The impact of mindfulness therapy combined with mentalization-based family therapy on suicidal ideation in adolescents with depressive disorder: randomized intervention study.

BACKGROUND: Adolescents with depression who engage in non-suicidal self harming behaviors are more likely to adopt negative coping strategies when faced with negative events. Therefore, these patients should be introduced to positive coping strategies. Evidences have showed that mindfulness-based interventions can positively impact the psychology of patients with mental disorders. This study was to explore the impact of a combination of mindfulness therapy and mentalization-based family therapy (MBFT) on suicidal ideation in adolescents with depressive disorder. METHODS: Eighty adolescent patients with depression and suicidal ideation admitted to our hospital from September 2021 to February 2022 were selected as subjects. They were divided into a control group and a study group using the random number table method, with each group comprising 40 subjects. The control group received MBFT, whereas the study group received both mindfulness therapy and MBFT. The psychological status and suicidal ideations of the two groups were compared before and after the intervention. RESULTS: The psychological health scores of both groups of patients were lower after the intervention, with the scores of the study group being lower than those of the control group (P < 0.05). The scores on the suicidal ideation scales for both groups were lower after intervention, and the study group scored lower than the control group (P < 0.05). The absolute values of the differences in psychological health scale scores and suicidal ideation scale scores before and after the intervention were higher in the study group than in the control group (P < 0.05). CONCLUSION: The combination of mindfulness therapy and MBFT can improve the psychological condition of adolescents with depression, reduce their suicidal ideations, and help them develop a healthy and positive outlook toward life, making this method worthy of clinical recommendation.

Seasonality and risk factor analysis of respiratory syncytial virus infection in children in Taiwan-A retrospective study from 1995 to 2005.

Respiratory syncytial virus (RSV) is one of the important pathogens leading to acute respiratory tract infection in infants and young children. We aimed to investigate the seasonality of RSV infection in different parts of Taiwan and to delineate the risk factors for severe RSV infections. We collected RSV-infected patients' data by retrospective chart review. A total of 1740 RSV-infected children aged under 18 years were enrolled. The infection was acquired during hospitalization in 103 (7.1%) children, while none of them required ventilator support or needed intensive care before RSV infection. The need for intensive care or ventilator support was significantly associated with congenital heart disease (CHD), chronic lung disease, and neuromuscular diseases. Age <1 year and nosocomially acquired infection are also significant predictors for the need of intensive care. Only the presence of CHD, especially acyanotic CHD, was significantly associated with a fatal outcome. RSV infection occurs all year round. Monthly distribution of RSV infections in Northern Taiwan showed a bimodal pattern, with one peak from March to May, and another from August to October. The distribution in Southern Taiwan showed a single peak from April to July. The occurrence of RSV correlates positively with temperature and rain. The bimodal seasonal distribution pattern in Northern Taiwan may be a transitional pattern shifting from a single high winter peak in temperate areas to a wider summer peak in tropical areas. Continuous surveillance is needed to explore the possible effect of global warming on the seasonality of RSV infection.

The secular trend of enterovirus A71 after the implementation of preventive measures in Taiwan.

BACKGROUND: Enterovirus A71 (EV A71) is one of the most important enteroviruses related to morbidity and mortality in children worldwide. This study aimed to analyse the secular trend of EV A71 in Taiwan from 1998 to 2020 and to evaluate the effectiveness of infection control measures. METHODS: We collected the epidemiological data of EV A71 from disease surveillance systems in Taiwan. We analysed the association between the secular trend of EV A71 and preventive measures such as hand washing, case isolation, and suspension of classes. RESULTS: The incidence of enterovirus infections with severe complications (EVSC) decreased from 16.25 per 100,000 children under six in 1998 to less than 9.73 per 100,000 children under six after 2012 (P = 0.0022). The mortality rate also decreased significantly, from 3.52 per 100,000 children under six in 1998 to 0 per 100,000 children under six in 2020 (P < 0.0001). The numbers of EVSC and fatalities were significantly higher in the years when EV A71 accounted for more than 10% of the annual predominant serotypes (p < 0.05). After the implementation of many non-pharmaceutical interventions in 2012, the incidence of EVSC and mortality rate decreased significantly (p < 0.001). CONCLUSIONS: After implementing active enterovirus surveillance and preventive measures, we found that the incidence of EVSC and fatalities due to EV A71 in Taiwan decreased significantly from 1998 to 2020. Continuous surveillance and strengthened infection control policies are still needed in the future.

Analysis of rice root bacterial microbiota of Nipponbare and IR24.

The root-associated bacterial microbiota is closely related to life activities of land plants, and its composition is affected by geographic locations and plant genotypes. However, the influence of plant genotypes on root microbiota in rice grown in northern China remains to be explained. In this study, we performed 16S rRNA gene amplicon sequencing to generate bacterial community profiles of two representative rice cultivars, Nipponbare and IR24. They are planted in Changping and Shangzhuang farms in Beijing and have reached the reproductive stage. We compared their root microbiota in details by Random Forest machine learning algorithm and network analysis. We found that the diversity of rice root microbiota was significantly affected by geographic locations and rice genotypes. Nipponbare and IR24 showed distinct taxonomic composition of the root microbiota and the interactions between different bacteria. Moreover, the root bacteria could be used as biomarkers to distinguish Nipponbare from IR24 across regions. Our study provides a theoretical basis for the in-depth understanding of rice root microbiota in Northern China and the improvement of rice breeding from the perspective of the interaction between root microorganisms and plants.

MDM2 rs2279744 polymorphism and endometrial cancer: a meta-analysis.

Case-control studies on the association between mouse double minute 2 homolog (MDM2) rs2279744 polymorphism and endometrial cancer have provided either controversial or inconclusive results. To clarify the effect of MDM2 rs2279744 polymorphism on the risk of endometrial cancer, a meta-analysis of all case-control observational studies was performed. Pooled odds ratios (ORs) for various polymorphisms were estimated using random and fixed effect models. Q-statistic was used to evaluate the homogeneity, and Egger and Begg tests were used to assess publication bias. Overall, the MDM2 rs2279744 polymorphism was associated with a risk of endometrial cancer (OR = 0.76; 95% CI = 0.64-0.90 for allele contrast, p = 0.002, P(het) = 0.003). The contrast of homozygotes and the recessive and dominant models produced the same pattern of results as the allele contrast. In the analysis stratified by ethnicity, significant associations were found in the Caucasian population in all of the genetic models. Our pooled data suggest evidence for a major role of MDM2 rs2279744 polymorphism in the carcinogenesis of endometrial cancer, especially among Caucasian populations.

Tripterygium glycosides impairs the proliferation of granulosa cells and decreases the reproductive outcomes in female rats.

This study was carried out to investigate the impact of tripterygium glycosides (TGs) on ovarian function of female rats in vitro and in vivo. In vitro studies showed that TG induced cells decrease at G1 phase and inhibited cell proliferation in rat granulosa cells. In vivo, female rats were intragastrically administered with TG at the dose of 60 mg/kg/day for consecutive 50 days. TG caused a prolonged estrous cycle, and a significant reduction in ovarian index, serum E2 level, and numbers of secondary and antral follicles (p < 0.05) in these rats. A significant reduction of viable embryos was demonstrated in TG-treated female rats after mating (p < 0.01). Further, we observed observed the reduced expression level of TGF-ß1 after TG treatment in vitro and in vivo. Moreover, the expression of Smad2 and AKT was also decreased after TG treatment. These results suggest that TG can impair ovarian function through Smads-mediated TGF-ß1 signal pathway.

FSH modulates the expression of inhibin-alpha and the secretion of inhibins via orphan nuclear receptor NUR77 in ovarian granulosa cells.

It has been previously reported that follicle-stimulating hormone (FSH) regulates the expression of inhibin-alpha in human granulosa cells, but the precise molecular pathway remains unknown. In the present study, we investigated the role of the orphan nuclear receptor, NUR77, in both the transcriptional regulation of the inhibin α-subunit gene and the secretion of inhibins. Our results showed that in a human granulosa cell tumor-derived cell line (KGN) and in human granulosa-lutein cells (hGL), FSH induced the expression of NUR77 and inhibin-alpha, although inhibin-alpha expression did not increased following FSH treatment if NUR77 was knocked down. Furthermore, simply overexpressing or reducing NUR77 levels affected inhibin-alpha expression, while NUR77 overexpression improved the secretion of inhibin A and B from human granulosa cells. In addition, chromatin immunoprecipitation-PCR, avidin-biotin-conjugated DNA precipitation, and luciferase reporter assays confirmed that NUR77 directly regulated the transcription of the inhibin-alpha gene through the specific NGFI-B response element located within its promoter. In the ovarian granulosa cells of the Nur77 knockout mice, the mRNA levels of inhibin-alpha were decreased relative to wild-type mice. These data indicate a role of NUR77 in the regulation of inhibin-alpha in ovarian granulosa cells.

Withdrawal of GnRH agonist decreases oestradiol and VEGF concentrations in high responders.

This study evaluated whether the withdrawal of a gonadotrophin-releasing hormone (GnRH) agonist before triggering ovulation reduces the incidence of ovarian hyperstimulation syndrome (OHSS) in high-risk infertility patients who were treated with gonadotrophins. GnRH agonist was withdrawn for 2 or 3 days when dominant follicles were ≥14 mm in diameter, according to the GnRH agonist long protocol. Non-withdrawal of GnRH agonist was used as control. The serum concentration of oestradiol on the ovulation trigger day was significantly decreased in the GnRH agonist withdrawal group compared with the control group (5750.78 ± 2344.77 pg/ml versus 8076.43 ± 1981.67 pg/ml); however, the number of retrieved oocytes and the fertilization rate were similar between the groups. In addition, the concentrations of vascular endothelial growth factor in plasma on day of human chorionic gonadotrophin administration and follicular fluid on the oocyte retrieval day were decreased following GnRH agonist withdrawal. In fresh embryo transfer cycles, rates of clinical pregnancy, implantation and OHSS were not different between the groups. When GnRH agonist withdrawal was followed by total embryos cryopreserved, the rate of OHSS was decreased compared with the control group (0% versus 8.70%). Clinical pregnancy rates in cryopreserved embryo transfer cycles were comparable between the two groups.

Survey of human papillomavirus types and their vertical transmission in pregnant women.

BACKGROUND: The prevalence, genotypes, and vertical transmission characteristics of human papillomavirus (HPV) among pregnant women from Nanjing, China was investigated. METHODS: Cervical cells were collected from healthy pregnant women (n = 3139; stage of gestation, 24.6 ± 2.1 weeks) for cytological evaluation and determination of HPV infection status. Exfoliated oral and genital cells were collected from neonates (<1-day-old, n = 233) whose mothers were positive for HPV DNA. We used HPV Gene Chip technology with 23 HPV genotype probes to conduct our analysis. RESULTS: Overall prevalence of HPV DNA among pregnant women was 13.4% (422/3139). The most frequently detected HPV genotypes were HPV-16 (29.6%, 125/422), -18 (14.7%, 62/422), and -58 (14.2%, 60/422). The rate of concordance for HPV DNA in maternal-neonatal pairs was 23.6% (55/233), with HPV type-specific concordance occurring in 26 cases. A higher prevalence of HPV DNA was apparent in female neonates compared with males (17.7 vs. 11.6%). CONCLUSIONS: The prevalence of cervical HPV DNA in pregnant women from Nanjing was low, with vertical transmission rates slightly higher. From our findings, we concluded that there was efficient vertical transmission of three HPV genotypes, with HPV-16 the most prevalent type in pregnant women and newborn babies.

[Prenatal diagnosis of a case with X-linked spondyloepiphyseal dysplasia tarda].

OBJECTIVE: To analyze TRAPPC2 gene mutation in a family with X-linked spondyloepiphyseal dysplasia tarda and to provide genetic counseling and prenatal diagnosis. METHODS: All of 4 exons of the TRAPPC2 gene and their flanking sequences in the proband and her father were analyzed with polymerase chain reaction and direct DNA sequencing. Genomic DNA of the probands' fetus was extracted from amniotic fluid sampled at 18th gestational week. Gender of the fetus was determined by the presence of SRY gene. The sequence of fetal TRAPPC2 gene was also analyzed. RESULTS: A c.209G>A mutation was identified in exon 4 of the TRAPPC2 gene in the proband and her father. The fetus of was determined to be a male and also have carried the c.209G>A mutation. CONCLUSION: A c.209G>A mutation of TRAPPC2 exon 4 probably underlies the clinical manifestations in this family. The proband is a carrier, and her fetus is a male carrying the same mutation. Prenatal diagnosis is an effective method for the prevention of the disease.

Sandwich stent located in the iliac artery dislodged into the thoracic aorta and its remedy.

The sandwich stent technique is a commonly used method to preserve unilateral internal iliac artery flow when treating iliac artery aneurysm. In this case, covered stent grafts (Viabahn, Gore) were used to build the iliac limb of a sandwich stent. However, if Viabahn is released without long sheath protection, the trigger wire is easily wound on another stent, resulting in the Viabahn delivery system being inseparable from the stent. If we drag it forcefully, it would easily cause the entire sandwich stent graft to shift or even fall into the thoracic aorta. This complication is catastrophic. Here we report the case of a patient whose sandwich stent system disengaged and entered the thoracic aorta. We took corresponding measures to remedy it.

Structurally diverse spirocyclic polycyclic polyprenylated acylphloroglucinols from Hypericum ascyron Linn. and their anti-tumor activity.

Ten spirocyclic polycyclic polyprenylated acylphloroglucinols (PPAP), hunascynols A-J (1-10), and 12 known analogs were isolated from the aerial parts of Hypericum ascyron Linn. Compounds 1 and 2, which share a 1,2-seco-spirocyclic PPAP skeleton, could be derived from spirocyclic PPAP, with a common octahydrospiro[cyclohexan-1,5'-indene]-2,4,6-trione core, through a cascade of Retro-Claisen, keto-enol tautomerism, and esterification reactions. Aldolization of normal spirocyclic PPAP yielded 3, which has a caged framework with a 6/5/6/5/6 ring system. The structures of these compounds were determined using spectroscopy and X-ray diffraction. The inhibitory activities of all isolates were tested in three human cancer cell lines and a zebrafish model. Compounds 1 and 2 displayed moderate cytotoxicity against HCT116 cells (IC50 6.87 and 9.86 µM, respectively). The mechanisms of these compounds were evaluated using Western blot assays. Compounds 3 and 5 inhibited the growth of sub-intestinal vessels in zebrafish embryos. Further, the target genes were screened using real-time PCR.

Serostatus of echovirus 11, coxsackievirus B3 and enterovirus D68 in cord blood: The implication of severe newborn enterovirus infection.

BACKGROUND: Maternal transplacental antibody is an important origins of passive immunity against neonatal enterovirus infection. Echovirus 11 (E11) and coxsackievirus B3 (CVB3) are important types causing neonatal infections. There were few investigations of enterovirus D68 (EVD68) infection in neonates. We aimed to investigate the serostatus of cord blood for these three enteroviruses and evaluate the factors associated with seropositivity. METHODS: We enrolled 222 parturient (gestational age 34-42 weeks) women aged 20-46 years old between January and October 2021. All participants underwent questionnaire investigation and we collected the cord blood to measure the neutralization antibodies against E11, CVB3 and EVD68. RESULTS: The cord blood seropositive rates were 18% (41/222), 60% (134/232) and 95% (211/222) for E11, CVB3 and EVD68, respectively (p < 0.001). Geometric mean titers were 3.3 (95% CI 2.9-3.8) for E11, 15.9 (95% CI 12.5-20.3) for CVB3 and 109.9 (95% CI 92.4-131.6) for EVD68. Younger parturient age (33.8 ± 3.6 versus 35.2 ± 4.4, p = 0.04) was related to E11 seropositivity. Neonatal sex, gestational age and birth body weight were not significantly different between the seropositive group and the seronegative group. CONCLUSION: Cord blood seropositive rate and geometric mean titer of E11 were very low, so a large proportion of newborns are susceptible to E11. The circulation of E11 was low after 2019 in Taiwan. A large cohort of immune naïve newborns existed currently due to lack of protective maternal antibodies. It is imminent to monitor the epidemiology of neonates with enterovirus infections and strengthen the relevant preventive policies.

Maternal and embryonic signals cause functional differentiation of luminal epithelial cells and receptivity establishment.

Embryo implantation requires temporospatial maternal-embryonic dialog. Using single-cell RNA sequencing for the uterus from 2.5 to 4.5 days post-coitum (DPC) and bulk sequencing for the corresponding embryos of 3.5 and 4.0 DPC pregnant mice, we found that estrogen-responsive luminal epithelial cells (EECs) functionally differentiated into adhesive epithelial cells (AECs) and supporting epithelial cells (SECs), promoted by progesterone. Along with maternal signals, embryonic Pdgfa and Efna3/4 signaling activated AECs and SECs, respectively, enhancing the attachment of embryos to the endometrium and furthering embryo development. This differentiation process was largely conserved between humans and mice. Notably, the developmental defects of SOX9-positive human endometrial epithelial cells (similar to mouse EEC) were related to thin endometrium, whereas functional defects of SEC-similar unciliated epithelial cells were related to recurrent implantation failure (RIF). Our findings provide insights into endometrial luminal epithelial cell development directed by maternal and embryonic signaling, which is crucial for endometrial receptivity.

[Change of labor duration:a systematic analysis].

OBJECTIVE: To evaluate the labor duration of healthy primiparas in the past 20 years compared with Friedman labor curve. METHODS: Published observational studies about labor duration in primiparas with singleton vertex presentation were searched in PubMed, EMBase, Cochrane library, CNKI, VIP and Wanfang database. The Cochrane Collaboration's RevMan 5.1 software was used for meta-analysis. RESULTS: Eleven literatures involving 4534 primiparas were included, which were eligible for the criteria to investigate the labor duration. Meta-analysis showed that the length of active phase was significantly different between what was showed in primiparas in the past 20 years and Friedman labor curve [P = 0.01, weighted mean difference (WMD) = 1.61, 95%CI: 0.38 to 2.83], and significant differences were also found in the second stage duration (P = 0.0006, WMD = -0.20, 95%CI: -0.31 to -0.09). CONCLUSIONS: Compared with Friedman labor curve, active phase length of healthy primiparas in the past 20 years was significantly longer and second stage length was shorter. Reassessing labor curve of healthy primiparas is required for more scientific guidance and less unnecessary interventions.

Carascynol A, a hybrid of caryophyllane-type terpenoid and a C6 unit degraded by polyprenylated acylphloroglucinols from Hypericum ascyron.

Carascynol A, an unprecedented 4/9/8 ring system hybrid with a peroxide bridge, was characterized from Hypericum ascyron. The architecture contains a caryophyllane-type moiety and a C6 unit derived from polyprenylated acylphloroglucinols. Its structure and absolute configuration were determined by comprehensive spectroscopic and X-ray diffraction data. Biologically, compound 1 inhibited cell proliferation in LoVo, SW480, and HCT116 cell lines (IC50 = 12.30-24.57 µM).

Effectiveness of case isolation and class suspension in mitigation of enterovirus transmission in children.

BACKGROUND: Appropriate mitigation strategy to minimize enterovirus (EV) transmission among children is essential to control severe EV epidemics. Scientific evidence for the effectiveness of case isolation and class suspension is lacking. METHODS: EV-infected children ≤ eight years are asked to stay at home for seven days. Classes were suspended for seven days if there are more than two classmates having an onset of herpangina or hand, foot, and mouth disease in one classroom within one week. Study subjects are divided into two groups, group A with class suspension for one week and group B without class suspension. RESULTS: Among 4153 reported EV-infected children from 1085 classes in May and June, 2015 were enrolled. Median incidence of EV infection in a class was 7% (range 3% -60%). The incidence was higher in group A (median 14%, range 3-60%) than that in group B (median 6%, range 3-80%) (P < 0.01). The median incidence is highest in day care center (20%), followed by kindergarten (8%), and primary school (4%) (P < 0.01). Most secondary cases in group A appeared within seven days after the disease onset of index case in the same class. The incidence of EV infection remained low and was similar between the two groups eight days and beyond after the disease onset of index cases. CONCLUSIONS: Targeted class suspension for seven days with case isolation for seven days is an effective measure to mitigate transmission of EV infection in children.

Recommendations and guidelines for the treatment of infections due to multidrug resistant organisms.

Antimicrobial drug resistance is one of the major threats to global health. It has made common infections increasingly difficult or impossible to treat, and leads to higher medical costs, prolonged hospital stays and increased mortality. Infection rates due to multidrug-resistant organisms (MDRO) are increasing globally. Active agents against MDRO are limited despite an increased in the availability of novel antibiotics in recent years. This guideline aims to assist clinicians in the management of infections due to MDRO. The 2019 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, comprising of infectious disease specialists from 14 medical centers in Taiwan, reviewed current evidences and drafted recommendations for the treatment of infections due to MDRO. A nationwide expert panel reviewed the recommendations during a consensus meeting in Aug 2020, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes recommendations for selecting antimicrobial therapy for infections caused by carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales, and vancomycin-resistant Enterococcus. The guideline takes into consideration the local epidemiology, and includes antimicrobial agents that may not yet be available in Taiwan. It is intended to serve as a clinical guide and not to supersede the clinical judgment of physicians in the management of individual patients.

[Molecular genetic study of MECP2 gene for a patient with typical Rett syndrome].

OBJECTIVE: To provide genetic diagnosis and counseling for a 2-year-old girl with typical Rett syndrome through analyzing the methyl-CpG binding protein 2 (MECP2) gene. METHODS: Potential mutation of the MECP2 gene was screened by DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis of members of the family as well as normal controls. Lymphocyte culture for karyotype analysis was carried out for the patient to exclude chromosomal abnormalities. RESULTS: The karyotype of the girl was normal. No variation of the MECP2 gene was detected in the patient by direct sequencing. A heterozygosis variation, c.1072G>A in exon 4 of the MECP2 gene was detected in a normal female control, which was not found in other controls. The son and daughter of the female control were respectively heterozygous and homozygous carriers of the same mutation. By MLPA analysis, a heterozygosis deletion of exon 3 and part of exon 4 was detected in the patient. cDNA amplification and sequencing confirmed the presence of a 1176 bp deletion (c.27-1202del1176). The same deletion was not detected in the parents. CONCLUSION: A large deletion in MECP2 gene was detected with MLPA in a patient featuring typical Rett syndrome. The same deletion was missed by sequencing analysis. With cDNA sequencing, the breakage point of the mutation can be mapped precisely.

[Appropriate prolongation of GnRH-a down-regulation improves the synchronism of follicular development].

OBJECTIVE: To determine the relatively appropriate actuation time for ovarian super-stimulation of IVF-ET by comparing the influences of different down-regulation days of chorionic gonadotrophin releasing hormone agonist (GnRH-a) upon the follicular diameter, endometrial thickness and the levels of follicle- stimulating hormone (FSH) , luteinizing hormone (LH) and estradiol (E2). METHODS: We adopted the long protocol of GnRH-a down-regulation in the midluteal phase for 42 patients undergoing IVF-ET. According to the time of GnRH-a down-regulation, we divided the patients into a 10 d, a 15 d and an 18 d group, measured their follicular diameters and endometrial thickness by B-mode ultrasonography, detected the levels of FSH, LH and E2 in the blood, and analyzed the influences of different days of GnRH-a down-regulation on the follicular diameter, endometrial thickness and sexual hormone levels. At 1, 7, 10 and 14 d of down-regulation, we compared the levels of FSH and LH in the blood before the injection of GnRH-a with those 2 and 3 h after it. RESULTS: At 10, 15 and 18 d after down-regulation, the ovarian follicles with the diameter of 3-4 mm accounted for 16.8, 7.09 and 10.38% (P < 0.05, 10 d vs 15 d and 18 d), those with the diameter of 4.5-7.0 mm made up 80.24, 89.55 and 84.62% (P < 0.05, 15 d vs 10 d and 18 d), and those with the diameter of 7.5-10 mm constituted 2.96, 3.36 and 5%, respectively. Endometrial thickness was (7.73 +/- 2.48) mm in the 10 d group, significantly thicker than (5.41 +/- 0.79) mm and (5.24 +/- 0.85) mm in the 15 d and 18 d groups (P < 0.05). The FSH levels in the 10 d, 15 d and 18 d groups were (3.70 +/- 1.10), (3.51 +/- 0.72) and (3.47 +/- 0.61) mIU/ml, the LH levels were (1.23 +/- 1.00), (1.09 +/- 0.47) and (1.22 +/- 0.72) mIU/ml, and the E2 levels were 41.84 +/- 36.81, 32.84 +/- 14.32 and 9.50 +/- 8.23, respectively, with no significant differences among the three groups. At 1, 7, 10 and 14 d of down-regulation, both FSH and LH levels in the blood were increased at 2 and 3 h after GnRH-a injection, most significantly at 1 d (1.87 +/- 1.49 vs 13.33 +/- 7.81 for FSH, 1.06 +/- 1.13 vs 47.40 +/- 29.97 for LH, (P < 0.05). CONCLUSION: In the long protocol of ovarian super-stimulation of IVF-ET, endometrial thickness and the levels of FSH, LH and E2 tended to be stable at 10 d of GnRH-a down-regulation. The percentage of the follicles with the diameter of 4.5-7.0 mm was higher at 15 d than at 10 d, but rose no more at 18 d except for an increased number of smaller follicles 3-4 mm in diameter. Therefore, appropriate prolongation of GnRH-a down-regulation can improve the synchronism of follicular development.