Objective:To analyze the relationship among thyroid autoimmunity (TAI), thyroid function, and gestational diabetes mellitus (GDM) in early pregnant women in Xi'an.Methods:A prospective study included pregnant women who underwent prenatal check-ups at the Northwest Women's and Children's Hospital from November 2020 to October 2021, with a gestational age of 6 to 14 weeks. Thyroid function, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and urinary iodine levels were measured, and the prevalence of thyroid disease and GDM was monitored. The subjects were divided into four groups: TPOAb positive only, TgAb positive only, both TPOAb and TgAb positive, and both TPOAb and TgAb negative, to compare the differences in the prevalence of thyroid disease and GDM among the groups. Statistical analysis was performed using Kruskal-Wallis rank-sum test, Bonferroni correction, Chi-square test, and a multivariate logistic regression model was used to analyze the relationship between TAI, thyroid disease, and GDM. Results:A total of 20 243 early pregnant women were included in this study, among which 1 615 (7.98%) were positive for TPOAb only; 865 (4.27%) were positive for TgAb only; 1 672 (8.26%) were positive for both TPOAb and TgAb (both positive group); and 16 091 (79.49%) were negative for both TPOAb and TgAb (both negative group). The thyroid stimulating hormone levels in the TPOAb positive only group, TgAb positive only group, and both positive group were significantly higher than those in the both negative group, respectively (Bonferroni correction, all P<0.05); the free thyroxine level in the TPOAb positive only group was significantly lower than that in the both negative group ( P<0.05). After adjusting for age, pre-pregnancy body mass index, and urinary iodine levels, multivariate logistic regression analysis showed that compared to the both negative group, the risk of developing hypothyroidism during pregnancy was significantly increased in the both positive group ( OR=11.49, 95% CI: 2.84-46.39); the risk of developing subclinical hypothyroidism during pregnancy was significantly increased in the TgAb positive only group ( OR=1.99, 95% CI: 1.05-3.76) and the both positive group ( OR=3.74, 95% CI: 2.49-5.63); the risk of developing GDM was significantly increased in the TgAb positive only group ( OR=1.43, 95% CI: 1.04-1.96) and the both positive group ( OR=1.94, 95% CI: 1.53-2.46). Among early pregnant women with normal thyroid function, after adjusting for age, pre-pregnancy body mass index, and urinary iodine levels, multivariate logistic regression analysis showed that compared to the both negative group, the risk of developing GDM was significantly increased in the TgAb positive only group ( OR=1.46, 95% CI: 1.06-2.02) and the both positive group ( OR=1.80, 95% CI: 1.40-2.32). Conclusion:TgAb positive only is a risk factor for subclinical hypothyroidism and GDM. Screening for thyroid autoantibodies, especially TgAb, during pregnancy helps in the early identification of high-risk pregnant women for thyroid dysfunction and GDM.

Objective:To analyze the relationship among thyroid autoimmunity (TAI), thyroid function, and gestational diabetes mellitus (GDM) in early pregnant women in Xi'an.Methods:A prospective study included pregnant women who underwent prenatal check-ups at the Northwest Women's and Children's Hospital from November 2020 to October 2021, with a gestational age of 6 to 14 weeks. Thyroid function, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and urinary iodine levels were measured, and the prevalence of thyroid disease and GDM was monitored. The subjects were divided into four groups: TPOAb positive only, TgAb positive only, both TPOAb and TgAb positive, and both TPOAb and TgAb negative, to compare the differences in the prevalence of thyroid disease and GDM among the groups. Statistical analysis was performed using Kruskal-Wallis rank-sum test, Bonferroni correction, Chi-square test, and a multivariate logistic regression model was used to analyze the relationship between TAI, thyroid disease, and GDM. Results:A total of 20 243 early pregnant women were included in this study, among which 1 615 (7.98%) were positive for TPOAb only; 865 (4.27%) were positive for TgAb only; 1 672 (8.26%) were positive for both TPOAb and TgAb (both positive group); and 16 091 (79.49%) were negative for both TPOAb and TgAb (both negative group). The thyroid stimulating hormone levels in the TPOAb positive only group, TgAb positive only group, and both positive group were significantly higher than those in the both negative group, respectively (Bonferroni correction, all P<0.05); the free thyroxine level in the TPOAb positive only group was significantly lower than that in the both negative group ( P<0.05). After adjusting for age, pre-pregnancy body mass index, and urinary iodine levels, multivariate logistic regression analysis showed that compared to the both negative group, the risk of developing hypothyroidism during pregnancy was significantly increased in the both positive group ( OR=11.49, 95% CI: 2.84-46.39); the risk of developing subclinical hypothyroidism during pregnancy was significantly increased in the TgAb positive only group ( OR=1.99, 95% CI: 1.05-3.76) and the both positive group ( OR=3.74, 95% CI: 2.49-5.63); the risk of developing GDM was significantly increased in the TgAb positive only group ( OR=1.43, 95% CI: 1.04-1.96) and the both positive group ( OR=1.94, 95% CI: 1.53-2.46). Among early pregnant women with normal thyroid function, after adjusting for age, pre-pregnancy body mass index, and urinary iodine levels, multivariate logistic regression analysis showed that compared to the both negative group, the risk of developing GDM was significantly increased in the TgAb positive only group ( OR=1.46, 95% CI: 1.06-2.02) and the both positive group ( OR=1.80, 95% CI: 1.40-2.32). Conclusion:TgAb positive only is a risk factor for subclinical hypothyroidism and GDM. Screening for thyroid autoantibodies, especially TgAb, during pregnancy helps in the early identification of high-risk pregnant women for thyroid dysfunction and GDM.

Objective:To study the clinical and immunological features of two case of rare antisynthetase syndrome (ASS), so as to improve the level of diagnosis and treatment.Methods:Two cases with rare antisynthetase syndrome admitted to the First Affiliated Hospital of Zhengzhou University from July 2020 to August 2022 were collected.Results:The two rare ASS were anti-Zo antibody and anti-Ha antibody positive patients, both of which had interstitial lung disease (ILD) as the main clinical manifestation and positive anti-Ro52 antibody. Two rare antisynthetase autoantibodies manifested cytoplasmic ANA indirect immunofluorescence (IIF) staining pattern, but it is different from the cytoplasmic dense speckled pattern of several common ASS antibodies. After treatment with glucocorticoids and immunosuppressants, case 1 died of respiratory failure due to a long course of disease and late diagnosis, the lung lesions of case 2 improved significantly.Conclusion:When encountering the cytoplasmic ANA fluorescent pattern in ILD patients, especially with anti-Ro52 antibody, it is necessary to screen more myositis specific antibodies to rule out the possibility of rare ASS.

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

Ovarian cancer is the third-most-common malignant reproductive tumor in women. According to the American Cancer Society, it has the highest mortality rate of gynecological tumors. The five-year survival rate was only 29% during the period from 1975 to 2008 (Reid et al., 2017). In recent decades, the five-year survival rate of ovarian cancer has remained around 30% despite continuous improvements in surgery, chemotherapy, radiotherapy, and other therapeutic methods. However, because of the particularity of the volume and location of ovarian tissue, the early symptoms of ovarian cancer are hidden, and there is a lack of highly sensitive and specific screening methods. Most patients have advanced metastasis, including abdominal metastasis, when they are diagnosed (Reid et al., 2017). Therefore, exploring the mechanism of ovarian cancer metastasis and finding early preventive measures are key to improving the survival rate and reducing mortality caused by ovarian cancer.
B7-H1 Antigen/biosynthesis* ; Cell Proliferation/drug effects* ; Chemokines/biosynthesis* ; Female ; Humans ; Ovarian Neoplasms/pathology* ; Survival Rate ; Up-Regulation

Objective To investigate the prevalence of iron deficiency(ID)and iron deficiency anemia (IDA) in pregnant women in urban areas of China. Methods The study was a national cross-sectional survey conducted from September 19th, 2016 to November 20th, 2016. According to the classification of the National Bureau of Statistics, all survey sites were set up in 6 regions of the country. Pregnant women were continuously selected using multistage stratified sampling. A total of 12 403 pregnant women were collected and examined for serum ferritin and hemoglobin levels. Results The median serum ferritin level during pregnancy was 20.60 μg/L(11.78-36.98 μg/L), the hemoglobin level was(118±12)g/L. With the progress of pregnancy, the levels of serum ferritin and hemoglobin decreased gradually. The median serum ferritin levels in the first, second trimester and third trimester were 54.30 μg/L(34.48-94.01 μg/L), 28.60 μg/L(16.40-50.52 μg/L), and 16.70 μg/L(10.20-27.00 μg/L)respectively(P<0.01). The mean hemoglobin levels were(127 ± 10)g/L,(119 ± 11)g/L and(117 ± 11)g/L respectively(P<0.01). The prevalence of ID in urban pregnant women was 48.16%(5 973/12 403), and IDA prevalence was 13.87% (1 720/12 403). The prevalence of IDA in the first, second trimester and third trimester were 1.96% (20/1 019), 8.40%(293/3 487)and 17.82%(1 407/7 897), respectively(P<0.01). The prevalence of standardized ID and IDA were significantly different in various regions of China(P<0.01). The standardized prevalence of ID were relatively higher in East China and Northeast China, 57.37% and 53.41% respectively, while it was the lowest in Southwest China, 30.51%. The standardized prevalence of IDA in South Central, Northwest, and East China were relatively high, 21.30%, 16.97% and 17.53% respectively, and the standardized prevalence of IDA in Southwest China was the lowest, 5.44%,the differents in various regions were significant(all P<0.01). Conclusion The current phenomenon of ID and IDA in pregnant women is still very common,and nutrition and health care during pregnancy should be strengthened.

Objective To study the effects of discoidin domain receptor 1 (DDR1) mediated phosphorylation of protein Tau on hypoxic-ischemic brain damage (HIBD) in neonatal rats and its possible mechanism.Methods Sixty-four seven-day-old male specific-pathogen-free Wistar rats were randomly divided into four groups with sixteen in each: Sham, HIBD, HIBD with normal saline (HIBD+NS) and HIBD with DDR1 inhibitor (HIBD+DI) groups. A rat model of HIBD was established by subjecting the rats to left common carotid artery ligation, followed by exposing them to hypoxia for two hours. In HIBD+DI group, the inhibitor of DDR1 was immediately injected into lateral cerebroventricles of the rats following modeling. Forty-eight hours after injection, tissues of left cerebral cortex were collected from each rat to evaluate histopathological changes with HE staining. Western-blotting was used to assess the phosphorylation levels of DDR1 and protein Tau. Enzyme-linked immunosorbent assay was performed to detect the concentrations of acetylcholine. Analysis of variance ort test were used for statistical analysis.Results (1) Damages in cerebral cortex: Percentages of abnormal neurons in the rats of HIBD group were higher than those in Sham group [(80.28±4.51)% vs (10.40±2.17)%,t=39.491,P<0.01]. Pyknotic or necrotic neurons in the rats of HIBD+DI group were less than those in HIBD+NS group [(31.91±3.05)% vs (82.01±7.20)%,t=18.123,P<0.01]. (2) Phosphorylation of DDR1 and protein Tau: Levels of phosphorylated DDR1 in the cerebral cortexes of rats in HIBD group were higher than those in Sham group (0.922±0.199 vs 0.095±0.023,t=10.379,P<0.01), and those levels in HIBD+NS group were higher than those in HIBD+DI group (1.200±0.171 vs 0.255±0.111,t=11.901, P<0.01). The phosphorylation of protein Tau was similar to that of DDR1 (0.919±0.228 vs 0.194±0.224 in HIBD and Sham groups,t=7.347; 1.100±0.167 vs 0.291±0.210 in HIBD+NS and HIBD+DI groups,t=9.447;bothP<0.01). (3) Levels of acetylcholine: Levels of acetylcholine in cerebral cortexes of rats in HIBD group were lower than those in Sham group [(3.685±0.472) vs (7.429±0.861) ng/g protein,t=10.781,P<0.01], and that levels in HIBD+DI group were higher than those in HIBD+NS group [(7.058±0.915) vs (2.521±0.723) ng/g protein,t=10.989,P<0.01].Conclusions Activation of DDR1 plays a key role in enhancing the phosphorylation of protein Tau and in reducing the secretion of acetylcholine in cerebral cortexes of rats with HIBD. Inhibitor of DDR1 could protect neonatal rats from HIBD through the decreasing of protein Tau phosphorylation and increasing of acetylcholine release by inhibiting the activation of DDR1.

Objective To study the effect of perinatal hypothyroidism (PHT) on hippocampal neuronal structure and function of neonatal rats.Methods Sixteen pregnant SD rats were randomly divided into control group and PHT group (n=8).The pregnant rats were subjected to gavage by normal saline or 6-propyl-2-thiouracil (PTU) every day from 15 d of pregnant to the end of lactation.After parturition,38 male neonatal rats from each group were chosen for the following study.On the 7th d of birth,15 neonatal rats from each group were sacrificed,and the concentrations of free triiodothyronine (FT) 3,FT4 and thyroid stimulating hormone (TSH) in serum and acetylcholine (Ach) in the hippocampus were detected by ELISA.Real-time PCR,Western blotting and immunohistochemistry were used to assess the expressions of neuronal nuclei antigen (NeuN) and microtubule-associated protein tau (MAPT)in transcriptional and protein levels orderly.The left neonatal rats at one month old were performed morris water maze test to evaluate the learning and memory abilities.Results ELISA results showed that both FT3 and FT4 significantly decreased but TSH increased significantly in serum of PHT rats as compared with those in the control group (P＜0.05);Ach in the hippocampus of PHT rats was reduced three folds as compared with those in control group,with significant difference (P＜0.05).Real-time PCR and Western blotting results showed that the mRNA and protein expression levels of NeuN and MAPT in PHT rats were markedly down-regulated as compared with those in the control group:0.25 and 0.12 fold ofmRNA level in control group,and 0.35 and 0.22 fold of protein level in control group,with significant differences (P＜0.05).Immunohistochemistry indicated decreased NeuN and MAPT expression levels of varying degrees in PHT rats.In the morris water maze,one-month-old rats with PHT showed significantly prolonged escape latency ([10.18±3.02] s) and lengthened total distance ([365.28±41.77] cm) as compared with the control rats ([24.36±5.15] s,[790.36±72.53] cm,P＜0.05).Conclusion PHT could result in reduced expressions of neuron markers,axons dysfunction and decreased secretion of neurotransmitter in the hippocampus of neonatal rats,and it could weaken the learning and memory abilities in long term.

Objective To study the effect of high-glucose-high-fat diet on expression and methylation of insulin receptor ( INSR) gene in F1 offspring. Methods Sixty 5-week-old male SD rats were randomly divided into two groups:normal diet group and high-glucose-high-fat diet group. After rats were fed for three months, all male rats were performed to copulate with normal female rats. The body weight, blood glucose, and blood insulin of neonatal rats of F1 offspring were measured. The genome DNA, total RNA, and total protein were extracted from livers, brains, and muscles of neonatal rats. Relative expression of INSR in both mRNA level and protein level were detected using a realtime PCR test and a Western blot test respectively. Methylation of INSR promoter was analyzed by a methylation specific PCR ( MSP ) . Results Both body weight and fasting glucose were without significant difference in two groups. In high-glucose-high-fat diet group, both the glucose tolerance and insulin tolerance of neonatal rats in F1 offspring were significantly decreased. Except that in brains, the expressions of INSR gene in livers and in muscles of neonatal rats in high-glucose-high-fat diet group were down-regulated in mRNA ( realtime PCR ) and protein levels ( Western blot) compared to the normal diet group. Meanwhile, the methylation of INSR gene in livers and muscles were strengthened in high-glucose-high-fat diet group. Conclusion A high-glucose-high-fat diet fed to male SD rats leads to the decrease in glucose tolerance, insulin tolerance, and the inhibition of expression of hepatic and muscle INSR gene in neonatal offspring. The methylation of INSR gene could be involved in this phenomenon.

OBJECTIVETo analyze pupils' neglect status aged 6-11 years in China's rural.

METHODSAccording to the principle of multi-stage stratified cluster sampling, to extract 7,943 pupils aged 6-11 years for the survey from 56 primary schools in 28 counties in nine provinces, from December 2012 to March 2013. Proceed questionnaire survey by the scale from "Neglect Evaluation Norms for pupils aged 6-8 years in Rural Areas of China" and "Neglect Evaluation Norms for pupils aged 9-11 years in Rural Areas of China". And analyze neglect rates and neglect degrees of the different grades, gender, family types and different levels of neglect.

RESULTSThe total neglect rate of China's rural pupils aged 6-8 and 9-11 years was 40.2% (1,258/3,130) and 42.5% (1,498/3,526) respectively, which differences had no statistical significant (χ2=3.59, P=0.058); the total neglect degree was 46.04±8.87 and 44.78±10.43 respectively, which differences had statistical significant (t=5.01, P<0.001); the differences of neglect rates and neglect degrees between male (41.4% (657/1,587) and 46.28±8.76) and female (39.0% (601/1,543) and 45.78±8.97) of aged 6-8 were all no statistical significant (χ2=1.87, P=0.171; t=1.49, P=0.136); the neglect rates and neglect degrees of male (46.3% (816/1,763) and 45.53±10.11) were higher than female (38.7% (682/1,763) and 44.06±10.69) in the group of aged 9-11, which differences were all statistical significant (χ2=20.84, t=3.97, P<0.001); the male neglect rate in the group of aged 6-8 in social neglect (11.7% (198/1,691)) and the neglect degree in educational neglect (48.09±9.70) were higher than female (9.4% (155/1,648) and 47.37±9.89), which differences were all statistical significance (χ2=14.55, P<0.001, t=2.22, P=0.026), the male neglect rate in the group of aged 9-11 in physical neglect (20.4% (398/1,954)) was higher than female (16.7% (326/1 957)), which differences had statistical significance (χ2=8.92, P=0.003).

CONCLUSIONThe neglect status of Chinese pupils aged 6-11 years in rural was serious, and we should find out risk factors and provide efficient prevention measures.

Child ; Child Abuse ; China ; Female ; Humans ; Male ; Physical Examination ; Pupil ; Risk Factors ; Rural Population ; Schools ; Surveys and Questionnaires