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Background: Little is known about the long-term risks of stroke and ischemic heart disease (IHD) in women who had a hysterectomy alone (HA) or with bilateral oophorectomy (HBO) for benign diseases, particularly in China where the burden of cardiovascular diseases (CVD) is high. We assessed mean levels of cardiovascular risk factors and relative risks of stroke and IHD in Chinese women who had a HA or HBO. Methods: A total of 302 510 women, aged 30 to 79 years were enrolled in the China Kadoorie Biobank from 2004 to 2008 and followed up for a mean of 9.8 years. The analysis involved premenopausal women without prior cardiovascular disease or cancer at enrollment. We calculated adjusted hazard ratios for incident cases of CVD and their pathological types (ischemic stroke, hemorrhagic stroke, and IHD) after HA and HBO. Analyses were stratified by age and region and adjusted for levels of education, household income, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, diabetes, self-reported health, and number of pregnancies. Results: Among 282 722 eligible women, 8478 had HA, and 1360 had HBO. Women who had HA had 9% higher risk of CVD after HA (hazard ratio, 1.09 [95% CI, 1.06–1.12]) and 19% higher risk of CVD after HBO (1.19 [95% CI, 1.12–1.26]) compared with women who did not. Both HA and HBO were associated with higher risks of ischemic stroke and IHD but not with hemorrhagic stroke. The relative risks of CVD associated with HA and HBO were more extreme at younger age of surgery. Conclusions: Women who had either HA or HBO have higher risks of ischemic stroke and IHD, and these risks should be evaluated when discussing these interventions. Additional screening for risk factors for CVD should be considered in women following HA and HBO operations, especially if such operations are performed at younger age.

This study aimed to describe the characteristics and lifestyle differences of spicy food consumption in 0.5 million adults. Participants were recruited from 2004 to 2008 in the baseline research of the CKB study. Higher frequency and stronger pungency degree in spicy food positively correlated with preference for salty taste, eating snacks/deep-fried foods, tea/alcohol drinking and tobacco smoking. Among weekly tea/alcohol drinkers and current regular smokers, participants with a higher frequency of spicy food consumption or preference for stronger pungency degree were more likely to prefer strong tea, drink alcohol exceed the healthy amount, drink alcohol in the morning every day, smoke ≥ 40 cigarettes per day, consume a larger amount of tea leaves, alcohol and cigarettes each day, and start habitual tea/alcohol drinking or smoking at an earlier age. Differences existed in lifestyle factors related to major chronic diseases according to spicy food consumption frequency and pungency degree among the Chinese population.

Background Timing of frozen embryo transfer (FET) in natural endometrial preparation cycles is often based on luteinizing hormone (LH) surge. However, some patients do not show spontaneous LH surge despite follicular maturation. The objective of this study was to evaluate the impact of spontaneous LH surge on pregnancy outcomes in modified natural cycles (mNC). Methods This retrospective analysis included 1897 FET cycles with modified natural endometrial preparation in normo-ovulatory women between January 1, 2015, to December 31, 2019, at our center: 920 cycles with spontaneous LH surge (≥ 20 IU/L) and 977 without. For cleavage embryos, FET was conducted 4 and 5 days after hCG injection in women with and without LH surge, respectively. For blastocysts, FET was conducted 6 and 7 days after hCG injection in women with and without LH surge, respectively. Multivariate regression was conducted to examine the factors associated with live birth. Results Live birth rate was 43.7% in patients with spontaneous LH surge vs. 43.8% in women without LH surge (P = 0.961). The two groups also had similar implantation rate (36.2% vs. 36.7%, P = 0.772), biochemical pregnancy rate (54.8% vs. 55.4%, P = 0.796) and clinical pregnancy rate (50.9% vs. 51.7%, P = 0.721). In multivariate regression, live birth was not associated with LH surge (aOR, 0.947, 95% CI, 0.769, 1.166). Conclusion Pregnancy outcomes were similar in mNC-FET in cycles with vs. without spontaneous LH surge if FET timing is adjusted.

Background Endometriosis, the presence of active endometrial tissue outside the lining membrane of the uterine cavity, is a common disease in women of childbearing age. The ectopic endometrium has some characteristics of tumor tissue, including invasive and migratory abilities. In addition, endometriosis is associated with inflammation and reduced cellular apoptosis. Methods Western blot analysis, qPCR, immunohistochemistry, immunofluorescence microscopy, Transwell assay, wound healing assay, and TUNEL staining. Results Interleukin-1β (IL-1β) induced WEE1 expression in endometrial stromal cells (ESCs), suggesting that WEE1 may be upregulated during the endometriosis-induced inflammatory response. Overexpression of WEE1 in cultured ESCs promoted ESC migration while inhibiting apoptosis, whereas WEE1 knockdown reduced ESC migration while promoting apoptosis. Inhibition of WEE1 attenuates fibrosis in ESCs and female C57BL/6 J mice. This pro-fibrotic effect of WEE1 was significantly decreased by treatment with the Wnt/β-catenin inhibitor XAV939, suggesting that WEE1 acts via the Wnt/β-catenin signaling pathway. Conclusion Our study demonstrates that WEE1 promotes ESC migration and fibrosis via the Wnt/β-catenin signaling pathway. Thus, WEE1 may serve as a potential therapeutic target for the treatment of endometriosis.

Background: Oral progestin has been used to prevent premature ovulation during follicle stimulation protocols performed in combination with a freeze-only strategy. However, no studies have determined how oral progestin clinically compares to gonadotropin-releasing hormone (GnRH) antagonists in women with normal ovulation. This study aimed to compare the efficacy and safety of controlled ovarian stimulation between progestin-primed ovarian stimulation (PPOS) protocol and GnRH antagonist (GnRH-ant) protocol.Methods: Young women with infertility and normal ovarian reserve who underwent in vitro fertilisation (IVF) treatments were screened and randomly allocated to the PPOS or GnRH-ant group. Women in the PPOS group underwent freeze-all and delayed embryo transfer, whilst fresh embryo transfer was preferred for those in the GnRH-ant group. The primary endpoint was the cumulative live birth rate (CLBR). Secondary endpoints included the incidence of premature luteinising hormone (LH) surge and the number of viable embryos.Results: CLBRs were similar in the PPOS and GnRH-ant group (55.75% vs. 52.87%, respectively, P > 0.05). No premature LH surge was observed during ovarian stimulation in the PPOS group, although six (3.45%) cases were observed in the GnRH-ant group. On the trigger day, LH level was lower in the PPOS group than in the GnRH-ant group (2.30 ± 1.78 mIU/ml vs. 3.66 ± 3.52 mIU/ml, P < 0.01). There were no differences in the number of retrieved oocytes, mature oocytes, or viable embryos between the two groups. Other clinical outcomes including implantation rates (37.27% vs. 36.77%), clinical pregnancy rates (55.75% vs. 55.89%), and miscarriage rates (12.28% vs. 13.76%) were comparable between the PPOS group and GnRH-ant group (P > 0.05). There was also no significant differences in newborn weights for singleton or twin births between the two groups (P > 0.05).Conclusion: Live birth outcomes are similar for PPOS and GnRH antagonist protocols in women with normal ovarian reserve. PPOS is likely to play a promising role in the freeze-only strategy given its simplicity and convenience for the patient. Trial registration: This trial was registered in the China Clinical Trial Registry on September 6, 2018 (number: ChiCTR1800018246).

BACKGROUND: Chromodomain helicase DNA-binding protein 7 (CHD7), which is associated with CHARGE (Coloboma, Heart defect, Atresia choanae, Restricted growth, Genital hypoplasia and Ear abnormality) syndrome is an important regulator in many vital developmental processes. However, its role during oocyte development remains unknown. METHODS: We screened the Gene Expression Omnibus (GEO) database for expression levels of CHD7 during folliculogenesis. We generated a conditional knockout (cKO) mouse strain with oocyte-specific deletion of CHD7 (Gdf9-Cre:Chd7(f/f)) using the Cre-loxP approach. Evaluation of follicle numbers and reproductive ability was then conducted. In addition, granulosa cell (GC) apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and cleaved caspase-3, using immunohistochemistry (IHC) and immunofluorescence (IF). GC proliferation was measured by Ki67 staining as evaluated by IHC. RESULTS: In our study, we demonstrated that CHD7 has high expression throughout all developmental stages of the oocyte. We found that deletion of Chd7 in oocytes can cause infertility or sub-fertility in female mice and is associated with decreased follicle numbers at all stages. In addition, we found that GC apoptosis was significantly higher in cKO mice. CONCLUSIONS: To our knowledge, our study has been the first to show that CHD7 plays a specific role during oogenesis. Our findings provide new insights into CHD7-related infertility.

Dopamine (DA) protected by an o-nitrobenzyl functionality on its phenolic group was synthesized as a photolabile catecholamine derivative. This compound, o-nitrobenzyl dopamine (NBDA), was more stable than DA in basic solution at pH 8.5 and will not self-polymerize when protected from light. UV irradiation of a methanolic solution of NBDA at 365 nm for 40 min induced ca. 85% deprotection. Taking advantage of the stability of NBDA, a one-pot spray coating technique for modifying surfaces with polydopamine (PDA) was developed. Using ethylene glycol with Tris buffer (pH 8.5) as the solvent for this technique, stainless steel substrates can be coated with a robust PDA layer. Silver was deposited on the PDA-coated surface after treatment with silver nitrate solution, and >80% of the deposited silver remained on the surface after 1 week immersion in water. The NBDA-Ag surface was highly effective in inhibiting Staphylococcus aureus (S. aureus) biofilm formation.

Surface charge and wettability, the two prominent physical factors governing protein adsorption and cell adhesion, have been extensively investigated in the literature. However, a comparison between these driving forces in terms of their independent and cooperative effects in affecting adhesion is rarely explored on a systematic and quantitative level. Herein, we formulate a protocol that features two-dimensional control over both surface charge and wettability with limited cross-parameter influence. This strategy is implemented by controlling both the polyion charge density in the layer-by-layer (LbL) assembly process and the polyion side-chain chemical structures. The 2D property matrix spans surface isoelectric points ranging from 5 to 9 and water contact angles from 35 to 70°, with other interferential factors (e.g., roughness) eliminated. The interplay between these two surface variables influences protein (bovine serum albumin, lysozyme) adsorption and 3T3 fibroblast cell adhesion. For proteins, we observe the presence of thresholds for surface wettability and electrostatic driving forces necessary to affect adhesion. Beyond these thresholds, the individual effects of electrostatic forces and wettability are observed. For fibroblast, both surface charge and wettability have an effect on its adhesion. The combined effects of positive charge and hydrophilicity lead to the highest cell adhesion, whereas negative charge and hydrophobicity lead to the lowest cell adhesion. Our design strategy can potentially form the basis for studying the distinct behaviors of electrostatic force or wettability driven interfacial phenomena and serve as a reference in future studies assessing protein adsorption and cell adhesion to surfaces with known charge and wettability within the property range studied here.