[Corrigendum] Next­generation sequencing analysis reveals that MTH­3, a novel curcuminoid derivative, suppresses the invasion of MDA­MB­231 triple­negative breast adenocarcinoma cells.

Subsequently to the publication of the article, an interested reader drew to the authors' attention that, in Fig. 2A on p. 5, the 'Control  (24 h)' and 'MTH­3 (1 µM; 24 h)' data panels contained partially overlapping data, such that they appeared to have been derived from the same original source. The authors have examined their original data, and realized that this error arose inadvertently as a consequence of having compiled this figure incorrectly. The revised version of Fig. 2, featuring the data from one of the repeated experiments in Fig. 2A, is shown below. The revised data shown for this figure do not affect the overall conclusions reported in the paper. The authors apologize to the Editor of Oncology Reports and to the readership for any inconvenience caused. [Oncology Reports 46: 133, 2021; DOI: 10.3892/or.2021.8084].

CDK7/CDK9 mediates transcriptional activation to prime paraptosis in cancer cells.

BACKGROUND: Paraptosis is a programmed cell death characterized by cytoplasmic vacuolation, which has been explored as an alternative method for cancer treatment and is associated with cancer resistance. However, the mechanisms underlying the progression of paraptosis in cancer cells remain largely unknown. METHODS: Paraptosis-inducing agents, CPYPP, cyclosporin A, and curcumin, were utilized to investigate the underlying mechanism of paraptosis. Next-generation sequencing and liquid chromatography-mass spectrometry analysis revealed significant changes in gene and protein expressions. Pharmacological and genetic approaches were employed to elucidate the transcriptional events related to paraptosis. Xenograft mouse models were employed to evaluate the potential of paraptosis as an anti-cancer strategy. RESULTS: CPYPP, cyclosporin A, and curcumin induced cytoplasmic vacuolization and triggered paraptosis in cancer cells. The paraptotic program involved reactive oxygen species (ROS) provocation and the activation of proteostatic dynamics, leading to transcriptional activation associated with redox homeostasis and proteostasis. Both pharmacological and genetic approaches suggested that cyclin-dependent kinase (CDK) 7/9 drive paraptotic progression in a mutually-dependent manner with heat shock proteins (HSPs). Proteostatic stress, such as accumulated cysteine-thiols, HSPs, ubiquitin-proteasome system, endoplasmic reticulum stress, and unfolded protein response, as well as ROS provocation primarily within the nucleus, enforced CDK7/CDK9-Rpb1 (RNAPII subunit B1) activation by potentiating its interaction with HSPs and protein kinase R in a forward loop, amplifying transcriptional regulation and thereby exacerbating proteotoxicity leading to initiate paraptosis. The xenograft mouse models of MDA-MB-231 breast cancer and docetaxel-resistant OECM-1 head and neck cancer cells further confirmed the induction of paraptosis against tumor growth. CONCLUSIONS: We propose a novel regulatory paradigm in which the activation of CDK7/CDK9-Rpb1 by nuclear proteostatic stress mediates transcriptional regulation to prime cancer cell paraptosis.

Mapping the gut microecological multi-omics signatures to serum metabolome and their impact on cardiometabolic health in elderly adults.

BACKGROUND: Mapping gut microecological features to serum metabolites (SMs) will help identify functional links between gut microbiome and cardiometabolic health. METHODS: This study encompassed 836-1021 adults over 9.7 year in a cohort, assessing metabolic syndrome (MS), carotid atherosclerotic plaque (CAP), and other metadata triennially. We analyzed mid-term microbial metagenomics, targeted fecal and serum metabolomics, host genetics, and serum proteomics. FINDINGS: Gut microbiota and metabolites (GMM) accounted for 15.1% overall variance in 168 SMs, with individual GMM factors explaining 5.65%-10.1%, host genetics 3.23%, and sociodemographic factors 5.95%. Specifically, GMM elucidated 5.5%-49.6% variance in the top 32 GMM-explained SMs. Each 20% increase in the 32 metabolite score (derived from the 32 SMs) correlated with 73% (95% confidence interval [CI]: 53%-95%) and 19% (95% CI: 11%-27%) increases in MS and CAP incidences, respectively. Among the 32 GMM-explained SMs, sebacic acid, indoleacetic acid, and eicosapentaenoic acid were linked to MS or CAP incidence. Serum proteomics revealed certain proteins, particularly the apolipoprotein family, mediated the relationship between GMM-SMs and cardiometabolic risks. INTERPRETATION: This study reveals the significant influence of GMM on SM profiles and illustrates the intricate connections between GMM-explained SMs, serum proteins, and the incidence of MS and CAP, providing insights into the roles of gut dysbiosis in cardiometabolic health via regulating blood metabolites. FUNDING: This study was jointly supported by the National Natural Science Foundation of China, Key Research and Development Program of Guangzhou, 5010 Program for Clinical Research of Sun Yat-sen University, and the 'Pioneer' and 'Leading goose' R&D Program of Zhejiang.

Impact of miscarriage and termination of pregnancy on subsequent pregnancies: A longitudinal study of maternal and paternal depression, anxiety and eudaimonia.

BACKGROUND: Although miscarriage and termination of pregnancy affect maternal mental illnesses on subsequent pregnancies, their effects on the positive mental health (e.g., eudaimonia) of both first-time and multi-time parents have received minimal attention, especially for fathers. This longitudinal study examines the effects of experiences of miscarriage and termination on parental well-being in subsequent pregnancies from prenatal to postpartum years, while simultaneously considering parity. METHODS: Pregnant women and their partners were recruited during early prenatal visits in Taiwan from 2011 to 2022 and were followed up from mid-pregnancy to 1 year postpartum. Six waves of self-reported assessments were employed. RESULTS: Of 1813 women, 11.3 % and 14.7 % had experiences of miscarriage and termination, respectively. Compared with the group without experiences of miscarriage or termination, experiences of miscarriage were associated with increased risks of paternal depression (adjusted odds ratio = 1.6, 95 % confidence interval [CI] = 1.13-2.27), higher levels of anxiety (adjusted ß = 1.83, 95 % CI = 0.21-3.46), and lower eudaimonia scores (adjusted ß = -1.09, 95 % CI = -1.99 to -0.19) from the prenatal to postpartum years, particularly among multiparous individuals. Additionally, experiences of termination were associated with increased risks of depression in their partner. LIMITATIONS: The experiences of miscarriage and TOP were self-reported and limited in acquiring more detailed information through questioning. CONCLUSIONS: These findings highlight the decreased well-being of men whose partners have undergone termination of pregnancy or experienced miscarriage, and stress the importance of interventions aimed at preventing adverse consequences among these individuals.

Effects of shift work on sleep quality and cardiovascular function in Taiwanese police officers.

This study aimed to investigate the effects of shift work on sleep quality, cardiovascular function, and physical activity (PA) levels in Taiwanese police officers. Twenty-one male police officers aged 26.9 ± 4.1 years old located in Taipei voluntarily participated in this study. The participants completed the resting heart rate (HR) and hemodynamic variables (e.g. blood pressure, BP) before and after day-time (DTW) and night-time (NTW) shift work phases (5 working days and 2 resting days for each phase). Additionally, an actigraphy was administered to measure PA and sleep patterns in the last 3 working days. The average total sleep time and sleep efficiency were 278.5 ± 79. 6 min and 72.9 ± 10%, respectively, in the NTW phases, which were significantly lower than that in the DTW phases. A comparison of the PA characteristics between the two phases revealed that a lower proportion of moderate-vigorous PA (1.2 ± 0.8%) and a greater proportion of sedentary behaviour PA (74.8 ± 6.4%) was found in the NTW phases. The results of hemodynamic measures demonstrated that the police officers have significantly elevated systolic BP by 3.3% and diastolic BP by 3.9% after the NTW phases. Furthermore, the NTW phases exhibited a significantly higher percentage change ratio of systolic BP and diastolic BP compared to the DTW phases. Compared with the DTW phases, the NTW phase was significantly more likely to report higher decreasing parasympathetic-related HR variability with a range of -5.9% to -7.8%. In conclusion, night-time shift work resulted in negative physiological changes leading to adverse effects on the health and well-being of Taiwanese police officers.

Assessment of sources and health risks of heavy metals in metropolitan household dust among preschool children: The LEAPP-HIT study.

The most common construction material used in Taiwan is concrete, potentially contaminated by geologic heavy metals (HMs). Younger children spend much time indoors, increasing HM exposure risks from household dust owing to their behaviors. We evaluated arsenic (As), cadmium (Cd), and lead (Pb) concentrations in fingernails among 280 preschoolers between 2017 and 2023. We also analyzed HM concentrations, including As, Cd, Pb, chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), iron (Fe), and manganese (Mn), in 90 household dust and 50 road dust samples from a residential area where children lived between 2019 and 2021 to deepen the understanding of sources and health risks of exposure to HMs from household dust. The average As, Cd, and Pb concentrations in fingernails were 0.12 ± 0.06, 0.05 ± 0.05, and 0.95 ± 0.77 µg/g, respectively. Soil parent materials, indoor construction activities, vehicle emissions, and mixed indoor combustion were the pollution sources of HMs in household dust. Higher Cr and Pb levels in household dust may pose non-carcinogenic risks to preschoolers. Addressing indoor construction and soil parent materials sources is vital for children's health. The finding of the present survey can be used for indoor environmental management to reduce the risks of HM exposure and avoid potential adverse health effects for younger children.

MRCK as a Potential Target for Claudin-Low Subtype of Breast Cancer.

To find new molecular targets for triple negative breast cancer (TNBC), we analyzed a large-scale drug screening dataset based on breast cancer subtypes. We discovered that BDP-9066, a specific MRCK inhibitor (MRCKi), may be an effective drug against TNBC. After confirming the efficacy and specificity of BDP-9066 against TNBC in vitro and in vivo, we further analyzed the underlying mechanism of specific activity of BDP-9066 against TNBC. Comparing the transcriptome of BDP-9066-sensitive and -resistant cells, the activation of the focal adhesion and YAP/TAZ pathway were found to play an important role in the sensitive cells. Furthermore, YAP/TAZ is indeed repressed by BDP-9066 in the sensitive cells, and active form of YAP suppresses the effects of BDP-9066. YAP/TAZ expression and activity are high in TNBC, especially the Claudin-low subtype, consistent with the expression of focal adhesion-related genes. Interestingly, NF-κB functions downstream of YAP/TAZ in TNBC cells and is suppressed by BDP-9066. Furthermore, the PI3 kinase pathway adversely affected the effects of BDP-9066 and that alpelisib, a PI3 kinase inhibitor, synergistically increased the effects of BDP-9066, in PIK3CA mutant TNBC cells. Taken together, we have shown for the first time that MRCKi can be new drugs against TNBC, particularly the Claudin-low subtype.

Associations between parental and postnatal metal mixture exposure and developmental delays in a Taiwanese longitudinal birth cohort of preschool children.

Studies have evaluated the impact of environmental exposure to neurotoxic metals on developmental delays (DDs). However, comprehensive understanding regarding the associations between parental and postnatal exposure to metal mixtures and the occurrence of DDs in offspring is limited. In this study, we assessed the relationships between parental and postnatal exposure to three metals (arsenic [As], cadmium [Cd], and lead [Pb], levels of which were measured in toenails) and suspected DDs (SDDs) in preschool children within a Taiwanese longitudinal birth cohort. In total between 2017 and 2021, 154 pairs of parents and their children under the age of 6 years were recruited, and 462 toenail samples and 154 completed questionnaires were collected. Metal concentrations in toenails were quantified using inductively coupled plasma-mass spectrometry after acid digestion of the toenails. We applied multivariable logistic regression and Bayesian kernel machine regression to evaluate the overall effect and to identify key components of the metal mixture that were associated with the SDD risk. Higher concentrations of As, Cd, and Pb were found in the toenails of the parents of children with SDDs compared with the toenails of the parents of children without SDDs. Our examination of the combined effects of exposure to the metal mixture revealed that As concentration in the father's toenail and Cd concentration in the mother's toenail were positively correlated with the risk of SDDs in their offspring. Notably, the effect of exposure to the metal mixture on the risk of SDDs was stronger in boys than in girls. Our findings suggest that parents taking measures to minimize their exposure to metals might enhance their children's developmental outcomes.

Cohort Profile: Guangzhou Nutrition and Health Study (GNHS): A Population-Based Multi-Omics Study.

BACKGROUND: The Guangzhou Nutrition and Health Study (GNHS) aims to assess the determinants of metabolic disease in nutritional aspects, as well as other environmental and genetic factors, and explore possible biomarkers and mechanisms with multi-omics integration. METHODS: The population-based sample of adults in Guangzhou, China (baseline: 40-83 years old; n = 5118) was followed up about every 3 years. All will be tracked via on-site follow-up and health information systems. We assessed detailed information on lifestyle factors, physical activities, dietary assessments, psychological health, cognitive function, body measurements, and muscle function. Instrument tests included dual-energy X-ray absorptiometry scanning, carotid artery and liver ultrasonography evaluations, vascular endothelial function evaluation, upper-abdomen and brain magnetic resonance imaging, and 14-d real-time continuous glucose monitoring tests. We also measured multi-omics, including host genome-wide genotyping, serum metabolome and proteome, gut microbiome (16S rRNA sequencing, metagenome, and internal transcribed spacer 2 sequencing), and fecal metabolome and proteome. RESULTS: The baseline surveys were conducted from 2008 to 2015. Now, we have completed 3 waves. The 3rd and 4th follow-ups have started but have yet to end. A total of 5118 participants aged 40-83 took part in the study. The median age at baseline was approximately 59.0 years and the proportion of female participants was about 69.4%. Among all the participants, 3628 (71%) completed at least one on-site follow-up with a median duration of 9.48 years. CONCLUSION: The cohort will provide data that have been influential in establishing the role of nutrition in metabolic diseases with multi-omics.

Effects of indoor air quality and home environmental characteristics on allergic diseases among preschool children in the Greater Taipei Area.

Indoor air quality and home environmental characteristics are potential factors associated with the onset and exacerbation of allergic diseases. Our study examined the effects of these factors on allergic diseases (i.e., asthma, allergic rhinitis, allergic conjunctivitis, and atopic dermatitis) among preschool children. We recruited a total of 120 preschool children from an ongoing birth cohort study in the Greater Taipei Area. A comprehensive environmental evaluation was conducted at each participant's residence and included measurements of indoor and outdoor air pollutants, fungal spores, endotoxins, and house dust mite allergens. A structured questionnaire was used to collect information on the allergic diseases and home environments of participants. Land-use characteristics and points of interest in the surrounding area of each home were analyzed. Other covariates were obtained from the cohort data. Multiple logistic regressions were used to examine the relationships between allergic diseases and covariates. We observed that all mean indoor air pollutant levels were below Taiwan's indoor air quality standards. After adjustment for covariates, the total number of fungal spores and the ozone, Der f 1, and endotoxin levels were significantly associated with increased risks of allergic diseases. Biological contaminants more significantly affected allergic diseases than other pollutants. Moreover, home environmental characteristics (e.g., living near power facilities and gas stations) were associated with an increased risk of allergic diseases. Regular and proper home sanitation is recommended to prevent the accumulation of indoor pollutants, especially biological contaminants. Living away from potential sources of pollution is also crucial for protecting the health of children.

Effects of mobile device use on emotional and behavioral problems in the CBCL among preschoolers: Do shared reading and maternal depression matter?

INTRODUCTION: Although mobile devices are used ubiquitously, studies on their detrimental effects on preschoolers are limited. Furthermore, no study has considered shared reading and mobile device usage simultaneously. Therefore, this study examined the effects of mobile devices and shared reading on preschoolers' development along with the effects of maternal depression on this association. MATERIALS AND METHODS: Mothers of 202 children aged 2-5 years were recruited in Taiwan. Maternal self-reported questionnaires on mobile device usage, shared reading, and child's emotional and behavioral development were collected. Multiple linear regression models were used for analyses. RESULTS: Mothers' higher usage time on mobile devices and an education level of college or less were significantly associated with the child's exceeding recommended use of mobile devices. Particularly among depressed mothers, preschoolers' exceeding recommended use of mobile devices was associated with more sleep (ß = 9.87, 95% confidence interval [CI] = 1.34, 18.40) and attention (ß = 7.20, 95% CI = 1.50, 12.91) problems, whereas shared reading was associated with less somatic complaints (ß = -16.19, 95% CI = -32.22, -0.15) and withdrawn (ß = -21.50, 95% CI = -40.52, -2.47), compared with their respective counterparts. CONCLUSION: Our study suggested the beneficial effects of shared reading. Moreover, we highlighted the adverse effects of preschoolers' exceeding recommended use of mobile device on sleep and attention problems, especially for children of mothers with depression.

Effects of preterm birth and postnatal exposure to metal mixtures on neurodevelopment in children at 24 months of age.

The effects of early-life metal exposure on neurodevelopment in very low birth weight preterm (VLBMP) children (with a birth weight of <1500 g and a gestational age of <37 weeks) have not been clearly established. We aimed to investigate associations of childhood exposure to multiple metals and preterm low birth weight with neurodevelopment among children at 24 months of corrected age. VLBWP children (n = 65) and normal birth weight term (NBWT) children (n = 87) were enrolled from Mackay Memorial Hospital in Taiwan between December 2011 and April 2015. Lead (Pb), cadmium (Cd), arsenic (As), methylmercury (MeHg), and selenium (Se) concentrations in the hair and fingernails were analyzed as biomarkers for metal exposure. The Bayley Scale of Infant and Toddler Development, Third Edition, was used to determine neurodevelopment levels. VLBWP children had significantly lower scores in all development domains compared to NBWT children. We also investigated preliminary exposure levels of VLBWP children to metals as reference values for future epidemiological and clinical survey. Fingernails are a useful biomarker for metal exposure to evaluate the effects on neurological development. A multivariable regression analysis revealed that fingernail Cd concentrations were significantly negatively associated with cognition (ß = -0.63, 95% confidence interval (CI): -1.17 to -0.08) and receptive language function (ß = -0.43, 95% CI: -0.82 to -0.04) among VLBWP children. VLBWP children with a 10-µg/g increase in the As concentration in their nails had a 8.67-point lower composite score in cognitive ability and a 1.82-point lower score in gross-motor functions. Effects of preterm birth and postnatal exposure to Cd and As were associated with poorer cognitive, receptive language, and gross-motor abilities. VLBWP children are at risk for neurodevelopmental impairments when exposed to metals. Further large-scale studies are needed assess to the risk of neurodevelopmental impairments when vulnerable children are exposed to metal mixtures.

Oral and inhalation bioaccessibility of mercury in contaminated soils and potential health risk to the kidneys and neurodevelopment of children in Taiwan.

Health risk assessments of exposure to mercury (Hg) from soils via ingestion and inhalation are indispensable for Taiwanese people living in the vicinity of Hg-contaminated sites. In this study, anthropogenic soils were collected from various polluted sources in Taiwan. In vitro oral and inhalation bioaccessible fractions of Hg were analyzed to avoid from overestimating the exposure risk. Discrepancies in oral and inhalation bioaccessible levels of Hg in soils were found using different in vitro assays with different pH levels and chemical compositions. The freshly contaminated soil (soil S7) polluted by chlor-alkali production activity sampled before the site was remediated had the highest total Hg concentration of 1346 mg/kg, with the highest oral bioaccessibility of 26.2% as analyzed by SW-846 Method 1340 and inhalation bioaccessibility of 30.5% as analyzed by modified Gamble's solution. The lesser extent of aging of Hg in soil S7 increased the Hg availability for humans, which was also found based on results of a sequential extraction procedure. Results of the hazard quotient showed that soil ingestion was the main pathway causing non-carcinogenic risks for children and adults. Children were also exposed to higher risks than were adults due to higher frequencies of hand-to-mouth behaviors and lower body weights. Furthermore, hazard index results adjusted for oral and inhalation bioaccessible Hg were lower than those obtained based on the total Hg content; however, an unacceptable value of the non-carcinogenic risk (> 1) for children living near soil S7 was still observed. This study suggests that children living near sites polluted for a short period of time may suffer potential renal effects regardless of the bioaccessibility. Our findings provide suggestions for decision makers on setting new strategies for managing risks of Hg-contaminated soils in Taiwan.

Inhibition of CDCP1 by 8-isopentenylnaringenin synergizes with EGFR inhibitors in lung cancer treatment.

CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance by regulating EGFR signaling pathways and is a potential target in lung cancer treatment. This study aims to identify a CDCP1 reducer that synergistically improves TKI treatment. Utilizing a high-throughput drug screening system, a phytoestrogen 8-isopentenylnaringenin (8PN) was identified. Upon 8PN treatment, CDCP1 protein levels and malignant features were reduced. 8PN exposure caused the accumulation of lung cancer cells in G0/G1 phase and increased the proportion of senescent cells. In EGFR TKI-resistant lung cancer cells, the combination of 8PN and TKI synergistically reduced cell malignance, inhibited downstream EGFR pathway signaling, and exerted additive effects on cell death. Moreover, combination therapy effectively reduced tumor growth and enhanced tumor necrosis in tumor xenograft mice models. Mechanistically, 8PN increased interleukin (IL)6 and IL8 expression, induced neutrophil infiltration, and enhanced neutrophil-mediated cytotoxicity to attenuate lung cancer cell growth. In conclusion, 8PN enhances the anticancer efficacy of EGFR TKI on lung cancer and triggers neutrophil-dependent necrosis, highlighting the potential to overcome TKI resistance in lung cancer patients who have EGFR mutation.

Monitoring and evaluating the dietary risk of trace elements content in bottled and hand-shaken tea in Taiwan.

Tea is the most frequently consumed beverage worldwide and is obtained from the leaves Camellia sinensis. The traditional way of tea consumption through brewing is gradually being replaced by the consumption of bottled and hand-shaken tea. Despite the different ways of tea consumption, trace elements accumulation and contamination of tea leaves have caused concerns. However, limited studies have reported trace element concentrations in different types of tea in bottled or hand-shaken tea and their health risks. This study aimed to determine the level of trace elements (V, Cr, Co, As, Cd, Pb, Mn, and Zn) in green tea, black tea, and Oolong tea in two varieties of products (bottled and hand-shaken tea). The health risks associated with tea consumption in various age subgroups among Taiwan's general population were also estimated. A Monte Carlo simulation was applied to estimate the distribution of daily trace elements intake through bottled and hand-shaken tea consumption. As to the non-carcinogenic risks, the Monte Carlo simulation showed that hand-shaken green tea had a higher percentage of hazard index (HI) >1 (1.08%~6.05%) among all age groups. As to carcinogenic risks, the Monte Carlo simulation showed that the risks of As exposure from bottled Oolong tea and hand-shaken black, green, and Oolong teas in the 90th percentile in >18 to ≤65 and >65-year-old groups were higher than 10-6. The current study findings provided some information about trace elements of both bottled and hand-shaken tea and human health risks in the general population of Taiwan.

Adverse effects of inadequate sleep duration patterns during pregnancy on toddlers suspected developmental delay: A longitudinal study.

BACKGROUND: Although studies have reported the effects of inadequate sleep on maternal health, few have examined the relationships of maternal sleep patterns with fetal health and early childhood development. This study investigated maternal sleep duration patterns from early pregnancy to 3-years postpartum and their effects on birth outcomes and child development. METHODS: This study recruited pregnant women and their partners during prenatal visits at five selected hospitals in the Taipei area; follow-up lasted from July 2011 to April 2021. A total of 1178 parents completed self-reported assessments from early pregnancy until childbirth and 544 completed eight assessments up to 3-years postpartum. Generalized estimated equation models were used for analyses. RESULTS: Group-based trajectory modeling was used to identify four trajectories of sleep duration patterns. Although maternal sleep duration was not associated with birth outcomes, maternal "short decreasing" and "stably short" sleep patterns were associated with a higher risk of suspected overall developmental delay and language developmental delay, respectively. Furthermore, an "extremely long decreasing" pattern was associated with a higher risk of suspected overall developmental delay, [adjusted odds ratio (aOR) = 2.97, 95% confidence interval (CI):1.39-6.36)], gross motor delay, (aOR = 3.14, 95% CI: 1.42-6.99) and language developmental delay (aOR = 4.59, 95% CI:1.62-13.00). The results were significant for the children of multiparous women. CONCLUSIONS: We identified a U-shaped distribution of risk between offspring developmental delay and maternal prenatal sleep duration, with the highest risk levels on both ends of the maternal prenatal sleep duration pattern. Interventions for maternal sleep are relatively straightforward to implement and should thus be a key part of standard prenatal care.

Associations of metal mixtures in the meconium with birth outcomes in northern Taiwan.

Previous studies investigated prenatal exposure to neurotoxic metals in relation to birth anthropometrics. However, limited information has been developed on associations with birth outcomes of fetal exposure to metal mixtures using the meconium as a biomarker. The purpose of this study was to evaluate relationships of the combined effects of mercury (Hg), lead (Pb), cadmium (Cd), and arsenic (As) concentrations in the meconium on birth outcomes (i.e., birth weight, birth length, and head circumference). This cross-sectional study was conducted in northern Taiwan between January 2007 and December 2009. We collected 526 meconium samples within the first 24 h after birth to measure the in utero mixed-metal exposure determined using inductively coupled plasma/mass spectrometry (ICP-MS). We used a multivariable regression and Bayesian kernel machine regression (BKMR) to estimate associations of the combined effects and identify important mixture components with growth impairments. Our results revealed Hg, Pb, Cd, and As concentrations in the meconium and enhanced the quantity of research on meconium analyses. The overall effects of Hg, Pb, Cd, and As concentrations in the meconium as prenatal exposure biomarkers were negatively associated with birth growth. Fetal exposure to Hg and Pb was correlated with decreased birth weights. Hg and Pb concentrations in the meconium were linearly inversely related to the birth weight, birth length, and head circumference. Effects of fetal exposure to As and Cd on birth outcomes were not obvious. A significant increasing relationship was detected between Hg concentrations in the meconium and maternal fish consumption during pregnancy. Higher Pb concentrations in the meconium were observed among infants of mothers who consumed Chinese herbal medicines. Reducing maternal fish consumption and Chinese herbal medicine consumption during pregnancy could limit infant exposure to metals.

Sex-differences in the effects of indoor air pollutants and household environment on preschool child cognitive development.

Air pollution, outdoor residential environment, indoor household characteristics, and parental mental health are potential factors associated with child development. However, few studies have simultaneously analyzed the association between the aforementioned factors and preschool child (aged 2-5 years) development. This study investigated the effects of those factors on child development and their potential modifying effects. A total of 142 participants were recruited from a birth cohort study in the Greater Taipei Area, and the evaluation was conducted at each participant's home from 2017 to 2020. Child cognitive development was assessed by psychologists using the Bayley Scales of Infant and Toddler Development and the Wechsler Preschool & Primary Scale of Intelligence. Household air pollutants, outdoor residential environment, indoor household characteristics, parental mental health, and other covariates were evaluated. Multiple regressions were used to examine the relationships between child development and covariates. Stratified analysis by child sex and parental mental health was conducted. Average indoor air pollutant levels were below Taiwan's Indoor Air Quality Standards. After adjustment for covariates, the indoor total volatile organic compounds (TVOCs) level was significantly associated with poor child development (per interquartile range increase in the TVOC level was associated with a 5.1 percentile decrease in child cognitive development). Sex difference was observed for the association between TVOC exposure and child development. Living near schools, burning incense at home, purchasing new furniture, and parental anxiety were related to child development. Indoor TVOC level was associated with poor child cognitive development, specifically with the girls. Indoor and outdoor residential environment and parental anxiety interfered with child development. TVOCs should be used cautiously at home to minimize child exposure. A low-pollution living environment should be provided to ensure children's healthy development.

Predictive model of early urinary continence recovery based on prostate gland MRI parameters after laparoscopic radical prostatectomy / 北京大学学报(医学版)

OBJECTIVE@#Constructing a predictive model for urinary incontinence after laparoscopic radical prostatectomy (LRP) based on prostatic gland related MRI parameters.@*METHODS@#In this study, 202 cases were included. All the patients were diagnosed with prostate cancer by prostate biopsy and underwent LRP surgery in Peking University Third Hospital. The preoperative MRI examination of all the patients was completed within 1 week before the prostate biopsy. Prostatic gland related parameters included prostate length, width, height, prostatic volume, intravesical prostatic protrusion length (IPPL), prostate apex shape, etc. From the first month after the operation, the recovery of urinary continence was followed up every month, and the recovery of urinary continence was based on the need not to use the urine pad all day long. Logistic multivariate regression analysis was used to analyze the influence of early postoperative recovery of urinary continence. Risk factors were used to draw the receiver operator characteristic (ROC) curves of each model to predict the recovery of postoperative urinary continence, and the difference of the area under the curve (AUC) was compared by DeLong test, and the clinical net benefit of the model was evaluated by decision curve analysis (DCA).@*RESULTS@#The average age of 202 patients was 69.0 (64.0, 75.5) years, the average prostate specific antigen (PSA) before puncture was 12.12 (7.36, 20.06) μg/L, and the Gleason score < 7 points and ≥ 7 points were 73 cases (36.2%) and 129 cases (63.9%) respectively, with 100 cases (49.5%) at T1/T2 clinical stage, and 102 cases (50.5%) at T3 stage. The prostatic volume measured by preoperative MRI was 35.4 (26.2, 51.1) mL, the ratio of the height to the width was 0.91 (0.77, 1.07), the membranous urethral length (MUL) was 15 (11, 16) mm, and the IPPL was 2 (0, 6) mm. The prostatic apex A-D subtypes were 67 cases (33.2%), 80 cases (39.6%), 24 cases (11.9%) and 31 cases (15.3%), respectively. The training set and validation set were 141 cases and 61 cases, respectively. The operations of all the patients were successfully completed, and the urinary continence rate was 59.4% (120/202) in the 3 months follow-up. The results of multivariate analysis of the training set showed that the MUL (P < 0.001), IPPL (P=0.017) and clinical stage (P=0.022) were independent risk factors for urinary incontinence in the early postoperative period (3 months). The nomogram and clinical decision curve were made according to the results of multivariate analysis. The AUC value of the training set was 0.885 (0.826, 0.944), and the AUC value of the validation set was 0.854 (0.757, 0.950). In the verification set, the Hosmer-Lemeshow goodness-of-fit test was performed on the model, and the Chi-square value was 5.426 (P=0.711).@*CONCLUSION@#Preoperative MUL, IPPL, and clinical stage are indepen-dent risk factors for incontinence after LRP. The nomogram developed based on the relevant parameters of MRI glands can effectively predict the recovery of early urinary continence after LRP. The results of this study require further large-scale clinical research to confirm.

Correlation between expression of Lin28B and C-myc in patients with laryngeal squamous cell carcinoma and clinicopathological features and prognosis / 中南大学学报(医学版)

OBJECTIVES@#Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of head and neck. Screening of target genes for malignant tumor therapy is one of the focuses of cancer research, with proto-oncogene and tumor suppressor gene as the breakthrough. It has become an urgent need to find the target gene related to the treatment and prognosis of LSCC.This study aims to explore the role of Lin28B and C-myc in LSCC by detecting the expressions of these two proteins and analyze the correlation between the expression of Lin28B and C-myc and clinicopathological features and prognosis of LSCC.@*METHODS@#We detected the expression of Lin28B and C-myc proteins in 102 specimens of LSCC and 90 specimens of adjacent tissues by immunochemistry, and analyzed the correlation between Lin28B and C-myc protein expressions in LSCC as well as the correlation between the expressions of the two proteins and the clinicopathological features of LSCC. At the same time, the Kaplan-Meier method was used to analyze the relation between Lin28B and C-myc protein levels with the postoperative survival rate of LSCC patients.@*RESULTS@#The protein levels of Lin28B and C-myc in the LSCC tissnes were significantly higher than those in the adjacent tissues (both P<0.05),and there was a positive correlation between the expression of Lin28B and C-myc in LSCC (r＝0.476, P<0.05). The expression of Lin28B protein was closely related to age, lymph node metastasis, clinical stage, tumor size, and pathological differentiation of LSCC patients (all P<0.05). while the expression of C-myc protein was closely related to lymph node metastasis, clinical stage, tumor size, and pathological differentiation of LSCC patients (all P<0.05). A relevant survival analysis showed that in patients with higher level of Lin28B (P＝0.001) or C-myc protein (P<0.001), the postoperative survival rate was relatively low.@*CONCLUSIONS@#Lin28B and C-myc proteins are highly expressed in LSCC with a positive correlation. Furthermore, they are closely related to lymph node metastasis, clinical stage, tumor size, pathological differentiation and prognosis, suggesting that both Lin28B and C-myc might be involved in the occurrence and development of LSCC.