Objective To investigate the effects of blocking gastrin receptor on the proliferation,apoptosis and expression of key proteins in the related pathway in gastric cancer cell lines.Methods In the experimental group,the gastric cancer cell lines SGC-7901 and AGS cells were treated with 5 mmol/L proglumide,a kind of a gastrin receptor antagonist.And the normal cultured gastric cancer cells SGC-7901 and AGS were used in control group.The growth of each group was detected by MTT assay;the cell growth curve was drawn by flow cytometry;the cell cycle of each group was detected by flow cytometry.Annexin V-FITC/PI double staining was used to detect the cell growth of apoptosis.The relative mRNA expression of β-catenin,nuclear factor-P65,mammalian target of rapamycin and glycogen synthase kinase 3 beta in Wnt,NF-κB and PI3K-AKT-MTOR pathways were detected by RT-qPCR.The expression of β-catenin protein was detected by Western blotting.Results After treatment with proglumide,the growth of the cells in the experimental group was lower than that in the control group;and the proportion of S phase cells in the cell cycle was also lower than that in the control group,but the proportion of cells in G0/G1 phase was higher than that in the control group(P<0.05).The percentage of apoptotic cells was also increased after treatment with proglumide(P<0.05).Furthermore,proglumide treatment significantly reduced the expression of β-catenin at both mRNA and protein levels(P<0.05).Conclusion Blocking gastrin receptor can down-regulate the expression of β-catenin,inhibit the cell proliferation and promote the cell apoptosis in gastric cancer cells.

Birth cohort is an important platform to study the effect of early-life exposure on health outcome, but large cohorts to investigate the effect of preconception exposure, especially paternal exposure, on reproductive health and birth outcome are limited. The Preconception Reproductive Health and Birth Outcome Cohort (PREBIC) is a prospective birth cohort study which pays equal attention to the contribution of environmental, psychological, behavioral as well as other factors to reproductive health and adverse birth outcomes in both men and women in Chongqing, China. PREBIC started in 2019 and plans to recruit 20 800 reproductive-age couples with child-bearing willingness. Followed up was conducted to understand the conception status of the women within two years. Women in pregnancy would be visited at first, second, third trimesters and after delivery. The offspring would be monitored until 2 years old to understand the incidences of preterm birth, low birth weight, birth defects, neurodevelopmental disorders and other outcomes. Related information and biospecimen collections (including semen, peripheral blood, urine, placenta, umbilical cord, cord blood and oral swab) were scheduled in each period. By January 2022, PREBIC had recruited 8 698 participants from all 38 districts in Chongqing. The goal of PREBIC is to establish one of the largest prospective preconception birth cohorts covering both men and women, which might provide a unique insight to understand the effects of the full reproductive cycle on reproductive health and adverse outcomes, with especial emphasis on preconception exposures.

Objective： ：To study the effect of silencing DKK1 (Dickkopf1) gene on the proliferation, cell cycle and apoptosis of gastric cancer AGS cells and the action mechanism. Methods： ：The DKK1-shRNA vector was constructed and transfected into AGS cells. The stably transfected cell lines were screened. The total protein and RNAof the transfected cells were extracted and the mRNAand protein expressions of DKK1 were detected by qPCR and WB, respectively. The experiment was divided into blank control group (Control), negative control group (shNC) and DKK1 silence group (DKK1-shRNA). CCK8 assay was used to detect the proliferation ofAGS cells of each group cultured for 0, 24, 48, 72, 96, 120 and 144 h, and flow cytometry was used to analyze the cell cycle and apoptosis in each group. The relationship between DKK1 and clinicopathological features of gastric cancer was analyzed after searching HPA database. Results：The gastric cancer AGS cells with stable DKK1 gene knockdown was successfully established, and it was confirmed that the mRNA and proteinexpressions of DKK1 in DKK1-shRNA group decreased by 72% and 47%, respectively, compared to shNC group (all P<0.05). The cell proliferation curve showed that, the cell proliferation in DKKl-shRNAgroup significantly decreased after 72 hour of culture compared with that in control and shNC groups (P<0.05). The cell number of S phase decreased from 32.06% to 25.87%, while the number of G2/M phase increased from 8.49% to 21.26% compared with shNC group (all P<0.05). The number of apoptotic cells also statistically increased from 10.34% to 20.65% (all P<0.05). The data of HPAdatabase showed that DKK1 mRNAlevel in gastric cancer tissues was significantly higher than that in normal tissues, and the high expression of DKK1 mRNAwas negatively correlat ed with the survival rate of gastric cancer patients. Conclusion: : Silencing DKK1 gene can inhibit the proliferation of gastric cancer cells, arrest cells in G2/M phase and promote cell apoptosis. DKK1 plays a pro-carcinogenic effect in gastric cancer.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Objective To explore the potential mechanism of Benzo(K)fluoranthene(BkF)on male reproductive injury in mice by proteomics and metabolomics.Methods Twenty healthy and clean male Kunming mice(6 weeks old,18±2 g)were randomly divided into control group(corn oil group),low-,medium-and high-dose BkF groups(7.5,15.0 and 30.0 mg/kg),with 5 mice in each group.The corresponding agents were gavaged at a dose of 10 mL/kg,5 d per week,for 35 consecutive days.After modeling,the rats were fasted for 10 h,and then sperm samples and testicular tissues were harvested.Computer assisted sperm analysis(CASA)was used to detect and analyze semen parameters.HE staining was employed to observe the histopathological structure of the testicular tissue.Bioinformatics analysis was applied to analyze the differential protein pathways.Volcano plot were conducted to analyze the top 10 differentially expressed proteins(DEPs)in the control and high-dose BkF group.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)untargeted metabolomics techniques were utilized to screen out differential metabolites.KEGG signaling pathway and KEGG annotation analyses and GO enrichment analysis were used to analyze the differential metabolites.Results Compared with the control group,the sperm number and motility of BkF-treated mice showed a decreased trend,with statistical differences(P＜0.05).Pathological observation showed that BkF treatment resulted in dilated seminal tubules and badly-arranged spermatogenic cells when compared with the control group.Proteomics analysis found that the protein levels of Spata46 and Rab5b were decreased,while those of Zscan21 and Aifm2 were increased(P＜0.01).Proteomic KEGG enrichment analysis showed that it was mainly involved in phagosome,protein export,ribosome and other pathways.GO enrichment analysis indicated that it was mainly involved in male meiosis I,histone acetylation,regulation of p53 signaling pathway,positive regulation of cell cycle,positive regulation of cell death and other signaling pathways.Metabonomics KEGG displayed that amino sugar and nucleotide sugar metabolism were most closely related to other metabolic pathways.Conclusion Proteomics and metabolomics analyses show that BkF exposure is associated with spermatogenesis,apoptosis and cell cycle,DNA damage,amino sugar and nucleotide sugar metabolism.

Circadian rhythm is a phenomenon of diurnal changes in life activities formed by a transcription-translation feedback loop of biological clock genes affected by external environmental conditions. The circadian rhythm system controls almost all physiological processes in the organism, and these processes will change as the external environment changes. Previous studies have shown that the hypothalamic-pituitary-thyroid axis in mammals is regulated by the central diurnal pacemaker of the suprachiasmatic nucleus of the hypothalamus, so part of the thyroid function is controlled by the biological clock, and the secretion of thyroid hormones in blood can present a circadian rhythm. However, the molecular mechanism of the biological clock's regulatory effect on thyroid is still unclear. Whether circadian rhythm interference is related to the disorder of thyroid function or the occurrence of thyroid diseases is worthy of attention. This paper focused on the research progress of biological clock, circadian rhythm, and thyroid function, specifically the characteristics of circadian rhythm of thyroid physiological function and the effects of sleep deprivation, light at night, and night shift work on thyroid function, elaborated the relationships of circadian rhythm disorder with thyroid function and thyroid diseases represented by thyroid malignant tumors. The review summarized that circadian rhythm disorder may disrupt the rhythmic secretion of thyroid hormones, but no clear conclusion is reached yet on any effect on thyroid diseases, especially thyroid malignant tumors, so it is necessary to further strengthen the relevant epidemiological and molecular mechanism research.