Objective:To investigate the relationship between plasma fluoride content, daily calcium intake and blood cell parameters in children and adolescents.Methods:This study was based on the National Health and Nutrition Examination Survey (NHANES) database of the United States from 2013 to 2016, with 3 684 children and adolescents aged 6 - 19 as the research subjects. Information on plasma fluoride content, daily calcium intake and blood cell parameters from the database were collected. Non-linear relationships between plasma fluoride content, daily calcium intake and blood cell parameters were analyzed using restricted cubic splines. If there was a non-linear relationship, the optimal inflection point was calculated using threshold/saturation effect analysis method. Subsequently, multiple linear regression models were used to analyze the associations among the three, and the modification effect of daily calcium intake (binary classification, stratified by median daily calcium intake) on the association between plasma fluoride content and blood cell parameters was analyzed.Results:There was no non-linear relationship between plasma fluoride content and white blood cell count, hemoglobin content and platelet count ( Pnon-linear > 0.05), but there was a non-linear relationship between plasma fluoride content and erythrocyte count and hematocrit ( Pnon-linear < 0.001). After adjusting for confounding factors, the optimal inflection points of the effects of plasma fluoride content on erythrocyte count and hematocrit were 0.54 and 0.31 μmol/L, respectively. There was no non-linear relationship between daily calcium intake and blood cell parameters ( Pnon-linear > 0.05). After adjusting for confounding factors, for every 1 μmol/L increase in plasma fluoride content, the white blood cell count increased by 0.49 × 10 9/L ( P = 0.009). There was a saturation effect in the association between plasma fluoride content, erythrocyte count and hematocrit: when plasma fluoride content was < 0.54 μmol/L, the erythrocyte count decreased by 0.46 × 10 12/L for every 1 μmol/L increase ( P < 0.001). When plasma fluoride content was < 0.31 μmol/L, the hematocrit decreased by 6.29% for every 1 μmol/L increase ( P = 0.006). The above associations were not statistically significant when plasma fluoride content was higher than the optimal inflection points ( P > 0.05). After stratification according to the median daily calcium intake, in the low-calcium group (daily calcium intake < 0.87 g), for every 1 μmol/L increase in plasma fluoride content, the white blood cell count increased by 0.77 × 10 9/L ( P = 0.001). When plasma fluoride content was < 0.54 μmol/L, the erythrocyte count decreased by 0.41 × 10 12/L for every 1 μmol/L increase ( P = 0.002). When plasma fluoride content was ≥0.54 μmol/L, erythrocyte count decreased by 0.47 × 10 12/L for every 1 μmol/L increase ( P < 0.001). When the plasma fluoride content was < 0.31 μmol/L, the hematocrit decreased by 8.29% for every 1 μmol/L increase ( P = 0.011). The above associations were not statistically significant in the high-calcium group (daily calcium intake ≥0.87 g, P > 0.05). There was an interaction of daily calcium intake and plasma fluoride content on platelet count ( Pinteraction = 0.070), as demonstrated by an increase in platelet count of 12.68 × 10 9/L ( P = 0.013) in the low-calcium group and a decrease in platelet count of 9.05 × 10 9/L ( P = 0.035) in the high-calcium group for every 1 μmol/L increase in plasma fluoride content. Conclusions:The blood cell parameters of children and adolescents are closely related to plasma fluoride content, but not directly related to daily calcium intake. However, the correlation between plasma fluoride content and blood cell parameters varies among different calcium intake populations, and daily calcium intake can modify the association between plasma fluoride content and platelet count.

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 screen differentially expressed circular RNA (circRNA) in rat articular chondrocyte injury induced by T-2 toxin, and explore the mechanism of cartilage injury.Methods:Twenty-four SD rats (males, body weight 60 - 80 g) were randomly divided into T-2 toxin group (administrated T-2 toxin 100 ng·g -1·d -1 by gavage) and control group (administrated equal amounts of deionized water by gavage) using a random number table method, 12 rats in each group. After 4 weeks of intervention, the articular cartilage was collected for transcriptome sequencing. Deseq2 software [ P < 0.05 and |log 2(fold change)| > 1, fold change was the multiple of differential expression] was used to identify differentially expressed circRNA. Based on the competing endogenous RNAs (ceRNA) hypothesis, the miRanda software was used to predict the microRNA (miRNA, miR) binding sites of differentially expressed circRNA, and Cytoscape 3.10.0 software was used to plot the circRNA-miRNA interaction network. MiRWalk 3.0, MiRDB, and miRTarBase softwares were used to predict downstream target genes, and Cytoscape 3.10.0 software was used to map the circRNA-miRNA-mRNA interaction network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the biological functions and enrichment pathways of target genes. Results:A total of 19 differentially expressed circRNAs were screened (including 10 upregulated and 9 downregulated). A total of 1 320 miRNAs binding sites and 16 target genes were predicted. Target gene enrichment analysis revealed significant enrichment of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathway ( P < 0.05). Tumour necrosis factor receptor-associated factor 6 (Traf6) and interleukin-1 receptor-associated kinase 1 (Irak1) were enriched in the MAPK and NF-κB signaling pathways, with corresponding miRNA and circRNA of miR-146a-5p and chr2: 94716330|94720889. Conclusion:Nineteen differentially expressed circRNAs in rat articular chondrocyte injury are successfully screened, and chr2: 94716330|94720889 may regulate the MAPK and NF-κB signaling pathways through the miR-146a-5p/Traf6/Irak1 axis, inducing articular chondrocyte injury.

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.

Background/Aims: Ulcerative colitis (UC) is an incurable, relapsing-remitting inflammatory disease that increases steadily. Mucosal healing has become the primary therapeutic objective for UC. Nevertheless, endoscopic assessments are invasive, expensive, time-consuming, and inconvenient. Therefore, it is crucial to develop a noninvasive predictive model to monitor endoscopic activity in patients with UC. Methods: Clinical data of 198 adult patients with UC were collected from January 2016 to August 2022 at Huadong Hospital, China. Results: Patients with UC were randomly divided into the training cohort (70%, n=138) and the validation cohort (30%, n=60). The receiver operating characteristic curve value for the training group was 0.858 (95% confidence interval [CI], 0.781 to 0.936), whereas it was 0.845 (95% CI, 0.731 to 0.960) for the validation group. The calibration curve employed the Hosmer-Lemeshow test (p>0.05) to demonstrate the consistency between the predicted and the actual probabilities in the nomogram of these two groups. The decision curve analysis validated that the nomogram had clinical usefulness. Conclusions The nomogram, which incorporated activated partial thromboplastin time, fecal occult blood test, β2-globulin level, and fibrinogen degradation products, served as a prospective tool for evaluating UC activity in clinical practices.

With the recent ongoing autumn/winter 2022 COVID-19 wave and the adjustment of public health control measures, there have been widespread SARS-CoV-2 infections in Chinese mainland. Here we have analyzed 369 viral genomes from recently diagnosed COVID-19 patients in Shanghai, identifying a large number of sublineages of the SARS-CoV-2 Omicron family. Phylogenetic analysis, coupled with contact history tracing, revealed simultaneous community transmission of two Omicron sublineages dominating the infections in some areas of China (BA.5.2 mainly in Guangzhou and Shanghai, and BF.7 mainly in Beijing) and two highly infectious sublineages recently imported from abroad (XBB and BQ.1). Publicly available data from August 31 to November 29, 2022 indicated an overall severe/critical case rate of 0.035% nationwide, while analysis of 5706 symptomatic patients treated at the Shanghai Public Health Center between September 1 and December 26, 2022 showed that 20 cases (0.35%) without comorbidities progressed into severe/critical conditions and 153 cases (2.68%) with COVID-19-exacerbated comorbidities progressed into severe/critical conditions. These observations shall alert healthcare providers to place more resources for the treatment of severe/critical cases. Furthermore, mathematical modeling predicts this autumn/winter wave might pass through major cities in China by the end of the year, whereas some middle and western provinces and rural areas would be hit by the upcoming infection wave in mid-to-late January 2023, and the duration and magnitude of upcoming outbreak could be dramatically enhanced by the extensive travels during the Spring Festival (January 21, 2023). Altogether, these preliminary data highlight the needs to allocate resources to early diagnosis and effective treatment of severe cases and the protection of vulnerable population, especially in the rural areas, to ensure the country's smooth exit from the ongoing pandemic and accelerate socio-economic recovery.

In recent years, the development of bispecific antibodies (bsAbs) has been rapid, with many new structures and target combinations being created. The boom in bsAbs has led to the successive issuance of industry guidance for their development in the US and China. However, there is a high degree of similarity in target selection, which could affect the development of diversity in bsAbs. This review presents a classification of various bsAbs for cancer therapy based on structure and target selection and examines the advantages of bsAbs over monoclonal antibodies (mAbs). Through database research, we have identified the preferences of available bsAbs combinations, suggesting rational target selection options and warning of potential wastage of medical resources. We have also compared the US and Chinese guidelines for bsAbs in order to provide a reference for their development.

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)

Objective:To analyze the clinical characteristics of patients with acute glyphosate herbicide poisoning and the differences in the severity of poisoning.Methods:A retrospective analysis was performed on patients with acute glyphosate herbicide poisoning admitted to the First Affiliated Hospital of Zhengzhou University from January 2014 to December 2020. The general information, exposure time, poisoning dose, poisoning cause, poisoning route, clinical manifestations, laboratory examination results during hospitalization, treatment measures, hospital stays and prognosis of the patients were collected. The patients were graded according to the poisoning severity scoring standard of Chinese Expert Consensus on Diagnosis and Treatment of Acute Poisoning in 2016. The highest severity score during hospitalization was used as the final grade. According to the final grade, asymptomatic and mild patients were included in the mild group, and moderate, severe and death patients were included in the severe group. The independent sample T test or Mann-Whitney U test was used for measurement data, and χ2 test or Fisher's exact test was used for counting data. The differences of general data and clinical data between the two groups were compared. Results:According to the inclusion and exclusion criteria, 83 patients with acute glyphosate herbicide poisoning were selected as the study subjects. All patients survived, mainly mild poisoning (56.6%), with a male to female ratio of 33∶50, and an average age of 39 years. The number of poisoning cases increased yearly (the highest in 2019), and most cases occurred in spring and summer. The main cause of poisoning was suicide (71.1%), direct oral administration (83.1%) was the primary route of poisoning, and the dominating clinical manifestations were digestive symptoms (71.1%). Laboratory tests showed increased white blood cell count (WBC), neutrophil percentage (NEUT %) and D-dimer, and decreased hemoglobin and potassium. Compared with the mild group, patients in the severe group were older [(51±17) years vs. (35±19) years], had a higher proportion of suicide and direct oral administration, a longer hospital stay [8.0 (4.8, 12.0) d vs. 3.0 (2.0, 5.5) d], a higher dose of poisoning [200.0 (50.0, 200.0) mL vs. 30.0 (11.3, 57.5) mL], and higher NEUT % within 24 h of admission [(83.4±10.4) vs. (73.2±12.8)]. The increase of WBC, NEUT %, aspartate aminotransferase, prothrombin time, D-dimer and the decrease of serum potassium were more common in the severe group than the mild group, with statistical significance (all P<0.05). Conclusions:The number of patients with acute glyphosate herbicide poisoning is increasing yearly. Generally, the condition is mild and the prognosis is satisfying. The severity is more serious in the middle-aged and elderly patients andthose with direct oral administration, high toxic dose, and high NEUT % within 24 h of admission. Severe poisoning is more likely to cause changes in laboratory indicators.

Objective:This study was aimed to explore the associations between the risk of dental fluorosis and the serum biomarkers of bone metabolism in children.Methods:A total of 502 children aged 7 - 12 years were selected by cluster sampling from 4 primary schools in Tongxu County, Kaifeng City, Henan Province from April to May 2017. Morning urine and fasting peripheral blood samples were collected from each participant. Urinary fluoride concentration was determined by fluoride ion selective electrode method. Serum calcium, phosphorus, alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), osteocalcin (OC), calcitonin (CT) and parathyroid hormone (PTH) levels were measured using an automatic biochemical analyzer. Dean method was used to evaluate the prevalence of dental fluorosis in children, and the participants were divided into dental fluorosis group ( n = 173) and control group ( n = 329) after being diagnosed by trained physicians for their dental fluorosis. The associations between the risk of dental fluorosis and the serum biomarkers of bone metabolism in children were analyzed by logistic regression. Results:The levels of serum phosphorus (mmol/L: 1.54 ± 0.19 vs 1.58 ± 0.21) and OC (ng/ml: 11.59 ± 5.22 vs 12.78 ± 5.88) in children in dental fluorosis group were significantly lower than those in children in control group ( P < 0.05). Logistic regression analysis showed that serum OC level affected the risk of dental fluorosis [odds ratio ( OR) = 0.96, 95% confidence interval ( CI): 0.92 - 0.99, P < 0.05]. The relative contribution of the biomarkers of bone metabolism to the risk of dental fluorosis in descending order were serum OC (36.34%), phosphorus (25.89%), BALP (13.16%), PTH (9.73%), calcium (9.44%), CT (3.72%) and ALP (1.72%). Conclusions:The prevalence of dental fluorosis in children is related to the changes of serum biomarkers of bone metabolism. Serum OC plays an important role in the occurrence of dental fluorosis.