metal mixtures and CKD were then evaluated by survey-multivariable logistic regression (SMLR), generalized weighted quantile sum (WQS), and Bayesian kernel machine regression (BKMR). Altogether, our study included 12,412 participants representing 572.6 million non-institutionalized US adults. Several single metals with the high quartile of exposure showed a positive association with the CKD ratio including Cd [(AOR = 1.873, 95% CI: 1.537, 2.284), Q4], Pb [(AOR = 1.559, 95% CI: 1.295, 1.880), Q4], and total Hg [(AOR = 1.169, 95% CI: 1.018, 1.343), Q2], while Mn [(AOR = 0.796, 95% CI: 0.684, 0.927), Q2] and Se [(AOR = 0.805, 95% CI: 0.664, 0.976), Q4] were negatively associated with the CKD ratio. In light of the positive fit of the WQS regression model, a significantly positive correlation was found between mixed metals and CKD (AOR = 1.373, 95% CI: 1.224, 1.539) after full covariate adjustment, and a similar finding was also detected in the BKMR model. Our study revealed that each single metal including Cd, Pb, and total Hg might have a positive association with CKD while this association was negative for both Mn and Se. The five metals might have a positive joint effect on CKD.

Joint effect of whole blood metals exposure with dyslipidemia in representative US adults in NHANES 2011-2020.

With little knowledge on the joint effects of metal exposure on dyslipidemia, we aimed to investigate the relationship between exposure to metal and dyslipidemia among US adults based on the National Health and Nutrition Examination Survey (NHANES). Based on the five NHANES waves (2011-2020), we selected five metals in blood as exposure, namely, cadmium (Cd), lead (Pb), total mercury (Hg), manganese (Mn), and selenium (Se), which were detected by inductively coupled plasma mass spectrometry. Survey-multivariable logistic regression, generalized weighted quantile sum (WQS), and Bayesian kernel machine regression (BKMR) were performed to determine whether dyslipidemia was associated with single metals or mixed metals. Our study included 12,526 participants aged from 20 to 80, representing 577.1 million non-institutionalized US adults. We found a positive association between several metals including Pb [adjusted odds ratio (AOR) = 1.332, 95%CI: 1.165, 1.522], total Hg (AOR = 1.264, 95%CI: 1.120, 1.427), Mn (AOR = 1.181, 95%CI: 1.046, 1.334), and Se (AOR = 1.771, 95%CI: 1.576, 1.992) and dyslipidemia. According to the WQS approach, metal mixtures were positively associated with dyslipidemia (AOR: 1.310, 95%CI: 1.216, 1.411) after a full-model adjustment. As is shown in the BKMR model, mixed metals tended to be positively associated with dyslipidemia ratios in a significant manner. Females, non-Hispanic White populations, people aged over 60, and those who did a little physical activity had a greater risk for dyslipidemia. Our findings suggest metals including Cd, Pb, Hg, Mn, and Se and their combinations may adversely affect dyslipidemia among US adults. Due to the cross-sectional nature of the study, it is possible that reverse causation may exist.

Association of urinary exposure to multiple metal(loid)s with kidney function from a national cross-sectional study.

BACKGROUND: Arsenic (As), cadmium (Cd) and copper (Cu) are hazardous for kidney function, while the effects of selenium (Se) and zinc (Zn) were unexplored for the narrow safe range of intake. Interactions exists between these multiple metal/metalloid exposures, but few studies have investigated the effects. METHODS: A cross-sectional survey was performed among 2210 adults across twelve provinces in China between 2020 and 2021. Urinary As, Cd, Cu, Se and Zn were measured using inductively coupled plasma-mass spectrometry (ICP-MS). Serum creatinine (Scr) and N-acetyl-beta-D glucosaminidases (urine NAG) were quantified in serum and urine, respectively. Kidney function was evaluated by the estimated glomerular filtration rate (eGFR). We employed logistic regression and Bayesian kernel machine regression (BKMR) models to explore the individual and joint effects of urinary metals/metalloids on the risk of impaired renal function (IRF) or chronic kidney disease (CKD), respectively. RESULTS: Association was found between As (OR = 1.24, 95 % CI: 1.03, 1.48), Cd (OR = 1.65, 95 % CI: 1.35, 2.02), Cu (OR = 1.90, 95 % CI: 1.59, 2.29), Se (OR = 1.51, 95 % CI: 1.24, 1.85) and Zn (OR = 1.33, 95 % CI: 1.09, 1.64) and the risk of CKD. Moreover, we observed association between As (OR = 1.18, 95 % CI: 1.07, 1.29), Cu (OR = 1.14, 95 % CI: 1.04, 1.25), Se (OR = 1.15, 95 % CI: 1.06, 1.26) and Zn (OR = 1.12, 95 % CI: 1.02, 1.22) and the risk of IRF. Additionally, it was found that Se exposure may strength the association of urinary As, Cd and Cu with IRF. Furthermore, it is worth noting that Se and Cu contributed greatest to the inverse association in IRF and CKD, respectively. CONCLUSION: Our findings suggested that metal/metalloid mixtures were associated with kidney dysfunction, Se and Cu were inverse factors. Additionally, interactions between them may affect the association. Further studies are needed to assess the potential risks for metal/metalloid exposures.

How Parental Predictors Jointly Affect the Risk of Offspring Congenital Heart Disease: A Nationwide Multicenter Study Based on the China Birth Cohort.

Objective: Congenital heart disease (CHD) is complex in its etiology. Its genetic causes have been investigated, whereas the non-genetic factor related studies are still limited. We aimed to identify dominant parental predictors and develop a predictive model and nomogram for the risk of offspring CHD. Methods: This was a retrospective study from November 2017 to December 2021 covering 44,578 participants, of which those from 4 hospitals in eastern China were assigned to the development cohort and those from 5 hospitals in central and western China were used as the external validation cohort. Univariable and multivariable analyses were used to select the dominant predictors of CHD among demographic characteristics, lifestyle behaviors, environmental pollution, maternal disease history, and the current pregnancy information. Multivariable logistic regression analysis was used to construct the model and nomogram using the selected predictors. The predictive model and the nomogram were both validated internally and externally. A web-based nomogram was developed to predict patient-specific probability for CHD. Results: Dominant risk factors for offspring CHD included increased maternal age [odds ratio (OR): 1.14, 95% CI: 1.10-1.19], increased paternal age (1.05, 95% CI: 1.02-1.09), maternal secondhand smoke exposure (2.89, 95% CI: 2.22-3.76), paternal drinking (1.41, 95% CI: 1.08-1.84), maternal pre-pregnancy diabetes (3.39, 95% CI: 1.95-5.87), maternal fever (3.35, 95% CI: 2.49-4.50), assisted reproductive technology (2.89, 95% CI: 2.13-3.94), and environmental pollution (1.61, 95% CI: 1.18-2.20). A higher household annual income (100,000-400,000 CNY: 0.47, 95% CI: 0.34-0.63; > 400,000 CNY: 0.23, 95% CI: 0.15-0.36), higher maternal education level (13-16 years: 0.68, 95% CI: 0.50-0.93; ≥ 17 years: 0.87, 95% CI: 0.55-1.37), maternal folic acid (0.21, 95% CI: 0.16-0.27), and multivitamin supplementation (0.33, 95% CI: 0.26-0.42) were protective factors. The nomogram showed good discrimination in both internal [area under the receiver-operating-characteristic curve (AUC): 0.843] and external validations (development cohort AUC: 0.849, external validation cohort AUC: 0.837). The calibration curves showed good agreement between the nomogram-predicted probability and actual presence of CHD. Conclusion: We revealed dominant parental predictors and presented a web-based nomogram for the risk of offspring CHD, which could be utilized as an effective tool for quantifying the individual risk of CHD and promptly identifying high-risk population.

Association Between Exposure to Outdoor Artificial Light at Night and Sleep Disorders Among Children in China.

Importance: Healthy sleep has an important role in the physical and mental health of children. However, few studies have investigated the association between outdoor artificial light at night (ALAN) and sleep disorders in children. Objective: To explore the associations between outdoor ALAN exposure and sleep disorders in children. Design, Setting, and Participants: This population-based cross-sectional study, part of the National Chinese Children Health Study, was conducted from April 1, 2012, to June 30, 2013, in the first stage and from May 1, 2016, to May 31, 2018, in the second stage in 55 districts of 14 cities in China. This analysis included 201 994 children and adolescents aged 2 to 18 years. Data were analyzed from February 20 to March 21, 2022. Exposures: Outdoor ALAN exposure (in nanowatts per centimeters squared per steradian) within 500 m of each participant's residential address obtained from the satellite imagery data, with a resolution of approximately 500 m. Main Outcomes and Measures: Sleep disorders were measured by the Chinese version of the Sleep Disturbance Scale for Children. Generalized linear mixed models were used to estimate the associations of outdoor ALAN with sleep scores and sleep disorders. Results: The study included 201 994 children and adolescents (mean [SD] age, 11.3 [3.2] years; 106 378 boys [52.7%]), 7166 (3.5%) of whom had sleep disorder symptoms. Outdoor ALAN exposure of study participants ranged from 0.02 to 113.48 nW/cm2/sr. Compared with the lowest quintile (Q1) of outdoor ALAN exposure, higher quintiles of exposure (Q2-Q5) were associated with an increase in total sleep scores of 0.81 (95% CI, 0.66-0.96) in Q2, 0.83 (95% CI, 0.68-0.97) in Q3, 0.62 (95% CI, 0.46-0.77) in Q4, and 0.53 (95% CI, 0.36-0.70) in Q5. Higher quintiles of exposure were also associated with odds ratios for sleep disorder of 1.34 (95% CI, 1.23-1.45) in Q2, 1.43 (95% CI, 1.32-1.55) in Q3, 1.31 (95% CI, 1.21-1.43) in Q4, and 1.25 (95% CI, 1.14-1.38) in Q5. Similar associations were observed for sleep disorder subtypes. In addition, greater effect estimates were found among children younger than 12 years. Conclusions and Relevance: The findings of this cross-sectional study suggest that sleep disorders are more prevalent among children residing in areas with high levels of outdoor ALAN and the associations are generally stronger in children younger than 12 years. These findings further suggest that effective control of outdoor ALAN may be an important measure for improving the quality of children's sleep.

[Epidemiologic survey on the prevalence and distribution of childhood functional constipation in the northern areas of China: a population-based study].

OBJECTIVE: Functional constipation (FC) is a common complaint in childhood but the prevalence still remains unclear, the aim of this study was to explore the prevalence of FC in childhood in the northern parts of China. METHODS: A screening program on FC in childhood was carried out in 5 northern cities (Beijing, Tianjin, Shenyang, Changchun, Harbin) of China according to symptoms under the Rome III criteria. Random clustered sampling of the inhabitants was carried out under stratification of cities, geographic zones, schools or nurseries. Sample size of each area was in proportion to the population of the area. The range of age was 4-14. All subjects under study were requested to fill in a questionnaire distributed by the teachers. The screening program was carried out immediately after a section survey was completed. All together, 20 000 questionnaires were distributed with 19 638 retrievals. According to the result of the screening, a small number of patients who met the criteria were further selected to undergo a detailed clinical examination in the hospital including laboratory examination, colonic transit time, defecography or/and barium enema, electromyologram and anorectal manometry to exclude organic disease of the colon. Simultaneously, a detailed questionnaire was requested to fill under the assistance of trained doctors or medical students. Prevalence of FC of the population was adjusted by the rate of correct diagnosis from the detailed study. RESULTS: The adjusted point prevalence of FC in 5 northern cities of China according to Rome III criteria was 4.73% with higher prevalence rate of FC seen in the Beijing area (5.02%) than in other cities (4.82%, 4.76%, 4.27%, 4.40%, with P < 0.001). Male to female ratio was 1.26:1 with majority of the FC fell in the 4 - 6 year olds (5.76%). CONCLUSION: FC appeared a common disorder in childhood in the northern parts of China which called for greater attention. Higher prevalence was noted in the age groups of 4-6.

[Preliminary study on diagnostic standard of functional constipation in children from five cities in North China].

OBJECTIVE: To explore the symptomatic criteria for diagnosis in children with functional constipation(FC) in North China. METHODS: A screening program for FC in children was carried out in 5 northern cities (Beijing, Tianjin, Shenyang, Changchun, Harbin) of China according to symptoms using Rome III( criteria. Random clustered sampling of the inhabitants was carried out under stratification of city, region and school or kindergarten. Sample size of each area was in proportion to the population of the area. The range of age was 4-14. All the subjects were requested to fill in a questionnaire distributed by the teacher. The screening program was carried out immediately after a plot survey. A total of 20,000 questionnaires were distributed and 19,638 retrieved. According to the result of the screening, a small number of patients who fulfilled the criteria were further selected to undergo detail clinical examinations in the hospital including laboratory examination, colonic transit time, defecography or/and barium enema, electromyogram and anorectal manometry to exclude organic disease of the colon. A detailed questionnaire was filled in with the assistance from a trained doctor or a medical student. Potential risk factors and the relative symptoms were explored by comparing frequencies between FC group and non-FC group using χ2 and Logistic analysis. RESULTS: Eighteen symptoms (defecation less than 3 times per week, dry hard sausage-shape stool, difficulty in defecation, abdominal pain, nausea and vomiting, etc) could exist in control group, but FC group had a higher frequency. The difference was statistically significant. Multivariable stepwise logistic regression analysis showed that defecation less than 3 times per week, hard sausage-shape feces, difficulty in defecation, and the need for laxative were associated with FC. The absence of other symptoms had no influence on diagnosis of FC. The sensitivity, specificity and diagnostic accuracy of symptomatic standard diagnostic test based on Rome III( criteria in FC children showed that ≥2 items had the best diagnostic accuracy but moderate sensitivity and specificity. CONCLUSION: The symptomatic criteria for FC diagnosis in children are suggested as follows: (1) defecation frequency less than 3 times per week; (2) dry, hard, sausage-shape stool in most defecation; (3) difficulty in most defecation; (4) use of medication or digital evacuation. FC can be considered when 2 of the above 4 criteria are met and the symptoms last at least 2 months.

A split-face study of intense pulsed light on photoaging skin in Chinese population.

BACKGROUND AND OBJECTIVES: Intense pulsed light (IPL) is regarded as the gold standard of nonablative photo-rejuvenation. Yet there is still a need to observe its efficacy and safety on dark skin using a split-face module. STUDY DESIGN/MATERIALS AND METHODS: Twenty-four Chinese women with photoaging were enrolled in this study. Patients were randomized to receive four IPL treatments at 3- to 4-week intervals on one side of face, with the other side spared as control. Changes of photoaging were evaluated using a global evaluation, an overall self-assessment, a Mexameter and a Corneometer. Skin biopsies were taken after four sessions of treatment on one side of face. The melanocyte density and the contents of melanin, collagen fibers, and elastic fibers were stained and used to evaluate the improvement on dyschromia and other signs of photoaging. RESULTS: The global scores of photoaging on treated side decreased significantly from 3.02 to 1.22, while it remained unchanged on the untreated side. Twenty-one of 24 patients (87.5%) rated their improvement as excellent or good. The difference on the values of melanin index and erythema index on treated side were significantly larger than those on untreated side after the 1st session, the 4th session and at 3-month follow-up (P<0.05). The melanin contents were significantly decreased and the collagen fibers were obviously increased only on treated side (P<0.05). Adverse effects of treated side were limited to mild pain and transient erythema. CONCLUSION: Using this split-face module, IPL treatment is proved both clinically and histologically to be effective in treating photoaging skin in Chinese population. Adverse effects were minimal and acceptable.

Protective effects of green tea extracts on photoaging and photommunosuppression.

OBJECTIVES: This study aimed to investigate whether the sunscreen-containing 2-5% green tea extracts (GTEs) protect ultraviolet irradiation (UVR)-induced photoaging and photoimmunosuppression. MATERIALS AND METHODS: Twenty volunteers were exposed to repetitive solar-simulated UVR (ssUVR) on the upper back at a dosage of 1.5 minimal erythema doses (MED) per day for four consecutive days. Thirty minutes before each UVR and 6, 24, and 48 h after the last UV exposure, the products containing vehicle, and 2-5% GTEs were applied onto five sites on the dorsal skin, respectively. The skin biopsies were obtained 72 h after the last UVR. The thickness of the stratum corneum and epidermis was measured under the microscope and the expression of cytokeratins (CK)-5/6, CK16, metalloproteinases (MMP)-2, MMP-9, and the CD1a(+) Langerhans cells (LCs) were determined using immunohistochemistry. RESULTS: Our results showed that UVR substantially induced cutaneous erythema, thickening of the epidermis, overexpression of CK5/6, CK16, MMP-2, MMP-9, and depletion of CD1a(+) LCs. The sunscreens containing different concentrations of GTEs conferred significant protection against the photoaging and photoimmunology-related biological events. Interestingly, the protective effects were not parallel to the concentrations of GTEs, with 2% and 3% GTEs showing the most efficacious photoprotection. CONCLUSIONS: GTEs-containing sunscreens have potential photoprotective effects on UVR-induced photoaging and photoimmunosuppression.

Efficacy and safety of intense pulsed light in treatment of melasma in Chinese patients.

BACKGROUND: Melasma is commonly seen in the Asian population. Traditional therapies are less effective and may cause adverse effects. OBJECTIVE: The objective was to study the efficacy and safety of a new intense pulsed light (IPL) device in the treatment of melasma in Chinese patients. METHODS: Eighty-nine women with melasma were enrolled in this open-labeled study. Subjects received a total of four IPL treatments at 3-week intervals. Changes in facial hyperpigmentation and telangiectasis were evaluated using an objective, skin colorimeter (Mexameter, Courage & Khazaka), the melasma area and severity index (MASI), and a global evaluation by the patients and blind investigators. RESULTS: Sixty-nine of 89 patients (77.5%) obtained 51% to 100% improvement, according to the overall evaluation by dermatologists. Self-assessment by the patients indicated that 63 of 89 patients (70.8) considered more than 50% or more improvement. Mean MASI scores decreased substantially from 15.2 to 4.5. Mexameter results demonstrated a significant decrease in the degree of pigmentation and erythema beneath the melasma lesions. Patients with the epidermal-type melasma responded better to treatment than the mixed type. Adverse actions were minimal. CONCLUSION: IPL treatment is a good option for patients with melasma. Adverse actions of IPL were minimal and acceptable.