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Objective: To analyse the relationship between the preoperative systemic immune-inflammation index (SII) and the relapse-free survival (RFS) of paediatric patients with Wilms' tumour (WT) after radical surgery, and to establish and validate a prognostic survival model., Study Design: Observational study. Place and Duration of the Study: Department of Oncologic Surgery, Anhui Children's Hospital of Fudan University, Hefei, China, from January 2013 to August 2023., Methodology: A retrospective analysis was conducted on 79 WT patients treated with radical resection, with their preoperative SII values computed. The best cut-off for SII was determined through the ROC curve, categorising patients into high and low SII groups. The Kaplan-Meier method and Cox-regression were used for survival analysis. A survival prognostic model was constructed and its predictive capability gauged (AUC of the ROC)., Results: The study included 79 WT patients with a median RFS of 65 months and an average of 75.5 ± 3.4 months. The optimal cut-off value for SII was 534.95. The low SII group had a higher RFS (Log-rank: χ2 = 9.380, p = 0.002). Preoperative SII (HR = 3.277, 95% CI: 1.167 - 9.200, p = 0.024), clinical staging (HR = 8.408, 95% CI: 2.604 - 27.147, p <0.001), and tissue differentiation (HR = 2.237, 95% CI: 1.043 - 5.828, p = 0.039) were independent risk factors for RFS. The model's diagnostic performance was 0.749 (95% CI: 0.636 - 0.861). Internal validation showed an AUC of 0.723 (95% CI: 0.608 - 0.838)., Conclusion: Lower preoperative SII suggests a more favourable prognosis. The SII-based nomogram efficiently forecasts post-radical surgery prognosis for WT., Key Words: Wilms' Tumour, Systemic immune-inflammation index, Relapse-free survival, Nomogram.

Background: Numerous recent studies have explored the association between metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of various extrahepatic cancers. However, the conclusions were inconclusive. The aim of this study was to clarify this relationship by conducting a robust meta-analysis., Methods: Systematic searches were conducted on PubMed, Embase and Web of Science databases to identify relevant cohort studies published prior to February 2024. Hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) were combined using a random-effects model in this meta-analysis., Results: Eighteen cohort studies (approximately 16.7 million participants) were finally included in this meta-analysis. MASLD was linked to a higher risk of extrahepatic cancers, such as gastric (n = 10, HR = 1.47, 95% CI: 1.07-2.01), colorectal (n = 13, HR = 1.33, 95% CI: 1.16-1.53), pancreatic (n = 8, HR = 1.41, 95% CI: 1.11-1.79), biliary tract (n = 5, HR = 1.27, 95% CI: 1.18-1.37), thyroid (n = 6, HR = 1.46, 95% CI: 1.02-2.09), urinary system (n = 10, HR = 1.45, 95% CI: 1.25-1.69), breast (n = 11, HR = 1.17, 95% CI: 1.08-1.26) and female genital organ cancers (n = 10, HR = 1.36, 95% CI: 1.11-1.66). However, there was no statistically significant association between MASLD and the risk of head and neck (n = 6, HR = 1.03, 95% CI: 99-1.07), oesophageal (n = 9, HR = 1.26, 95% CI: 0.86-1.86), lung (n = 9, HR = 1.01, 95% CI: 0.92-1.10), prostate (n = 9, HR = 1.06, 95% CI: 0.94-1.19) or small intestine cancer (n = 2, HR = 1.75, 95% CI: 1.00-3.06)., Conclusions: This latest large-scale meta-analysis indicated that MASLD was associated with an increased risk of various extrahepatic cancers, such as gastric, colorectal, pancreatic, biliary duct, thyroid, urinary system, breast, skin and female genital cancers. Further research is needed to investigate the mechanisms underlying these associations., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

The regulatory mechanism of the transcription factor GATA3 in the differentiation and maturation process of extravillous trophoblasts (EVT) in early pregnancy placenta, as well as its relevance to the occurrence of pregnancy disorders, remains poorly understood. This study leveraged single-cell RNA sequencing data from placental organoid models and placental tissue to explore the dynamic changes in GATA3 expression during EVT maturation. The expression pattern exhibited an initial upregulation followed by subsequent downregulation, with aberrant GATA3 localization observed in cases of recurrent miscarriage (RM). By identifying global targets regulated by GATA3 in primary placental EVT cells, JEG3, and HTR8/SVneo cell lines, this study offered insights into its regulatory mechanisms across different EVT cell models. Shared regulatory targets among these cell types and activation of trophoblast cell marker genes emphasized the importance of GATA3 in EVT differentiation and maturation. Knockdown of GATA3 in JEG3 cells led to repression of GATA3-induced epithelial-mesenchymal transition (EMT), as evidenced by changes in marker gene expression levels and enhanced migration ability. Additionally, interference with GATA3 accelerated cellular senescence, as indicated by reduced proliferation rates and increased activity levels for senescence-associated β-galactosidase enzyme, along with elevated expression levels for senescence-associated genes. This study provides comprehensive insights into the dual role of GATA3 in regulating EMT and cellular senescence during EVT differentiation, shedding light on the dynamic changes in GATA3 expression in normal and pathological placental conditions., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Maternal lipid metabolism has been implicated in elevating the risk of adverse pregnancy outcomes, which is a particularly significant concern in twin pregnancies. However, the precise relationship between early pregnancy dyslipidemia and the risk of preterm birth (PTB) in twin pregnancies remains unclear., Methods: This retrospective cohort study included women with twin pregnancies between January 2018 and December 2023. Early pregnancy blood lipid profiles, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), were examined. Dyslipidemia was diagnosed based on the diagnostic criteria outlined in the 2016 guidelines for the prevention and treatment of dyslipidemia in Chinese adults. PTB was defined as birth occurring before 37 weeks of pregnancy. Logistic regression models were used to evaluate the association of early pregnancy dyslipidemia with PTB in twin pregnancies., Results: A total of 613 women with twin pregnancies were included, and 141 women were complicated with dyslipidemia. The incidence of PTB < 37 weeks was significantly higher in the dyslipidemia group compared to the group without dyslipidemia (64.5% vs. 50.4%, P = 0.003). After adjusting for confounding factors, dyslipidemia was positively associated with PTB < 37 weeks (adjusted odds ratio: 1.71; 95% confidence interval: 1.13-2.58). However, these associations varied depending on the chorionicity and mode of conception of the twins. The positive associations between early pregnancy dyslipidemia and PTB < 37 weeks remained significant only in spontaneously conceived (SC) or dichorionic diamniotic (DCDA) twin pregnancies. No statistically significant associations were observed between dyslipidemia and the other secondary outcomes., Conclusion: Early pregnancy dyslipidemia was positively associated with PTB < 37 weeks in twin pregnancies, and this association remained significant in SC or DCDA twin pregnancies. Comprehensive lipid profile assessment in the first trimester may be beneficial for patients' monitoring and implementing interventions to mitigate adverse pregnancy outcomes., (© 2024. The Author(s).)

Background: The syncytiotrophoblast (SCT) layer in the placenta serves as a crucial physical barrier separating maternal-fetal circulation, facilitating essential signal and substance exchange between the mother and fetus. Any abnormalities in its formation or function can result in various maternal syndromes, such as preeclampsia. The transition of proliferative villous cytotrophoblasts (VCT) from the mitotic cell cycle to the G0 phase is a prerequisite for VCT differentiation and their fusion into SCT. The imprinting gene P57 Kip2 , specifically expressed in intermediate VCT capable of fusion, plays a pivotal role in driving this key event. Moreover, aberrant expression of P57 Kip2 has been linked to pathological placental conditions and adverse fetal outcomes., Methods: Validation of STK40 interaction with P57 Kip2 using rigid molecular simulation docking and co-immunoprecipitation. STK40 expression was modulated by lentivirus in BeWo cells, and the effect of STK40 on trophoblast fusion was assessed by real-time quantitative PCR, western blot, immunofluorescence, and cell viability and proliferation assays. Co-immunoprecipitation, transcriptome sequencing, and western blot were used to determine the potential mechanisms by which STK40 regulates P57 Kip2 ., Results: In this study, STK40 has been identified as a novel interacting protein with P57 Kip2 , and its expression is down-regulated during the fusion process of trophoblast cells. Overexpressing STK40 inhibited cell fusion in BeWo cells while stimulating mitotic cell cycle activity. Further experiments indicated that this effect is attributed to its specific binding to the CDK-binding and the Cyclin-binding domains of P57 Kip2 , mediating the E3 ubiquitin ligase COP1-mediated ubiquitination and degradation of P57 Kip2 . Moreover, abnormally high expression of STK40 might significantly contribute to the occurrence of preeclampsia., Conclusions: This study offers new insights into the role of STK40 in regulating the protein-level homeostasis of P57 Kip2 during placental development., (© 2024. The Author(s).)

Study Question: Does exposure to a mixture of ambient air pollutants during specific exposure periods influence clinical pregnancy rates in women undergoing IVF/ICSI-embryo transfer (ET) cycles?, Summary Answer: The specific exposure period from ET to the serum hCG test was identified as a critical exposure window as exposure to sulfur dioxide (SO 2 ) or a combination of air pollutants was associated with a decreased likelihood of clinical pregnancy., What Is Known Already: Exposure to a single pollutant may impact pregnancy outcomes in women undergoing ART. However, in daily life, individuals often encounter mixed pollution, and limited research exists on the effects of mixed air pollutants and the specific exposure periods., Study Design Size Duration: This retrospective cohort study involved infertile patients who underwent their initial IVF/ICSI-ET cycle at an assisted reproduction center between January 2020 and January 2023. Exclusions were applied for patients meeting specific criteria, such as no fresh ET, incomplete clinical and address information, residency outside the 17 cities in the Sichuan Basin, age over 45 years, use of donor semen, thin endometrium (<8 mm) and infertility factors unrelated to tubal or ovulation issues. In total, 5208 individuals were included in the study., Participants/materials Setting Methods: Daily average levels of six air pollutants (fine particulate matter (PM 2.5 ), inhalable particulate matter (PM 10 ), SO 2 , nitrogen dioxide (NO 2 ), carbon monoxide (CO), and ozone (O 3 )) were acquired from air quality monitoring stations. The cumulative average levels of various pollutants were determined using the inverse distance weighting (IDW) method across four distinct exposure periods (Period 1: 90 days before oocyte retrieval; Period 2: oocyte retrieval to ET; Period 3: ET to serum hCG test; Period 4: 90 days before oocyte retrieval to serum hCG test). Single-pollutant logistic regression, two-pollutant logistic regression, Quantile g-computation (QG-C) regression, and Bayesian kernel machine regression (BKMR) were employed to evaluate the influence of pollutants on clinical pregnancy rates. Stratified analyses were executed to discern potentially vulnerable populations., Main Results and the Role of Chance: The clinical pregnancy rate for participants during the study period was 54.53%. Single-pollutant logistic models indicated that for PM 2.5 during specific exposure Period 1 (adjusted odds ratio [aOR] = 0.83, 95% CI: 0.70-0.99) and specific exposure Period 4 (aOR = 0.83, 95% CI: 0.69-0.98), and SO 2 in specific exposure Period 3 (aOR = 0.92, 95% CI: 0.86-0.99), each interquartile range (IQR) increment exhibited an association with a decreased probability of clinical pregnancy. Consistent results were observed with dual air pollution models. In the multi-pollution analysis, QG-C indicated a 12% reduction in clinical pregnancy rates per IQR increment of mixed pollutants during specific exposure Period 3 (aOR = 0.89, 95% CI: 0.79-0.99). Among these pollutants, SO 2 (33.40%) and NO 2 (33.40%) contributed the most to the negative effects. The results from BKMR and QG-C were consistent. Stratified analysis revealed increased susceptibility to ambient air pollution among individuals who underwent transfer of two embryos, those with BMI ≥ 24 kg/m 2 and those under 35 years old., Limitations Reasons for Caution: Caution was advised in interpreting the results due to the retrospective nature of the study, which was prone to selection bias from non-random sampling. Smoking and alcohol, known confounding factors in IVF/ICSI-ET, were not accounted for. Only successful cycles that reached the hCG test were included, excluding a few patients who did not reach the ET stage. While IDW was used to estimate pollutant concentrations at residential addresses, data on participants' work locations and activity patterns were not collected, potentially affecting the accuracy of exposure prediction., Wider Implications of the Findings: Exposure to a mixture of pollutants, spanning from ET to the serum hCG test (Period 3), appeared to be correlated with a diminished probability of achieving clinical pregnancy. This association suggested a potential impact of mixed pollutants on the interaction between embryos and the endometrium, as well as embryo implantation during this critical stage, potentially contributing to clinical pregnancy failure. This underscored the importance of providing women undergoing ART with comprehensive information to comprehend the potential environmental influences and motivating them to adopt suitable protective measures when feasible, thereby mitigating potential adverse effects of contaminants on reproductive health., Study Funding/competing Interests: This work received support from the National Key Research and Development Program of China (No. 2023YFC2705900), the National Natural Science Foundation of China (Nos. 82171664, 81971391, 82171668), the Natural Science Foundation of Chongqing Municipality of China (Nos. CSTB2022NSCQ-LZX0062, CSTB2023TIAD-KPX0052) and the Foundation of State Key Laboratory of Ultrasound in Medicine and Engineering (No. 2021KFKT013). The authors report no conflicts of interest., Trial Registration Number: N/A., Competing Interests: The authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Objective: The purpose of this study is to investigate the role of high mobility group protein B1 (HMGB1) in placental development and fetal growth., Methods: We employed the Cre-loxP recombination system to establish a placenta-specific HMGB1 knockout mouse model. Breeding HMGB1flox/flox mice with Elf5-Cre mice facilitated the knockout, leveraging Elf5 expression in extra-embryonic ectoderm, ectoplacental cone, and trophoblast giant cells at 12.5 days of embryonic development. The primary goal of this model was to elucidate the molecular mechanism of HMGB1 in placental development, assessing parameters such as placental weight, fetal weight, and bone development. Additionally, we utilized lentiviral interference and overexpression of HMGB1 in human trophoblast cells to further investigate HMGB1's functional role., Results: Our findings indicate that the HMGB1flox/floxElf5cre/+ mouse displays fetal growth restriction, characterized by decreased placental and fetal weight and impaired bone development. The absence of HMGB1 inhibits autophagosome formation, impairs lysosomal degradation, and disrupts autophagic flux. Depletion of HMGB1 in human trophoblast cells also suppresses cell viability, proliferation, migration, and invasion by inhibiting the ERK signaling pathway. Overexpression of HMGB1 observed the opposite phenotypes., Conclusions: HMGB1 participates in the regulation of autophagy through the ERK signaling pathway and affects placental development., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The etiology of preeclampsia (PE), a complex and multifactorial condition, remains incompletely understood. DNA methylation, which is primarily regulated by three DNA methyltransferases (DNMTs), DNMT1, DNMT3A, and DNMT3B, plays a vital role in early embryonic development and trophectoderm differentiation. Yet, how DNMTs modulate trophoblast fusion and PE development remains unclear. In this study, we found that the DNMTs expression was downregulated during trophoblast cells fusion. Downregulation of DNMTs was observed during the reconstruction of the denuded syncytiotrophoblast (STB) layer of placental explants. Additionally, overexpression of DNMTs inhibited trophoblast fusion. Conversely, treatment with the DNA methylation inhibitor 5-aza-CdR decreased the expression of DNMTs and promoted trophoblast fusion. A combined analysis of DNA methylation data and gene transcriptome data obtained from the primary cytotrophoblasts (CTBs) fusion process identified 104 potential methylation-regulated differentially expressed genes (MeDEGs) with upregulated expression due to DNA demethylation, including CD59, TNFAIP3, SDC1, and CDK6. The transcription regulation region (TRR) of TNFAIP3 showed a hypomethylation with induction of 5-aza-CdR, which facilitated CREB recruitment and thereby participated in regulating trophoblast fusion. More importantly, clinical correlation analysis of PE showed that the abnormal increase in DNMTs may be involved in the development of PE. This study identified placental DNA methylation-regulated genes that may contribute to PE, offering a novel perspective on the role of epigenetics in trophoblast fusion and its implication in PE development., (© 2024 Federation of American Societies for Experimental Biology.)

Objective: To explore the optimal models for predicting the formation of high-quality embryos in Poor Ovarian Response (POR) Patients with Progestin-Primed Ovarian Stimulation (PPOS) using machine learning algorithms., Methods: A retrospective analysis was conducted on the clinical data of 4,216 POR cycles who underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) at Sichuan Jinxin Xinan Women and Children's Hospital from January 2015 to December 2021. Based on the presence of high-quality cleavage embryos 72 h post-fertilization, the samples were divided into the high-quality cleavage embryo group (N = 1950) and the non-high-quality cleavage embryo group (N = 2266). Additionally, based on whether high-quality blastocysts were observed following full blastocyst culture, the samples were categorized into the high-quality blastocyst group (N = 124) and the non-high-quality blastocyst group (N = 1800). The factors influencing the formation of high-quality embryos were analyzed using logistic regression. The predictive models based on machine learning methods were constructed and evaluated accordingly., Results: Differential analysis revealed that there are statistically significant differences in 14 factors between high-quality and non-high-quality cleavage embryos. Logistic regression analysis identified 14 factors as influential in forming high-quality cleavage embryos. In models excluding three variables (retrieved oocytes, MII oocytes, and 2PN fertilized oocytes), the XGBoost model performed slightly better (AUC = 0.672, 95% CI = 0.636-0.708). Conversely, in models including these three variables, the Random Forest model exhibited the best performance (AUC = 0.788, 95% CI = 0.759-0.818). In the analysis of high-quality blastocysts, significant differences were found in 17 factors. Logistic regression analysis indicated that 13 factors influence the formation of high-quality blastocysts. Including these variables in the predictive model, the XGBoost model showed the highest performance (AUC = 0.813, 95% CI = 0.741-0.884)., Conclusion: We developed a predictive model for the formation of high-quality embryos using machine learning methods for patients with POR undergoing treatment with the PPOS protocol. This model can help infertility patients better understand the likelihood of forming high-quality embryos following treatment and help clinicians better understand and predict treatment outcomes, thus facilitating more targeted and effective interventions., (© 2024. The Author(s).)

Background: In the realm of assisted reproduction, a subset of infertile patients demonstrates high ovarian response following controlled ovarian stimulation (COS), with approximately 29.7% facing the risk of Ovarian Hyperstimulation Syndrome (OHSS). Management of OHSS risk often necessitates embryo transfer cancellation, leading to delayed prospects of successful pregnancy and significant psychological distress. Regrettably, these patients have received limited research attention, particularly regarding their metabolic profile. In this study, we aim to utilize gas chromatography-mass spectrometry (GC-MS) to reveal these patients' unique serum metabolic profiles and provide insights into the disease's pathogenesis., Methods: We categorized 145 infertile women into two main groups: the CON infertility group from tubal infertility patients and the Polycystic Ovary Syndrome (PCOS) infertility group. Within these groups, we further subdivided them into four categories: patients with normal ovarian response (CON-NOR group), patients with high ovarian response and at risk for OHSS (CON-HOR group) within the CON group, as well as patients with normal ovarian response (PCOS-NOR group) and patients with high ovarian response and at risk for OHSS (PCOS-HOR group) within the PCOS group. Serum metabolic profiles were analyzed using GC-MS. The risk criteria for OHSS were: the number of developing follicles > 20, peak Estradiol (E2) > 4000pg/mL, and Anti-Müllerian Hormone (AMH) levels > 4.5ng/mL., Results: The serum metabolomics analysis revealed four different metabolites within the CON group and 14 within the PCOS group. Remarkably, 10-pentadecenoic acid emerged as a discernible risk metabolite for the CON-HOR, also found to be a differential metabolite between CON-NOR and PCOS groups. cysteine and 5-methoxytryptamine were also identified as risk metabolites for the PCOS-HOR. Furthermore, KEGG analysis unveiled significant enrichment of the aminoacyl-tRNA biosynthesis pathway among the metabolites differing between PCOS-NOR and PCOS-HOR., Conclusion: Our study highlights significant metabolite differences between patients with normal ovarian response and those with high ovarian response and at risk for OHSS within both the tubal infertility control group and PCOS infertility group. Importantly, we observe metabolic similarities between patients with PCOS and those with a high ovarian response but without PCOS, suggesting potential parallels in their underlying causes., (© 2024. The Author(s).)

Study Question: Can exposure to palmitic acid (PA), a common saturated fatty acid, modulate autophagy in both human and mouse trophoblast cells through the regulation of acyl-coenzyme A-binding protein (ACBP)?, Summary Answer: PA exposure before and during pregnancy impairs placental development through mechanisms involving placental autophagy and ACBP expression., What Is Known Already: High-fat diets, including PA, have been implicated in adverse effects on human placental and fetal development. Despite this recognition, the precise molecular mechanisms underlying these effects are not fully understood., Study Design, Size, Duration: Extravillous trophoblast (EVT) cell line HTR-8/SVneo and human trophoblast stem cell (hTSC)-derived EVT (hTSCs-EVT) were exposed to PA or vehicle control for 24 h. Female wild-type C57BL/6 mice were divided into PA and control groups (n = 10 per group) and subjected to a 12-week dietary intervention. Afterward, they were mated with male wild-type C57BL/6 mice and euthanized on Day 14 of gestation. Female ACBPflox/flox mice were also randomly assigned to control and PA-exposed groups (each with 10 mice), undergoing the same dietary intervention and mating with ACBPflox/floxELF5-Cre male mice, followed by euthanasia on Day 14 of gestation. The study assessed the effects of PA on mouse embryonic development and placental autophagy. Additionally, the role of ACBP in the pathogenesis of PA-induced placental toxicity was investigated., Participants/materials, Setting, Methods: The findings were validated using real-time PCR, Western blot, immunofluorescence, transmission electron microscopy, and shRNA knockdown approaches., Main Results and the Role of Chance: Exposure to PA-upregulated ACBP expression in both human HTR-8/SVneo cells and hTSCs-EVT, as well as in mouse placenta. PA exposure also induced autophagic dysfunction in HTR-8/SVneo cells, hTSCs-EVT, and mouse placenta. Through studies on ACBP placental conditional knockout mice and ACBP knockdown human trophoblast cells, it was revealed that reduced ACBP expression led to trophoblast malfunction and affected the expression of autophagy-related proteins LC3B-II and P62, thereby impacting embryonic development. Conversely, ACBP knockdown partially mitigated PA-induced impairment of placental trophoblast autophagy, observed both in vitro in human trophoblast cells and in vivo in mice., Large Scale Data: N/A., Limitations, Reasons for Caution: Primary EVT cells from early pregnancy are fragile, limiting research use. Maintaining their viability is tough, affecting data reliability. The study lacks depth to explore PA diet cessation effects after 12 weeks. Without follow-up, understanding postdiet impacts on pregnancy stages is incomplete. Placental abnormalities linked to elevated PA diet in embryos lack confirmation due to absence of control groups. Clarifying if issues stem solely from PA exposure is difficult without proper controls., Wider Implications of the Findings: Consuming a high-fat diet before and during pregnancy may result in complications or challenges in successfully carrying the pregnancy to term. It suggests that such dietary habits can have detrimental effects on the health of both the mother and the developing fetus., Study Funding/competing Interest(s): This work was supported in part by the National Natural Science Foundation of China (82171664, 82301909) and the Natural Science Foundation of Chongqing Municipality of China (CSTB2022NS·CQ-LZX0062, cstc2019jcyj-msxmX0749, and cstc2021jcyj-msxmX0236). The authors declare that they have no conflict of interest., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The transformation and implementation of clinical practice guidelines for integrated traditional Chinese medicine (TCM) and Western medicine (WM) is crucial to the adoption of medical science and technological findings and is an important way for TCM to be made available to the world. First, clinical practice guidelines (CPGs) of TCM and WM integration in recent years was analyzed to clarify the current situation and problems in the existing guidelines according to the following four perspectives: (1) perspective of TCM and WM integration in guidelines, (2) diagnosis Using integrated TCM and WM, (3) integration of TCM and WM treatment, (4) promoting TCM and WM integration. Secondly, the information and quality evaluation of CPGs for integrated Chinese and Western medicine in 2020-2022 were analyzed to explore the degree and methods of integration of Chinese and Western medicine guidelines. And last this study aimed to lay a foundation for the further establishment of Chinese characteristic, repeatable, and calculable clinical practice guidelines of TCM and WM integration., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The influence of SARS-CoV-2 infection after embryo transfer on early pregnancy outcomes in in vitro fertilization or intracytoplasmic sperm injection-embryo transfer treatment remains inadequately understood. This knowledge gap endures despite an abundance of studies investigating the repercussions of preceding SARS-CoV-2 infection on early pregnancy outcomes in spontaneous pregnancies., Objective: This study aimed to investigate the association between SARS-CoV-2 infection within 10 weeks after embryo transfer and early pregnancy outcomes in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment., Study Design: This prospective cohort study was conducted at a single public in vitro fertilization center in China. Female patients aged 20 to 39 years, with a body mass index ranging from 18 to 30 kg/m 2 , undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, were enrolled between September 2022 and December 2022, with follow-up extended until March 2023. The study tracked SARS-CoV-2 infection time (≤14 days, ≤28 days, and ≤10 weeks after embryo transfer), symptoms, vaccination status, the interval between vaccination and embryo transfer, and early pregnancy outcomes, encompassing biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate. The study used single-factor analysis and multivariate logistic regression to examine the association between SARS-CoV-2 infection status, along with other relevant factors, and the early pregnancy outcomes., Results: A total of 857 female patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment were analyzed. In the first stage, SARS-CoV-2 infection within 14 days after embryo transfer did not have a significant negative association with the biochemical pregnancy rate (adjusted odds ratio, 0.74; 95% confidence interval, 0.51-1.09). In the second stage, SARS-CoV-2 infection within 28 days after embryo transfer had no significant association with the implantation rate (36.6% in infected vs 44.0% in uninfected group; P=.181). No statistically significant association was found with the clinical pregnancy rate after adjusting for confounding factors (adjusted odds ratio, 0.69; 95% confidence interval, 0.56-1.09). In the third stage, SARS-CoV-2 infection within 10 weeks after embryo transfer had no significant association with the early miscarriage rate (adjusted odds ratio, 0.77; 95% confidence interval, 0.35-1.71)., Conclusion: Our study suggests that SARS-CoV-2 infection within 10 weeks after embryo transfer may not be negatively associated with the biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. It is important to note that these findings are specific to the target population of in vitro fertilization/intracytoplasmic sperm injection patients aged 20 to 39 years, without previous SARS-CoV-2 infection, and with a body mass index of 18 to 30 kg/m 2 . This information offers valuable insights, addressing current concerns and providing a clearer understanding of the actual risk associated with SARS-CoV-2 infection after embryo transfer., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this retrospective study conducted at Sichuan Jinxin Xinan Women and Children's Hospital spanning January 2015 to December 2021, our objective was to investigate the impact of embryo cryopreservation duration on outcomes in frozen embryo transfer. Participants, totaling 47,006 cycles, were classified into 3 groups based on cryopreservation duration: ≤1 year (Group 1), 1 to 6 years (Group 2), and ≥6 years (Group 3). Employing various statistical analyses, including 1-way ANOVA, Kruskal-Wallis test, chi-square test, and a generalized estimating equation model, we rigorously adjusted for confounding factors. Primary outcomes encompassed clinical pregnancy rate and Live Birth Rate (LBR), while secondary outcomes included biochemical pregnancy rate, multiple pregnancy rate, ectopic pregnancy rate, early and late miscarriage rates, preterm birth rate, neonatal birth weight, weeks at birth, and newborn sex. Patient distribution across cryopreservation duration groups was as follows: Group 1 (40,461 cycles), Group 2 (6337 cycles), and Group 3 (208 cycles). Postcontrolling for confounding factors, Group 1 exhibited a decreased likelihood of achieving biochemical pregnancy rate, clinical pregnancy rate, and LBR (OR < 1, aOR < 1, P < .05). Furthermore, an elevated incidence of ectopic pregnancy was observed (OR > 1, aOR > 1), notably significant after 6 years of freezing time [aOR = 4.141, 95% confidence intervals (1.013-16.921), P = .05]. Cryopreservation exceeding 1 year was associated with an increased risk of early miscarriage and preterm birth (OR > 1, aOR > 1). No statistically significant differences were observed in birth weight or sex between groups. However, male infant birth rates were consistently higher than those of female infants across all groups. In conclusion, favorable pregnancy outcomes align with embryo cryopreservation durations within 1 year, while freezing for more than 1 year may diminish clinical pregnancy and LBRs, concurrently elevating the risk of ectopic pregnancy and preterm birth., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Previous observational studies have revealed a potential link between non-alcoholic fatty liver disease (NAFLD) and gestational diabetes mellitus (GDM), but their causal relationship remains unclear. Thus, this study aimed to examine whether a causal link exists between genetically determined NAFLD and GDM., Methods: Utilizing publicly accessible genome-wide association studies (GWAS), a two-sample bidirectional Mendelian randomization (MR) analysis was conducted. The GWASs data pertaining to NAFLD and GDM were obtained from the UK Biobank Consortium and FinnGen database in primary analysis, respectively. The random-effects inverse variance weighted (IVW) method was utilized as primary analysis method. Several sensitivity analyses were utilized to verify the robustness of the results. Additionally, we also analyzed the causal effect of potential shared influencing factors on these two conditions., Results: The result of the IVW method showed that there was no significant causal relationship between genetically determined NAFLD and GDM (OR = 0.98, 95% CI: 0.90-1.07, P = 0.691). Similarly, our reverse MR analysis failed to detect a significant causal effect of GDM on NAFLD (OR = 1.14, 95% CI: 0.97-1.36, P = 0.118). Sensitivity analyses further confirmed the robustness of the results. Moreover, we found that genetically determined body mass index, waist-to-hip ratio, triglycerides, and television viewing time may be positively correlated with NAFLD and GDM, while high-density lipoprotein cholesterol and apolipoprotein A-I may both be negatively correlated with NAFLD and GDM., Conclusions: The current bidirectional MR study failed to provide sufficient genetic evidence for the causal relationship between NAFLD and GDM., (© 2024. The Author(s).)

Objective: The aim of this study was to elucidate the relationship between venous lactate levels and the severity of acute pancreatitis (AP)., Patients and Methods: Retrospective data analysis was conducted on patients diagnosed with acute pancreatitis. The comparative assessment encompassed baseline characteristics, laboratory data, illness severity, local consequences, and organ failure instances. This comparison was performed between patients exhibiting normal serum lactic acid levels (HL) and those displaying elevated HL levels. The association between serum HL levels and other pertinent clinical markers was investigated using linear regression. Logistic regression analysis was employed to evaluate the utility of elevated serum lactate levels in identifying high-risk groups., Results: Significantly elevated serum HL levels were observed in patients with moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) in contrast to those with mild acute pancreatitis (MAP) (p<0.01). Multivariate logistic analysis demonstrated that higher lactate levels independently predicted organ failure (95% CI 0.738-0.902, p<0.05). Receiver operating characteristic (ROC) curve analysis indicated that the lactate (LAC) cut-off value of 2.45 mmol/L yielded sensitivity and specificity values of 76.5% and 79.1%, respectively, for predicting AP-associated organ failure. The corresponding area under the curve (AUC) was 0.820., Conclusions: In AP patients, elevated serum HL levels signify disease severity and hold predictive potential for assessing the risk of organ failure.

Background and Objective: Recently, vonoprazan-amoxicillin (VA) dual therapy has been reported as a promising approach for Helicobacter pylori (H. pylori) eradication. However, the effects of VA therapy versus bismuth-containing quadruple therapy (BQT) on H. pylori eradication remains unclear. The objective of this meta-analysis was to compare the effects of VA dual therapy with BQT for H. pylori eradication., Methods: A comprehensive search of the literature was conducted from the beginning to September 2023, utilizing PubMed, Embase, the Cochrane Library and Web of Science database. A random-effects model was used to perform a meta-analysis to determine the pooled relative risk (RR) with 95% confidence intervals (CIs). Moreover, trial sequential analysis (TSA) was conducted to evaluate the conclusiveness of the H. pylori eradication rate., Results: Six randomized controlled trials (RCTs) with 1233 patients were included. The VA therapy has similar eradication rate (ITT analysis: 87% vs. 85.7%, RR = 1.01, 95% CI: 0.93-1.09, p = 0.84; PP analysis: 92.5% vs. 93.2%, RR = 1.00, 95% CI: 0.94-1.06, p = 0.97) and compliance (RR = 1.01, 95% CI: 0.99-1.03, p = 0.32) compared to BQT. The VA therapy group had a significantly lower incidence of total adverse events than the BQT group (16.3% vs. 40.0%, RR = 0.45, 95% CI: 0.37-0.55, p < 0.00001). The TSA result showed that the effect was conclusive., Conclusions: Current evidence indicated that VA therapy is just as successful as BQT in eliminating H. pylori, yet it has fewer adverse events and similar compliance., (© 2023 John Wiley & Sons Ltd.)

Background: Vonoprazan-amoxicillin (VA) dual therapy has recently been proposed to eradicate Helicobacter pylori (H. pylori) with controversial results. We, therefore, conducted a meta-analysis to assess the effect of this therapy for H. pylori eradication., Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science database from inception until November 2022, collecting randomized controlled trials (RCTs) comparing VA dual therapy with other regimens for H. pylori eradication. Pooled relative risks (RRs) were calculated using random effects model., Results: Five RCTs were ultimately included. Compared with the vonoprazan-amoxicillin-clarithromycin (VAC) triple therapy, the eradication rate of VA dual therapy was lower in intention-to-treat (ITT) analysis (n = 3 RCTs, RR = 0.94, 95% CI: 0.88-0.99, P = 0.03), but there was no significant difference between them in the per-protocol (PP) analysis (RR = 0.96, 95% CI: 0.91-1.01, P = 0.11). For clarithromycin-resistant H. pylori strains, the eradication rate of VA dual therapy was significantly higher than that of the VAC triple therapy (n = 2 RCTs, RR = 1.20, 95% CI: 1.03-1.39, P = 0.02). Compared with the PPI-based triple therapy (PAC), VA dual therapy had a superior eradication rate (n = 2 RCTs, ITT analysis: RR = 1.13, 95% CI: 1.04-1.23, P = 0.003; PP analysis: pooled RR = 1.14, 95% CI: 1.06-1.22, P = 0.0004). Compared with VAC or PAC triple therapy, VA dual therapy has a similar incidence of total adverse events and compliance., Conclusions: VA dual therapy had a similar effect compared to VAC triple therapy and was superior to PAC triple therapy. Future RCTs are needed to ascertain the optimal dosage and duration of vonoprazan and amoxicillin, and the effect of VA dual therapy compared with the mainstream regimens recommended by current guidelines., Competing Interests: None

Purpose: Fetal growth restriction (FGR) is a common complication characterized by impaired placental function and unfavorable pregnancy outcomes. This study aims to elucidate the expression pattern of miR-181d-5p in FGR placentas and explore its effects on trophoblast fusion., Methods: The expression pattern of miR-181d-5p in human FGR placentas were evaluated using qRT-PCR. Western blot, qRT-PCR, and Immunofluorescence analysis were performed in a Forskolin (FSK)-induced BeWo cell fusion model following the transfection of miR-181d-5p mimic or inhibitor. Potential target genes for miR-181d-5p were identified by screening miRNA databases. The interaction between miR-181d-5p and Luman/CREB3 Recruitment Factor (CREBRF) was determined through a luciferase assay. Moreover, the effect of CREBRF on BeWo cell fusion was examined under hypoxic conditions., Results: Aberrant up-regulation of miR-181d-5p and altered expression of trophoblast fusion makers, including glial cell missing 1 (GCM1), Syncytin1 (Syn1), and E-cadherin (ECAD), were found in human FGR placentas. A down-regulation of miR-181d-5p expression was observed in the FSK-induced BeWo cell fusion model. Transfection of the miR-181d-5p mimic resulted in the inhibition of BeWo cell fusion, characterized by a down-regulation of GCM1 and Syn1, accompanied by an up-regulation of ECAD. Conversely, the miR-181d-5p inhibitor promoted BeWo cell fusion. Furthermore, miR-181d-5p exhibited negative regulation of CREBRF, which was significantly down-regulated in the hypoxia-induced BeWo cell model. The overexpression of CREBRF was effectively ameliorated the impaired BeWo cell fusion induced by hypoxia., Conclusions: Our study demonstrated that miR-181d-5p, which is elevated in FGR placenta, inhibited the BeWo cell fusion through negatively regulating the expression of CREBRF., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In Brief: Obese PCOS mice display metabolic and endocrine disorders that manifest as abnormal metabolism of glucose and dysfunctions in the reproductive system. This study demonstrates that emodin alleviates most of these conditions possibly via the HMGB1/TLR4/NF-kB pathway., Abstract: PCOS is a reproductive disorder with an unclear etiology. It affects 5-10% of women worldwide and is largely associated with impaired glucose metabolism and obesity. HMGB1 is a nuclear protein associated with impaired glucose metabolism and PCOS. We sought to investigate the potential therapeutic effects of emodin on glucose metabolism and ovarian functions in PCOS mice via the HMGB1 molecular pathway. A high-fat diet (HFD) and dehydroepiandrosterone (DHEA)- induced PCOS mouse model comprising four experimental groups was established: control, PCOS, PCOS plus emodin, and PCOS plus vehicle groups. Emodin administration attenuated obesity, elevated fasting glucose levels, impaired glucose tolerance, and insulin resistance, and improved the polycystic ovarian morphology of PCOS mice. Additionally, it lowered elevated serum HMGB1, LH, and testosterone levels in PCOS mice. Elevated ovarian protein and mRNA levels of HMGB1 and TLR4 in PCOS mice were also lowered following emodin treatment. Furthermore, emodin lowered high NF-ĸB/65 protein levels in the ovaries of PCOS mice. Immunohistochemical staining of the ovaries revealed strong HMGB1, TLR4, and AR expressions in PCOS mice, which were lowered by emodin treatment. Moreover, emodin significantly increased GLUT4, IRS2, and INSR levels that were lowered by PCOS. Overall, our study showed that emodin alleviated the impaired glucose metabolism and improved ovarian function in PCOS mice, possibly via the HMGB1/TLR4/NF-ĸB signaling pathway. Thus, emodin could be considered a potential therapeutic agent in the management of PCOS.

Introduction: Obesity has detrimental influences on women reproductive health. There is little experience in optimizing controlled ovarian hyperstimulation (COH) protocols to treat Chinese obese patients who are undergoing in vitro fertilization and embryo transfer (IVF-ET) therapy., Methods: The clinical outcome differences were retrospectively analyzed among obese patients who received gonadotrophin-releasing hormone agonist (GnRH-a), GnRH antagonist (GnRH-ant), micro dose GnRH-a (mGnRH-a) and GnRH-a long protocol in IVF-ET cycle at Chengdu Jinjiang Hospital for Women's and Children's Health from January 2014 to December 2019., Results: The transplantation rate of the GnRH-a long protocol group (59.1%) was higher than that of the GnRH-ant (25.9%) and mGnRH-a (36.7%) groups. The total live birth rate of the GnRH-a long protocol group (46.2%) was higher than that of the GnRH-a group (25.9%) and GnRH-ant group (40.3%). The total number of frozen embryos in the GnRH-ant group was higher than in the other groups ( P  < 0.05). After adjusting for confounding factors, the logistic regression analysis showed that the GnRH-a long protocol group had higher probabilities of biochemical pregnancy, clinical pregnancy, and live birth than the GnRH-a protocol group. The Gn dose in the mGnRH-a group was higher than the other three groups. Whether single or twin, there were similar neonatal outcomes among the four groups including premature birth rate, Apgar score, newborn weight, and length., Conclusion: For young obese patients undergoing IVF-ET, the GnRH-a long protocol for COH gives better pregnancy outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Network Meta-analysis was employed to compare the efficacy of Chinese medicine injections for activating blood and resolving stasis combined with conventional western medicine in the treatment of acute ischemic stroke and the effects on platelet aggregation rate, fibrinogen(FIB), and hypersensitive C-reactive protein(hs-CRP), with a view to providing evidence-based medicine reference for clinical medication. CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, Cochrane Library, and EMbase were searched for randomized controlled trial(RCT) on the treatment of acute ischemic stroke with Salvia Miltiorrhiza Ligustrazine Injection, Danhong Injection, Shuxuetong Injection, Xueshuantong Injection, Shuxuening Injection, Safflower Yellow Pigment Injection, and Ginkgo Diterpene Lactone Meglumine Injection combined with conventional western medicine. The retrieval time was from database inception to March 18, 2023. The articles were extracted by two researchers and their quality was evaluated. R 4.2.2 was used for network Meta-analysis. A total of 87 RCTs involving 8 580 patients were included. Network Meta-analysis showed that, in terms of reducing National Institutes of Health stroke scale(NIHSS) scores, the surface under the cumulative ranking curve(SUCRA) showed the order of Xueshuantong Injection + conventional western medicine(88.7%) &gt; Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(73.7%) &gt; Shuxuetong Injection + conventional western medicine(69.7%) &gt; Shuxuening Injection + conventional western medicine(51.8%) &gt; Danhong Injection + conventional western medicine(43.7%) &gt; Safflower Yellow Pigment Injection + conventional western medicine(36.8%) &gt; Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(35.3%) &gt; conventional western medicine(1.7%). In terms of improving clinical total effective rate, SUCRA showed the order of Danhong Injection + conventional western medicine(63.0%) &gt; Shuxuening Injection + conventional western medicine(59.0%) &gt; Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(58.9%) &gt; Safflower Yellow Pigment Injection + conventional western medicine(57.1%) &gt; Xueshuantong Injection + conventional western medicine(56.8%) &gt; Shuxuetong Injection + conventional western medicine(54.6%) &gt; Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(50.5%) &gt; conventional western medicine(0.03%). In terms of improving Barthel index, SUCRA showed the order of Danhong Injection + conventional western medicine(84.7%) &gt; Shuxuetong Injection + conventional western medicine(72.4%) &gt; Safflower Yellow Pigment Injection + conventional western medicine(61.6%) &gt; Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(44.6%) &gt; Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(43.2%) &gt; Shuxuening Injection + conventional western medicine(42.2%) &gt; conventional western medicine(1.4%). In terms of reducing platelet aggregation rate, SUCRA showed the order of Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(82.4%) &gt; Shuxuetong Injection + conventional western medicine(81.6%) &gt; Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(40.7%) &gt; Danhong Injection + conventional western medicine(37.3%) &gt; conventional western medicine(8.0%). In terms of reducing FIB, SUCRA showed the order of Danhong Injection + conventional western medicine(81.0%) &gt; Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(71.9%) &gt; Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(70.0%) &gt; Shuxuetong Injection + conventional western medicine(46.7%) &gt; Xueshuantong Injection + conventional western medicine(22.6%) &gt; conventional western medicine(8.7%). In terms of reducing hs-CRP, SUCRA showed the order of Shuxuening Injection + conventional western medicine(89.9%) &gt; Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(78.8%) &gt; Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(52.4%) &gt; Danhong Injection + conventional western medicine(47.6%) &gt; Xueshuantong Injection + conventional western medicine(43.5%) &gt; Shuxuetong Injection + conventional Western medicine(35.6%) &gt; conventional western medicine(2.3%). The results indicated that Xueshuantong Injection + conventional western medicine, Danhong Injection + conventional western medicine, and Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine ranked the top three. Xueshuantong Injection + conventional western medicine had the best effect on reducing NIHSS scores. Danhong Injection + conventional western medicine showed the best performance of improving clinical total effective rate, improving Barthel index, and reducing FIB in the blood. Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine had the best effect on reducing platelet aggregation rate in the blood. Shuxuening Injection + conventional western medicine had the best effect on reducing hs-CRP. However, more high-quality RCTs are needed for verification in the future to provide more reliable evidence-based medical reference.

The aim of this study was to determine the impact of glycyrrhizin, an inhibitor of high mobility group box 1, on glucose metabolic disorders and ovarian dysfunction in mice with polycystic ovary syndrome. We generated a polycystic ovary syndrome mouse model by using dehydroepiandrosterone plus high-fat diet. Glycyrrhizin (100 mg/kg) was intraperitoneally injected into the polycystic ovary syndrome mice and the effects on body weight, glucose tolerance, insulin sensitivity, estrous cycle, hormone profiles, ovarian pathology, glucolipid metabolism, and some molecular mechanisms were investigated. Increased number of cystic follicles, hormonal disorders, impaired glucose tolerance, and decreased insulin sensitivity in the polycystic ovary syndrome mice were reverted by glycyrrhizin. The increased high mobility group box 1 levels in the serum and ovarian tissues of the polycystic ovary syndrome mice were also reduced by glycyrrhizin. Furthermore, increased expressions of toll-like receptor 9, myeloid differentiation factor 88, and nuclear factor kappa B as well as reduced expressions of insulin receptor, phosphorylated protein kinase B, and glucose transporter type 4 were restored by glycyrrhizin in the polycystic ovary syndrome mice. Glycyrrhizin could suppress the polycystic ovary syndrome-induced upregulation of high mobility group box 1, several inflammatory marker genes, and the toll-like receptor 9/myeloid differentiation factor 88/nuclear factor kappa B pathways, while inhibiting the insulin receptor/phosphorylated protein kinase B/glucose transporter type 4 pathways. Hence, glycyrrhizin is a promising therapeutic agent against polycystic ovary syndrome., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objective: Numerous observational studies have been conducted to investigate the potential association between inflammatory bowel disease (IBD) and prostate cancer (PCa). However, a definitive conclusion has yet to be established. We therefore performed a meta-analysis to explore the relationship between these two conditions., Methods: PubMed, Embase, and Web of Science databases were systematically searched to identify all relevant cohort studies that investigated the association between IBD and risk of incident PCa published from inception to February 2023. The pooled hazard ratios (HRs) with 95% confidence intervals (CI) was calculated as effect size for the outcome based on random-effects model meta-analysis., Results: A total of 18 cohort studies with 592,853 participants were included. The meta-analysis revealed that IBD was linked to an elevated risk of incident PCa (HR = 1.20, 95% CI: 1.06-1.37, P = 0.004). Further subgroup analyses revealed that ulcerative colitis (UC) was linked to an increased risk of incident PCa (HR = 1.20, 95% CI: 1.06-1.38, P = 0.006), while Crohn's disease (CD) is not significantly associated with a higher risk of PCa (HR = 1.03, 95% CI: 0.91-1.17, P = 0.65). There was a significant correlation between IBD and an elevated risk of incident PCa in the European population, but such a correlation was not observed in the Asian and North American populations. Sensitivity analyses indicated that our results were robust., Conclusions: Our latest evidence indicates that IBD was linked to an elevated risk of incident PCa, especially in UC patients and the European population., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The wide application of silicon dioxide nanoparticles (SiO 2 NPs) has raised concerns about their harmful effects on reproduction. The purpose of this research was to investigate the toxic effects and the possible mechanisms by which SiO 2 NPs affect decidualization and pregnancy progression. We found that SiO 2 NPs could inhibit decidualization, both in mice and in human endometrial stromal cells (HESCs). Embryo resorption was also evident in mice treated with SiO 2 NPs. When HESCs were treated with SiO 2 NPs, decidualization was inhibited and there was an increase in intracellular lysosomes and autophagosomes as well as the blockage of autophagic flux. Interestingly, a reduction of autophagosome accumulation via 3-methyladenine (3MA) significantly restored the decidualization of HESCs. In summary, our results indicate that SiO 2 NPs can affect embryo survival by impairing decidualization through a dysfunctional autophagic process., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Objectives: Recent observational studies have investigated the association between Helicobacter pylori ( H. pylori ) infection and pancreatic cancer with conflicting data. Therefore, we conducted a systematic review and meta-analysis to assess the potential association., Design: This is a systematic review and meta-analysis., Methods: We searched three databases (PubMed, Embase, and Web of Science) from inception to 30 August 2022. The summary results as odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were pooled by generic inverse variance method based on random-effects model., Results: A total of 20 observational studies involving 67,718 participants were included in the meta-analysis. Meta-analysis of data from 12 case-control studies and 5 nested case-control studies showed that there was no significant association between H. pylori infection and the risk of pancreatic cancer (OR = 1.20, 95% CI = 0.95-1.51, p  = 0.13). Similarly, we also did not find significant association between cytotoxin-associated gene A (CagA) positive strains, CagA negative strains, vacuolating cytotoxin gene A (VacA) positive strains H. pylori infection, and the risk of pancreatic cancer. Meta-analysis of data from three cohort studies showed that H. pylori infection was not significantly associated with an increased risk of incident pancreatic cancer (HR = 1.26, 95% CI = 0.65-2.42, p  = 0.50)., Conclusion: We found insufficient evidence to support the proposed association between H. pylori infection and increased risk of pancreatic cancer. To better understand any association, future evidence from large, well-designed, high-quality prospective cohort studies that accounts for diverse ethnic populations, certain H. pylori strains, and confounding factors would be useful to settle this controversy., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Background: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism, ovarian dysfunction and polycystic ovarian morphology. Gut microbiota dysbiosis and metabolite are associated with PCOS clinical parameters. Yulin Tong Bu formula (YLTB), a traditional Chinese medicine formula, has been recently indicated to be capable of ameliorating polycystic ovary symptoms and correcting abnormal glucose metabolism. However, the therapeutic mechanism of YLTB on PCOS has not been fully elucidated., Methods: A pseudo sterile mouse model was established during this four-day acclimatization phase by giving the animals an antibiotic cocktail to remove the gut microbiota. Here, the therapeutic effects of YLTB on PCOS were investigated using dehydroepiandrosterone plus high-fat diet-induced PCOS mice model. Female prepuberal mice were randomly divided into three groups; namely, the control group, PCOS group and YLTB (38.68 g·kg -1 ·day -1 ) group. To test whether this effect is associated with the gut microbiota, we performed 16S rRNA sequencing studies to analyze the fecal microbiota of mice. The relationships among metabolites, gut microbiota, and PCOS phenotypes were further explored by using Spearman correlation analysis. Then, the effect of metabolite ferulic acid was then validated in PCOS mice., Results: Our results showed that YLTB treatment ameliorated PCOS features (ovarian dysfunction, delayed glucose clearance, decreased insulin sensitivity, deregulation of glucolipid metabolism and hormones, etc.) and significantly attenuated PCOS gut microbiota dysbiosis. Spearman correlation analysis showed that metabolites such as ferulic acid and folic acid are negatively correlated with PCOS clinical parameters. The effect of ferulic acid was similar to that of YLTB. In addition, the bacterial species such as Bacteroides dorei and Bacteroides fragilis were found to be positively related to PCOS clinical parameters, using the association study analysis., Conclusion: These results suggest that YLTB treatment systematically regulates the interaction between the gut microbiota and the associated metabolites to ameliorate PCOS, providing a solid theoretical basis for further validation of YLTB effect on human PCOS trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Su, Wang, Yang, Wu, Xia, Bao, Ding, Feng and Fu.)

Introduction: The aim of our study is to explore the value of serum glycosylated hemoglobin A1c (HbA1c) in disease severity and clinical outcomes of acute pancreatitis (AP)., Research Design and Methods: Patients with AP were included from January 2013 to December 2020, retrospectively, dividing into normal serum HbA1c level (N-HbA1c) group and high serum HbA1c level (H-HbA1c) group according to the criteria HbA1c <6.5%. We compared patient characteristics, biochemical parameters, disease severity, and clinical outcomes of patients with AP in two groups. Besides, we evaluated the efficacy of serum HbA1c to predict organ failure (OF) in AP patients by receiver operating curve (ROC)., Results: We included 441 patients with AP, including 247 patients in N-HbA1c group and 194 patients in H-HbA1c group. Serum HbA1c level was positively correlated with Atlanta classification, systemic inflammatory response syndrome, local complication, and OF (all p<0.05). Ranson, BISAP (bedside index of severity in acute pancreatitis), and CT severity index scores in patients with H-HbA1c were markedly higher than those in patients with N-HbA1c (all p<0.01). ROC showed that the best critical point for predicting the development of OF in AP with serum HbA1c is 7.05% (area under the ROC curve=0.79). Logistic regression analysis showed H-HbA1c was the independent risk factor for the development of OF in AP. Interestingly, in patients with presence history of diabetes and HbA1c <6.5%, the severity of AP was significantly lower than that in H-HbA1c group. Besides, there was no significant difference between with and without history of diabetes in N-HbA1c group., Conclusions: Generally known, diabetes is closely related to the development of AP, and strict control of blood glucose can improve the related complications. Thus, the level of glycemic control before the onset of AP (HbA1c as an indicator) is the key to poor prognosis of AP, rather than basic history of diabetes. Elevated serum HbA1c level can become the potential indicator for predicting the disease severity of AP., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The management of patients with poor ovarian response (POR) remains a major challenge for fertility specialists in in vitro fertilization-embryo transfer (IVF-ET). In this retrospective cohort study, we aimed to evaluate the clinical effect of sequential transfer on pregnancy outcomes in patients with POR. A total of 3579 POR patients who underwent the first frozen embryo transfer (FET) cycle were enrolled from January 2018 to April 2021. The patients were divided into three groups according to the embryo transfer (ET) strategy adopted: a study group that included POR patients in whom a cleavage-stage embryo (day 3) and a blastocyst (day 5/6) were transferred (sequential transfer group), and two control groups in whom two cleavage-stage embryos (D3-dET group) or two blastocysts (D5/6-dET group) were transferred. The study group was matched with the control groups at a ratio of 1:4 by propensity score matching (PSM). The main pregnancy outcomes measured were the live birth rate and multiple pregnancy rate. After PSM, the live birth rate in the sequential transfer group was significantly higher than that in the D3-dET group (44.2% vs. 34.3%, P = 0.019), and was similar to that in the D5/6-dET group (44.2% vs. 45.3%; P = 0.90). In addition, there was no increase in the risk of multiple pregnancy among POR patients undergoing sequential transfer compared with both D3-dET (26.7% vs. 25.6%, P = 0.85) and D5/6-dET (26.7% vs. 28.4%, P = 0.97) groups. These findings imply that sequential transfer is an effective option for POR patients and could be utilized after careful consideration., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Objective: Recently, a large number of trials on proton pump inhibitor-amoxicillin-containing high-dose dual therapy (HDDT) versus bismuth-containing quadruple therapy (BQT) for Helicobacter pylori ( H. pylori ) eradication have been published with controversial and inconsistent conclusions. The aim of this meta-analysis was to determine the effects of HDDT for H. pylori eradication compared to BQT., Design: A systematic review and meta-analysis was conducted., Methods: PubMed, Embase, and the Cochrane library database were searched to collect all randomized controlled trials (RCTs) assessing the effects of HDDT versus BQT to H. pylori eradication from inception to September 2022. Meta-analysis was conducted to estimate the pooled relative risk (RR) with 95% confidence intervals (CIs) using a random-effects model. Quality of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluation system. Trial sequential analysis (TSA) was performed to determine the reliability and conclusiveness., Results: A total of 14 RCTs with 5121 patients were included. The results of meta-analysis showed that there was no statistical significance in the eradication rate between HDDT and BQT (intention-to-treat analysis: 86.7% versus 85.1%, RR = 1.01, 95% CI: 0.98-1.04; per-protocol analysis: 89.9% versus 89.4%, RR = 1.01, 95% CI: 0.98-1.03; moderate-quality evidence). The incidence of total adverse effects in HDDT group was significantly lower than in BQT group (5.9% versus 34.1%, RR = 0.42, 95% CI: 0.34-0.50; low-quality evidence). No statistical significance was observed in compliance between HDDT and BQT (RR = 1.01, 95% CI, 1.00-1.03, p  = 0.07; low-quality evidence). The TSA result for H. pylori eradication rate indicated that the effect was conclusive., Conclusions: Evidence from our updated meta-analysis suggests that HDDT is as effective as BQT in eradicating H. pylori , with fewer adverse effects and similar compliance., Registration: Open Science Framework registries (No: osf.io/th4vd)., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Objectives: Resuscitation transfer of embryos after elective cryopreservation has been widely applied in in vitro fertilization-embryo transfer (IVF-ET) therapy for human infertility or sterility owing to higher embryo implantation rates. This method separates oocyte retrieval from embryo transfer. The optimal time for frozen embryo transfer (FET) remains unknown. Therefore, this study mainly compares the advantages and disadvantages of delayed FET and immediate FET through retrospective analysis., Methods: We analyzed real world data of patients who underwent resuscitation transplantation between October 2019 and July 2021 at the Reproductive Center of Chengdu Jinjiang Hospital for Women's and Children's Health. Propensity score matching was applied to control potential confounding factors. A total of 5,549 patients who received at least one FET were analyzed. Patients undergoing transplantation within 60 days of oocyte retrieval were included in the immediate FET group ( n = 1,265) and those undergoing transplantation > 60 days after retrieval were included in the delayed FET group ( n = 4,284)., Results: Live birth rates between the two groups were comparable (45.25% vs. 45.76%, p = 0.757). Moreover, no difference was observed in the rates of biochemical pregnancy (64.50% vs. 66.80%), clinical pregnancy (55.24% vs. 56.83%), ectopic pregnancy (1.47% vs. 1.39%), early miscarriage (14.41% vs. 16.20%), late miscarriage (2.21% vs. 2.09%), singleton premature delivery (16.67% vs. 18.29%), and neonatal deformity (1.97% vs. 1.80%). After stratifying the patients based on the type of embryo transferred, number of embryos transferred, FET protocol, and good prognosis criteria, live birth rates remained comparable between the two groups ( p > 0.05)., Conclusion: Pregnancy outcomes were comparable between the immediate and delayed FET groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wan, Chen, Wang, Tan, Yu, Lv, Zhong, Tang, Ding, Xia and Li.)

Objective: To compare the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle outcomes between patients with low and normal serum luteinizing hormone (LH) levels on the day after a gonadotropin-releasing hormone agonist (GnRH-a) single trigger. We further investigated the efficacy of human chorionic gonadotropin (hCG) retrigger on IVF cycle outcomes in patients with low LH levels after GnRH-a single trigger., Methods: We retrospectively analyzed 957 infertile patients (tubal factor, ovulation disorders, male sperm factor, or unexplained infertility) who were treated with IVF/ICSI at the Chengdu Xinan Gynecology Hospital from July 2017 to December 2020. Patients received sufficient GnRH-a single trigger were divided into two groups based on the serum LH levels on the next day of trigger: normal serum LH levels (≥ 10 mIU/mL) group (control group, n = 906) and low LH levels (< 10 mIU/mL) group (experimental group, n = 51). And the efficacy of hCG retrigger on IVF/ICSI cycle outcomes in 10 patients with low LH levels after GnRH-a single trigger., Results: There were no significant differences in IVF/ICSI cycle outcomes, including egg yield, two pronuclei fertilization rate, excellent embryo rate, or live birth rate of frozen-thawed embryos between patients with low and normal LH levels after GnRH-a trigger. It showed significantly higher risk of ovarian hyperstimulation syndrome in the group of low LH levels [ 0.7%(1/137) vs. 8.5%(4/47), P = 0.016] compared with the group of normal LH levels who received GnRH-a single trigger. The hCG retrigger had no obvious efficacy on cycle outcomes in patients with low LH levels, including oocytes retrieved, fertilization rate, embryo conditions, and live birth rate of frozen-thawed cycles., Conclusion: The IVF/ICSI cycle outcomes of patients with low LH levels on the day after GnRH-a administration were similar to those of patients with normal LH levels. Blood LH test might not be required on the day following the trigger. The hCG retrigger did not have any effect on the cycle outcomes, suggesting that immediate retriggering with hCG was unnecessary., (© 2022. The Author(s).)

Background: Serum ferritin (SF), as an acute-phase response protein, is used to reflect the degree of oxidative stress and systemic inflammatory responses. This study was designed to assess the effect of elevated SF levels on the severity of acute pancreatitis (AP)., Methods: From January 2013 to December 2020, 200 consecutive patients with AP were retrospectively reviewed to analyze the relationships among the etiologies of pancreatitis, the severity of the disease and SF levels. The receiver operating characteristic (ROC) curve and logistic regression analysis were used to assess whether elevated SF levels could predict the onset of organ failure in AP., Results: 92 (46%) had high SF levels (> 275 ng/ml). SF levels were not associated with the etiology of AP disease. Among patients with high SF levels, there was a significant increase in the proportion of patients with severe AP (23.1% vs. 76.9%) and a higher proportion of systemic inflammatory response scores (25.9% vs. 44.6%) in comparison to patients with normal SF levels. The area under the ROC curve for SF in predicting persistent organ failure was 0.812 [95% confidence interval 0.721-0.904]., Conclusions: F concentrations were positively correlated with the severity of AP, and quantitative assessment of SF can predict disease severity and organ failure in patients with AP., (© 2022. The Author(s).)

Objective: To explore the effects of hydroxyacyl-CoA dehydrogenase alpha subunit (HADHA) on the migration and invasion of HTR-8/SVneo cells, a human trophoblast cell line, and its potential mechanism of action., Methods: Immunofluorescence staining was done to evaluate the expression levels of HADHA in samples of normal villi and recurrent spontaneous abortion (RSA) villi at 6-8 weeks. Lentiviral infection system was used to construct stable HTR-8/SVneo cell lines with HADHA overexpression and knockdown. Western blot, qRT-PCR, Wound-healing assay, and Transwell assay were used to determine the effect of HADHA on the migration and invasion of HTR-8/SVneo cells and the expression of relevant genes. Transcriptome sequencing and bioinformatics analysis were done to screen for the potential target genes and signaling pathways regulated by HADHA. The specific molecular mechanism of how HADHA regulates the migration and invasion of HTR-8/SVneo cells was examined by adding the inhibitor of protein kinase B (PKB/AKT)., Results: HADHA was highly expressed in extravillous trophoblasts (EVT) of RSA villus samples as compared with samples from the normal control group. In HTR-8/SVneo cells overexpressing HADHA , the expression levels of migration and invasion-related genes, including HLA - G , MMP 2, MMP 9, and NCAD , were decreased ( P <0.01, P <0.05), and the migration and invasion abilities of HTR-8/SVneo cells were weakened ( P <0.05). HADHA knockdown increased the expression levels of HLA - G , MMP 2, MMP 9, and NCAD ( P <0.01, P <0.05), and promoted the migration and invasion of HTR-8/SVneo cells ( P <0.05). In addition, HADHA overexpression decreased the phosphorylation levels of PI3K and AKT ( P <0.05) and inhibited the PI3K/AKT signaling pathway. HADHA knockdown activated the PI3K/AKT signaling pathway. When MK-2206, an AKT inhibitor, was added to stable HTR-8/SVneo cell lines with HADHA knockdown, the migration and invasion of the cells were significantly reduced., Conclusion: HADHA inhibits the migration and invasion of HTR-8/SVneo cells by inhibiting the PI3K/AKT signaling pathway., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Background: The GnRH agonist long-acting protocol and GnRH antagonist protocol are widely used in ovarian stimulation. Which protocol eliciting higher live birth rate for IVF/ICSI patients with different ages, different ovarian reserves and different body mass index (BMI) has not been studied. However, among these protocols, the one that elicits higher live birth in IVF/ICSI patients with different ages, ovarian reserves and body mass indexes (BMI) has not been identified., Methods: This was a retrospective cohort study about 8579 women who underwent the first IVF-ET from January, 2018 to August, 2021. Propensity Score Matching (PSM) was used to improve the comparability between two protocols., Results: After PSM, significant higher live birth rates were found in the GnRH agonist long-acting protocol compared to GnRH antagonist protocol (44.04% vs. 38.32%) (p<0.001). Stratified analysis showed that for those with AMH levels between 3 ng/ml and 6 ng/ml, with BMI ≥ 24 kg/m 2 and were aged ≥ 30 years old, and for those women with BMI < 24kg/m 2 and were aged ≥30 years whose AMH levels were ≤ 3ng/ml, the GnRH agonist long-acting protocol was more likely to elicit live births [OR (95%CI), 2.13(1.19,3.80)], [OR (95%CI), 1.41(1.05,1.91)]. However, among women with BMI ≥ 24kg/m 2 and were aged ≥30 years whose AMH levels were ≤ 3ng/ml, the GnRH agonist long-acting protocol had a lower possibility of eliciting live births [OR (95%CI), 0.54(0.32,0.90)]. Also, among women with AMH levels between 3 ng/ml and 6 ng/ml, with BMI ≥ 24 kg/m 2 and with age < 30 years and for those with AMH levels between 3 ng/ml and 6 ng/ml, regardless of age, and with BMI<24kg/m2,, the possibility of live births was similar between the two protocols [OR (95%CI), 1.06(0.60,1.89)], [OR (95%CI), 1.38(0.97,1.97)], [OR (95%CI), 0.99(0.72,1.37)]. Among the women with AMH levels ≤ 3 ng/ml and with were aged < 30years, regardless of BMI, the possibility of live birth was similar between the two protocols [OR (95%CI), 1.02(0.68,1.54)], [OR (95%CI), 1.43(0.68,2.98)]. Moreover, among women with AMH levels ≥ 6ng/ml, the possibility of live birth was similar between the two protocols [OR (95%CI),1.42(0.75,2.69)], [OR (95%CI),1.02(0.19,5.35)], [OR (95%CI), 1.68(0.81,3.51)], [OR (95%CI), 0.51(0.10,2.55)]., Conclusions: The suitability of the GnRH agonist long-acting protocol or GnRH antagonist protocol to infertility patients is dependent on specific biological characteristics of the patients., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2022 Chen, Meng, Zhong, Tang, Li, Feng, Adu-Gyamfi, Jia, Lv, Geng, Zhu, He, Wan and Ding.)

Purpose: The aim of this study was to investigate whether 11q loss of heterozygosity (LOH) aberration would impact the response of the primary tumor to neoadjuvant chemotherapy or to the degree of surgical resection in neuroblastoma (NB) patients with MYCN amplification., Methods: The clinical data of 42 NB patients with MYCN amplification who were newly diagnosed and received treatments at our hospital from 2011 to 2020 were retrospectively analyzed. According to the results of the segmental chromosome aberration analysis, the patients enrolled were assigned to an 11qLOH positive group and an 11qLOH negative group., Results: There was no significant difference in the mean number of chemotherapy courses completed before surgery between the 11qLOH positive and 11qLOH negative groups ( p = 0.242). Each of the 42 patients had metaiodobenzylguanidine (MIBG) scans both before and after neoadjuvant chemotherapy. The percentage of patients who had a clinical MIBG change in the 11qLOH positive group was lower than the percentage in the 11qLOH negative group (27.27 vs. 66.67%, p = 0.030). The 11qLOH negative group seemed to have a higher rate of surgical resection (≥90%); however, the difference between the two groups was not statistically significant ( p = 0.088). Furthermore, the 11qLOH negative group did not show significantly superior event-free survival and overall survival rates compared with the 11qLOH positive group., Conclusions: This study showed that patients with NB and MYCN amplification in combination with 11qLOH might be less likely to respond to neoadjuvant chemotherapy when compared with patients with NB and MYCN amplification without 11qLOH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lu, Qu, Duan, Zuo, Sai, Rui, Gong, Ding and Gao.)

Background: Although coronavirus disease 2019 (COVID-19) is considered to be a disease that mainly involves the respiratory system, an increasing number of studies have reported that COVID-19 patients had pancreatic enzymes (PE) elevation and even pancreatic injury. The study aims to determine the prevalence of PE elevation, and the relationship between elevated PE and prognosis in COVID-19 patients., Methods: A comprehensive literature search was conducted according to the PRISMA guideline in PubMed, Embase, Scopus, Web of Science, and Google Scholar for studies reporting PE elevation in patients with COVID-19 from 1st January 2020 to 24th November 2021., Results: A total of 13 studies (24,353 participants) were included in our review. The pooled prevalence of PE elevation in COVID-19 patients was 24% (18%-31%), the pooled odds ratio (OR) of mortality was 2.5 (1.7-3.6), the pooled OR of ICU admission was 4.4 (2.8-6.8), and the pooled OR of kidney injury, respiratory failure and liver injury were 3.5 (1.6-7.4), 2.0 (0.5-8.7), and 2.3 (1.4-3.9) respectively. In addition, the subgroup analysis revealed that although PE elevated to > 3 × upper normal limit (ULN) was significantly related to the mortality (OR = 4.4, 2.1-9.4), it seemed that mild elevation of PE to 1-3 ULN also had a considerable risk of mortality (OR = 2.3, 1.5-3.5)., Conclusions: PE elevation was a common phenomenon in patients with COVID-19, and was associated with poor clinical outcomes. However, due to the limited numbers of included studies, the result of our study still needed to be validated., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display&#95;record.php?RecordID=295630, identifier: CRD42021295630., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Ge, Yang, Cai, Ding, Hu and Lu.)

Human cytotrophoblast (CTB) differentiation into syncytiotrophoblast (STB) is essential for placental formation and function. Understanding the molecular mechanisms involved in trophoblast differentiation is necessary as it would help in the development of novel therapeutic agents to treat placentation-mediated pregnancy complications. In this study, we found a common upregulated gene, ADAM-like Decysin-1 (ADAMDEC1), from five published microarray and RNA-sequencing datasets. Interference to ADAMDEC1 impaired forskolin-induced BeWo cells differentiation, while ADAMDEC1 overexpression promoted BeWo cells and 3D JEG-3 spheroids differentiation. Interestingly, ADAMDEC1 may inhibit Thrombospondin 1 rather than E-cadherin to trigger the activation of the cAMP signal pathway during CTB differentiation into STB. More importantly, a decreasing in ADAMDEC1 might be involved in the development of preeclampsia. Therefore, ADAMDEC1 is expected to become a new target for prediction of and intervention in placenta-derived pregnancy diseases., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Problem: Natural killer (NK) cells from the peripheral blood and spleen represent the source from which various tissues replenish their immune cell populations. Hyperandrogenism and high interleukin-2 (IL-2) levels are factors present in polycystic ovary syndrome (PCOS). These factors and metformin, one of the commonest medications used in treating PCOS, may have an impact on NK cells. However, this is presently unknown. Here, we aimed to assess the distribution of peripheral blood and splenic NK cells and their CD2 and CD94 expression patterns in a PCOS mouse model and test whether metformin could reverse these effects., Method of Study: Four mouse groups were designed as follows (n = 15/group): control, PCOS, PCOS plus vehicle, PCOS plus metformin. Dehydroepiandrosterone and a high-fat diet were administered to induce the PCOS mouse model. Flow cytometry was used to analyze the expressions of CD2 and CD94 on peripheral blood and splenic NK cells., Results: PCOS mice had a low surface-density of CD2 on peripheral blood NK cells and a decreased percentage of CD2+ splenic NK cells. Metformin administration did not significantly influence these changes; however, it reduced the splenic NK cell counts., Conclusions: Our findings proved the association of PCOS with an altered expression of CD2 on peripheral blood and splenic NK cells and that of metformin with a lowered splenic NK cell reserve in PCOS conditions. These findings could further unlock key mechanisms in PCOS pathophysiology and in the mechanism of action of metformin, towards improving PCOS management., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Decidualization of uterine stromal cells plays an important role in the establishment of normal pregnancy. Previous studies have demonstrated that Acyl-CoA binding protein (Acbp) is critical to cellular proliferation, differentiation, mitochondrial functions, and autophagy. The characterization and physiological function of Acbp during decidualization remain largely unknown. In the present study, we conducted the expression profile of Acbp in the endometrium of early pregnant mice. With the occurrence of decidualization, the expression of Acbp gradually increased. Similarly, Acbp expression was also strongly expressed in decidualized cells following artificial decidualization, both in vivo and in vitro. We applied the mice pseudopregnancy model to reveal that the expression of Acbp in the endometrium of early pregnant mice was not induced by embryonic signaling. Moreover, P4 significantly upregulated the expression of Acbp, whereas E2 appeared to have no regulating effect on Acbp expression in uterine stromal cells. Concurrently, we found that interfering with Acbp attenuated decidualization, and that might due to mitochondrial dysfunctions and the inhibition of fatty acid oxidation. The level of autophagy was increased after knocking down Acbp. During induced decidualization, the expression of ACBP was decreased with the treatment of rapamycin (an autophagy inducer), while increased with the addition of Chloroquine (an autophagy inhibitor). Our work suggests that Acbp plays an essential role in the proliferation and differentiation of stromal cells during decidualization through regulating mitochondrial functions, fatty acid oxidation, and autophagy.

Background: In frozen embryo transfer (FET), there is limited consensus on the best means of endometrial preparation in terms of the reproductive outcomes in women with polycystic ovary syndrome (PCOS). The present study aimed to compare the pregnancy and neonatal outcomes following artificial cycle FET (AC-FET) with or without gonadotropin-releasing hormone agonist (GnRH-a) pretreatment among women with PCOS., Methods: A total of 4503 FET cycles that satisfied the inclusion criteria were enrolled in this retrospective cohort study between 2015 and 2020. The GnRH-a group received GnRH-a pretreatment while the AC-FET group did not. Propensity score matching (PSM) method and multivariate logistic regression analysis were performed to adjust for potential confounding factors., Results: After PSM, women in the GnRH-a group suffered a significantly lower miscarriage rate (11.2% vs. 17.1%, P = 0.033) and a higher live birth rate (LBR) compared with those in the AC-FET group (63.1% vs. 56.8%, P = 0.043). No differences were observed in the rates of biochemical pregnancy, clinical pregnancy and ectopic pregnancy between the two groups. A higher mean gestational age at birth was observed in the GnRH-a group than in the AC-FET group (39.80 ± 2.01 vs. 38.17 ± 2.13, P = 0.009). The incidence of neonatal preterm birth (PTB) in the GnRH-a group was lower than that in the AC-FET group (7.4% vs. 14.9%, P = 0.009). Singleton newborns conceived after GnRH-a group were more likely to be small for gestational age (SGA) than those born after AC-FET group (16.4% vs. 6.8%, P = 0.009). However, no significant differences were found between the two groups in terms of mean birthweight, apgar score, the rates of macrosomia, large for gestational age and low birth weight., Conclusion(s): In women with PCOS who underwent AC-FET, GnRH-a pretreatment was significantly associated with a higher live birth rate and a reduced risk of neonatal PTB. However, there was a concomitant increase in the risk of developing SGA babies., (© 2022. The Author(s).)

Background: Childhood asthma has substantial effects on children's health. It is important to identify influencing factors in early life in the development of childhood asthma. We aim to evaluate the effects of early-life factors and indoor environmental exposure on childhood asthma in Chongqing, China., Method: We designed a case-control study to enrol children with asthma aged 3 to < 14 years old and controls in Chongqing, China. The "Children's Early Life and Indoor Environment Survey" was used to collect the early-life factors and indoor environmental exposure of foetuses in utero and of infants during the first 3 years of life. A multivariate logistic regression model was used to evaluate the association between independent variables and childhood asthma and the interaction of early-life factors and environmental exposure., Results: A total of 160 asthma cases and 247 controls were included in this study. The mean ages of the cases and controls were 5.53 ± 1.88 and 5.72 ± 2.34 years, respectively (P = 0.192). Early-life factors and indoor environmental exposure were independently associated with childhood asthma. Infectious diseases of the respiratory system in children under 3 years old [adjusted odds ratio (OR) = 5.76, 95% confidence interval (CI) 2.49-13.30], bedroom air conditioner use (adjusted OR = 4.61, 95% CI 1.45-14.64), and bedroom dampness/mould (adjusted OR = 2.98, 95% CI 1.54-5.75) ranked as the three most significant exposures associated with the risk of childhood asthma. Other factors associated with an increased risk of childhood asthma included second-hand smoke exposure in early life (adjusted OR = 1.93, 95% CI 1.24-3.00), neonatal pneumonia (adjusted OR = 1.90, 95% CI 1.05-3.42) and maternal allergic diseases during pregnancy (adjusted OR = 2.13, 95% CI 1.10-4.10). The interaction effects of child second-hand smoke exposure with other covariates were not found to be statistically significant., Conclusions: Early-life factors and indoor environmental exposure are closely related to childhood asthma in Chongqing, China. Further interventions and management in the early life of children should be considered to prevent and control childhood asthma in Chongqing and similar cities., (© 2022. Children's Hospital, Zhejiang University School of Medicine.)

Mediator complex subunit 12 (MED12) is the most frequently mutated gene in uterine leiomyomas (ULs)-with a frequency of up to 85%-suggesting that it plays key roles in the pathogenesis of ULs. However, there is no established relationship between genetic alteration and other risk factors of UL pathogenesis such as the patient's age, weight, and race. In this meta-analysis, we established an association between these risk factors and the frequency of MED12 mutation. We also established the relationship between MED12 mutation with the number and size of tumors in a patient. A systematic literature search was performed for studies published by May 2020 and performed a meta-analysis according to PRISMA guidelines. Twenty-five studies were included in the analysis, representing 3151 tissue samples. MED12 mutations were more common in Black (74.5%) as compared to White (65.8%) and Asian (53.2%) patients. There was no significant relationship between the patient's age and the frequency of mutations (OR 0.73, 95% CI 0.38 to 1.41). MED12 mutations were common in patients barring small-sized (OR 1.46, 95% CI 1.09 to 1.95) multiple (OR 0.39, 95% CI 0.17 to 0.92) tumors. For the patient's weight, studies were few and the outcome was not statistically significant. This meta-analysis provides valuable information on the relationship between the patient's clinical characteristics and frequency of MED12 mutation among patients barring ULs, which is relevant for understanding the pathogenesis of ULs.Protocol registration: The protocol was registered in PROSPERO with registration number CRD42019123439., (© 2021. Society for Reproductive Investigation.)