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With the explosion of the MetaVerse concept and the burgeoning of VR (Virtual Reality) technology, VR has been applied in diverse scenariosfor examplesocial networking, games, education, online retail, house inspections, exhibition tours, training, virtual concerts and so on. Learning in the 3D environment of virtual reality can bring people an immersive interactive experience, which can improve the learners efficiency and deepen understanding. Music learning mainly includes the cultivation of rhythm (or sense of music, also including intonation), mainly relying on ears, followed by muscle memory, and the immersion of VR games is an optimal solution for music learning. This work proposes a VR-based drum learning game to solve several troubling problems such that when drummers practice real drums at home, the sound gets too loud, and the real drums occupy a large space, going out to practice drums will take much time. But to play drums in VR game, just put on a portable VR glass and pick up the touch controllers, drum players can practice at anytime, anywhere. What's more, it's very easy for novice to get started quickly. Another conspicuous advantage of VR is it provides an immersive experience for usersincluding a 360-degree panoramic screen, spatial audio, and authentic atmosphere.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 is sweeping the world, threatening millions of lives and drastically altering our ways of living. According to current studies, failure to either activate or eliminate inflammatory responses timely and properly at certain stages could result in the progression of the disease. In other words, robust immune responses to coronavirus disease 2019 (COVID-19) are critical. However, they do not theoretically present in some special groups of people, including the young, the aged, patients with autoimmunity or cancer. Differences also do occur between men and women. Our immune system evolves to ensure delicate coordination at different stages of life. The innate immune cells mainly consisted of myeloid lineage cells, including neutrophils, basophils, eosinophils, dendritic cells and mast cells; they possess phagocytic capacity to different degrees at different stages of life. They are firstly recruited upon infection and may activate the adaptive immunity when needed. The adaptive immune cells, on the other way, are comprised mainly of lymphoid lineages. As one grows up, the adaptive immunity matures and expands its memory repertoire, accompanied by an adjustment in quantity and quality. In this review, we would summarise and analyse the immunological characteristics of these groups from the perspective of the immune system ‘evolution’ as well as ‘revolution’ that has been studied and speculated so far, which would aid the comprehensive understanding of COVID-19 and personalised-treatment strategy.

Immune checkpoint inhibition has emerged as an effective treatment for multiple solid tumors, including advanced-stage breast cancer (BC). During the past decade, the US Food and Drug Administration has approved a number of agents for immune checkpoint blockade (ICB). However, the limited data on monotherapy anti-tumor activity in BC underscores the need for robust predictive biomarker development. Here, we used weighted gene coexpression network analysis of genes differentially expressed between BC and normal tissue to identify genes coexpressed with programmed death-1 (PD-1) and its ligand (PD-L1). Tumor Immune Estimation Resource and Gene Expression Profiling Interaction Analysis were used to assess the relationship between gene expression and the abundance of tumor-infiltrating lymphocytes (TILs). We found that chloride intracellular channel protein 2 (CLIC2) was not only coexpressed with PD-1 and PD-L1, but its increased expression was associated with a favorable prognosis and enrichment of multiple TIL types, particularly CD8+ T cells. These results suggest that CLIC2 is a potentially useful biomarker for identifying BC patients who could benefit from ICB.

Human papillomavirus (HPV)16 gene mutation is usually associated with persistent HPV infection and cervical intraepithelial neoplasia (CIN). However, the functional implications of HPV16 mutations remain poorly understood.145 LCR/E6/E7 of the HPV16 isolates were amplified and sequenced, and HPV16 integration status was detected. In total, 89 SNPs (68 in the LCR, 13 in E6, 8 in E7) were discovered, 11 of which were nonsynonymous mutations (8 in E6, 3 in E7). The H85Y and E120D variants in E6 were significantly reduced in the high-grade squamous intraepithelial lesion (HSIL) group compared to theHSIL group (P = .046 and .005), conversely the N29S in E7(P = .01). Amino acid substitutions (D32N/E, E36Q, H85Y, and E120D in E6 and N29H/S and R77C in E7) were predicted to have an effect on conserved structural and functional residues, and five amino acid substitutions (H85Y, E36Q, I34L, and D32E in E6; R77C in E7) would potentially change the secondary structure. "6329GT," a potential binding site for TATA-binding protein, is the most common in LCR variants. A4 (Asian) was associated with an increased risk of HSIL compared to A1-3(P = .009). The H85/E120 in E6 and N29 in HPV16 E7 might play a critical role in carcinogenesis by disrupting p53 and Rb degradation due to affecting their interaction, respectively. In a word, the findings in this study provide preventative and therapeutic interventions of HPV16 -related cervical lesions/cancer.

Objectives Recent studies have shown the presence of SARS‐CoV‐2 in the tissues of clinically recovered patients and persistent immune symptoms in discharged patients for up to several months. Pregnant patients were shown to be a high‐risk group for COVID‐19. Based on these findings, we assessed SARS‐CoV‐2 nucleic acid and protein retention in the placentas of pregnant women who had fully recovered from COVID‐19 and cytokine fluctuations in maternal and foetal tissues. Materials and Methods Remnant SARS‐CoV‐2 in the term placenta was detected using nucleic acid amplification and immunohistochemical staining of the SARS‐CoV‐2 protein. The infiltration of CD14+ macrophages into the placental villi was detected by immunostaining. The cytokines in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens at delivery were profiled using the Luminex assay. Results Residual SARS‐CoV‐2 nucleic acid and protein were detected in the term placentas of recovered pregnant women. The infiltration of CD14+ macrophages into the placental villi of the recovered pregnant women was higher than that in the controls. Furthermore, the cytokine levels in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens fluctuated significantly. Conclusions Our study showed that SARS‐CoV‐2 nucleic acid (in one patient) and protein (in five patients) were present in the placentas of clinically recovered pregnant patients for more than 3 months after diagnosis. The immune responses induced by the virus may lead to prolonged and persistent symptoms in the maternal plasma, placenta, umbilical cord, cord blood and amniotic fluid., Remnant SARS‐CoV‐2 virus RNA and protein could be detected in the term placentas of recovered pregnant women. Immune responses of maternal plasma, placenta, umbilical cord, cord blood, and amniotic fluid were activated by the viruses may persist even longer in vivo

Since December 2019, Wuhan, China, has experienced an outbreak of coronavirus disease (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pregnant women are deductively considered to be in immunosuppressive condition for the safety of semi-allograft fetuses, which increases the risk of being infected by the virus. In this review, we analyzed the unique immunological characteristics of pregnant women and reviewed their known outcomes at different trimesters from the perspective of underlying mechanisms that have been studied and speculated so far.

COVID-19 not only poses a huge threat to public health, but also affects people’s mental health. Take scientific and effective psychological crisis intervention to prevent large-scale negative emotional contagion is an important task for epidemic prevention and control. This paper established a sentiment classification model to make sentiment annotation (positive and negative) about the 105,536 epidemic comments in 86 days on the official Weibo of People’s Daily, the test results showed that the accuracy of the model reached 88%, and the AUC value was greater than 0.9. Based on the marked data set, we explored the potential law between the changes in Internet public opinion and epidemic situation in China. First of all, we found that most of the Weibo users showed positive emotions, and the negative emotions were mainly caused by the fear and concern about the epidemic itself and the doubts about the work of the government. Secondly, there is a strong correlation between the changes of epidemic situation and people’s emotion. Also, we divided the epidemic into three period. The proportion of people’s negative emotions showed a similar trend with the number of newly confirmed cases in the growth and decay period, and the extinction period. In addition, we also found that women have more positive emotional performance than men, and the high-impact groups is also more positive than the low-impact groups. We hope that these conclusions can help China and other countries experiencing severe epidemics to guide publics respond.

Insufficient invasion ability of trophoblasts might be associated with the development of recurrent miscarriage (RM). Ubiquitin-specific protease 25 (USP25) can regulate the processes of invasion and migration in different types of cancer cells. However, the effect of USP25 on trophoblasts and its roles in the development of RM are unknown. In this study, we first analyzed the USP25 expression in placental villous tissues from RM patients, and then assessed the roles of USP25 in epithelial-to-mesenchymal transition (EMT), invasion and migration of trophoblasts. Furthermore, bioinformatics prediction and luciferase reporter assay were used to explore the mechanism of microRNA on USP25 expression, and regulation of USP25 expression in trophoblasts was assessed following transfection with microRNA mimics or inhibitor. The results showed that the expression of USP25 in the placental villous tissues was downregulated in RM patients. Knockdown of USP25 suppressed the EMT process, the invasion and migration capability of trophoblast cells, while overexpression of USP25 exhibited opposite results. Mechanistically, miR-27a-3p could regulate USP25 expression by binding to the 3'-untranslated region of USP25 in trophoblasts. Quantitative real-time polymerase chain reaction results found the expression of miR-27a-3p were negatively related to USP25 in RM patients. MiR-27a-3p mimics inhibited but miR-27a-3p inhibitor enhanced the migration and invasion capability of trophoblasts. Furthermore, sh-USP25 counteracted the promotion of invasion and migration mediated by the miR-27a-3p inhibitor. Taken together, these data indicate that USP25 downregulation by miR-27a-3p contributes to the EMT process, thereby inhibiting the migration and invasion of trophoblast cells, and these findings might provide potential biomarkers for RM.

With the development of human society, factors that contribute to the impairment of female fertility is accumulating. Lifestyle-related risk factors, occupational risk factors, and iatrogenic factors, including cancer and anti-cancer treatments, have been recognized with their negative effects on the function of female reproductive system. However, the exact influences and their possible mechanism have not been elucidated yet. It is impossible to accurately estimate the indexes of female fertility, but many researchers have put forward that the general fertility has inclined through the past decades. Thus the demand for fertility preservation has increased more and more dramatically. Here we described some of the factors which may influence female reproductive system and methods for fertility preservation in response to female infertility.

Introduction There has been no report regarding the impact on male sexual life or sexual function by changes in lifestyle during the coronavirus disease 2019 (COVID-19) epidemic. Aim To investigate the changes in sexual life and sexual function of Chinese men during the COVID-19 epidemic. Methods An online questionnaire was created and the survey was administered through social media to Chinese adult men. Main Outcome Measure The main end point was the deteriorated erectile function or ejaculatory control ability, defined by self-evaluation or by decreased International Index of Erectile Function-5 items (IIEF-5) scores or increased premature ejaculation diagnostic tool (PEDT) scores. Results Altogether, 612 questionnaires were collected. About 322 (52.6%) subjects were unmarried. About 8.4% and 8.5% subjects reported deteriorated erectile function or ejaculation control ability by self-evaluation, whereas 31.9% and 17.9% subjects showed decreased IIEF-5 scores or increased PEDT scores. Subjects with deteriorated erectile function by self-evaluation and decreased IIEF-5 scores had higher General Anxiety Disorder-7 (P < .001 and P = .001) and higher Patient Health Questionnaire-9 score (P < .001 and P = .002) after the epidemic, decreased frequency of sexual life (P < .001 and P < .001) and physical exercise (P = .009 and .007) after the epidemic. Subjects with deteriorated ejaculation control ability by self-evaluation and increased PEDT scores had higher General Anxiety Disorder-7 (P < .001 and P < .001) and higher Patient Health Questionnaire-9 score (P < .001 and P = .002) after the epidemic. Subjects with decreased frequency of sexual life had reduced income (P < .001), increased anxiety (P < .001) and depression (P < .001). Married subjects had higher proportion of improved depression (P = .048) and increased frequency of sexual life (P = .010). Conclusion During the COVID-19 epidemic, decreased sexual function was present in a certain proportion of adult men, and the risk factors include increased anxiety and depression, and decreased frequency of sexual life.

With the development of human society, factors that contribute to the impairment of female fertility is accumulating. Lifestyle-related risk factors, occupational risk factors, and iatrogenic factors, including cancer and anti-cancer treatments, have been recognized with their negative effects on the function of female reproductive system. However, the exact influences and their possible mechanism have not been elucidated yet. It is impossible to accurately estimate the indexes of female fertility, but many researchers have put forward that the general fertility has inclined through the past decades. Thus the demand for fertility preservation has increased more and more dramatically. Here we described some of the factors which may influence female reproductive system and methods for fertility preservation in response to female infertility.

Recurrent pregnancy loss (RPL) is affecting 3-5% of the women who are expecting to have babies annually. However, the molecular changes of RPL patients have not been well characterized before. In the current study, we aimed to discover the differentially expressed genes (DEGs) in decidua from RPL patients by utilizing RNA sequencing (RNA-seq) technology. Four RPL patients and three control women were recruited to conduct RNA-seq, and 153 genes comprising 69 were upregulated and 84 downregulated showed different expression levels between the health control and RPL groups. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to identify potential biological processes associated with RPL. We recognized that type I interferon signaling pathway and TNF signaling pathway are significantly upregulated in women with RPL. Upregulated expression of MX1, IFI27, and ISG15 in type I interferon signaling pathway and TNFRSF21 in TNF signaling pathway were validated by an extended sample of 15 RPL patients and 12 control women, by quantitative real-time polymerase chain reaction (qRT-PCR). In conclusion, the results of the current study revealed molecular changes in decidua which may reflect the intrauterine circumstance when pregnancy loss happens and potentially contributes to RPL.

Background Different endometrial patterns have an important effect on the relationship between endometrial thickness (EMT) and clinical pregnancy rate. There is a significant difference in age, selection of cycle protocols, and clinical pregnancy rates among four groups with diverse endometrial patterns. Methods This retrospective study aimed to assess the association between EMT on human chorionic gonadotropin (HCG) administration day and the clinical outcome of fresh in vitro fertilization (IVF). The 5th, 50th, and 95th percentiles for EMT were determined as 8, 11, and 14 mm, respectively. Patients were sub-divided into four groups based on their EMT in different endometrial patterns (Group 1: 11 and ≤ 14 mm; Group 4: > 14 mm). We divided patients into three groups based on their endometrial pattern and evaluated the correlation between EMT and clinical pregnancy rate. Results We found a positive correlation between pregnancy rates and EMT in all endometrial patterns. Multiple logistic regression analysis proved age, duration of infertility, cycle protocols, number of embryos transferred, progesterone on HCG day, endometrial patterns, and EMT have significant effects on clinical pregnancy rates. Meanwhile, there was a significant difference in age, selection of cycle protocols, and clinical pregnancy rates among four groups with diverse endometrial patterns. Conclusions Different endometrial patterns have an important effect on the relationship between EMT and clinical pregnancy rate.

Background: Coronavirus disease 2019 (COVID-19) has rapidly spread to more than 200 countries. Thus far, reports regarding multi-center data from throughout gestation in women with COVID-19 and newborn outcomes are scarce.Methods: We retrospectively reviewed data from 92 pregnant women with COVID-19 (PW-COVID-19) and their 78 newborns from 27 hospitals in 12 regions of Hubei, China. The demographic, epidemiological, clinical, laboratory, and therapeutic data and pregnancy, perinatal, and neonatal outcomes were analyzed. Follow-up was censored until April 7, 2020.Findings: Median maternal age was 31.0 years (IQR 28·0-33·0), with nine patients in the first trimester, five in the second trimester, and 78 in the third trimester. None of the patients died, and most (92·4%) recovered and were discharged. Seventy-five deliveries (including three sets of twins) comprised 66 cesarean sections and nine vaginal deliveries, with 21 preterm and 57 full-term infants. Seventeen live births had radiological findings of pulmonary infection. One newborn tested positive for SARS-CoV-2 nucleic acid, and three newborns were viral antibody-positive: two IgG (+) and IgM (-), and one IgG (+) and IgM (+). The median suspected duration of virus exposure was 7 days (IQR 0 to 27).Interpretation: Compared to the pregnant women with other viral infections, such as SARS, MERS, and Zika virus infection, PW-COVID-19 had similar manifestations and relatively better outcomes. The termination time and delivery mode in PW-COVID-19 should be evaluated based on both the maternal and fetal situations. The possibility of maternal-to-fetal transmission of SARS-CoV-2 requires further investigation.Authors Shujie Liao and Renjie Wang contributed equally to this work.

COVID-19 has become the most serious public health emergency in the world recently. It not only poses a huge threat to public health, but also affects people's mental health. Take scientific and effective psychological crisis intervention to prevent large-scale negative emotional contagion is an important task for epidemic prevention and control. However, the free and open social network platform has brought challenges to it. In combination with the natural language processing technology and Python's SnowNLP library, this paper established a sentiment classification model to make sentiment annotation (positive and negative) on the 105,536 epidemic comments in 86 days on the official Weibo of People's Daily, the test results showed that the accuracy of the model reached 88%, and the AUC value was greater than 0.9. Based on the marked data set, we explored the potential law between the changes in Internet public opinion and epidemic situation in China. First of all, we found that during the epidemic, most of the Weibo users in China showed positive emotions, and the negative emotions were mainly caused by the fear and concern about the epidemic itself and the doubts about the work of the government. Secondly, there is a strong correlation between the changes of epidemic situation and people's emotion. Also, we divided the epidemic into three period. The proportion of people’s negative emotions showed a similar trend with the number of newly confirmed cases in the growth and decay period, and during the extinction period, it shows the same trend with the number of newly imported cases. In addition, we also found that women have more positive emotional performance than men, and the high-impact groups is also more positive than the low-impact groups. We hope that these conclusions can help China and other countries experiencing severe epidemics to control online public opinion, guide publics respond to such emergencies scientifically and improve the work of the government. Funding Statement: This work was supported by the National Natural Science Foundation of China (81672085;71871169;81372804;U1933120), the Chinese Medical Association of Clinical Medicine special funds for scientific research projects (17020400709), and the Hubei Provincial Natural Science Foundation of China (2019CFA062). Declaration of Interests: The authors have no conflicts of interest to report.

To date, very few studies have reported on the relationship between live birth gender and embryo development kinetics. This study included 1735 women undergoing in vitro fertilization or intracytoplasmic sperm injection by using a time-lapse system. Finally, a total of 228 qualified patients with 100% implantation and known live birth information were included in the analysis. There were 174 male live births and 134 female live births. The time to 3 (t3), 4 (t4), and 5 (t5) cell development of male embryos was significantly shorter/earlier than female embryos (P < 0.05). The duration of the second cell cycle (cc2) in male embryos was significantly shorter than female embryos (P = 0.002). Multivariate logistic regression showed that only t3 had a significant correlation with live birth gender; the odds ratio (OR) was 0.786, 95% confidence interval (CI) was 0.625-0.988 (P < 0.05). When morphokinetic parameters were divided into groups based on quartiles, embryos within the sex ranges were observed to have significantly different proportions of male and female live births (P < 0.05). The results showed that t3 (

This study presents a new 10 year of liquid water cloud droplet number concentration (Nd) climatology, and analyzes its long-term variation on both regional and global scales based on accurate depolarization ratio measurement from CALIPSO and 3.7 μm cloud effective radius retrieval from MODIS. Compared with the widely used passive retrieval method (e.g., MODIS retrieval), which considers Nd as function of cloud optical depth, geometry thickness and effective radius, retrieval method of the new Nd dataset has a weak dependence upon the cloud adiabatic assumption and eliminates the possible bias caused by multilayer clouds. Statistical results show that the annual cycle and long-term variability of Nd retrieved by CALIPSO agree reasonably well with those obtained from MODIS retrieval method, especially over the stratocumulus regions (correlation coefficient >0.9). Multiple regression models and contribution calculation verify that the variability of sulfate mass concentration dominates the long-term variation of Nd over most regions, even though the contribution factors and rates vary with different regions, temperatures and methods. In addition, our study also indicates that the impact of BC and OC on Nd should not be ignored, especially for supercooled water clouds over those important biomass burning regions. These results demonstrate the temperature-dependent Nd climatology derived from CALIOP has potential to be beneficial to climate research and reduce the uncertainties in estimates of the aerosol indirect effect in the model simulations.

An intense summer dust storm over East Asia during June 24–27, 2010, was systematically analyzed based on the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) and a variety of in situ measurements and satellite retrievals. The results showed that the WRF-Chem model captures the spatial and temporal distributions of meteorological factors and dust aerosol in summer over East Asia well. This summer dust storm is initiated by the approach of a transverse trough in the northwestern Xinjiang. Because of the passage of the cutoff-low, a large amount of cold air is transported southward and further enhanced by the narrow valleys of the Altai and Tianshan Mountains, which results in higher wind speeds and huge dust emissions over the Taklimakan Desert (TD). Dust emission fluxes over the TD areas are high as 54 µg m−2 s−1 on June 25. The dust aerosol from the TD then sweeps across Inner Mongolia, Ningxia and Mongolia, and some are also transported eastward to Beijing, Tianjin, Hebei, and even South Korea and Japan. The simulations further show that summer dust over East Asia exerts an important influence on the radiation budget in the Earth-atmosphere system. Dust heats the atmosphere at a maximum heating rate of 0.14 K day−1, effectively changing the vertical stability of the atmosphere and affecting climate change at regional and even global scales. The average direct radiative forcing induced by dust particles over the TD at all-sky is −6.0, −16.8 and 10.8 W m−2 at the top of the atmosphere, the surface, and in the atmosphere, respectively. The discussion about radiative forcing induced by summer dust provides confidence for future investigation of summer dust impact on cloud properties and precipitation efficiency in the eastern China.

The 2019 novel coronavirus disease is spreading all over the world. Pregnant women and infants require particular concern, owing to the special immune conditions. A case of a pregnant woman who was exposed to SARS‐CoV‐2 at 34+1 weeks gestation and chose to continue pregnancy is reported. Without obvious symptoms or signs, the woman did not receive any treatment before delivery, and gave birth at 37+5 weeks to a neonate with positive immunoglobulin G for SARS‐CoV‐2 and negative nucleic acid tests. The mother was given anti‐infection, oxytocin, and fluid rehydration treatment after delivery. Both mother and infant recovered well after a three‐month follow‐up. Continued expectation to deliver at term instead of preterm can decrease the potential risk of severe perinatal and infant complications and is beneficial to the development of the neonate. More studies are required to confirm the presence of vertical transmission., A case study of a pregnant woman who was exposed to SARS‐CoV‐2 at 34+1 weeks gestation and continued expectation until 37+5 weeks with a healthy neonate is reported.

Antral follicle count (AFC) has been widely investigated for the prediction of clinical pregnancy or live birth. This study discussed the effects of AFC quartile levels on pregnancy outcomes combined with female age, female cause of infertility, and ovarian response undergoing in vitro fertilization (IVF) treatment. At present, many research about AFC mainly discuss its impact on clinical practice at different thresholds, or the analyses of AFC with respect to assisted reproductive technology outcomes under using different ovarian stimulation protocols. Factors that include ovarian sensitivity index, female age, and infertility cause are all independent predictors of live birth undergoing IVF/intracytoplasmic sperm injection, while few researchers discussed influence of female-related factors for clinical outcomes in different AFC fields. A total of 8269 infertile women who were stimulated with a long protocol with normal menstrual cycles were enrolled in the study, and patients were categorized into 4 groups based on AFC quartiles (1–8, 9–12, 13–17, and ≥18 antral follicles). The clinical pregnancy rates increased in the 4 AFC groups (28.25% vs 35.38% vs 37.38% vs 40.13%), and there was a negative association between age and the 4 AFC groups. In addition, female cause of infertility like polycystic ovary syndrome, Tubal factor, and other causes had great significance on clinical outcome, and ovarian response in medium (9–16 oocytes retrieved) had the highest clinical pregnancy rate at AFC quartiles of 1 to 8, 9 to 12, 13 to 17, and ≥18 antral follicles. This study concludes that the female-related parameters (female cause of infertility, female age, and ovarian response) combined with AFC can be useful to estimate the probability of clinical pregnancy.

Cervical cancer is one of the most common cancers threatening women's health, and the persistent infection of high-risk human papillomavirus (HPV) is closely related to the pathogenesis of cervical cancer and many other cancers. The carcinogenesis is a complex process from precancerous lesion to cancer, which provides an excellent window for clinical prevention, diagnosis, and treatment. However, despite the various preventions and treatments such as HPV screening, prophylactic HPV vaccines, surgery, radiotherapy, and chemotherapy, the disease burden remains heavy worldwide. Currently, three types of prophylactic vaccines, quadrivalent HPV vaccine, bivalent HPV vaccine, and a new nonavalent HPV vaccine, are commercially available. Although these vaccines are effective in protecting against 90% of HPV infection, they provide limited benefits to eliminate pre-existing infections. Therefore, new progress has been made in the development of therapeutic vaccines. Therapeutic vaccines differ from prophylactic vaccines in that they aim to stimulate cell-mediated immunity and kill the infected cells rather than neutralizing antibodies. This review aims at systematically covering the progress, current status and future prospects of various vaccines in development for the prevention and treatment of HPV-associated lesions and cancers and laying foundations for the development of the new original vaccine.

A successful pregnancy requires sophisticated regulation of uterine microenvironment to guarantee the existence of semi-allogeneic conceptus without immune rejection. T follicular regulatory (Tfr) cells exert a suppressive effect on Tfh-cell expansion, B-cell response, and antibody production. Although accumulating evidence has demonstrated that dysregulations of Tfr cells can bring on various immunological diseases, their immunomodulatory roles during pregnancy still remain unheeded. Herein, we introduced an allogeneic normal-pregnant mouse model and found that CD4+CXCR5hiPD-1hiFoxp3+ Tfr cells were preferentially accumulated in the uterus at mid-gestation and displayed a distinct phenotype. In addition, the absence of PDL1 resulted in increased fetal resorption by favoring Tfr cells accumulation and upregulating PD-1 expression on these cells. However, PDL1 blockade affected neither the ratio of Tfh/Tfr cells nor the maturation and differentiation of B cells. Overall, our results are the first to present a correlation of Tfr cells accumulation with healthy allogeneic pregnancy and PDL1 blockade-induced miscarriage, and to indicate that appropriate assembly of Tfr cells is important for pregnancy maintenance. Since blockade of PD-1-PDL1 pathway leads to more Tfr cells and fetal losses, the reproductive safety must be taken into consideration when PD-1/PD-L1 checkpoint blockade immunotherapy is used in pregnancy.

Insufficient trophoblast invasion is the key factor for the occurrence of recurrent spontaneous abortions (RSA). Our previous studies identified Yin Yang 1 (YY1) as a transcription factor involved in the regulation of trophoblast invasiveness at the maternal-fetal interface. Long noncoding RNAs (lncRNAs) can regulate gene expression and autophagy in many ways. The purpose of this study was to explore the relationship between YY1 and lncRNAs and the mechanism by which lncRNAs affect the biological behavior of trophoblasts. Bioinformatic analysis predicted that YY1 had three binding sites in the plasmacytoma variant translocation 1 (PVT1) promoter region. Chromatin immunoprecipitation experiments and electrophoretic mobility shift assays verified that YY1 can directly bind to the PVT1 promoter. Compared with its expression levels in human placental villi tissue samples from the normal pregnancy group, the PVT1 expression levels were significantly lower in tissues from the RSA group. PVT1 knockdown significantly reduced adhesion, invasion, autophagy, and mTOR expression in HTR-8/SVneo cells and greatly increased apoptosis in vitro. This study revealed a novel regulatory pathway in which YY1 can act directly on PVT1 promoter to regulate its transcription, which further affects trophoblast invasion and adhesion by regulating autophagy via the mTOR pathway, and these effects might be involved in RSA pathogenesis.

Objective: The aim of this study was to explore the benefits of in vitro fertilization (IVF) for patients and hospitals under different protocols and if IVF treatment should be incorporated into health care. Perspective: The government should consider including IVF treatment in health insurance. Hospitals and patients could obtain the best benefit by following the hospital's recommended protocol. Setting: This retrospective study was conducted from January 2014 to August 2017 at an academic hospital. Methods: A total of 7440 patients used gonadotropin-releasing hormone agonists (GnRHa) protocol, 2619 patients used, gonadotropin-releasing hormone antagonists (GnRHant) protocol, and 1514 patients used GnRHa ultra-long protocol. Primary outcomes were live birth rate (LBR), cost-effectiveness, hospital revenue, and government investment. Results: The cycle times for the GnRHa protocol and the GnRHa ultra-long protocol were significantly higher than the GnRHant protocol. Patients who were ≤29 years chose the GnRHant protocol. The cost of a successful cycle was 67,579.39 ± 9,917.55 ¥ and LBR was 29.25%. Patients who were >30 years had the GnRHa protocol as the dominant strategy, as it was more effective at lower costs and higher LBR. When patients were >30 to ≤34 years, the cost of a successful cycle was 66,556.7 ± 8,448.08 ¥ and the LBR was 31.05%. When patients were >35 years, the cost of a successful cycle was 83,297.92 ± 10,918.05 ¥ and the LBR was 25.07%. The government reimbursement for a cycle ranged between 11,372.12 ± 2,147.71 ¥ and 12,753.67 ± 1,905.02 ¥. Conclusions: The government should consider including IVF treatment in health insurance. Hospitals recommend the GnRHant protocol for patients 30 years old, to obtain the best benefits. Patients could obtain the best benefit by using the protocol recommended by the hospital.

The objective of this paper was to compare the effect of recombinant follicle-stimulating hormone (rFSH) and urinary follicle-stimulating hormone (uFSH) on pregnancy rates and live birth rates with the gonadotropin-releasing hormone (GnRH) antagonist protocol in China. This retrospective study was conducted from January 2014 through August 2017. Patients treated with uFSH had significantly higher levels of luteinizing hormone (3.79 mIU/ml vs. 3.09 mIU/ml) and progesterone (0.93 ng/ml vs. 1.16 ng/ml) on the day of human chorionic gonadotropin (HCG) administration, and they also had higher pregnancy rates (24.19% vs. 22.86%). There was no significant difference in the rate of live births. In the logistic regression results of the rFSH group, the pregnancy rate was positively correlated with the level of luteinizing hormone, with an odds ratio (OR) of 1.09 (95% confidence interval [CI]: 1.00–1.18; P = 0.048). In the uFSH group, the pregnancy rate was negatively correlated with the progesterone level on the day of HCG administration, with an OR of 0.47 (95% CI: 0.27–0.77; P = 0.004). Our research concluded that uFSH performed better than rFSH in terms of pregnancy rates when it was associated with the GnRH antagonist protocol. Meanwhile, no significant differences in the rate of live births were observed between the two groups.

Chemotherapeutic agents are extensively used to treat malignancies. However, chemotherapy-induced ovarian damage and reduced fertility are severe side effects. Recently, stem cell transplantation has been reported to be an effective strategy for premature ovarian insufficiency (POI) treatment, but safety can still be an issue in stem cell-based therapy. Here, we show the protective effects of human umbilical cord mesenchymal stem cell-derived conditioned medium (hUCMSC-CM) on a cisplatin (Cs)-induced ovarian injury model. hUCMSC-CM can relieve Cs-induced depletion of follicles and preserve fertility. In addition, hUCMSC-CM can decrease apoptosis of oocytes and granulosa cells induced by Cs. RNA sequencing analysis reveals the differentially expressed genes of ovaries after Cs and hUCMSC-CM treatments, including genes involved in cell apoptosis. Furthermore, we show that the granulocyte colony-stimulating factor (G-CSF)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway plays an important role in protecting granulosa cells from Cs-induced apoptosis. Together, we confirm the protective effects of hUCMSC-CM on ovarian reserve and fertility in mice treated with Cs, highlighting the remarkable therapeutic effects of hUCMSC-CM.

In recent years, most countries around the world have faced increasing pressures in the realm of emergency management than ever before. Medical service organization selection is one of the most vital facets of emergency management. Meanwhile, during the selection process, many criteria may conflict with one another and information is uncertain, rendering decision-making processes complex. Hence, multi-objective optimization, fuzzy way and stochastic theories serve as suitable means of addressing such problems. In this paper, a fuzzy multi-objective linear model is developed to overcome medical service organization selection issues and uncertain information. Meanwhile, a fuzzy objective and weight are applied to enable the decision-maker to select suitable schemes while considering stochastic medical service demand. Moreover, real data cannot been obtained. Hence, according to actual conditions, we assume relative information. For illustrative purposes, a numerical example is presented to verify the effectiveness of the proposed model from experimental data.

With the development of economics, oil has an important influence on social stability. The key challenge for oil import is steady supply. However, in this article, we do not focus on this aspect but the fluctuation of crude oil price when emergency and release of strategic petroleum reserves occur. It is a very complex research in real-life environment. In this situation, case analysis is the best tool for solving this problem. Our model is formulated in such a way as to simultaneously consider new oil price breakpoints, different emergency and so on. For solving the problem, a new programming is developed. Finally, an analysis is presented to illustrate the proposed method. The results show: (1) Natural disasters have less influences on crude oil price than social conflicts. As the impact of Hurricane Katrina is 3.27, less than 4.044 of Libyan conflict, and the subsequent influence is also limited, 5 days less than 8 days of the conflict. (2) Releases of strategic petroleum reserves are effective for the reliefs of oil price fluctuations caused by emergencies, respectively 41.05, 6.48 and 5, presenting a weakening trend of stabilizing role.

Coronavirus disease 2019 (COVID‐19) is spreading worldwide. All aspects of pregnancy management from conception to delivery to puerperium as risks facing newborns are herein, reviewed. Maternal home management and prenatal care management protection, delivery timing or mode selection, delivery process management, and subsequent puerperal protection are crucial. In this Review, the features and treatment strategies, especially emphasizing the safety of antiviral drugs for pregnant women, the wearing of face masks, and practicing of personal hygiene (e.g., handwashing, disinfection, home cleaning, and ventilation) are reviewed as essential protective measures. It is recommended to provide online consultation, telemedicine, and remote fetal heart rate monitoring and set the flow point for prenatal examination to encourage prenatal examination at home or postponing examinations (except nuchal translucency at 11‐13+6 weeks, Oscar Test at 16 weeks, and fetal ultrasound at 20–24 weeks). It is shown that the precise formulation of follow‐up strategies for pregnant women with COVID‐19 is necessary., The 2019 novel coronavirus (2019‐nCoV) spread throughout the world rapidly. All aspects of pregnancy management from conception to delivery to puerperium, and including risks for newborns are reviewed in the paper.

Artificial intelligence (AI) has experienced rapid growth over the past few years, moving from the experimental to the implementation phase in various fields, including medicine. Advances in learning algorithms and theories, the availability of large datasets and improvements in computing power have contributed to breakthroughs in current AI applications. Machine learning (ML), a subset of AI, allows computers to detect patterns from large complex datasets automatically and uses these patterns to make predictions. AI is proving to be increasingly applicable to healthcare, and multiple machine learning techniques have been used to improve the performance of assisted reproductive technology (ART). Despite various challenges, the integration of AI and reproductive medicine is bound to give an essential direction to medical development in the future. In this review, we discuss the basic aspects of AI and machine learning, and we address the applications, potential limitations and challenges of AI. We also highlight the prospects and future directions in the context of reproductive medicine.

Continuous improvement in diagnosis and treatment has significantly increased the survival of cancer patients. Treatments for neoplastic disease, including radiotherapy, chemotherapy, and surgery or combined therapy with the above methods, may lead to premature ovarian insufficiency (POI) or substantial male germ cell loss. For the patients it is a seriously double whammy. Therefore, reproductive medicine experts strongly suggest that all young patients diagnosed with a malignant tumor should immediately undergo a consultation with suggestions for fertility and endocrine function protection and preservation. Here, we discuss the background knowledge, methods, indications, pros and cons, and experimental and clinical applications of fertility preservation, and new strategies for future fertility conservation to help physicians, especially oncologist, pediatrician, hematologist, and surgeons, become aware of the concepts, methods, and importance of fertility and endocrine function protection. We also hope to help doctors develop novel personalized strategies for fertility conservation according to patients' own conditions, tumor types, treatment methods, recurrence rate and so on. This review focuses on changing and enhancing the fertility preservation idea, further investigations in clinical and translational medicine will help ensure the development of novel personalized treatments, to help cancer patients have healthy children or maintain endocrine function once they are in remission. This is just the ultimate dream of oncofertility.