The role of clinical trials in advancing reproductive medicine: a comprehensive overview

Reproductive health encompasses the entire spectrum of reproductive processes and functions throughout a person’s life,playing a vital role in the harmonious development of populations,economies,and societies.This critical aspect has garnered increasing global attention.Ensuring sexual and reproductive health stands as a fundamental step toward achieving the United Nations Sustainable Development Goal(SDG)by 2030[1].Despite extensive efforts,both China and the world at large confront a multitude of reproductive challenges.These challenges encompass declining fertility rates[2,3],high prevalence of birth defects,and the presence of various reproductive diseases that threaten fetal development.These issues contribute to emotional distress,relationship problems,social stigmatization,and an increased risk of adult-onset diseases,imposing a significant burden on individuals and society[2].In the realm of human reproductive health research,epidemiological approaches have played a pivotal role.

Application and Challenge of Preimplantation Genetic Testing in Reproductive Medicine

There has been a very rapid development in the area of preimplantation genetic testing(PGT)since the first baby applied PGT technology in the world was born in the last 30 years.As an alternative treatment of prenatal diagnosis,the transfer of the fetus with normal testing result has benefited many families.PGT is mainly classified into PGT for aneuploidies(PGT-A),PGT for chromosomal structural rearrangement(PGT-SR),and PGT for monogenic/single-gene defects(PGT-M).Here,we reviewed the application,development,limitations,and challenges of the current PGT in reproductive medicine.

Marker Ki-67 is a potential biomarker for the diagnosis and prognosis of prostate cancer based on two cohorts

BACKGROUND Prostate cancer(PCa)is a widespread malignancy,predominantly affecting elderly males,and current methods for diagnosis and treatment of this disease continue to fall short.The marker Ki-67(MKI67)has been previously demonstrated to correlate with the proliferation and metastasis of various cancer cells,including those of PCa.Hence,verifying the association between MKI67 and the diagnosis and prognosis of PCa,using bioinformatics databases and clinical data analysis,carries significant clinical implications.AIM To explore the diagnostic and prognostic efficacy of antigens identified by MKI67 expression in PCa.METHODS For cohort 1,the efficacy of MKI67 diagnosis was evaluated using data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.For cohort 2,the diagnostic and prognostic power of MKI67 expression was further validated using data from 271 patients with clinical PCa.RESULTS In cohort 1,MKI67 expression was correlated with prostate-specific antigen(PSA),Gleason Score,T stage,and N stage.The receiver operating characteristic(ROC)curve showed a strong diagnostic ability,and the Kaplan-Meier method demonstrated that MKI67 expression was negatively associated with the progression-free interval(PFI).The time-ROC curve displayed a weak prognostic capability for MKI67 expression in PCa.In cohort 2,MKI67 expression was significantly related to the Gleason Score,T stage,and N stage;however,it was negatively associated with the PFI.The time-ROC curve revealed the stronger prognostic capability of MKI67 in patients with PCa.Multivariate COX regression analysis was performed to select risk factors,including PSA level,N stage,and MKI67 expression.A nomogram was established to predict the 3-year PFI.CONCLUSION MKI67 expression was positively associated with the Gleason Score,T stage,and N stage and showed a strong diagnostic and prognostic ability in PCa.

Germ cell-specific deletion of Pex3 reveals essential roles of PEX3-dependent peroxisomes in spermiogenesis

Peroxisomes are organelles enclosed by a single membrane and are present in various species.The abruption of peroxisomes is correlated with peroxisome biogenesis disorders and single peroxisomal enzyme deficiencies that induce diverse diseases in different organs.However,little is known about the protein compositions and corresponding roles of heterogeneous peroxisomes in various organs.Through transcriptomic and proteomic analyses,we observed heterogenous peroxisomal components among different organs,as well as between testicular somatic cells and different developmental stages of germ cells.As Pex3 is expressed in both germ cells and Sertoli cells,we generated Pex3 germ cell-and Sertoli cell-specific knockout mice.While Pex3 deletion in Sertoli cells did not affect spermatogenesis,the deletion in germ cells resulted in male sterility,manifested as the destruction of intercellular bridges between spermatids and the formation of multinucleated giant cells.Proteomic analysis of the Pex3-deleted spermatids revealed defective expressions of peroxisomal proteins and spermiogenesis-related proteins.These findings provide new insights that PEX3-dependent peroxisomes are essential for germ cells undergoing spermiogenesis,but not for Sertoli cells.

Emerging mechanisms and implications of c GAS-STING signaling in cancer immunotherapy strategies

The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment.Within this landscape,the innate immune system,a critical sentinel protecting against tumor incursion,is a key player.The cyclic GMP-AMP synthase(c GAS)and stimulator of interferon genes(STING)pathway has been found to be a linchpin of innate immunity:activation of this signaling pathway orchestrates the production of type I interferon(IFN-α/β),thus fostering the maturation,differentiation,and mobilization of immune effectors in the tumor microenvironment.Furthermore,STING activation facilitates the release and presentation of tumor antigens,and therefore is an attractive target for cancer immunotherapy.Current strategies to activate the STING pathway,including use of pharmacological agonists,have made substantial advancements,particularly when combined with immune checkpoint inhibitors.These approaches have shown promise in preclinical and clinical settings,by enhancing patient survival rates.This review describes the evolving understanding of the c GAS-STING pathway's involvement in tumor biology and therapy.Moreover,this review explores classical and non-classical STING agonists,providing insights into their mechanisms of action and potential for optimizing immunotherapy strategies.Despite challenges and complexities,the c GAS-STING pathway,a promising avenue for enhancing cancer treatment efficacy,has the potential to revolutionize patient outcomes.

Protective effects of quercetin against H2O2 induced KGN cells injury

Background:Oxidative stress is one of the key contributors to cellular senescence and ovarian aging.Quercetin has a variety of physiological activities such as antioxidant.Given that hydrogen peroxide can cause oxidative damage to cells,the present study is designed to verify the protective effect of quercetin on human ovarian granulosa tumor cell line under oxidative stress.Methods:Cell counting kit-8 and lactate dehydrogenase assays examined cell viability and toxicity.Flow cytometry detected reactive oxygen species accumulation.Glutathione level was measured to analyze the oxidation resistance.Cell apoptosis was evaluated by Hoechst 33258 staining,acridine orange/Ethidium Bromide staining and western blot.The mitochondrial structure was observed under a transmission electron microscope.Mitochondrial membrane integrity was detected by JC-1 staining and western blot.Results:Hydrogen peroxide could induce cell injury,promote reactive oxygen species accumulation,and lead to glutathione depletion.hydrogen peroxide also resulted in mitochondrial morphological damage and depolarization,which activate caspase3/9 subsequently.However,quercetin could mitigate these damages.Conclusions:Present study found that hydrogen peroxide induced oxidative stress and mitochondrial apoptosis of human ovarian granulosa tumor cell line cells,which could be attenuated by quercetin.

Extensive prediction of drug response in mutation-subtype-specific LUAD with machine learning approach

Lung cancer is the most prevalent cancer diagnosis and the leading cause of cancer death worldwide.Therapeutic failure in lung cancer(LUAD)is heavily influenced by drug resistance.This challenge stems from the diverse cell populations within the tumor,each having unique genetic,epigenetic,and phenotypic profiles.Such variations lead to varied therapeutic responses,thereby contributing to tumor relapse and disease progression.Methods:The Genomics of Drug Sensitivity in Cancer(GDSC)database was used in this investigation to obtain the mRNA expression dataset,genomic mutation profile,and drug sensitivity information of NSCLS.Machine Learning(ML)methods,including Random Forest(RF),Artificial Neurol Network(ANN),and Support Vector Machine(SVM),were used to predict the response status of each compound based on the mRNA and mutation characteristics determined using statistical methods.The most suitable method for each drug was proposed by comparing the prediction accuracy of different ML methods,and the selected mRNA and mutation characteristics were identified as molecular features for the drug-responsive cancer subtype.Finally,the prognostic influence of molecular features on the mutational subtype of LUAD in publicly available datasets.Results:Our analyses yielded 1,564 gene features and 45 mutational features for 46 drugs.Applying the ML approach to predict the drug response for each medication revealed an upstanding performance for SVM in predicting Afuresertib drug response(area under the curve[AUC]0.875)using CIT,GAS2L3,STAG3L3,ATP2B4-mut,and IL15RA-mut as molecular features.Furthermore,the ANN algorithm using 9 mRNA characteristics demonstrated the highest prediction performance(AUC 0.780)in Gefitinib with CCL23-mut.Conclusion:This work extensively investigated the mRNA and mutation signatures associated with drug response in LUAD using a machine-learning approach and proposed a priority algorithm to predict drug response for different drugs.

Timing theory integrated nursing combined behavior change integrated theory of nursing on primiparous influence

BACKGROUND The comprehension and utilization of timing theory and behavior change can offer a more extensive and individualized provision of support and treatment alternatives for primipara.This has the potential to enhance the psychological well-being and overall quality of life for primipara,while also furnishing healthcare providers with efficacious interventions to tackle the psychological and physiological obstacles encountered during the stages of pregnancy and postpartum.AIM To explore the effect of timing theory combined with behavior change on selfefficacy,negative emotions and quality of life in patients with primipara.METHODS A total of 80 primipara cases were selected and admitted to our hospital between August 2020 and May 2022.These cases were divided into two groups,namely the observation group and the control group,with 40 cases in each group.The nursing interventions differed between the two groups,with the control group receiving routine nursing and the observation group receiving integrated nursing based on the timing theory and behavior change.The study aimed to compare the pre-and post-nursing scores of Chinese Perceived Stress Scale(CPSS),Edinburgh Postpartum Depression Scale(EPDS),Self-rating Anxiety Scale(SAS),breast milk knowledge,self-efficacy,and SF-36 quality of life in both groups.RESULTS After nursing,the CPSS,EPDS,and SAS scores of the two groups was significantly lower than that before nursing,and the CPSS,EPDS,and SAS scores of the observation group was significantly lower than that of the control group(P=0.002,P=0.011,and P=0.001 respectively).After nursing,the breastfeeding knowledge mastery,selfefficacy,and SF-36 quality of life scores was significantly higher than that before nursing,and the breastfeeding knowledge mastery(P=0.013),self-efficacy(P=0.008),and SF-36 quality of life(P=0.011)scores of the observation group was significantly higher than that of the control group.CONCLUSION The integration of timing theory and behavior change integrated theory has been found to be an effective approach in alleviating negative mood and stress experienced by primipara individuals,while also enhancing their selfefficacy and overall quality of life.This study focuses on the key concepts of timing theory,behavior change,primipara individuals,negative mood,and quality of life.

Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

Knowledge, attitudes, and practices regarding Covid-19 and their relationship with Covid-19 booster vaccination status among women with infertility

Objective:To elucidate the relationship among knowledge,attitudes,and practices regarding Covid-19 and their relationship with booster vaccination status among women with infertility.Methods:This questionnaire-based cross-sectional study was performed online and offline among women with infertility who visited an infertility clinic in Jakarta,Indonesia.We assessed the patient’s knowledge,attitudes,and practices regarding Covid-19 and their relationship with booster vaccination status and sociodemographic profile.Results:A total of 178 subjects participated in this study,and most participants(92.6%)had received booster Covid-19 vaccines.From the questionnaire,74.2%had good knowledge,and 99.4%had good attitudes regarding Covid-19;however,only 57.9%of patients had good practices.A weak positive correlation existed between knowledge and attitudes(r=0.11,P=0.13)and a moderate negative correlation between attitudes and practices(r=-0.44,P=0.56).Participants’knowledge about vaccines and infertility was correlated with booster vaccination status(P=0.04).Academic background(P=0.01)and attitudes(P=0.01)were also correlated with booster vaccination status.The significant determinants of hesitance of receiving Covid-19 booster vaccines were high school education or below(OR=0.08,95%CI 0.02-0.36)and poor practices(OR=0.21,95%CI 0.05-0.95).Conclusions:The majority of the participants had received the Covid-19 booster vaccine and had good knowledge and attitudes but poor practices regarding Covid-19.Most participants had poor knowledge about the relationship between infertility and the Covid-19 vaccine.The general population should be more informed and reminded about practices to prevent Covid-19 and the relationship between vaccination and fertility to increase the number of people who receive Covid-19 booster vaccines.

Clinical nursing value of predictive nursing in reducing complications of pregnant women undergoing short-term massive blood transfusion during cesarean section

BACKGROUND Cesarean hemorrhage is one of the serious complications,and short-term massive blood transfusion can easily cause postoperative infection and physical stress response.However,predictive nursing intervention has important clinical significance for it.AIM To explore the effect of predictive nursing intervention on the stress response and complications of women undergoing short-term mass blood transfusion during cesarean section(CS).METHODS A clinical medical record of 100 pregnant women undergoing rapid mass blood transfusion during sections from June 2019 to June 2021.According to the different nursing methods,patients divided into control group(n=50)and observation group(n=50).Among them,the control group implemented routine nursing,and the observation group implemented predictive nursing intervention based on the control group.Moreover,compared the differences in stress res-ponse,complications,and pain scores before and after the nursing of pregnant women undergoing rapid mass blood transfusion during CS.RESULTS The anxiety and depression scores of pregnant women in the two groups were significantly improved after nursing,and the psychological stress response of the observation group was significantly lower than that of the control group(P<0.05).The heart rate and mean arterial pressure(MAP)of the observation group during delivery were lower than those of the control group,and the MAP at the end of delivery was lower than that of the control group(P<0.05).Moreover,different pain scores improved significantly in both groups,with the observation group considerably less than the control group(P<0.05).After nursing,complications such as skin rash,urinary retention,chills,diarrhea,and anaphylactic shock in the observation group were 18%,which significantly higher than in the control group(4%)(P<0.05).CONCLUSION Predictive nursing intervention can effectively relieve the pain,reduce the incidence of complications,improve mood and stress response,and serve as a reference value for the nursing of women undergoing rapid mass transfusion during CS.

Exploration of standard dosage for GnRH antagonist protocol and dosage adjustments after premature luteinizing hormone surge

The gonadotropin-releasing hormone (GnRH) antagonist protocol has emerged as an efficacious alternative to the GnRH agonist protocol for controlled ovarian hyperstimulation (COH) during in vitro fertilization (IVF) cycles, and has been demonstrated applicability in infertile female patients with diverse ovarian responses. While the clinical implementation of the antagonist COH protocol has achieved widespread consensus, opportunities for refinement persist. Therefore, this review article focuses on the advantages and disadvantages of GnRH antagonist protocol, the selection of optimal standard doses, and the strategies for adjusting antagonist doses after the premature luteinizing hormone (LH) surge, aiming to provide more reasonable and scientific recommendations for the application of this scheme.

Downregulation of the circadian clock gene period 2 aggravates prognosis in breast cancer patients with obesity

Background:Obese individuals diagnosed with breast cancer often experience a less favorable prognosis;however,the underlying mechanisms linking obesity to breast cancer outcomes remain elusive.This study aimed to identify and validate novel prognostic markers associated with breast cancer in patients with obesity.Methods:We conducted a reanalysis of gene expression profiles from normal-weight,overweight,and obese breast cancer patients to identify candidate genes.Subsequently,we validated the protein levels of these candidates using immunohistochemistry.Finally,we investigated the association between candidate genes and breast cancer prognosis at Tongji Hospital,utilizing data from an 8-year follow-up through the Kaplan-Meier method and univariate and multivariate Cox regression models.Results:The fold change of the circadian clock gene period 2(PER2),which exhibited a declining trend with increasing body mass index,was 0.76 in obese patients compared with normal-weight patients.The expression rates of PER2 protein were 44.7%,51.5%,and 61.3%in normal-weight,overweight,and obese patients,respectively.The 8-year recurrence-free survival rates were 75.9%,69.6%,and 64.1%,whereas the 8-year overall survival rates were 86.8%,83.0%,and 76.1%in normal-weight,overweight,and obese patients,respectively(P<0.05).Furthermore,the 8-year recurrence-free survival rates were 66.2%and 76.4%,and the 8-year overall survival rates were 79.9%and 86.3%in the low and high PER2 expression groups,respectively(P<0.05).The unadjusted hazard ratio for PER2 was 1.550(95%confidence interval,1.029–2.335),and the adjusted hazard ratio was 3.003(95%confidence interval,1.838–4.907).Conclusions:Our findings indicate that low PER2 expression serves as an independent risk factor for breast cancer prognosis and may contribute to the unfavorable outcomes observed in obese patients.

Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis

The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://gxmujyzmolab.cn:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

Insights and implications of sexual dimorphism in osteoporosis

Osteoporosis,a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture,has led to a high risk of fatal osteoporotic fractures worldwide.Accumulating evidence has revealed that sexual dimorphism is a notable feature of osteoporosis,with sex-specific differences in epidemiology and pathogenesis.Specifically,females are more susceptible than males to osteoporosis,while males are more prone to disability or death from the disease.To date,sex chromosome abnormalities and steroid hormones have been proven to contribute greatly to sexual dimorphism in osteoporosis by regulating the functions of bone cells.Understanding the sex-specific differences in osteoporosis and its related complications is essential for improving treatment strategies tailored to women and men.This literature review focuses on the mechanisms underlying sexual dimorphism in osteoporosis,mainly in a population of aging patients,chronic glucocorticoid administration,and diabetes.Moreover,we highlight the implications of sexual dimorphism for developing therapeutics and preventive strategies and screening approaches tailored to women and men.Additionally,the challenges in translating bench research to bedside treatments and future directions to overcome these obstacles will be discussed.

Relationship Between Gene-Phenotype and Clinical Manifestations of Chromosomal Copy Number Variations Indicated by Non-Invasive Prenatal Testing

Objective:To analyze the clinical value of non-invasive prenatal testing(NIPT)in detecting chromosomal copy number variations(CNVs)and to explore the relationship between gene expression and clinical manifestations of chromosomal copy number variations.Methods:3551 naturally conceived singleton pregnant women who underwent NIPT were included in this study.The NIPT revealed abnormalities other than sex chromosome abnormalities and trisomy 13,18,and 21.Pregnant women with chromosome copy number variations underwent genetic counseling and prenatal ultrasound examination.Interventional prenatal diagnosis and chromosome microarray analysis(CMA)were performed.The clinical phenotypes and pregnancy outcomes of different prenatal diagnoses were analyzed.Additionally,a follow-up was conducted by telephone to track fetal development after birth,at six months,and one year post-birth.Results:A total of 53 cases among 3551 cases showed chromosomal copy number variation.Interventional prenatal diagnosis was performed in 36 cases:27 cases were negative and 8 were consistent with the NIPT test results.This indicates that NIPT’s positive predictive value(PPV)in CNVs is 22.22%.Conclusion:NIPT has certain clinical significance in screening chromosome copy number variations and is expected to become a routine screening for chromosomal microdeletions and microduplications.However,further interventional prenatal diagnosis is still needed to identify fetal CNVs.

Low Level of Cystic Fibrosis Transmembrane Conductance Regulator Is Associated with Human Sperm Autophagy and Vitality

Low sperm motility is one of the main causes of male infertility. Cystic fibrosis transmembrane conductance regulator (CFTR, an anion channel protein) is related to the progressive motility of sperm. CFTR disruptor CFTRinh-172 or forskolin (FSK) in this study were used to treat human sperm separately, and the rates of sperm autophagy and progressive motility, mitochondrial membrane potential (MMP) and ATP concentration, and the expression levels of related factors were detected to explore their relationship. It was showed that sperms treated with CFTRinh-172 or FSK reduced the levels of cAMP, CFTR and PKA, but increased sperm autophagy rate, expression levels of AMPK and LC3B. However, reactive oxygen species content had no significant difference. It was indicated that low level of CFTR performed with cAMP and its downstream effectors such as PKA and AMPK to regulate mitochondrial structure and function, leading to increased autophagy rate and reduced vitality of sperm.

Comparison of sperm retrieval and reproductive outcome in azoospermic men with testicular failure and obstructive azoospermia treated for infertility

We assessed the rates of sperm retrieval and intracytoplasmic sperm injection outcomes, including the neonatal profile of infants conceived, in men with testicular failure. Three-hundred and sixty-five men with testicular failure who underwent micro-dissection testicular sperm extraction were included in this study. We compared their outcomes with 40 men with testicular failure who used donor sperm for injections due to failed retrieval, and 146 men with obstructive azoospermia who underwent percutaneous sperm retrieval. The retrieval rate in testicular failure was 41.4%, and the results were lower than the obstructed azoospermia （100%; adjusted odds ratio： 0.033; 95% Ch 0.007-0.164; P 〈 0.001）. Live birth rates after sperm injections were lower in men with testicular failure （19.9%） compared with donor sperm （37.5%; adjusted OR： 0.377 （95% Ch 0.233-0.609, P 〈 0.001）） and obstructive azoospermia （34.2%; adjusted OR： 0.403 （95% CI： 0.241-0.676, P= 0.001）. Newborn parameters of infants conceived were not significantly different among the groups. We concluded that the chances of obtaining sperm on retrieval and achieving a live birth after intracytoplasmic sperm injection （ICSI） are reduced in men with testicular failure. The profile of infants conceived after sperm injection does not seem to be negatively affected by testicular failure.

Sexual and reproductive health service needs of university/ college students： updates from a survey in Shanghai, China

Aim： To promote the provision of reproductive health services to young people by exploring the attitudes and perceptions of university students in Shanghai, China, toward reproductive health. Methods： From July 2004 to May 2006, 5 243 students from 14 universities in Shanghai took part in our survey. Topics covered the demands of reproductive health-care services, attitudes towards and experience with sex, exposure to pornographic material, and knowledge on sexual health and sexually transmitted infections （STIs）/AIDS. Results： Of the 5 067 students who provided valid answer sheets, 50.05% were female and 49.95% were male, 14.86% were medical students, and 85.14% had non-medical backgrounds. A total of 38.4% of respondents had received reproductive health education previously. The majority of students supported school-based reproductive health education, and also acquired information about sex predominantly from books, schoolmates, and the Internet. Premarital sexual behavior was opposed by 17.7% of survey participants, and 37.5% could identify all the three types of STIs listed in the questionnaire. Although 83.7% knew how HIV is transmitted, only 55.7% knew when to use a condom and 57.8% knew that the use of condoms could reduce the risk of HIV infection. Conclusion： The reproductive health service is lagging behind current attitudes and demands of university students. Although students＇ attitudes towards sexual matters are liberal, their knowledge about reproductive health and STIs/AIDS is still limited. It is therefore necessary to provide effective and confidential reproductive health services to young people.

Persistent organic pollutants and male reproductive health

Environmental contaminants such as persistent organic pollutants （POPs） are man-made bioaccumulative compounds with long half-lives that are found throughout the world as a result of heavy use in a variety of consumer products during the twentieth century. Wildlife and animal studies have long suggested adverse effects of exposure to these compounds on human reproductive health, which, according to the endocrine disrupter hypothesis, are ascribed to the compounds＇ potential to interfere with endocrine signaling, especially when exposure occurs during certain phases of fetal and childhood development. An extensive number of epidemiological studies have addressed the possible effects of exposure to POPs on male reproductive health, but the results are conflicting. Thus far, most studies have focused on investigating exposure and the different reproductive health outcomes during adulthood. Some studies have addressed the potential harmful effects of fetal exposure with respect to malformations at birth and/ or reproductive development, whereas only a few studies have been able to evaluate whether intrauterine exposure to POPs has long-term consequences for male reproductive health with measurable effects on semen quality markers and reproductive hormone levels in adulthood. Humans are not exposed to a single compound at a time, but rather, to a variety of different substances with potential divergent hormonal effects. Hence, how to best analyze epidemiological data on combined exposures remains a significant challenge. This review on POPs will focus on current knowledge regarding the potential effects of exposure to POPs during fetal and childhood life and during adulthood on male reproductive health, including a critical revision of the endocrine disruption hypothesis, a comment on pubertal development as part of reproductive development and a comment on how to account for combined exposures in epidemiological research.