The etiology of polycystic ovary syndrome (PCOS) is complex and variable, and there is no exact cause or good treatment method. Most of the methods of hormones are used to temporarily meet the needs of patients. Experimental evidence has shown that trehalose has, anti-apoptotic, anti-oxidative, glucose-lowering, and insulin resistance effects. However, whether trehalose has a therapeutic effect on PCOS is unknown. It has been reported that the ovarian renin-angiotensin system (OVRAS) is involved in the development of PCOS, but it has not been fully elucidated. This study aims to explore the effect of trehalose on PCOS and elucidate the related OVRAS mechanism. We first observed that body weight, estrous cycle, ovarian follicles at all levels, glucose tolerance, serum hormones, and insulin resistance were improved by trehalose treatment in the PCOS mouse model. Moreover, trehalose treatment also ameliorated ovarian oxidative stress and apoptosis in PCOS mice, as determined by TUNNEL apoptosis staining, total SOD in ovarian homogenate, and WB assay. OVRAS mainly involves two classic pathways, namely the ACE/AngII/AT1R/AT2R, and ACE2 / Ang1-7/ MASR, Which play different functions. In PCOS mouse ovaries, we found that ACE/AngII/AT1R was up-regulated and ACE2/Ang1-7/MASR and AT2R were down-regulated by PCR and WB experiments, However, trehalose treatment changed its direction. In addition, we also found that trehalose ameliorated DHEA-induced oxidative stress and apoptosis in KGN by PCR and WB experiments, mainly by down-regulating ACE/AngII/AT1R. Our study shows that trehalose improves symptoms of PCOS mainly by down-regulating ACE/AngII/AT1R, revealing a potential therapeutic target for PCOS.

Premature ovarian insufficiency (POI) is a serious disease significantly affecting the physical and mental health of women of reproductive age, not just impacting fertility outcomes. Ovarian damage due to chemotherapy remains a major cause of this condition. Recent studies have indicated the involvement of the long non-coding RNA HOTAIR in the progression of various diseases, showcasing important biological functions, yet its role in POI remains unclear. We conducted microarray dataset analysis and qRT-PCR experiments, demonstrating downregulation of HOTAIR expression in ovarian tissue and granulosa cells. Various functional experiments using plasmids overexpressing HOTAIR confirmed its promotion of cisplatin-induced granulosa cell autophagy and proliferation. Mechanistically, dual-luciferase assays showed that HOTAIR modulates ATG14 levels in POI by binding miR-148b-3p, thereby enhancing levels of autophagy and proliferation. In this study, we first explored the impact of miR-148b-3p on POI and found that overexpression of miR-148b-3p reversed the promotion of autophagy and proliferation induced by HOTAIR overexpression. The inhibitory effect of miR-148b-3p inhibitor on KGN cell autophagy and proliferation improvement could also be reversed by silencing ATG14. Overall, our findings indicate the promoting role of HOTAIR in POI and its potential as a biomarker for POI by modulating the miR-148b-3p/ATG14 axis to improve mechanisms of autophagy and proliferation in POI.

Objective: To investigate the association between the local renin-angiotensin system (RAS) in human follicular fluid (hFF) and age, ovarian function, in vitro fertilization (IVF) outcome. Design: Study on the correlation of non-intervention. Setting: Reproductive Medicine Center, First Affiliated Hospital of Soochow University. Sample: hFF of 139 women who received IVF simply because of their husband’s factors from January 2021 to February 2022. Methods: The correlation between age and RAS in hFF was analyzed by simple linear regression, and multivariate linear regression was used to further analyze the correlation between the RAS and IVF outcome. Main Outcome Measures: The levels of RAS components in hFF were measured, including Renin, ACE, ACE2, AngⅡ and Ang(1-7). Results: ①The influence of age on ACE-AngⅡ-AT1/2R axis was more significant than that on ACE2-Ang(1-7)-MAS axis in hFF; ②Provides evidence that gonadotropins mediate RAS activation of local ovarian follicles; ③It is still impossible to prove the effect of RAS on steroid hormone production, at least in ovarian follicles RAS cannot affect steroid hormones in the systemic circulation; ④Age and the level of RAS components in hFF have certain clinical value in predicting the number of oocyte retrieval and the rate of MⅡ maturation. Conclusions: The local RAS in ovarian follicles is affected by age and correlated with ovarian function and IVF outcome.

BACKGROUND:Assisted reproductive technology (ART) is associated with an increased risk of adverse metabolic health in offspring, and these findings have been demonstrated in animal models without parental infertility issues. However, it is unclear what changes lead to abnormal metabolism. The activation of the renin-angiotensin system (RAS) has been related to various aspects of metabolic syndrome. Thus, we focused on the local RAS of the liver, which is the central organ for glucose and lipid metabolism in offspring conceived by in vitro fertilization (IVF), and studied the role of local liver RAS in metabolic diseases.METHODS:Male C57BL/6 mouse offspring obtained by natural pregnancy and IVF were fed a standard chow diet or a high-fat diet (HFD) from 4 weeks of age through 16 weeks of age. We assessed glucose and lipid metabolism, hepatic histopathology, and the gene and protein expression of key RAS components. In addition, the blocker losartan was used from 4 weeks of age through 16 weeks of age to investigate the regulatory mechanisms of abnormal local RAS on metabolic activity in the IVF offspring liver.RESULTS:The growth trajectories of IVF offspring body and liver weights were different from those of naturally pregnant offspring. Impaired glucose tolerance (IGT) and insulin resistance (IR) occurred in IVF-conceived male offspring. After continuous HFD feeding, male offspring in the IVF group underwent earlier and more severe IR. Furthermore, there was a trend of lipid accumulation in the livers of chow-fed IVF offspring. Hepatic steatosis was also more serious in the IVF offspring after HFD treatment. Type 1 receptor (AT1R), which is the primary receptor mediating the action of angiotensin (Ang) II, has been confirmed to be upregulated in IVF offspring livers. Losartan reduced or even eliminated most of the significant differences between the IVF and NC groups after HFD consumption.CONCLUSIONS:The upregulation of AT1R expression in the liver increased the activity of the local RAS, resulting in abnormal glucose and lipid metabolism and lipid accumulation in the liver, significantly increasing the risk of nonalcoholic fatty liver disease (NAFLD) in IVF offspring.

Background NIPT is becoming increasingly important as its use becomes more widespread in China. More details are urgently needed on the correlation between maternal risk factors and fetal aneuploidy, and how these factors affect the accuracy of prenatal aneuploidy screening. Methods Information on the pregnant women was collected, including maternal age, gestational age, specific medical history and results of prenatal aneuploidy screening. Additionally, the OR, validity and predictive value were also calculated. Results A total of 12,186 analysable karyotype reports were collected with 372 (3.05%) fetal aneuploidies, including 161 (1.32%) T21, 81 (0.66%) T18, 41 (0.34%) T13 and 89 (0.73%) SCAs. The OR was highest for maternal age less than 20 years (6.65), followed by over 40 years (3.59) and 35–39 years (2.48). T13 (16.95) and T18 (9.40) were more frequent in the over-40 group ( P < 0.01 ); T13 (3.62/5.76) and SCAs (2.49/3.95) in the 35–39 group ( P < 0.01 ). Cases with a history of fetal malformation had the highest OR (35.94), followed by RSA (13.08): the former was more likely to have T13 (50.65) ( P < 0.01 ) and the latter more likely to have T18 (20.50) ( P < 0.01 ). The sensitivity of primary screening was 73.24% and the NPV was 98.23%. The TPR for NIPT was 100.00% and the respective PPVs for T21, T18, T13 and SCAs were 89.92, 69.77, 53.49 and 43.24%, respectively. The accuracy of NIPT increased with increasing gestational age (0.81). In contrast, the accuracy of NIPT decreased with maternal age (1.12) and IVF-ET history (4.15). Conclusions ①Pregnant patients with maternal age below 20 years had higher risk of aneuploidy, especially in T13; ②A history of fetal malformations is more risky than RSA, with the former more likely to have T13 and the latter more likely to have T18; ③Primary screening essentially achieves the goal of identifying a normal karyotype, and NIPT can accurately screen for fetal aneuploidy; ④A number of maternal risk factors may influence the accuracy of NIPT diagnosis, including older age, premature testing, or a history of IVF-ET. In conclusion, this study provides a reliable theoretical basis for optimizing prenatal aneuploidy screening strategies and improving population quality.

Objective The COVID-19 pandemic has been the most serious public health emergency encountered in modern assisted reproductive technology (ART) development. In order to identify lessons learned, this study reviews the effect of the pandemic on ART institutions and human sperm banks in China, and summarizes the experiences and reflections of Chinese scholars post-pandemic era. Methods This review is based on multiple consensus statements on the COVID-19 pandemic issued by Chinese experts as well as current national regulations and principles in ART institutions and human sperm banks to document the current situation of ART services in China, describe the impact of the pandemic on these services, and offer Chinese reflections on worrying issues in the post-pandemic era. Results China reached one million ART cycles in 2016, and there are currently 540 ART medical institutions and 27 human sperm banks, with 540 licensed for AIH, 91 for AID, 415 for conventional IVF and ICSI and 85 for PGT. Of these, only 4 institutions carry out 10,000 cycles or more annually, and the proportion of institutions with less than 1,000 cycles has reached 66%, which means that a considerable number of ART institutions are still not saturated. As a consequence of the COVID-19 pandemic, 63.6% of ART providers and 95.5% of human sperm banks suspended operations. By the end of May 2020, China, as an early country affected by the pandemic achieved a national resumption rate of ART medical services of 99.2% and that of human sperm banks of 100.0%. Reports from the first and largest human sperm bank in China showed that qualification, semen concentration and sperm viability rates measured at primary screening have significantly decreased post-pandemic. Much like in other countries, Chinese experts developed a consensus on prevention and control measures during the pandemic. In principle, all ART activities should be suspended during acute phases of infection spread. Chinese scholars highlight that attention should be paid to young patients with fertility requirements during and after COVID-19, and emphasize the importance of fertility evaluation and clinical intervention. In addition, couples should be reminded that during ART treatment, disinfectants should not be used excessively to minimize risks of damaging the reproductive system, gametes and zygotes. At the same time, timely and reasonable guidance for tackling negative emotions from stress response is needed to provide reassurance and to avoid irrational fear and excessive stress. Seminal parameters should be re-examined 2 months after SARS-CoV-2 vaccination, and ART treatments recommenced if no abnormalities are detected. Conclusions Given the growing frequency of outbreaks of global infectious diseases in recent years, ART institutions and human sperm banks should pay attention to improving their prevention and control capabilities. To a certain extent, decisions and measures adopted in China during COVID-19 pandemic are worthy of recognition and acceptance. Chinese scholars have discussed, proactively responded to and understand the key issues surrounding ART development during the pandemic with the aim of contributing to the substantial progress and healthy development of ART services in the world.

Premature ovarian insufficiency, characterized by ovarian infertility and low fertility, has become a significant problem in developed countries due to its propensity for late delivery. It has been described that the vital role of lncRNA in the development and progression of POI. The aim of this work was to create a POI-based lncRNA–mRNA network (POILMN) to recognize key lncRNAs. Overall, differently expressed mRNAs (DEGs) and differently expressed lncRNAs (DELs) were achieved by using the AnnoProbe and limma R packages. POI-based lncRNA–mRNA network (POILMN) construction was carried out using the tinyarray R package and hypergeometric distribution. To identify key lncRNAs, we used CentiScaPe plug-in Cytoscape as a screening tool. In total, 244 differentially expressed lncRNAs (DELs) and 288 differentially expressed mRNAs (DEGs) were obtained in this study. Also, 177 lncRNA/mRNA pairs (including 39 lncRNAs and 86 mRNAs) were selected using the hypergeometric test. Finally, we identified four lncRNA (HCP5, NUTM2A-AS1, GABPB1-IT1, and SMIM25) intersections by topological analysis between two centralities (degree and betweenness), and we explored their subnetwork GO and KEGG pathway enrichment analysis. Here, we have provided strong evidence for a relationship with apoptosis, DNA repair damage, and energy metabolism terms and pathways in the key lncRNAs in our POI-based lncRNA–mRNA network. In addition, we evaluated the localization information of genes related to POI and found that genes were more distributed on chromosomes 15, 16, 17, and 19. However, more experiments are needed to confirm the functional significance of such predicted lncRNA/mRNA. In conclusion, our study identified four long non-coding RNA molecules that may be relevant to the progress of premature ovarian insufficiency.

Abstract Objective Retrospective analysis of maternal risk factors for fetal aneuploidy and evaluation of the clinical value of prenatal screening.Methods The information of pregnant women was collected, and the OR value, authenticity index and prediction value index were calculated.Results A total of 12,186 analysable karyotype reports were collected, and 372 cases(3.05%) of fetal aneuploidy were found, including T21 161 cases(1.32%), T18 81 cases(0.66%), T13 41 cases(0.34%), and SCAs 89 cases(0.73%). Maternal age <20 years old has the highest OR(6.65), followed by ≥40(3.59) and 35-39(2.48). History of fetal malformation has the highest OR(35.94), followed by IVF-ET(17.04) and RSA(13.08). The sensitivity of the preliminary screening was 73.24%, and the NPV was 98.23%. The TPR of NIPT was 100.00%, and the PPV for T21, T18, T13, and SCAs was 89.92%, 69.77%, 53.49%, and 43.24%. The reliability of NIPT and gestational age(0.81) are positively correlated, while had a negative correlation with maternal age(1.12) and the history of IVF-ET.Conclusion Our results support the correlation between maternal risk factors and fetal aneuploidy & reliability of screening. The above conclusions provide a reliable theoretical basis for developing prenatal screening strategies and improving reproductive health.

Background Pneumonia is a serious problem that threatens the health of newborns. This study aimed to investigate the clinical characteristics of hospitalized term and preterm infants with community-acquired viral pneumonia. Methods This was a retrospective analysis of cases of community-acquired viral pneumonia in the Neonatal Department. Nasopharyngeal aspirate (NPA) samples were collected for pathogen detection, and clinical data were collected. We analysed pathogenic species and clinical characteristics among these infants. Results RSV is the main virus in term infants, and parainfluenza virus (PIV) 3 is the main virus in preterm infants. Patients infected with PIV3 were more susceptible to coinfection with bacteria than those with respiratory syncytial virus (RSV) infection (p < 0.05). Preterm infants infected with PIV3 were more likely to be coinfected with bacteria than term infants (p < 0.05), mainly gram-negative bacteria (especially Klebsiella pneumonia). Term infants with bacterial infection were more prone to fever, cyanosis, moist rales, three concave signs, elevated C-reactive protein (CRP) levels, respiratory failure and the need for higher level of oxygen support and mechanical ventilation than those with simple viral infection (p < 0.05). The incidence of hyponatremia in neonatal community-acquired pneumonia (CAP) was high. Conclusions RSV and PIV3 were the leading causes of neonatal viral CAP. PIV3 infection is the main cause of viral CAP in preterm infants, and these individuals are more likely to be coinfected with bacteria than term infants, mainly gram-negative bacteria. Term infants with CAP coinfected with bacteria were more likely to have greater disease severity than those with single viral infections.

Abstract Background Previous studies have found that there is the local renin-angiotensin system (RAS) in human ovary, and it independently plays a regulatory role in ovarian function. Age-related reproductive aging is an inevitable process. To explore the relationship between RAS components in human follicular fluid (hFF) and age, ovarian function, so as to help clinical evaluation of oocyte quality and prediction of in vitro fertilization (IVF) outcome. Methods hFF of 139 women who received IVF simply because of their husband's factors from January 2021 to February 2022. The levels of RAS components in hFF were measured, including Renin, ACE, ACE2, AngⅡ and Ang(1–7). The correlation between age and RAS in hFF was analyzed by simple linear regression, and multivariate linear regression was used to further analyze the correlation between the RAS and IVF outcome. Results A total of 139 samples of analysable hFF were obtained in this study. It was found that there was a linear negative correlation between age and renin, ACE, AngⅡ, ACE/ACE2, AngⅡ/Ang(1–7) (Pearson's r < 0, P < 0.05), while the linear relationship with ACE2 and Ang (1–7) was not significant (P > 0.05). It was found that bFSH and bLH were correlated with age, ACE-AngⅡ-AT1/2R axis, ACE2-Ang(1–7)-MAS axis (P < 0.05), AFC was correlated with age, ACE2-Ang(1–7)-MAS axis (P < 0.05), and bAMH was only correlated with age (P < 0.01). There was no correlation between RAS and bE2, bP, bPRL, bT (P > 0.05). It was found that the number of oocyte retrieval and MⅡ maturation rate were correlated with age, renin, ACE-AngⅡ-AT1/2R axis and ACE2-Ang(1–7)-MAS axis (P < 0.05), and the rate of 2PN embryos, transplantable embryos, high-quality embryos were only correlated with age (P < 0.01). Conclusions ①The influence of age on ACE-AngⅡ-AT1/2R axis was more significant than that on ACE2-Ang(1–7)-MAS axis in hFF; ②Provides evidence that gonadotropins mediate RAS activation of local ovarian follicles; ③It is still impossible to prove the effect of RAS on steroid hormone production, at least in ovarian follicles RAS cannot affect steroid hormones in the systemic circulation; ④Age and the level of RAS components in hFF have certain clinical value in predicting the number of oocyte retrieval and the rate of MⅡ maturation.

OBJECTIVE:Sepsis represents a complex disease with the dysregulated inflammatory response. The purpose of this study is to explore the role of interleukin 17 (IL-17, also known as IL-17A) in the occurrence and development of pediatric sepsis.METHODS:We established the sepsis neonatal rat model with the method of intraperitoneal injection of Escherichia coli (E coli). At each target time point, we got the blood from heart after anesthetizing animals, and the lung and liver tissues were fixed in formalin. Immunohistochemistry and enzyme-linked immunosorbent assay assay was used to analyze the expression of IL-17A in the lung/liver and plasma respectively. A public data set of neonatal sepsis gene microarray was used to verify our result, and explore main functions of IL-17A in sepsis.RESULTS:The expression levels of IL-17A in the plasma, lung and liver gradually increased with the extension of the experimental time in sepsis group, and were significantly higher than control group at 4 hours after injection of E coli (P < 0.01). In our study, we found the levels of IL-17A mRNA in pediatric sepsis group were significantly higher than control group, which is consistent with the neonatal rat septicemia model. In addition, through the functional (GO) enrichment analysis, we found the genes associated with IL-17A in pediatric sepsis are mainly enriched in the functions of immune response and cell membrane formation.CONCLUSION:IL-17A might be a potential therapeutic target for pediatric sepsis.