STAT3, a member of the signal transducer and activator of transcription family, is abnormally activated in chronic inflammation-related tumors including liver cancer. As a key signal molecule in the microenvironment of liver cancer and inflammation, STAT3 not only participates in the inflammation-cancer transformation during the development of liver cancer, but also promotes the proliferation, invasion, and metastasis of hepatoma cells through many ways, and therefore, it may be a potential target for the treatment of liver cancer. This article reviews the recent advances in the association between STAT3 and liver cancer.

Objective:To study the relationship between fluoride exposure and adrenocorticotropic hormone (ACTH)/cortisol (CORT) in rural children in eastern Henan, and to reveal the modifying effect of brain-derived neurotrophic factor (BDNF) gene polymorphism.Methods:A total of 463 children aged 7 - 12 (245 boys and 218 girls) from 4 primary schools in Tongxu County, Henan Province were recruited by a cluster sampling method for questionnaire survey, physical examination, and collection of morning urine and fasting venous blood. The concentrations of urinary fluoride and creatinine were determined by a fluoride ion selective electrode method and picric acid method, respectively. Serum ACTH and CORT levels were determined with a fully automated biochemical analyzer, and the genotyping of BDNF gene loci of single nucleotide polymorphism was conducted by a customized 48-Plex SNPscan TM reagent kit. Besides, the relationships between urinary fluoride concentrations and serum ACTH/CORT levels in children were analyzed by multiple linear regression models. The interaction term between urinary fluoride concentration and BDNF gene polymorphism was established, and the interaction between unit point gene polymorphism and environment on serum ACTH or CORT levels of children was analyzed by multiple linear regression. Results:For every 1 mg/L increase in urinary fluoride concentration, serum ACTH level in girls increased by 1.98 pg/ml [95% confidence interval ( CI): 0.71, 3.24; P = 0.002], while serum CORT level in boys decreased by 37.48 ng/ml (95% CI: - 63.99, - 10.97; P = 0.006). Regardless of stratified analysis, the urinary fluoride concentration of individuals carrying the TA genotype at the rs6484320 locus was positively correlated with serum ACTH level (β > 0, P < 0.05); in addition, there was a positive correlation between urinary fluoride concentration and serum ACTH level in the total population and boys carrying the CC genotype of rs7103873 locus (β > 0, P < 0.05); and the serum ACTH and CORT levels in girls carrying the AA genotype of rs12291186 locus were positively correlated with urinary fluoride concentration (β > 0, P < 0.05). The interaction analysis showed that there was an interaction between urinary fluoride concentrations and rs6484320/rs7103873 loci polymorphisms on serum ACTH level in the total population and boys ( Pinteraction < 0.1), as well as urinary fluoride concentrations and rs12291186 locus polymorphism on serum CORT level in girls ( Pinteraction = 0.035). Conclusions:Urinary fluoride concentration is associated with increased serum ACTH level in girls and decreased serum CORT level in boys. BDNF gene polymorphism can modify the association between fluoride exposure and serum ACTH or CORT levels in children, and the modification effect varies by gender.

Objective:To study the relationship between adult fluoride exposure and grip strength in rural areas of China with fluorosis, as well as the roles of basal metabolic rate (BMR) and body fat percentage (BFP) in the association between fluoride exposure and grip strength.Methods:From April to May 2017, a cluster sampling method was used to conduct a questionnaire survey, physical examination, and biological sample collection on residents aged 18 - 60 in Tongxu County, Kaifeng City, Henan Province (epidemic areas of drinking-water-borne fluorosis). A total of 1 168 subjects were included in the study, including 427 males and 741 females. The fluoride ion selective electrode method and the picric acid method were used to determine the concentrations of urine fluoride and urine creatinine, and the adjusted urine fluoride concentration (CUF) was calculated. BMR and BFP were measured by a bioelectrical impendence method, and the grip strength was measured by a Jamar grip dynamometer. The relationship between CUF, BMR, BFP and grip strength were analyzed using a generalized linear model regression. The mediation effect model was used to assess the mediating effect of BMR and BFP on the association between CUF and grip strength.Results:Female grip strength decreased by 0.28 kg ( P = 0.043) for every 1.00 mg/L increment in CUF. No similar association was found between the two in males ( P = 0.744). Regardless of gender stratification, BMR was positively correlated with grip strength ( P < 0.001). For every 1.00% increase in BFP, female grip strength decreased by 0.18 kg ( P = 0.043). The mediation effect model analysis results showed that the mediation effect ratios of BMR and BFP in the association between CUF and grip strength in female were 65.1% ( P < 0.001) and 8.4% ( P = 0.111), respectively. Conclusion:Fluoride exposure is associated with changes in female grip strength, and BMR changes play a partial mediating role in the association between fluoride exposure and female grip strength.

Objective:To investigate the factors related to child care environment and the association between child care environment and children′s early development.Methods:Using stratified cluster random sampling, a total of 22 509 children newly enrolled to kindergarten from 187 kindergartens of 16 districts in Shanghai in 2017 were enrolled. A survey was conducted by parent-reported questionnaire. The index of child care environment (ICCE) and the early human capacity index were used to evaluate family child care environment and children′s early development respectively. The sample was divided into four groups based on the ICCE score: the lowest family childcare environment (ICCE≤10 scores), lower middle (ICCE=11 scores), upper middle (ICCE=12 scores), and the highest (ICCE=13 scores). The linear regression model and Logistic regression model were used to analyze the factors related to child care environment and the association between child care environment and children′s early development respectively.Results:A total of 22 067 children aged (44±7) months, including 11 425 boys (51.8%) and 10 642 girls (48.2%), participated in this study. The multnomial linear regression revealed girls, higher maternal education, higher household annual income, single-child, non-divorced parents, and early breastfeeding experience were protective factors of child care environment for children newly enrolled to kindergarten ( β=0.064, 0.238, 0.119, 0.096, 0.113, and 0.032; 95% confidence interval ( CI): 0.020-0.108, 0.175-0.302, 0.058-0.180, 0.046-0.146, -0.012-0.242, and -0.051-0.116; all P<0.01). The multinomial Logistic regression revealed compared with the highest child care environment group, the odds ratio of children′s early development risks in upper midclle, lower middle, and the lowest child care environment groups were 1.543 (95% CI: 1.373-1.735, P<0.01), 2.537 (95% CI: 2.254-2.856, P<0.01), and 4.198 (95% CI: 3.757-4.690, P<0.01), respectively. Conclusions:The child care environment is not only significantly related to family structure and socioeconomic status, but also to early breastfeeding experience. The child care environment plays an important role in promoting childhood early development.

OBJECTIVE：To explore the therap eutic effects and its mech anism of Jianpi yiqi decoction on diethylnitrosamine （DEN）induced liver cancer model rats. METHODS ：Totally 80 male SD rats were divided into normal group ，model group ， Nod-like receptor family 3（NLRP3）inhibition group （MCC950，4.5 mg/kg），caspase-1 inhibitory group （VX-765，4.5 mg/kg）， Jianpi yiqi decoction low-dose ，medium-dose and high-dose groups （5.25，10.5，21 g/kg），with 10 rats in each group except for 20 rats in model group （10 of them were only used to judge whether modeling was successful ）. Rats in each group were intraperitoneally injected with DEN （70 mg/kg）to induce liver cancer model ，except for the rats in normal group which were replaced by normal saline. After modeling ，normal group and model group were given normal saline intragastrically ；inhibitor groups were given relevant medicine intraperitoneally ；Jianpi yiqi decoction groups were given relevant medicine intragastrically ， once a day ，for consecutive 4 weeks. After last administration ，histopathological morphology of liver tissue was observed. The contents of serum inflammatory factors TNF-α and IL-1β were detected. The expression of NLRP3 and programmed cell necrosis associated protein （ASC，pro-caspase-1，RIP1，RIP3 and MLKL ）in liver tissue were detected. RESULTS ：Compared with the normal group ，the hepatocytes of model group showed varying， degrees of steatosis ，enlarged nuclei ，lumpy，bleeding and necrosis，accompanied by proliferative foci and nodules. Liver 198086， tissue injury index ，serum content of TNF-α and IL-1β as well as the protein expression of NLRP 3，ASC，pro-caspase-1，RIP1，RIP3 and MLKL in liver tissue were significantly increased （P＜0.05 or P＜0.01）. Compared with model 防治。E-mail：sherwin_zhuo@126.com group，there were still a large number of inflammatory cell infiltration in the liver tissue of rats in Jianpi yiqi decoction low-dose and medium dose groups ，while the inflammatory cell infiltration of rats in high-dose group and inhibitor groups decreased significantly ；the liver tissue injury index and above indexes levels in serum and liver tissue were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：Jianpi yiqi decoction shows therapeutic effect on liver cancer model rats ，the mechanism of which may be associated with down-regulating the expression of NLRP3 inflammasome and inhibiting programmed cell necrosis.

BACKGROUND: Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 ( MTHFD1 ) polymorphisms have important roles in neurodevelopment. However, the association of MTHFD1 polymorphisms with children's intelligence changes in endemic fluorosis areas has been rarely explored. METHODS: A cross-sectional study was conducted in four randomly selected primary schools in Tongxu County, Henan Province, from April to May in 2017. A total of 694 children aged 8 to 12 years were included in the study with the recruitment by the cluster sampling method. Urinary fluoride (UF) and urinary creatinine were separately determined using the fluoride ion-selective electrode and creatinine assay kit. Children were classified as the high fluoride group and control group according to the median of urinary creatinine-adjusted urinary fluoride (UF Cr ) level. Four loci of MTHFD1 were genotyped, and the Combined Raven's Test was used to evaluate children's intelligence quotient (IQ). Generalized linear model and multinomial logistic regression model were performed to analyze the associations between children's UF Cr level, MTHFD1 polymorphisms, and intelligence. The general linear model was used to explore the effects of gene-environment and gene-gene interaction on intelligence. RESULTS: In the high fluoride group, children's IQ scores decreased by 2.502 when the UF Cr level increased by 1.0 mg/L (β = -2.502, 95% confidence interval [CI]:-4.411, -0.593), and the possibility for having "excellent" intelligence decreased by 46.3% (odds ratio = 0.537, 95% CI: 0.290, 0.994). Children with the GG genotype showed increased IQ scores than those with the AA genotype of rs11627387 locus in the high fluoride group ( P   <  0.05). Interactions between fluoride exposure and MTHFD1 polymorphisms on intelligence were observed (Pinteraction < 0.05). CONCLUSION Our findings suggest that excessive fluoride exposure may have adverse effects on children's intelligence, and changes in children's intelligence may be associated with the interaction between fluoride and MTHFD1 polymorphisms.
Child ; Creatinine ; Cross-Sectional Studies ; Fluorides/urine* ; Formate-Tetrahydrofolate Ligase ; Humans ; Intelligence/genetics* ; Methylenetetrahydrofolate Dehydrogenase (NADP) ; Methylenetetrahydrofolate Reductase (NADPH2)