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Previous studies have shown that PHF21A is associated with the initiation and progression of various tumors. However, its role in hepatocellular carcinoma (HCC) is still unclear. Thus, this study aimed to determine the expression and clinical significance of PHF21A in HCC. PHF21A expression in 201 liver cancer samples and 129 adjacent normal tissues was detected by immunohistochemistry. The correlation between PHF21A expression and the clinicopathological features and prognosis of HCC was verified in 70 other liver tissue microarray samples. The relationship between PHF21A expression and HCC immune cell infiltration was explored via the Tumor Immune Estimation Resource (TIMER). The mechanism underlying the effect of PHF21A on HCC progression was analyzed by gene set enrichment analysis (GSEA) and protein‒protein interaction (PPI) network analysis. Immunohistochemical staining showed that PHF21A expression in HCC tissue was significantly lower than that in adjacent nontumor liver tissue and was associated with patient sex, tumor size, metastasis, and Edmondson grade (p0.05). Kaplan-Meier analysis demonstrated that low PHF21A expression was associated with a poor prognosis, and Cox regression analysis showed that PHF21A was an independent predictor of prognosis. TIMER analysis showed that PHF21A is positively correlated with tumor immune cell infiltration levels. Functional annotation indicated that PHF21A is involved in important pathways, including transcriptional deregulation pathways in cancer. Finally, in vitro experiments confirmed the low expression of PHF21A in HCC cells. PHF21A affects the progression and prognosis of HCC, suggesting that PHF21A may play an important role in monitoring and preventing the development of HCC.

While the associations among ambient pollutants and various pregnancy complications are well documented, the effect of ambient pollutants on intrahepatic cholestasis of pregnancy (ICP) has not been examined. This study aimed to explore the effects of ambient pollutants and sunshine duration on ICP.The study enrolled 169,971 pregnant women who delivered between 2015 and 2020 in two hospitals. The associations between ICP and exposure to ambient pollutants and sunshine duration, averaged throughout different periods (including the 3 months before conception, 1st trimester and 2nd trimester), were estimated using a generalized linear model. The interaction effects of ambient pollutants and sunshine duration on ICP were estimated.The fitted curves for ICP incidence were similar to the temporal trends of PMExposure to PM

Background: As a growing health problem, maternal obesity may have an adverse effect on offspring neurodevelopment. The effects of maternal overweight and obesity and excessive gestational weight gain on offspring intelligence remains unclear. This meta-analysis aimed to assess the influence of prepregnancy body mass index (BMI) and gestational weight gain on children’s intelligence.Methods: We systematically searched PubMed, Embase, Cochrane Library and Ovid Medline from their inception through July 2020. Studies assessing the association between prepregnancy BMI or gestational weight gain and children’s intelligence (from 3 years to 10 years) were screened manually before final inclusion. We included prospective and retrospective cohorts that analysed the association between prepregnancy BMI or gestational weight gain and intelligence of offspring. We used the Mantel-Haenszel fixed-effects method to compute the weight mean difference (WMD) and 95% confidence interval (CI) of each study.Results: Twelve articles were included in the systematic review, and six of them were included in the meta-analysis. There was a significant full-scale IQ reduction in children of overweight and obese women, with WMDs of -3.25 (95% CI: -3.05, -2.42) and -4.85 (95% CI: -5.93, -3.76), respectively. Compared with that in the control group, the WMDs for performance IQ were -2.40 (95% CI: -3.45, -1.34) and -5.28 (95% CI: -7.22, -3.34) in the overweight and obesity groups, respectively, and the WMDs for verbal IQ were -3.47 (95% CI: -4.38, -2.56) and -5.71 (95% CI: -7.13, -4.29), respectively. However, there was no significant reduction in children’s full-scale intelligence scores due to excessive weight gain; the WMD was -0.14 (95% CI: -0.92, 0.65).Conclusions: Prepregnancy overweight and obesity might have disadvantageous consequences on children’s intelligence; however, we observed no significant difference between excessive and normal gestational weight gain. Therefore, weight control before pregnancy is more important than that during pregnancy in terms of children’s intelligence.Trial registration: This systematic review and meta-analysis have been registered in PROSPERO (Number: CRD42020199215).

While the effects of ambient pollutants on adverse perinatal outcomes have been studied, most studies have focused on preterm birth, stillbirth, and low birthweight. Few studies have examined the effects of ambient pollutants on prelabor rupture of membranes (PROM). This study was designed to explore the acute effects of ambient pollutants on both term PROM (TPROM) and preterm PROM (PPROM). We enrolled pregnant women receiving antenatal care between October 2013 and December 2019 at the International Peace Maternity and Child Health Hospital (IPMCHH). The effects of ambient pollutants (including PM2.5, PM10, SO2, CO, NO2, and 8-h O3) on TPROM and PPROM were estimated using generalized additive models (GAMs). Exposure-response relationship curves were also evaluated using GAMs after adjustment for confounding factors. Potential lagged effects were examined using various lag models. The data of 100,200 pregnant women who delivered at IPMCHH were analyzed. The fitted spline curves for PPROM were similar to the temporal trends of PM2.5, PM10, SO2, CO and NO2 but not O3, while those for TPROM were different from the temporal trends of all six air pollutants. An increased risk of PPROM was associated with increased concentrations of PM2.5, PM10, SO2 and CO on lag days 2 and 3, while no association was found between PPROM and daily concentration of O3. After adjustment for confounding factors, there was a shift in the exposure-response curves, indicating associations between PPROM and PM2.5, PM10, SO2, and CO on lag days 2-3. Interaction effects of PM2.5, PM10, SO2, and CO were also found to increase the risk of PPROM. In conclusion, acute exposures to six critical air pollutants were not associated with an increased risk of TPROM; however, PM2.5, PM10, SO2, and CO were found to interact, increasing the risk for PPROM on lag days 2 and 3.

Maternal supraphysiological estradiol (E2) environment during pregnancy leads to adverse perinatal outcomes. However, the influence of oocyte exposure to high E2 levels on perinatal outcomes remains unknown. Thus, a retrospective cohort study was conducted to explore the effect of high E2 level induced by controlled ovarian stimulation (COH) on further outcomes after frozen embryo transfer (FET). The study included all FET cycles (n = 10,581) between 2014 and 2017. All cycles were categorized into three groups according to the E2 level on the day of the human Chorionic Gonadotropin trigger. Odds ratios (ORs) and their confidence intervals (CIs) were calculated to evaluate the association between E2 level during COH and pregnancy outcomes and subsequent neonatal outcomes. From our findings, higher E2 level was associated with lower percentage of chemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth as well as increased frequency of early miscarriage. Preterm births were more common among singletons in women with higher E2 level during COH (aOR1 = 1.93, 95% CI: 1.22–3.06; aOR2 = 2.05, 95% CI: 1.33–3.06). Incidence of small for gestational age (SGA) was more common in both singletons (aOR1 = 2.01, 95% CI: 1.30–3.11; aOR2 = 2.51, 95% CI: 1.69–3.74) and multiples (aOR1 = 1.58, 95% CI: 1.03–2.45; aOR2 = 1.99, 95% CI: 1.05–3.84) among women with relatively higher E2 level. No association was found between high E2 level during COH and the percentage of macrosomia or large for gestational age. In summary, oocyte exposure to high E2 level during COH should be brought to our attention, since the pregnancy rate decreasing and the risk of preterm birth and SGA increasing following FET.

Ying Zhu,1,2,* Xiang-Yu Wang,1,2,* Yu Zhang,1,2,* Da Xu,1,2,* Jian Dong,3,4 Ze Zhang,1,2 Chen-He Yi,1,2 Hu-Liang Jia,1,2 Xin Yang1,2 1Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China; 2Institutes of Cancer Metastasis, Fudan University, Shanghai 200040, China; 3Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710061, China; 4Institute of Advanced Surgical Technology and Engineering, First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710061, China *These authors contributed equally to this work Background: Agents targeting the programmed death ligand 1 (PD-L1)/programmed death receptor 1 immune checkpoint exhibited promising clinical outcomes in a variety of malignant tumors, including intrahepatic cholangiocarcinoma (ICC). However, the relationship between PD-L1 expression and CD8+ T-cell immune responses is not well defined in ICC.Patients and methods: We investigated PD-L1 expression immunohistochemistry in formalin-fixed, paraffin-embedded tissues from 192 ICC patients undergoing curative resection and correlated our results with the clinicopathologic features and prognosis. We also quantified CD8+ T-cell infiltration in ICC specimens and evaluated the relationship between PD-L1 expression and CD8+ T-cell infiltration. After incubating human ICC cell lines (HCCC9810 and RBE) with interferon (IFN)-γ, we measured thePD-L1 expression of these ICC cells by Western blot and flow cytometry.Results: Only 34 patients (17.7%) showed ≥5% membranous PD-L1 expression on tumor cells, and tumoral PD-L1 overexpression (≥5%) was significantly associated with superior overall survival (P=0.012) and disease-free survival (P=0.018). A significant positive association was found between PD-L1 expression and the presence of CD8+ T-cells. In fresh frozen ICC specimens, IFN-γ was found to be significantly correlated with PD-L1 and CD8A gene expression, as evaluated by reverse transcription-polymerase chain reaction. Moreover, stimulation of the HCCC9810 and RBE cells with recombinant IFN-γ, secreted by CD8+ T-cells rapidly induced PD-L1 upregulation in these cell lines in vitro.Conclusion: Tumor PD-L1 overexpression is mainly stimulated by activated CD8+ T-cells pre-existing in the ICC microenvironment, and PD-L1 is a favorable prognostic factor for the patients. These observations suggest that anti-PD-L1/programmed death receptor 1 therapy may benefit ICC patients with tumor cell PD-L1 expression and the presence of CD8+ T-cells. Keywords: tumor microenvironment, adaptive immune resistance, PD-L1, CD8+ T-cell, IFN-&gamma