Does Child Maltreatment Reduce or Increase Empathy? A Systematic Review and Meta-analysis.

Arguments about the associations between child maltreatment and empathy remain controversial. This systematic review and meta-analysis aim to estimate the direction and magnitude of the relationships between child abuse and neglect and empathy. Four English databases (Web of Science, PsycInfo, PubMed, and Cochrane Library), three Chinese databases (China National Knowledge Infrastructure, Wanfang, and Weipu), and grey literature were systematically searched. We extracted data related to the associations between child maltreatment and empathy and pooled them using random effects models. A total of 24 eligible studies involving 22,580 participants and 176 estimates were included in the analyses. Overall, child maltreatment was significantly related to reduced empathy (r_ = -0.15, 95% CI [-0.17, -0.13]). Specifically, the rank-order mean effect size of subtypes of maltreatment on empathy is: emotional neglect (r_ = -0.18, 95% CI [-0.25, -0.12]) > physical neglect (r_ = -0.16, 95% CI [-0.23, -0.09]) > emotional abuse (r_ = -0.15, 95% CI [-0.21, -0.10]) > physical abuse (r_ = -0.12, 95% CI [-0.17, -0.07]) > sexual abuse (r_ = -0.07, 95% CI [-0.14, -0.01]). Furthermore, the meta-regression results suggested that the aggregated associations between child maltreatment and empathy were not inflated by publication bias, but they were moderated by the age of respondents, sample size, publication language, empathy measurement, and maltreatment type. The results indicate that general maltreatment and its subtypes are associated with reduced empathy. Parent training and empathy enhancement programs should be designed to help children with a history of childhood maltreatment, respectively, from an early stage.

Associations between Phthalate Metabolite Concentrations in Follicular Fluid and Reproductive Outcomes among Women Undergoing in Vitro Fertilization/Intracytoplasmic Sperm Injection Treatment.

BACKGROUND: Phthalates have been reported to impair fertility in various studies. However, evidence exploring the associations between phthalate metabolites in follicular fluid (FF) and reproductive outcomes is lacking. OBJECTIVES: To investigate the associations between phthalate metabolite concentrations in FF and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes among women recruited from a fertility clinic. METHODS: We included 641 women undergoing IVF/ICSI treatment from December 2018 to January 2020. The levels of eight phthalate metabolites, including monoethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), were quantified in FF collected on the oocyte retrieval day. Associations between quartiles of individual phthalate metabolite concentrations and nine IVF/ICSI outcomes, including oocyte yield, mature oocyte number, two distinct pronuclei (2PN) zygote number, fertilization rate, blastocyst formation rate, implantation, clinical pregnancy, miscarriage, and live birth, were estimated with generalized linear models. The effects of phthalate mixtures on IVF/ICSI outcomes were assessed using Bayesian kernel machine regression (BKMR) models. RESULTS: After adjusting for relevant confounders, elevated quartiles of MBzP, MEHHP, and MEHP in FF were inversely associated with the numbers of retrieved oocytes, mature oocytes, and 2PN zygotes (all p for trends <0.10). In comparison with the lowest quartile, the highest quartile of molar sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP) was associated with a reduction of 9.1% [95% confidence interval (CI): -17.1%, -0.37%] and 10.3% (95% CI: -18.8%, -0.94%) in yielded oocyte and mature oocyte numbers, respectively. Furthermore, the BKMR models revealed inverse associations between phthalate mixtures and the numbers of retrieved oocytes and mature oocytes. We generally found null results for implantation, clinical pregnancy, miscarriage, and live birth. DISCUSSION: Certain phthalate metabolites in FF are inversely associated with the numbers of retrieved oocytes, mature oocytes, and 2PN zygotes among women undergoing IVF/ICSI treatment. https://doi.org/10.1289/EHP11998.

Uterine niche is associated with adverse in vitro fertilization and intracytoplasmic sperm injection outcomes: a retrospective cohort study.

OBJECTIVE: To investigate the relationship between uterine niche and reproductive outcomes of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). DESIGN: A retrospective cohort study. SETTING: A reproductive medicine center. PATIENT(S): A total of 2,449 women with cesarean section history who underwent 2,874 IVF/ICSI cycles between January 2015 and December 2019. INTERVENTION(S): A defect deeper than 2 mm visible under three-dimensional transvaginal sonography or hysteroscopy was defined as uterine niche. The IVF/ICSI outcomes of the first embryo transfer were obtained by telephone interview 1 year after embryo transfer regardless of fresh embryos or frozen-thawed embryos. Generalized estimating equations, logistic regression analyses, and propensity score matching were applied to clarify the relationship between uterine niche and IVF/ICSI outcomes. MAIN OUTCOME MEASURE(S): Primary outcome was live birth rate. Secondary outcomes were positive human chorionic gonadotropin test results, clinical pregnancy rate, implantation rate, miscarriage rate, and ectopic pregnancy rate. RESULTS: After excluding 48 cycles for uterine malformation; 18 cycles for chromosome abnormality; 281 cycles for no available embryo or no embryo transfer; 5 cycles for oocyte donation; and 7 cycles for loss of follow-up, we finally included 2,231 women with 2,515 cycles in our study. Compared with women without niche, women with niche had reduced live birth rate (18.99% vs. 31.51%, : 0.51, 95% CI: 0.34-0.77), positive human chorionic gonadotropin test rate (34.08% vs. 46.40%, adjusted odds ratio [aOR]: 0.61, 95% confidence interval [CI]: 0.43-0.87), clinical pregnancy rate (29.05% vs. 42.25%, aOR: 0.57, 95% CI: 0.39-0.82) and implantation rate (25.87% vs. 36.95%, aOR: 0.53, 95% CI: 0.38-0.76). In all the sensitivity analyses, the niche group had a 7.28% to 18.22% increase in miscarriage rate even not all of them were statistically significant. CONCLUSION(S): Uterine niche may have a detrimental effect on subsequent fertility of women with cesarean section history undergoing IVF/ICSI treatment. Practitioners should be noted that women with uterine niches may be associated with adverse IVF/ICSI outcomes.

Urinary phthalate metabolites and the risk of endometrial polyp: A pilot study from the TREE cohort.

Phthalates, as endocrine disrupting chemicals that can alter the endogenous hormones, may be involved in the incidence of endometrial polyp, a benign hormone-dependent condition. We conducted a pilot case-control study from the Tongji Reproductive and Environmental (TREE) cohort to investigate the associations between phthalate exposures and the risk of endometrial polyp. A total of 40 endometrial polyp patients were matched to 80 controls by age and body mass index in the ratio of 1:2. Two spot urine samples from each subject were quantified for eight phthalate metabolites to enhance exposure assessment. The conditional logistic regression and quantile-based g-computation models were separately used to explore the associations between individual and mixture of urinary phthalate metabolites and the risk of endometrial polyp. After adjusting for covariates, individual chemical analyses showed that urinary monobenzyl phthalate (MBzP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethylhexyl) phthalate (MEHHP) and the sum of di(2-ethylhexyl) phthalate (ΣDEHP) were associated with increased risks of endometrial polyp, with adjusted odds ratios ranging from 2.62 (95% CI: 0.88, 7.84) for MECPP to 6.96 (95% CI: 1.87, 25.87) for ΣDEHP comparing the extreme exposure categories (all P for trends <0.05 or = 0.057). These associations still persisted when these exposures were modeled as continuous variables. Chemical mixture analyses showed that a simultaneous one-quartile increase in concentrations of eight phthalate metabolites was associated with an elevated odds ratio of 3.14 (95% CI: 1.49, 6.60) in endometrial polyp. Our data suggests that exposure to individual benzylbutyl phthalate (BBzP) and DEHP, as well as mixture of phthalates is associated with increased risk of endometrial polyp. This may inform public health recommendations and policies to avoid phthalate exposures for improving female reproductive health.

Anti-müllerian hormone as a predictor for live birth among women undergoing IVF/ICSI in different age groups: an update of systematic review and meta-analysis.

PURPOSE: To update the evidence of anti-müllerian hormone (AMH) as predictive factors for live birth outcome in women undergoing assisted conception and discover the modulating effect of age. METHODS: PubMed, Embase, Medline, and Web of Science were searched for studies published until June 2021. We included studies that measured serum AMH levels and reported the subsequent live birth outcomes. Random effects models and hierarchical summary receiver operating characteristics (HSROC) models were used. The QUADAS-2 checklist was employed to assess the quality of the included studies. RESULTS: We included 27 studies (27,029 women) investigating the relationship between AMH and live birth outcome after assisted conception. The diagnostic odds ratios (DOR) from random effects models were ruled out due to high heterogeneity. Our findings suggested that AMH was associated with live birth. The DOR was 2.21 (95% CI 1.89-2.59), and 2.49 (95% CI 1.26-4.91) for studies on women with unspecified ovarian reserve and women with low ovarian reserve, respectively. The DOR of those with advanced ages was 2.50 (95% CI 1.87-2.60). For younger women, the DOR was 1.41 (95% CI 0.99-2.02). HSROCs showed that AMH had no predictive ability towards live birth in women with diminished ovarian reserve or younger age. Exclusion of Chinese cohorts lowered the heterogeneity. CONCLUSIONS: This study revealed that AMH had better prediction for live birth in advanced-age women. AMH may have implicative predictive value for assisted conception counseling of couples of advanced ages.

Rescue in vitro maturation may increase the pregnancy outcomes among women undergoing intracytoplasmic sperm injection.

Introduction: To investigate whether rescue in vitro maturation (R-IVM) improves the reproductive outcomes among women undergoing intracytoplasmic sperm injection (ICSI) after one oocyte retrieved cycle. Methods: Between January 2019 and December 2020, 2602 women who underwent ICSI in the Reproductive Medicine Center of Tongji Hospital, Wuhan, China, were included in our retrospective cohort study. There were 2112 women undergoing only ICSI and 490 women with R-IVM followed by ICSI. The intermediate reproductive outcomes and pregnancy outcomes were assessed, including the number of normally fertilized embryos, number of cleaved embryos, number of good-quality embryos, number of day-3 available embryos, number of embryos cultured past day-3, number of blastocysts, number of available blastocysts, biochemical pregnancy, miscarriage, clinical pregnancy and live birth. The perinatal outcomes were also assessed, including preterm birth and birth weight. The abovementioned outcomes were also calculated for in vivo matured and R-IVM oocytes separately in women undergoing ICSI with R-IVM group. Results: Compared with the women who underwent only ICSI, those who underwent ICSI with R-IVM had higher numbers of MII oocytes, normally fertilized embryos, cleaved embryos, day-3 available embryos, embryos cultured past day-3, and higher oocyte maturation rate, available embryo rate than women undergoing only ICSI. Additionally, we found that women undergoing ICSI with R-IVM had an increased chance of clinical pregnancy (adjusted OR=1.50, 95% CI: 1.17-1.93) and cumulative live birth (adjusted OR=1.35, 95% CI: 1.07-1.71). After propensity score matching (PSM), the cumulative live birth rate was 60.1% for women undergoing ICSI with R-IVM versus 54.9% for women undergoing only ICSI (OR=1.24, 95% CI: 0.94-1.63). The reproductive outcomes were also significantly different when calculated for in vivo matured and R-IVM oocytes separately in women undergoing ICSI with R-IVM group. All live births from R-IVM embryos were healthy and without malformations or complications. Conclusion: R-IVM may improve the reproductive outcomes of women undergoing ICSI. It may also provide a reference for the safety of R-IVM. This study maybe support a routine application of R-IVM among patients who intend to undergo ICSI.

The association between caffeine and alcohol consumption and IVF/ICSI outcomes: A systematic review and dose-response meta-analysis.

INTRODUCTION: The objective of this study was to evaluate the association between caffeine and alcohol consumption and in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) outcomes. MATERIAL AND METHODS: The protocol was registered in the PROSPERO database on May 23, 2021 (registration number: CRD42021256649), and updated on August 4, 2022. Two researchers performed a literature search in the PubMed, Embase, and MEDLINE databases for articles published before July 15, 2022 independently. Studies investigating the association between caffeine and alcohol consumption and IVF/ICSI outcomes were included, and studies reporting the consumption amount were analyzed using a one-stage robust error meta-regression-based method to explore potential dose-response relation. Funnel plot was used to assess publication bias if more than 10 studies were included. RESULTS: Twelve studies on caffeine consumption and 14 studies on alcohol consumption were included in the systematic review, of which seven and nine were eligible for the meta-analysis. These studies included 26 922 women and/or their spouses who underwent IVF/ICSI treatment. Women's and men's caffeine consumption was not significantly associated with the pregnancy rate (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.85-1.12; OR 0.93, 95% CI 0.75-1.14; respectively) and the live birth rate (OR 0.98, 95% CI 0.89-1.08; OR 0.98, 95% CI 0.86-1.12; respectively) of IVF/ICSI. Maternal alcohol consumption was negatively associated with pregnancy after IVF/ICSI treatment (OR 0.83, 95% CI 0.69-1.01). Paternal alcohol consumption was negatively associated with partner's live birth after IVF/ICSI treatment (OR 0.88, 95% CI 0.79-0.99). Compared with abstainers, the chance of achieving a pregnancy after IVF/ICSI treatment decreased by 7% for women who consumed 84 g alcohol per week (OR 0.93, 95% CI 0.90-0.98), and the chance of partners achieving a live birth decreased by 9% for men who consumed 84 g alcohol per week (OR 0.91, 95% CI 0.88-0.94). CONCLUSIONS: There was no association between caffeine consumption and pregnancy or live birth rate of IVF/ICSI. Women's alcohol consumption was associated with decreased pregnancy rate after IVF/ICSI treatment when weekly consumption was greater than 84 g. Men's alcohol consumption was associated with decreased live birth rate after IVF/ICSI treatment when weekly consumption was greater than 84 g.

Associations of sleep characteristics with outcomes of IVF/ICSI treatment: a prospective cohort study.

STUDY QUESTION: Are sleep characteristics associated with outcomes of IVF/ICSI treatment? SUMMARY ANSWER: Nocturnal sleep <7 h/night and disturbed sleep are related to impaired oocyte and embryo yield, while longer nocturnal sleep might reduce the chance of a successful pregnancy, and the associations between nocturnal sleep duration and IVF/ICSI outcomes are modified by maternal age and subjective sleep quality. WHAT IS KNOWN ALREADY: Disturbed sleep and circadian rhythm contribute to impaired fecundity in the general population, but the effects of sleep characteristics on IVF/ICSI outcomes are largely unknown. STUDY DESIGN, SIZE, DURATION: This study was conducted among 1276 women undergoing IVF/ICSI treatment between December 2018 and September 2019 based on the Tongji Reproductive and Environmental cohort. Owing to the limited number of multiple cycles, we included only the outcomes of their first IVF/ICSI cycle in the current analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on sleep characteristics were collected via questionnaires on the day of oocyte retrieval. IVF/ICSI outcomes were abstracted from medical records. Quasi-Poisson, quasi-binomial or logistic regression models were used to assess the relations between sleep characteristics and reproductive outcomes after adjusting for relevant confounders. We also performed stratified analyses by subjective sleep quality (good versus poor) and maternal age (≤30 versus >30 years). MAIN RESULTS AND THE ROLE OF CHANCE: Compared with women who slept 7 to <8 h/night, those who slept <7 h/night exhibited decreases in the number of retrieved and mature oocytes of 11.5% (95% CI: -21.3%, -0.48%) and 11.9% (95% CI: -22.4%, -0.03%), respectively. A mid-sleep time (MST) earlier than 2:21 a.m. (<2:21 a.m.) or later than 3:00 a.m. (≥3:00 a.m.) and poor subjective sleep quality were inversely associated with the fertilization rate. Women who had trouble falling asleep more than three times per week had a lower number of mature oocytes (-10.5%, 95% CI: -18.6%, -1.6%), normal fertilized oocytes (-14.8%, 95% CI: -23.7%, -4.8%) and good-quality embryos (-15.1%, 95% CI: -25.4%, -3.5%) than those who had no such trouble. In addition, women who slept 9 to <10 h/night had a lower chance of clinical pregnancy compared to women who slept 7 to <8 h/night (odds ratio = 0.65, 95% CI: 0.44, 0.98). In the stratified analyses, the positive associations of nocturnal sleep duration with the number of good-quality embryos and fertilization rate existed only among the women with poor subjective sleep quality (P for interaction = 0.02 and 0.03, respectively). Additionally, we found that the positive associations of nocturnal sleep duration with implantation or clinical pregnancy only existed among women aged over 30 years (P for interaction = 0.04 and 0.01, respectively). LIMITATIONS, REASONS FOR CAUTION: Sleep characteristics are self-reported, which may lead to misclassification. MST serves as a proxy of chronotype and may be non-differentially misclassified resulting in an underestimate of the association of interest. Measuring sleep characteristics on the day of oocyte retrieval may lead to bias. Chance findings cannot be excluded because of the limited number of women with <7 h or ≥10 h nocturnal sleep and multiple testing. Our results may be biased by other confounders and may not be generalizable to women of other ethnicities. WIDER IMPLICATIONS OF THE FINDINGS: Unhealthy sleep characteristics, including short nocturnal sleep, inappropriate sleep time, poor subjective sleep quality and having trouble falling asleep, may impair oocyte quantity and its potential to mature or be fertilized. Long nocturnal sleep might reduce the chance of clinical pregnancy among infertile females, especially women younger than 30 years old. Prolonged nocturnal sleep duration may be a potential beneficial behavior for improving IVF/ICSI outcomes for women aged over 30 years and women with poor subjective sleep quality, which requires further investigation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (81771654) and the National Key R&D Program of China (No. 2018YFC1004201). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Associations between drinking water disinfection byproducts and menstrual cycle characteristics: A cross-sectional study among women attending an infertility clinic.

Disinfection byproducts (DBPs) have been shown to alter ovarian steroidogenesis and cause estrous cyclicity disturbance and prolongation in experimental studies, however human studies are lacking. We aimed to evaluate the cross-sectional associations between drinking water DBPs and menstrual cycle characteristics. A total of 1078 women attending an infertility clinic in Wuhan, China were included between December 2018 and January 2020. Characteristics of menstrual cycle were collected by questionnaires. Concentrations of dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were measured in urine as biomarkers of drinking water DBPs. Multivariate logistic and linear regression models were used to evaluate the associations between urinary DCAA and TCAA concentrations and menstrual cycle characteristics. Higher urinary DCAA concentrations were associated with increased odds ratios (ORs) of irregular menstrual cycle (OR = 1.80; 95% CI: 0.97, 3.33 for the highest vs. lowest quartile; P for trend = 0.05) and long menstrual cycle (OR = 1.62; 95% CI: 0.97, 2.70 for the highest vs. lowest quartile; P for trend = 0.06), as well as prolonged variation in cycle length (ß = 1.27 days; 95% CI: -0.11, 2.66 for the highest vs. lowest quartile; P for trend = 0.04). Higher urinary TCAA concentrations were associated with prolonged bleeding duration (ß = 0.23 days; 95% CI: -0.06, 0.51 for the highest vs. lowest quartile; P for trend = 0.07). These results suggest that exposure to drinking water DBPs is associated with menstrual cycle disturbances. These findings are warranted to confirm in other studies.

Human Umbilical Cord Mesenchymal Stem Cells Improve Ovarian Function in Chemotherapy-Induced Premature Ovarian Failure Mice Through Inhibiting Apoptosis and Inflammation via a Paracrine Mechanism.

Human umbilical cord mesenchymal stem cell (UC-MSC) application is a promising arising therapy for the treatment of premature ovarian failure (POF). However, little is known about the inflammation regulatory effects of human umbilical cord MSCs (UC-MSCs) on chemotherapy-induced ovarian damage, regardless of in vivo or in vitro. This study was designed to investigate the therapeutic effects of UC-MSC transplantation and underlying mechanisms regarding both apoptosis and inflammation in POF mice. The chemotherapy-induced POF models were induced by intraperitoneal injection of cyclophosphamide. Ovarian function parameters, granulosa cell (GC) apoptosis, and inflammation were examined. Morphological staining showed that UC-MSC treatment increased the ovary size, and the numbers of primary and secondary follicles, but decreased the number of atretic follicles. Estradiol levels in the UC-MSC-treated group were increased while follicle-stimulating hormone levels were reduced compared to those in the POF group. UC-MSCs inhibited cyclophosphamide-induced GC apoptosis and inflammation. Meanwhile, phosphorylation of AKT and P38 was elevated after UC-MSC treatment. Tracking of UC-MSCs in vivo indicated that transplanted UC-MSCs were only located in the interstitium of ovaries rather than in follicles. Importantly, UC-MSC-derived extracellular vesicles protected GCs from alkylating agent-induced apoptosis and inflammation in vitro. Our results suggest that UC-MSC transplantation can reduce ovary injury and improve ovarian function in chemotherapy-induced POF mice through anti-apoptotic and anti-inflammatory effects via a paracrine mechanism.

Multiple Epstein-Barr virus strains in patients with infectious mononucleosis: comparison of ex vivo samples with in vitro isolates by use of heteroduplex tracking assays.

Recent work using a heteroduplex tracking assay (HTA) to identify resident viral sequences has suggested that patients with infectious mononucleosis (IM) who are undergoing primary Epstein-Barr virus (EBV) infection frequently harbor different EBV strains. Here, we examine samples from patients with IM by use of a new Epstein-Barr nuclear antigen 2 HTA alongside the established latent membrane protein 1 HTA. Coresident allelic sequences were detected in ex vivo blood and throat wash samples from 13 of 14 patients with IM; most patients carried 2 or more type 1 strains, 1 patient carried 2 type 2 strains, and 1 patient carried both virus types. In contrast, coresident strains were detected in only 2 of 14 patients by in vitro B cell transformation, despite screening >20 isolates/patient. We infer that coacquisition of multiple strains is common in patients with IM, although only 1 strain tends to be rescued in vitro; whether nonrescued strains are present in low abundance or are transformation defective remains to be determined.

[Inhibiting target gene expression and controlling growth of Epstein-Barr virus transformed cells by antisense RNA transcripts].

BACKGROUND & OBJECTIVES: The latent membrane protein gene (LMP) of Epstein-Barr virus (EBV) was thought to play an important role in the carcinogenesis of nasopharyngeal carcinoma (NPC). In this study, the authors investigated the effects of antisense RNA (AsRNA) on LMP for down regulating at the target gene over expression in EBV transformed lymphoid cells, and set up an antisense system to inhibit LMP expression. METHODS: Constructing the single strand antisense transcription system in vitro, the authors have got large amount of AsRNA. Designing and setting up an antisense tracing system in situ (ATSIS), the authors could observe the living particles of AsRNA/sense RNA duplex dimer. With time lapse phase-contrast microscopy, the agglutination phenotype on living cells was easily detected by MTT test, the inhibition rate on EBV transformed cells was calculated. RESULTS: LMP 1.9 fragment ligated into pGEM vector in reverse orientation have been constructed and produced a plentiful amount of AsLMPmRNA which could incorporated into both B95-8 and C1936 cell lines by endophagocytosis and formed the duplex dimer of As/Sense RNA. This particles have been visualized in situ when labelling 35S isotope by ATSIS. When AsLMPmRNA acted as agents for specific inhibition to LMP over expression, the transform phenotype of cell agglutination have been suppressed and MTT particle formatin was apparently reduced both two EBV tansformed cell lines. CONCLUSION: AsLMPmRNA targets at sense strand have a high effectiveness of down-regulation on EBV-LMP overexpression. This down regulating function of LMP and growth inhibition on transformed cell is demonstrated by the antisenes tracing system in situ (ATSIS). The results provide a clue to overcome the latent EBV infection in human bodies all living long time and to prevent it inducing NPC in high incidence area by antisense strategies.