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Objective: This study aimed to explore the combination effects of prenatal exposure to environment tobacco smoke (ETS) and nutrients supplement during pregnancy on childhood obesity in preschoolers., Methods: A cross-sectional study was conducted with 58,814 child-mother dyads from 235 kindergartens in Longhua District of Shenzhen, China in 2021. A self-administered structured questionnaire was completed by mothers to collect socio-demographic characteristics, prenatal ETS exposure, and nutrients supplement in pregnancy, and preschoolers' heights and weights were measured at the same time. After controlling for potential confounding variables, logistic regression models and cross-analyses were used to examine the independent and combination effects of maternal prenatal ETS exposure and nutrients supplementation during pregnancy on obesity in preschool children., Results: The results of our study showed that prenatal ETS exposure increased the risk of childhood obesity (AOR = 1.22, 95% CI = 1.11-1.34) in preschoolers. In addition, risk of childhood obesity was significantly higher when mothers didn't take supplements of multivitamins (AOR = 1.12, 95% CI = 1.05-1.20), folic acid (AOR = 1.23, 95% CI = 1.10-1.37) and iron (AOR = 1.11, 95% CI = 1.04-1.19) during pregnancy. The cross-over analysis showed that the combination of prenatal ETS exposure with mothers taking no multivitamins (AOR = 1.40, 95% CI = 1.21-1.62), no folic acid (AOR = 1.55, 95% CI = 1.12-2.14) and no iron (AOR = 1.38, 95% CI = 1.19-1.59) during pregnancy also increased the risk of obesity among Chinese preschoolers. We also discovered additive interactive effects between prenatal ETS exposure and no maternal multivitamin, folic acid and iron supplementation in pregnancy on the risk of obesity in preschoolers., Conclusion: The combination of prenatal exposure to ETS with no supplementation of these nutrients might jointly increase the risk of childhood obesity. Public health interventions are needed to reduce prenatal exposure to ETS and to encourage mothers to take appropriate multivitamin, folic acid and iron supplements during pregnancy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Zhang, Strodl, Yang, Yin, Wen, Sun, Xian, Zhao and Chen.)

Background: Sleep problems in preschoolers are becoming increasingly prominent, and the association between sleep status and anxiety symptoms has attracted growing attention. However, studies investigating the relationship between bedtime and nighttime sleep duration in preschoolers and their anxiety symptoms remain scant. We used the large sample data from the Longhua Cohort Study of Children in Shenzhen, China (LCCS) to analyze the association between bedtime and sleep in preschoolers and their anxiety symptoms., Methods: A cross-sectional study of 69,138 preschoolers in Longhua District, Shenzhen, China was conducted in 2022. Data on sociodemographic characteristics of families, bedtime, nighttime sleep duration of preschoolers, and their anxiety symptoms (measured by the Spence Preschool Children Anxiety Scale) were collected through a structured questionnaire completed by the parents. Using binary logistic regression models, the relationship between bedtime, nighttime sleep duration, and childhood anxiety symptoms was examined., Results: The bedtimes of preschoolers were concentrated between 21:01-22:00 (52.41%). Among the preschoolers, 38.70% had bedtimes later than 22:00, and 75.49% had insufficient nighttime sleep duration. The positive screening rate for anxiety symptoms among preschoolers was 3.50%. After adjusting for confounding factors using binary logistic regression models, compared with preschoolers with bedtime ≤21:00, The OR (95%CI) values of anxiety in preschoolers with bedtime ≥23:01, 22:01-23:00 and 21:01-22:00 were 2.86 (2.21-3.69), 1.51 (1.27-1.79) and 1.48 (1.26-1.76), respectively. Compared with those with sufficient nighttime sleep duration, the OR (95%CI) of children with nighttime sleep duration less than 9 h was 1.36 (1.23-1.51)., Conclusion: An association exists between bedtime and nighttime sleep duration in preschoolers and their anxiety symptoms. Preschoolers with 21:00 for bedtime and a nighttime sleep duration of 10 h may have lower anxiety symptoms. These findings support the importance of adequate sleep for preventing anxiety symptoms in children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qiu, Yin, Yang, Li, Lu, Li, Yang, Wen, Zhang, Zhang, Lei, Wang and Wu.)

Excessive drinking is one of the main causes of liver cancer. In the process of alcohol metabolism, aldehyde dehydrogenase 2 (ALDH2) is the key enzyme of acetaldehyde metabolism. ALDH2 gene deficiency is positively associated with the risk of hepatocellular carcinoma (HCC). However, no studies have shown a connection between ALDH2 and another metabolic regulatory gene, SLC3A2. In this study, we analyzed the expression levels of ALDH2 and SLC3A2 in liver cancer tissues based on the TCGA database. Subsequently, we constructed ALDH2 knockout and SLC3A2 knock-in transgenic mice to check the roles of ALDH2 and SLC3A2 in tumorigenesis in vivo. In addition, we examined the mechanisms of ALDH2 and SLC3A2 in HCC cells using small RNA interference technology. Consistent with previous studies, we also confirmed the functions of ALDH2 in inhibiting hepatocarcinogenesis, while SLC3A2 had the opposite effect. The main finding of this study is that ALDH2 inhibited BSG expression through the TGF-β1 pathway, which indirectly inhibited SLC3A2 expression; subsequently, the sphingolipid metabolism pathway was also inhibited in HCC cells. Therefore, SLC3A2 is a novel target for HCC treatment., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Ferroptosis results from metabolic dysregulation and is closely linked to liver cancer. Although a ferroptosis-related gene signature in liver cancer has been established, the precise regulatory mechanism is still unclear. To identify shared pathogenic genes linked to ferroptosis across liver cancer patients from diverse racial backgrounds, we evaluated various ferroptosis-related genes, constructing a signature for both Asian and White patients using The Cancer Genome Atlas (TCGA) database. Based on the differential expression and functionality of ferroptosis-associated genes, we selected Farnesyl diphosphate farnesyl transferase 1 (FDFT1), Acyl-CoA synthetase long-chain 4 (ACSL4) and Endoplasmic reticulum membrane protein complex 2 (EMC2) for further study in liver cancer cells. FDFT1, ACSL4 and EMC2 induced ferroptosis of liver cancer cells though upregulation of reactive oxygen species (ROS) levels and downregulation of glutathione peroxidase (GPX4). Current data indicate no notable influence of racial differences on the functionality of ferroptosis-related genes. Our data suggests potential novel therapeutic avenues for liver cancer treatment., Competing Interests: None., (AJCR Copyright © 2023.)

A range of studies have shown that prenatal maternal stress (PNMS) exposure is associated with offspring autistic-like behaviors, however the potential pathways remain unexplored. This study aimed to evaluate the mediating role of parent-child interactions in early life in the association between PNMS exposure and preschoolers' autistic-like behaviors. Data from 65,928 child-parent dyads were obtained via a primary caregiver-reported questionnaire administered as part of the Longhua Child Cohort Study. To strengthen confidence in the reliability of the results, the analyses were initially conducted on a random selection of 70% of the total sample, and then validated on the remaining 30% of the sample. Analysis of covariance and multiple linear models were employed to estimate the associations between PNMS exposure, parent-child interactions in early life, and children's autistic-like behaviors. The results showed that PNMS exposure was positively associated with the presence of autistic-like behaviors at preschool age. The total indirect effect of the frequency of positive parent-child interactions in early life accounted for 9.69% or 8.99% of the variance of the association. Our findings indicate that parent-child interactions in early life might function as potential mediators of the association between PNMS and the increased risk of offspring autistic-like behaviors.

Electronic screens have become an integral part of modern life, accompanied with growing concerns for children's neuropsychological development. This study aimed to evaluate the associations between measures of early life screen exposure and hyperactive behaviors among preschool children. The study also aimed to investigate their cumulative effects and the critical window for these associations. A cross-sectional survey was conducted among 52 625 mother-child dyads at preschools in LongHua District of Shenzhen, China. A self-administered structured questionnaire was used to assess socio-demographic characteristics, duration of children's electronic screen exposure in each of the first 3 years following birth and the presence of current hyperactive behaviors. A series of logistic regression models were used to examine the relationship between previous screen time and current hyperactive behaviors. A crossover analysis was used to explore the critical window for a significant relationship between screen time and hyperactive behaviors. We found that exposure to electronic screens in the first 3 years of life was associated with hyperactive behaviors in preschool children. A cumulative effect was shown in children with an average daily screen time less than 60 min, with adjusted ORs increasing from 1.262 to 1.989 as screen exposure years increased from 1 to 3 years. A critical window was identified in that children in the first 2 years after birth were vulnerable to electronic screen exposure. Exposure to televisions, mobile phones, and computers were all related to elevated risks for hyperactive behaviors. In conclusion, early screen exposure appears to increase the risk for hyperactive behaviors in preschool children with the presence of a cumulative effect, a critical window and different electronic screens having similar effects.

Background: Liver cancer seriously threatens human health. Natural killer (NK) cells are an important part of the innate immune system and have strong anti-tumor ability. Immunotherapy based on NK cells has become a hot topic in the treatment of liver cancer., Methods: In this study, we checked the serum DKK3 (sDKK3) and circulating CD56 bright NK cells using ELISA and flow cytometry, respectively, in the blood of liver cancer patients. The effect on recombinant human DKK3 (rhDKK3) on CD56 bright NK cells was analyzed in vitro., Results: We found low levels of sDKK3 in liver cancer patients and a negative correlation between sDKK3 and circulating CD56 bright NK cells. In addition, we found that DKK3 induced the differentiation and improved the cytotoxicity of CD56 bright NK cells for the first time. It could be used as an agonist for NK cell-based immunotherapy., Conclusions: Improving the clinical efficacy of NK cells through DKK3 will become a new strategy for cancer immunotherapy.

Different ethnic groups have different incidence rate of hepatocellular carcinoma (HCC). In addition to lifestyle and environmental factors, genetic susceptibility is also an important reason. In this study, we screened the immune related genes and stromal related genes in White and Asian liver cancer patients cohort of The Cancer Genome Atlas (TCGA) the using ESTIMATE algorithm. Hub genes that significantly associated with overall survival (OS) were selected from White and Asian liver cancer patients, respectively. In addition, we validated the functions of two hub genes, IL-18RAP and GPM6A, in vivo and in vitro . We confirmed different races have different tumor immune microenvironments. Immune microenvironment can influence and change the efficacy of immunotherapy for liver cancer patients., Competing Interests: None., (AJCR Copyright © 2023.)

Cancer stem cells (CSCs) are a subset of cancer cells with stem cell characteristics. The discovery of CSCs has opened a new era for cancer research. CSCs not only play a critical role in tumorigenesis, but also are responsible for the failure of cancer treatments. Here, we performed weighted gene co-expression network analysis (WGCNA) to identify key stemness genes and prognostic signatures using the data of an Asian liver cancer patient cohort and a White liver cancer patient cohort in The Cancer Genome Atlas (TCGA) database. To compare the difference in tumorigenesis between the Asian patients and the White patients, the prognostic value of the key genes from the Asian patients was evaluated in the White patient cohort and vice versa. We found that some key genes could predict the survival of the patients regardless of race. In addition, the key genes, NUCB2 and KLF4A, were selected from Asian patients and White patients, respectively, for further experimental validation. Knocking down NUCB2 could inhibit the activity of the AKT/mTOR signaling pathway and reverse the epithelial-mesenchymal transition (EMT) in liver cancer cells. We also confirmed that the knockdown of KLF4A suppressed ABCG2 activity and reduced the side population (SP) in liver cancer cells for the first time. Our results suggest that the stemness index is a useful method to identify key genes in tumorigenesis. Compared to the analysis for all patients, applying this index to the analysis of the patients of different races will provide more potential therapeutic targets for cancer treatment., Competing Interests: None., (AJCR Copyright © 2023.)

Cancer stem cells (CSCs) have high tumorigenicity, high metastasis and high resistance to treatment. They are the key factors for the growth, metastasis and drug resistance of malignant tumors, and are also the important reason for the occurrence and recurrence of tumors. Metabolic reprogramming refers to the metabolic changes that occur when tumor cells provide sufficient energy and nutrients for themselves. Metabolic reprogramming plays an important role in regulating the growth and activity of cancer cells and cancer stem cells. In addition, the immune cells or stromal cells in the tumor microenvironment (TME) will change due to the metabolic reprogramming of cancer cells. Summarizing the characteristics and molecular mechanisms of metabolic reprogramming of cancer stem cells will provide new ideas for the comprehensive treatment of malignant tumors. In this review, we summarized the changes of the main metabolic pathways in cancer cells and cancer stem cells.

In this review, we discussed an interesting case infected with "COVID-19" (Corona Virus Disease 2019). The patients with Hodgkin's lymphoma recovered after infection with COVID-19. It may be that COVID-19 activates the patient's immune system, or it may be a coincidence. COVID-19 spike protein can interact with CD147 and use it as an entry to invade host cells. CD147 is a partner of SLC3A2, which is the chaperone subunit of cystine/glutamate reverse transporter (system XC). The catalytic subunit of system XC is SLC7A11. SLC7A11 mediated cysteine uptake plays a key role in ferroptosis. Through literature review and data analysis, we suggest that CD147, as a new potential COVID-19 infection entry, may also lead to ferroptosis of host cells. Our hypothesis is that spike protein of COVID-19 induced ferroptosis in host cells via CD147/SLC3A2/SLC7A11 complex. This is another explanation for the cancer patient recovered after COVID-19 infection., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Most patients with liver cancer were found late and lost the chance of surgery. Liquid biopsy can monitor the risk of tumor recurrence and metastasis, quickly evaluate the curative effect of tumor treatment, and is conducive to early screening and auxiliary diagnosis of high-risk groups. Amino acid (AA) profiling has been used to the diagnosis and the prognosis for cancers. However, little was known about the profiles of AA of liver cancer. In this study, we used tRNA in Cancer database to analyze the AA levels in liver cancer tissues. Blood samples of patients with liver cancer were collected and analyzed using the automatic AA analyzer. We found that valine, isoleucine, and leucine were decreased significantly both in the plasma and the tumor tissues of patients with liver cancer. However, upregulation of methionine was observed in tissues and plasma of patients with liver cancer. Interestingly, tyrosine, and phenylalanine were decreased in tumor tissue but increased in the plasma of patients with liver cancer. This is the first report provided an overview of AA profile in both plasma and tissue for patients with liver cancer. AA levels can be used as diagnostic and prognostic markers of patients with liver cancer., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (© 2022 the author(s), published by De Gruyter.)

Background: Screen time during early life has increased dramatically among Chinese children. Excessive screen time has raised growing concerns about the neuropsychological development of children. The effects of screen exposure on early life and the boundary between screen time and hyperactive behaviors are well worth investigating. We examined associations between screen time and hyperactive behaviors in children under the age of 3 years using data from the Longhua Children Cohort Study (LCCS)., Methods: A cross-sectional study was conducted among 42,841 3-year-old children from Longhua District, Shenzhen. Information on socio-demographic characteristics, children's annual screen time since birth, and hyperactive behaviors (measured by the Conners Parental Symptom Questionnaire) was collected through self-administered structured questionnaires completed by the primary caregiver. A series of logistic regression models assessed the association between screen time and hyperactive behaviors., Results: The average daily screen time of children under the age of 3 years was 55.83 ± 58.54 min, and screen time increased with age. Binomial logistic regression analysis found that the earlier the screen exposure, the greater the risk of hyperactive behaviors. Using binary logistic regression model, after controlling for confounding factors, the study found that more screen time was more associated with hyperactive behaviors. For children aged 0-3 years with daily screen time exceeding 90, 120, 150, and 180 min, the risk values for hyperactive behaviors were 1.98 [95% confidence interval (CI): 1.05, 3.78), 2.71 (95%CI:1.38, 5.30), 3.17 (95% CI: 1.50, 6.65), and 4.62 (95% CI: 2.45, 8.71)], respectively., Conclusion: Early screen exposure may be associated with hyperactive behaviors in children under the age of 3 years. More than 90 min of screen time per day in children under 3 years was associated with hyperactive behaviors. The findings support the importance of screen time interventions for children under 3 years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Yin, Qiu, Wen, Yang, Zhang, Zhao, Wang, Hong, Lu and Jing.)

There is growing evidence that cooking oil fumes (COFs) are harmful indoor air pollutants. However, there is a dearth of research investigating whether maternal COFs exposure during pregnancy may affect children's autistic-like behaviors in China. This study aimed to explore this association, and examine the effects of different cooking fuels and ventilation methods used by mothers on the presence of autistic-like behaviors. This study analyzed the survey data of the Longhua Child Cohort Study in 2017 with a total of 62,372 mothers enrolled in this study. A self-administrative questionnaire was used to collect information on socio-demographic characteristics, cooking habits during pregnancy, and autistic-like behaviors (measured using the Autism Behavior Checklist). After adjusting for potential confounders, the results showed that compared with children whose mothers never cooked during pregnancy, children whose mothers cooked sometimes, often, always during pregnancy had the higher risk of autistic-like behaviors. As the amounts of COFs exposed to and the frequency of cooking during pregnancy increased, the risk of a child's autistic-like behaviors also increased. Mothers using natural gas as cooking fuels had a lower risk of their child having autistic-like behaviors, compared with mothers using coal or other cooking fuels. Furthermore, pregnant women using ventilation measures during cooking significantly decreased likelihood of the presence of autistic-like behaviors in their children. These results suggest that maternal exposure to COFs during pregnancy may increase the likelihood of the presence of autistic-like behaviors in offspring. These findings support a recommendation that pregnant women should avoid exposure to COFs and use clean fuels and ventilation equipment in kitchens to reduce the risk of autistic-like behaviors in children., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Although environmental tobacco smoke (ETS) exposure is considered to be a severe public health problem and a modifiable risk factor for preterm birth (PTB), we still lack a comprehensive understanding of the PTB risk associated with trimester-specific prenatal ETS exposure. This study aimed to examine the accumulation of risk across trimester ETS exposure and the critical window of the association between maternal ETS exposure during pregnancy and PTB. A total of 63,038 mother-child pairs were involved in the analysis of the 2017 survey of Longhua Child Cohort Study. Information about socio-demographic characteristics, prenatal ETS exposure, and birth outcomes were collected using a self-report questionnaire. A series of logistic regression models were employed to assess the associations between prenatal ETS exposure and PTB. We found that maternal ETS exposure during pregnancy significantly increased the risk of PTB and this association increased with both the average level of daily ETS exposure and the number of trimesters of ETS exposure. Moreover, mothers who were initially exposed to ETS in the 1st trimester of pregnancy had significant higher risk of PTB (OR = 1.34, 95% CI: 1.25-1.44). Furthermore, mothers exposed to ETS in the 1st trimester only (OR = 1.26, 95%CI: 1.04-1.50), in both 1st and 2nd trimester (OR = 1.35, 95%CI: 1.08-1.67) and throughout pregnancy (OR = 1.35, 95%CI: 1.24-1.46) experienced a significantly high risk of PTB. Prenatal maternal ETS exposure during only the 2nd trimester also resulted in a high risk of PTB with marginal significance (OR = 1.33, 95% CI:0.78-2.13). To conclude, the 1st and early 2nd trimester might be the critical window for prenatal ETS exposure causing PTB., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Breast cancer is one of the deadly tumors in women, and its incidence continues to increase. This study aimed to identify novel therapeutic molecules using RNA sequencing (RNA-seq) data of breast cancer from our hospital. Methods: 30 pairs of human breast cancer tissue and matched normal tissue were collected and RNA sequenced in our hospital. Differentially expressed genes (DEGs) were calculated with raw data by the R package "edgeR", and functionally annotated using R package "clusterProfiler". Tumor-infiltrating immune cells (TIICs) were estimated using a website tool TIMER 2.0. Effects of key genes on therapeutic efficacy were analyzed using RNA-seq data and drug sensitivity data from two databases: the Cancer Cell Line Encyclopedia (CCLE) and the Cancer Therapeutics Response Portal (CTRP). Results: There were 2,953 DEGs between cancerous and matched normal tissue, as well as 975 DEGs between primary breast cancer and metastatic breast cancer. These genes were primarily enriched in PI3K-Akt signaling pathway, calcium signaling pathway, cAMP signaling pathway, and cell cycle. Notably, CD8 + T cell, M0 macrophage, M1 macrophage, regulatory T cell and follicular helper T cell were significantly elevated in cancerous tissue as compared with matched normal tissue. Eventually, we found five genes ( GALNTL5, MLIP, HMCN2, LRRN4CL, and DUOX2 ) were markedly corelated with CD8 + T cell infiltration and cytotoxicity, and associated with therapeutic response. Conclusion: We found five key genes associated with tumor progression, CD8 + T cell and therapeutic efficacy. The findings would provide potential molecular targets for the treatment of breast cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Tong, Wei, Chen, Liang, Tang, Wu, Wen, Yang, Liang and Shen.)

Indoor air pollution is a recognized risk factor for a range of negative health outcomes. This study aimed to investigate the association between maternal prenatal exposure to indoor air pollution and the presence of autistic-like behaviors among preschool children. Data were obtained from the Longhua Child Cohort Study in 2017, in which we enrolled a total of 65 317 preschool children. Associations between maternal exposure to four sources of indoor air pollution (e.g., cooking, environmental tobacco smoke (ETS), mosquito coils, and home decoration) during pregnancy and preschool children's autistic traits were analyzed using multivariate logistic regression. Our results showed that maternal exposure to indoor air pollution from four different sources during pregnancy was associated with the presence of children's autistic-like behaviors. There was dose-response relationship between the accumulative exposure to the four different indoor air pollution sources and the risk of autistic-like behaviors. Furthermore, we found a significant additive interaction between prenatal exposure to both cooking and mosquito coil incense on the risk of autistic-like behaviors. Maternal prenatal exposure to the indoor air pollution from four sources might increase with the risk of autistic-like behaviors being present among preschool children, with an additive interaction effect between some pollution sources., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Few studies have evaluated the association between children's exposure to environmental tobacco smoke (ETS) in early life (during pregnancy, from birth to one year and from one to three years) and autistic-like behaviors. This study aimed to explore this association., Methods: This cross-sectional study analyzed data collected in 2017 as part of the Longhua Child Cohort Study. Autistic-like behaviors were measured using the Autism Behavior Checklist (ABC). Data on ETS exposure and autistic-like behaviors of children were collected via self-administered questionnaires completed by the mothers. Multivariate logistic regression models were undertaken to assess the associations., Results: Of the 65,243 participants included in this study, 1958 children met criteria for having autistic-like behaviors. The results showed that children were more likely to exhibit autistic-like behaviors when they were exposed to ETS in early life (AOR = 1.38; 95% CI = 1.26-1.52), compared to preschoolers without ETS exposure at any period of their early life. Compared with their unexposed counterparts, children who were exposed to ETS during gestation (AOR = 1.42; 95% CI = 1.29-1.57), or from birth to one year old (AOR = 1.42; 95% CI = 1.19-1.69) had significantly increased risk of autistic-like behaviors. In addition, with the increase in duration of exposure and average number of cigarettes smoked in the child's immediate environment, the risk of autistic-like behaviors increased., Conclusion: Our study indicated that children's ETS exposure in early life was significantly associated with autistic-like behaviors. When children's exposure to cigarettes in early life increased in duration and number, the likelihood of the presence of autistic-like behaviors was higher., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Exposure to prenatal maternal stress (PNMS) has been implicated as a risk factor for a range of psychiatric disorders in children. However, there have been a few studies showing inconsistent associations between PNMS and offspring autistic-like behaviours. We therefore aimed to examine whether trimester-specific PNMS exposure might be related to an increased risk of autistic-like behaviours among preschoolers. Using data from Longhua Children Cohort Study, mothers of 65,931 preschool children were asked to recall their level of PNMS in each of the three trimesters of pregnancy, while children's current autistic-like behaviours were assessed using the Autism Behaviour Checklist. A series of Cox regression models were fitted to assess the association between PNMS exposure and autistic-like behaviours. After adjusting for potential confounders, the Cox regression models showed that PNMS exposure, especially during the second pregnant trimester, was significantly and positively associated with the presence of children's autistic-like behaviours. The strength of these associations was enhanced with the increase of PNMS exposure level. Furthermore, based on different permutations of exposure versus no exposure in each trimester, the participants were divided into eight groups. A cross-over analysis confirmed the aforementioned finding that the second pregnant trimester might be the sensitive period for PNMS exposure increasing the risk of autistic-like behaviours. Our findings supported the hypothesis of an association between PNMS exposure and autistic-like behaviours among preschoolers. Preventive interventions should be trialled to examine whether minimizing maternal psychological stress during pregnancy, especially the second trimester, may reduce the risk of offspring autistic-like behaviours., (© 2020 John Wiley & Sons Ltd.)

Screen time is becoming increasingly common in daily life. Early and excessive screen use has raised growing concerns for children's neuropsychological development. The purpose of this study was to evaluate the association between exposure to screen time in early life and the presence of autistic-like behaviors among preschool children. 29,461 child-caregiver dyads at kindergartens in Longhua New District of Shenzhen, China, were enrolled in this cross-sectional study. Information concerning socio-demographic characteristics, frequency and duration of children's electronic screen exposure for each year since birth, and autistic-like behaviors (measured by the Autism Behavior Checklist) were collected using a self-administered structured questionnaire completed by the primary caregivers. A series of logistic regression models assessed the association between screen time and autistic-like behaviors. Results indicated that younger initial age, longer daily screen time and longer cumulative years of screen exposure since birth were associated with the presence of autistic-like behaviors at preschool age. The risk was enhanced with the increase of both daily screen time and cumulative years of screen exposure during preschool period. Moreover, the cross-over analysis indicated that the first three years following birth might be a sensitive period for children when screen exposure increases the risk of experiencing autistic-like behaviors. In conclusion, our study implied that screen exposure in early life might increase the occurrence of autistic-like behaviors among preschoolers. These findings support the need for early interventions into preschoolers' screen use, however longitudinal studies are necessary to further confirm the causal relationship between early screen time and the incidence of later autistic-like behaviors among preschool children.

Cooking is one of the main sources of indoor air pollution in China. Given emerging evidence of a link between air pollutants and neurodevelopmental delays, we examined whether maternal experiences with cooking during gestation might increase their child's hyperactivity at 3 years of age. The participants involved 45 518 mothers of children who were newly enrolled at kindergarten in the Longhua District of Shenzhen from 2015 to 2017. The results show that maternal exposure to cooking fumes during pregnancy was related to an increased risk of their offspring having hyperactivity behaviors at the age of 3 years. Compared with pregnant mothers who never cooked, pregnant mothers who cooked sometimes, often, or always had children who showed a significantly higher hyperactivity risk. Households using cooking fuels such as coal, gas during the mothers' pregnancy, exhibited more hyperactivity behaviors in the young child when compared to those using electricity for cooking. In addition, poor ventilation during cooking, while mothers were pregnant, was found to be a significant risk factor for clinical levels of the offspring's hyperactive behaviors. Furthermore, the positive association with maternal cooking during pregnancy and their offsprings' hyperactivity was relatively consistent across strata defined by social class, education, and other covariates., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study aimed to explore the association between teacher's type D personality (TDP) and children's hyperactive behaviors, along with the moderation effect of parental TDP and the mediation effect of the teacher-student relationship. In this prospective study, a total of 25,852 children were surveyed from 2014 to 2016 in Longhua District of Shenzhen, China, and followed up 1 year later. At baseline, parents provided data on parental TDP and children's hyperactive behaviors, while teachers reported on their TDP. At follow-up, parents provided data on children's hyperactive behaviors again, and teachers described their relationship with each student. Two-level multilevel logistic models were conducted to assess the influence of a teacher's TDP, parental TDP, and their interaction on children's hyperactive behaviors. Mediation analysis was used to examine the mediating role of the teacher-student relationship. Results indicated that teachers' TDP was not a significant predictor of children's hyperactive behaviors after 1 year in kindergarten. Conversely, maternal and paternal TDP were prospectively and positively associated with children's subsequent hyperactive behaviors. However, the children with a TDP teacher, a TDP mother, and/or a TDP father had higher risk of hyperactive behaviors than those with either a TDP teacher or a TDP mother or a TDP father. In addition, the teacher-student relationship was not a significant mediator between teacher's TDP and children's hyperactive behaviors. Further, researchers may consider the effect of the combination of teacher's TDP, maternal TDP, and paternal TDP on hyperactive behaviors in children in further studies., (Copyright © 2019 He, Strodl, Liu, Ruan, Yin, Wen, Sun, Xian, Jiang, Jing, Jin, Wu and Chen.)

Background: DNA-Dependent Protein Kinase Catalytic Subunit (PRKDC), a key component of the DNA damage repair pathway, is associated with chemotherapy resistance and tumor progression., Methods: Here we analyzed transcriptome data of ~2,000 breast cancer patients and performed functional studies in vitro to investigate the function of PRKDC in breast cancer., Results: Our results revealed overexpression of PRKDC in multiple breast cancer subtypes. Consistent with patients' data, overexpression of PRKDC was also observed in breast cancer cell lines compared to normal breast epithelial cells. Knockdown of PRKDC in MCF-7 and T47D breast cancer cell lines resulted in proliferation inhibition, reduced colony formation and G2/M cell cycle arrest. Furthermore, we showed that PRKDC knockdown induced proliferation inhibition through activation of p38 MAPK, but not ERK MAPK, signaling pathway in breast cancer cells. Blockage of p38 MAPK signaling could largely rescue proliferation inhibition and cell cycle arrest induced by PRKDC knockdown. Moreover, we analyzed gene expression and clinical data from six independent breast cancer cohorts containing ~1,000 patients. In all cohorts, our results consistently showed that high expression of PRKDC was significantly associated with poor survival in both treated and untreated breast cancer patients., Conclusion: Together, our results suggest that high expression of PRKDC facilitates breast cancer cell growth via regulation of p38 MAPK signaling, and is a prognostic marker for poor survival in breast cancer patients., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Background: Prenatal exposure to air pollutants has been suggested as a possible etiologic factor for the occurrence of ADHD or ADHD-like behaviors. But we still lack a comprehensive assessment of household air pollutants exposure on the development of ADHD-like behaviors during childhood., Object: We aimed to assess whether prenatal household inhalants exposure is associated with preschoolers' ADHD-like behaviors in a nonclinical population., Methods: This study used the baseline data of the Longhua Child Cohort Study. During 2015-2017, we recruited 42,983 mothers and their kindergarten-aged children who enrolled at kindergarten in the Longhua district of Shenzhen, to obtain the demographic data and relevant exposure information through self-administrated questionnaire survey. The source of prenatal household inhalants exposure include cooking fumes, environmental tobacco smoke, mosqutio coils, home renovated and indoor burning incense. Logistic and censored least absolute deviations (CLAD) models were used to reveal the association between prenatal exposure to household air pollutants and hyperactive behaviors in child., Results: We found that exposure to five types of household inhalants during pregnancy were independently associated with an increased risk of child hyperactive behaviors. Moreover, we observed a significant interaction between exposure to environmental tobacco smoke and cooking fumes during gestation on child hyperactive behaviors in CLAD models. We also found a significant joint effect between burning mosquito coils and incense during gestation for child hyperactive behaviors risk both in CLAD and Logistic models. Furthermore, a household inhalants exposure index was used to demonstrate a dose-response relationship between the cumulative effect of exposure to the five household air pollutants and child hyperactivity., Conclusions: Our results suggest that prenatal exposure to different household inhalants might increase the risk of children's hyperactive behaviors at around 3 years of age with the presence of interaction effects between some inhalants., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A hallmark of gastric cancer is the high rate of genomic instability associated with deregulation of DNA damage repair pathways. DNA-Dependent Protein Kinase Catalytic Subunit (PRKDC) is a key component of the non-homologous end-joining (NHEJ) pathway. By reanalyzing transcriptome data of 80 pairs of gastric cancer tumors and the adjacent normal tissues from non-treated patients, we identified PRKDC as the top upregulated DNA damage repair genes in gastric cancer. High expression of PRKDC is associated with poor survival of gastric cancer patients, and genomic amplification of the gene is frequently observed across most gastric cancer subtypes. Knockdown of PRKDC in gastric cell lines resulted in reduced proliferation and cell cycle arrest. Furthermore, we showed that loss of PRKDC induced DNA damage and enhanced gastric cancer cell chemosensitivity to DNA-damaging reagents. Together, our results suggest that PRKDC is a prognostic marker of poor survival and is a putative target to overcome chemoresistance in gastric cancer., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

The catalytic subunit p110δ of phosphoinositide 3-kinase (PI3K) encoded by PIK3CD has been implicated in some human solid tumors. However, its roles in colorectal cancer (CRC) remain largely unknown. Here we found that PIK3CD was overexpressed in colon cancer tissues and CRC cell lines and was an independent predictor for overall survival (OS) of patients with colon cancer. The ectopic overexpression of PIK3CD significantly promoted CRC cell growth, migration and invasion in vitro and tumor growth in vivo. In contrast, inhibition of PIK3CD by specific small-interfering RNA or idelalisib dramatically suppressed CRC cell growth, migration and invasion in vitro and tumor growth in vivo. Moreover, PIK3CD overexpression increased AKT activity, nuclear translocation of β-catenin and T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity and decreased glycogen synthase kinase 3β (GSK-3β) activity, whereas PIK3CD inhibition exhibited the opposite effects. Furthermore, PIK3CD-mediated cell growth, migration and invasion were reversed by blockade of AKT signaling or depletion of β-catenin. In addition, PIK3CD expression in colon cancer tissues positively correlated with β-catenin abnormal expression, which was an independent predictor for OS of colon cancer patients. Taken together, our findings demonstrate that PIK3CD is an independent prognostic factor in CRC and that PIK3CD induces CRC cell growth, migration and invasion by activating AKT/GSK-3β/β-catenin signaling, suggesting that PIK3CD might be a novel prognostic biomarker and a potential therapeutic target for CRC., (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

CD133 is a wildly used cancer stem cell marker. The purpose of this study was to explore the significance of CD133 mRNA in human cancers mainly based on The Cancer Genome Atlas (TCGA) database. Bioinformatic analyses were done by using public repositories, including BioGPS, SAGE Genie tools, Oncomine analysis, Regulome Explorer, COSMIC analysis, and Kaplan-Meier Plotter. The main findings in this study were: 1) High CD133 mRNA was correlated with a benign survival rate of gastric cancer and lung cancer; 2) Transmembrane protein 125 (TMEM125) in bladder urothelial carcinoma and intercellular adhesion molecule 2 (ICAM2) in ovarian serous cystadenocarcinoma were closely related to CD133 expression; 3) The location and the topological structure of CD133 protein were not determined by its transcript variant in cancer cells; 4) CD38 and CD200 may be used as novel surface markers for solid cancers. However, the mechanism of these findings is not completely clear, further studies have to be performed in the future.

Background: Previous studies have demonstrated the impacts of genetic, family, and community factors on child conduct problems (CPs). However, little is understood regarding the association between family childcare types and child conduct problem behaviors, as well as whether and to what extent caregiver-child interaction mediates the above association. Methods: 9,289 children first entering kindergartens in the Longhua New District of Shenzhen, China were enrolled in this cross-sectional study. Primary caregivers were invited to fulfill a self-administered structured questionnaire containing data regarding socio-demographics, family childcare types, caregiver-child interaction, and child conduct problem behaviors (measured by the Conners' Conduct Problem Subscale). A series of multiple logistic and linear regression models were employed to assess the associations among family childcare, caregiver-child interaction, and child conduct problem behaviors. Results: Family childcare types other than by parents together (i.e., mother alone, mother with others, grandparents, or changing caregivers) were all significantly associated with higher risks of conduct problem behaviors in young children (adjusted ORs ranged from 2.18 to 2.55, and adjusted βs ranged from 0.043 to 0.073; all p < 0.05), after adjusting for confounders including child age, gender, parental education level, parental age at pregnancy, marital status, and family income. The following family childcare types (mother alone, or grandparents, or changing caregivers) vs. the childcare by parents together showed significant relative indirect effects on conduct problem behaviors through caregiver-child interaction, indicating the significant mediation effect of caregiver-child interaction on the above associations. Mediation of caregiver-child interaction on the effect of being cared by mother with others relative to care by parents together on child conduct problem behaviors was yet non-significant. Conclusions: Family childcare types other than by parents together are associated with increased risks for conduct problem behaviors in young children. Caregiver-child interaction may function as a potential mediator for the above association.

Antenatal training through music and maternal talk to the unborn fetus is a topic of general interest for parents-to-be in China, but we still lack a comprehensive assessment of their effects on the development of autistic-like behaviors during early childhood. During 2014-2016, 34,749 parents of children around the age of 3 years who were enrolled at kindergarten in the Longhua district of Shenzhen participated in this study. Self-administered questionnaires regarding demographics, antenatal music training, and maternal talk to the fetus during pregnancy were completed by the children's primary caregivers. Autistic-like behaviors were assessed using the Autism Behavioral Checklist. Tobit regression analyses revealed that antenatal music training and maternal talk to the fetus was associated with a reduction in autistic-like behaviors in children, with a dose-dependent relationship. Furthermore, factorial analysis of covariance indicated a significant interaction effect between antenatal music training and maternal talk to the fetus on the autistic-like behaviors and found that children who often experienced antenatal music training and maternal talk concurrently had the lowest risk of autistic-like behaviors, while children who were never exposed to maternal talk and only sometimes experienced antenatal music training had the highest risk. Our results suggest that antenatal training through both music and maternal talk to the unborn fetus might reduce the risk of children's autistic-like behaviors at around 3 years of age.

Background: This study was carried out to investigate the correlation between CD133 and non-small cell lung cancer (NSCLC) clinicopathological features and its impact on survival of the patients with NSCLC., Methods: In the first, we detected the level and localization of CD133 protein in NSCLC specimens and confirmed that CD133 expression was closely linked to poor prognosis of NSCLC. Secondly, TCGA genomic data for LUNG (Provisional) was retrieved and analyzed for genetic alterations of CD133 in different lung cancer subtypes. In the last, a comprehensive literature search for relevant studies published up to December 2015 was performed using Medline, EMBASE Classic + EMBASE, and The Cochrane Central Register of Controlled Trials., Results and Conclusion: Both our experimental results and pooled results of previous studies indicated that CD133 may be used as a prognostic marker for the patients with NSCLC. However, more studies are required to evaluate CD133 potential use in predicting patients' outcome.

This study aimed to examine the association between prenatal environmental tobacco smoke (ETS) exposure and hyperactivity behaviors in young children. A cross-sectional study was undertaken among 21,243 participants from all of the kindergartens in Longhua District of Shenzhen, China. Multivariate logistic regression models and hierarchical linear models were employed to assess the associations. After adjusting for potential confounders of gender, preterm birth, birth asphyxiation, etc., prenatal ETS exposure was significantly associated with an increased risk of hyperactivity behaviors in young children (OR (95% CI) = 1.51 (1.28-1.77); β (95% CI) = 0.017 (0.013-0.020)). Along with increases in children's prenatal ETS exposure dose (measured by daily ETS exposure duration, daily cigarette consumption by household members, and overall score of prenatal ETS exposure), the children were also increasingly more likely to exhibit hyperactivity behaviors. Furthermore, children whose mothers had prenatal ETS exposure in any one or more of the pregnancy trimesters were more likely to exhibit hyperactivity behaviors as compared with those born to non-exposure mothers (all p < 0.05). Overall, prenatal ETS exposure could be associated with a detrimental impact on offspring's hyperactivity behaviors, and public health efforts are needed to reduce prenatal ETS exposure., Competing Interests: The authors declare no conflict of interest.

Aims and Objectives: To examine the independent effect of frailty on quality of life., Background: The World Health Organisation has proposed that frailty be used to indicate a lack of successful ageing. However, studies investigating the relationship between frail phenotypes and quality of life are lacking., Design: This research employed a cross-sectional design., Methods: The Study of Osteoporotic Fractures index was used based on the following three criteria: unexpected weight loss, inability to rise from a chair without using the armrests five times, and feeling a lack of energy. Participants who fulfilled more than two, one or zero criteria were considered as frail, prefrail or robust respectively. Moreover, this study used the Taiwanese version of the World Health Organisation Quality of Life-BREF to assess the quality of life of older people. A multiple linear regression was performed to investigate the independent effect of frail status on each quality of life subscale., Results: A total of 239 older people [average age = 74·77 years; standard deviation = 7·02 years; 104 males (43·5%) and 135 females (56·5%)] participated in this study. The multiple linear regression analysis showed that the older people who were more advanced in age and had been diagnosed with a greater number of chronic diseases had a lower comprehensive quality of life. The Study of Osteoporotic Fractures index was associated only with the environmental domain of the World Health Organisation Quality of Life-BREF., Conclusions: Compared with robust and prefrail older people, frail older people have worse biomarkers, health statuses, and quality of life. The Study of Osteoporotic Fractures index was correlated only with the quality of life environmental domain., Relevance to Clinical Practice: Professional nurses must understand the differences among frail, prefrail and robust older people with regard to their biomarkers, health status, and quality of life. In addition, a comprehensive nursing intervention programme must be developed to improve the quality of life of older people., (© 2016 John Wiley & Sons Ltd.)

The World Health Organization has defined elderly individuals living independently as an 'at risk' group. This vulnerable population thus faces a disproportionate amount of frailty, disabilities and/or death. In this study, the total number of participants was 276, with 13 incomplete responses, resulting in 263 valid questionnaires. Frailty status of the subjects (n = 263) was evaluated according to the frailty criteria of osteoporotic fractures study. Overall, 35% of the study participants were frail, 19.8% were pre-frail and 45.2% were non-frail. Additionally, compared with non-frail, solitary elderly individuals with basic activities of daily living limitation or heart failure more easily became pre-frail. The research demonstrates a high prevalence of frailty in urban Taiwanese solitary elderly individuals. Pre-frailty and frailty significantly impacts health, owing to their strong association with cardiovascular disease, disability and fracture. Results of this study could provide a valuable reference material for health-care providers and potentially facilitate an important foundation for the planning of nursing interventions care., (© 2014 Wiley Publishing Asia Pty Ltd.)

Background: Selective neurectomy of the innervating nerves of the gastrocnemius muscle is a popular method employed for calf reduction. However, accidental injury to the untargeted adjacent nerves could happen. This study aims to provide detailed morphometry of the motor branches from the tibial nerve innervating the gastrocnemius muscle, the soleus and the medial sural cutaneous nerve in the popliteal fossa., Methods: 23 lower legs from female cadavers were dissected to explore the origin, length of and the spatial relationship between the four branches given off from the tibial nerve in the popliteal fossa., Results: Our study showed there were seven origin patterns existing among the four nerve branches; the origin of the branches to the medial and lateral heads of the gastrocnemius muscle was located ranging from -16 mm to 22 mm away from the midpoint of the line between the lateral and medial condyles of the femur; In 95% of the specimens, the location of the origin of the nerve branch to the medial head was proximal to its lateral counterpart. The nerve to the medial head was often given off from the medial aspect or the posteromedial aspect of the tibial nerve, while the other three often from the lateral aspect., Conclusions: A variety of origin patterns among the nerves to the lateral and medial gastrocnemius muscle, the nerve to the soleus muscle and the sural cutaneous nerve exist, necessitating the formulation of diversifying surgical strategies preoperatively and the meticulous and sequential dissection intra-operatively to ensure the lowest level of accidental injury., (Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Aims: To explore new resources of methane-utilizing micro-organism and develop a microbial biosensing system for monitoring methane released from natural and semi-natural ecosystems., Methods and Results: A methane (CH(4))-utilizing bacterial strain was isolated from paddy soil using CH(4) as the sole carbon source and identified as Klebsiella sp. ME17 by phenotyping and 16S rDNA sequence analysis. The efficiency of CH(4) utilization of strain ME17 was 83.2% by gas chromatography analysis. A microbial biosensing system for CH(4) detection was developed by combining immobilized cells of strain ME17 with a dissolved oxygen sensor. It was found that response time of the system to CH(4) was <90s. The dissolved O(2) consumption increased with increasing CH(4) from 0% to 16.0% (v/v) demonstrating a positive linear relationship with a low detection limit of 0.2% (v/v). The relative standard deviation is 3.48%., Conclusions: Klebsiella sp. ME17 isolate is capable of utilizing CH(4). The microbial biosensing system of strain ME17 has been successfully applied to measure standard CH(4) sample with satisfactory results., Significance and Impact of the Study: This study suggests that certain strains of Klebsiella genus are capable of utilizing CH(4). Our proposed method appears very attractive for CH(4) measurement in coal mine.

To investigate effects of rat bone marrow mesenchymal stem cells (rBMMSC) on hematopoiesis after allo-hematopoietic stem cell transplantation (HSCT), allogeneic BMT model from Fischer 344 rats (RT-1Al) to Wistar rats (RT-1Au) was established; effects of MSCs on hematopoietic reconstitution were studied by survival rate, peripheral blood counts, histological analysis and FACS at day 30 after transplantation. The results showed that (1) MSCs from donor Fisher344 could survive in recipient irradiated by lethal dose and could be found in the thymus, spleen and bone marrow of the recipient at 30 days after cotransplantation with BM by measuring EGFP gene. (2) Cotransplanation of MSCs and BM improved hematopoietic reconstitution. Lymphocyte and platelet counts of peripheral blood in cotransplantation group were higher than those in the control group. Active hematopoiesis and increase of bone marrow nucleated cells were observed in cotransplantation group. MSCs significantly enhanced hematopoiesis of B lymphocyte and megakaryocytopoietic lineages by FACS analysis. It is concluded that (1) MSCs of Fisher344 can be found in the thymus, spleen, bone marrow of the recipients at 30 days after cotransplantion by measuring EGFP gene. (2) hematopoietic reconstitution is significantly enhanced by MSCs cotransplanted with BM.

Objective: To investigate the effect and its mechanism of reducing graft-versus-host disease (GVHD) by in vitro blockade of CD(40)-CD(40)L pathway in vitro, the donor T lymphocytes cultured in vitro with anti-CD(40)L mAb were transfused in bone marrow transplantation (BMT) GVHD mouse model., Methods: C57BL/6(H-2b) spleen T cells were isolated as responder cells, and BALB/c(H-2d) spleen cells as stimulator cells. They were cocultured with or without Anti-CD(40)L mAb as anti-CD(40)L mAb group and control group, respectively. At day 5, the mixed lymphocyte response (MLR)-culture cells mixed with bone marrow cells and transfused respectively into the TBI conditioned recipient mice. The mice were divided into two groups: group A, bone marrow cells (2 x 10(6)) and spleen T lymphocytes (2 x 10(6)) from MLR control group; group B, bone marrow cells (2 x 10(6)) and spleen T lymphocytes (2 x 10(6)) from MLR anti-CD(40)L mAb group. The GVHD incidence and hematopoietic reconstitution were observed. Peripheral blood sera and spleen cells of the recipients mice were harvested at scheduled time points for the measurement of cytokines and T cell immunophenotyping with flow cytometry., Results: The incidence of GVHD in group A was 100% (10/10), and in group B was 20% (2/10). The percentage of H-2D(b) positive cells in group B (n = 8) was (93.54 +/- 2.32)% at day 40 after transplantation. The levels of cytokines in serum from group B were significantly lower than those from group A (P < 0.05). The expressions of CD(4)(+), CD(8)(+), CD(4)(+)CD(25)(+), CD(8)(+)CD(25)(+), CD(4)(+)CD(69)(+), CD(8)(+)CD(69)(+) and CD(4)(+)CD(40)L(+) were lower in group B than in group A (P < 0.05). The expressions of CD(8)(+)CD(40)L(+) and CD(4)(+)CD(45)RA(+) were similar in the two groups (P > 0.05)., Conclusion: Blockade of CD(40)-CD(40)L interaction in vitro could induce immune tolerance in vivo, reduce aGVHD in aGVHD mice model and form chimerism, which was mediated by inhibiting the Th1 and Th2 cytokines production, inducing tolerance of CD(4)(+) and CD(8)(+) cells to alloantigens. The obstruction of T cells activation after tolerance happened mainly at the early and mature phase of T cells activation. These provided the experimental basis for the use of anti-CD(40)L mAb in the clinical transplantation to prevent aGVHD.