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Objective: To observe the effects of heat-sensitive moxibustion on corticotropin releasing hormone (CRH), adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) in rats with irritable bowel syndrome (IBS), and to explore the possible mechanism of heat-sensitive moxibustion on IBS., Methods: According to random number table, 56 SD male rats were randomly divided into a blank group ( n =8), a model group ( n =8), a moxibustion group ( n =32), and a mifepristone group (RU-486 group, n =8). The rats in the blank group were treated with normal feeding; the rats in the model group, RU-486 group and moxibustion group were treated with chronic non-predictable stimulation for 21 days to establish IBS model. After model establishment, the rats in the moxibustion group were treated with moxibustion at "Mingmen" (GV 4) for 40 min, once a day for 14 days; the tail temperature was recorded every 5 min; according to the change of tail temperature, the rats were divided into a heat-sensitive moxibustion group and a non-heat-sensitive moxibustion group, and 8 rats were randomly selected in the two groups. The rats in the RU-486 group were treated with gastric administration of RU-486 for 14 days, while the rats in the blank group, model group and moxibustion groups were treated with identical volume of 0.9% NaCl. The rat general condition, body mass, behavioristics, intestinal propulsive rate and visceral sensitivity were observed in each group; ELISA method was used to detect serum CRH, ACTH and CORT; optical microscope was applied to observe the morphological changes of colon., Results: (1) After model establishment, rats were in rest state, fatigued, with withered hair and dim ear; the stool was dry or watery; the body mass were slowly increased; the number of crossed grid and standing frequency were significantly reduced; visceral sensitivity was increased and intestinal propulsion rate was decreased; no obvious inflammatory cell infiltration was observed under microscope. (2) After intervention, compared with the blank group, the body mass and visceral sensitivity in the RU-486 group were not significantly different (both P >0.05), but the intestinal propulsion rate was decreased significantly ( P <0.01). Compared with the blank group, the body mass of heat-sensitive moxibustion group and non-heat-sensitive moxibustion group was lower (both P <0.01), but the visceral sensitivity and intestinal propulsion rate were similar (both P >0.05). Compared with the model group, the body mass and visceral sensitivity were improved in the RU-486 group ( P <0.05, P <0.01), but the intestinal propulsion rate was similar ( P >0.05). The body mass, visceral sensitivity and intestinal propulsion rate of the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group were superior to those of the model group ( P <0.05, P <0.01), and the body mass and intestinal propulsion rate of heat-sensitive moxibustion group were superior to those of non-heat-sensitive moxibustion group (both P <0.05). (3) After intervention, compared with the blank group, the contents of CRH, ACTH and CORT in the model group were significantly increased ( P <0.05, P <0.01). Compared with the model group, the contents of CRH, ACTH and CORT of the heat-sensitive moxibustion group were statistically reduced ( P <0.05, P <0.01), and the contents of CRH and ACTH in the non-heat-sensitive moxibustion group were statistically reduced ( P <0.05, P <0.01); the content of CRH in the RU-486 group was reduced ( P <0.05), but the contents of ACTH and CORT were increased ( P <0.05, P <0.01). Compared with the non-heat-sensitive moxibustion group, the heat-sensitive moxibustion group was better in the improvement of CRH ( P <0.05), but there was no significant difference of ACTH and CORT between the two groups (both P >0.05)., Conclusion: Heat-sensitive moxibustion could reduce the contents of CRH, ACTH and CORT through the HPA axis, and improve the function of gastrointestinal motility to treat IBS.

Objective: To assess the efficacy and safety of mifepristone combined with oral or vaginal misoprostol for termination of pregnancy between 8 and 16 weeks of gestation., Methods: This was a randomized, multi-center, open clinical trial. A total of 625 women at 8-16 weeks of gestation were randomized to receive 200 mg oral mifepristone followed by either oral misoprostol 400 µg every 3 hours or vaginal misoprostol 400 µg every 6 hours for a maximum of 4 doses 36-48 hours later. There were 417 women in oral group with 198 at 8-9 weeks and 219 at 10-16 weeks, while 208 women in vaginal group with 99 at 8-9 weeks and 109 at 10-16 weeks. The outcome measures were the success abortion rate, induction to abortion interval, the amount of bleeding, reoccurrence of menstruation and adverse events., Results: Abortion rate was significantly higher in vaginal group [98.1% (202/206)] than that in oral group [94.0% (390/415), P = 0.023]; concerning termination of pregnancy at 8-9 weeks and 10-16 weeks respectively, there were no significant differences between oral and vaginal groups (P = 0.156, P = 0.073). The induction to abortion interval was no significant difference in oral and vaginal group in different gestational weeks (P = 0.238, P = 0.273). The average induction to abortion interval was (4.1 ± 6.6) hours and (6.0 ± 4.5) hours respectively in terminating 8-9 weeks and 10-16 weeks of gestation. Concerning the amount of bleeding within 2 hours of placenta expulsion, there was significant difference between oral group [(63 ± 46) ml] and vaginal group [(55 ± 45) ml] in terminating 8-9 weeks of gestation (P = 0.047), while there was no significant difference between groups in terminating 10-16 weeks of gestation [oral group (76 ± 52) ml versus vaginal group (76 ± 61) ml, P = 0.507]. The reoccurrence of menstruation was about 37 days in both oral and vaginal groups. Two cases of incomplete abortion were serious adverse events (SAE) relating to treatment. The common adverse events (AE) of nausea and vomiting were significantly higher in oral group [57.2% (239/417), 36.3% (151/417)] than those in vaginal group [45.4% (94/208), 26.1% (54/208); P = 0.005, 0.011]., Conclusion: Oral or vaginal misoprostol combined with mifepristone, is effective and safe for termination of pregnancy between 8 and 16 weeks of gestation.

Objective: To explore the lowest effective dosage of mifepristone combined with misoprostol in terminating ultra-early pregnancy., Methods: All the cases of ultra-early pregnancy classified by amenorrhea days, β-hCG and vaginal B-ultrasonic were randomly divided into two groups. One hundred cases in G1 group (minimized dosage) were orally administered 25 mg mifepristone once a day for 2 days and combined with 200 µg misoprostol 48 hours later, while 150 mg mifepristone combined with 600 µg misoprostol 48 hours later were given to 100 cases in G2 group (normal dosage). All cases were observed for 6 hours after taking misoprostol and returned for assessment three days later., Results: None missing. Expulsion of conceptus: G1 and G2 group were 22 (22.0%, 22/100) and 25 (25.0%, 25/100; P > 0.05). Failure rate: cases with incomplete abortion were 1 (1.0%, 1/100) and 2 (2.0%, 2/100) in G1 and G2 group, hospitalization for suspected ectopic pregnancies both was 1 (1.0%). Bleeding: bleeding cases during the administration of mifepristone in G1 and G2 group were 71 (71.0%, 71/100) and 78 (78.0%, 78/100; P > 0.05); the mean bleeding time were (5.3 ± 1.4) days and (6.0 ± 1.5) days (P < 0.01). Other side effects: in G1 group, majority showed light nausea (7.0%, 7/100) and light abdominal pain (20.0%, 20/100). Menses recovery: 99 (99.0%, 99/100) for G1 group and 98 (98.0%, 98/100) for G2 group to recovery on scheduled time. Satisfactions: both were 99 (99.0%, 99/100). Except mean bleeding days and side-effects, the differences above showed no significance (P > 0.05)., Conclusion: It is safe and effective treatment with the lowest dosages of mifepristone and misoprostol to terminate ultra-early pregnancies.

Objective: To observe the effects of Nrf2 gene expression induced by RU486 at different doses on A549 cell damage induced by paraquat (PQ)., Methods: After A549 cells transfected with Ad-RUNrf2 were treated by RU486 at the doses of 10(-10), 10(-9), 10(-8) and 10(-7) mol/L for 6 h, A549 cell cultures were exposed to 10(-3) mol/L of PQ for 48 h. Then qRT-PCR and EMSA assays were used to detect the expression of Nrf2 gene, and qRT-PCR and ELISA assays were utilized to measure the effects of Nrf2 gene on the expression of the inflammatory cytokines IL-6, IL-10 and TNF-α, apoptotic factors Caspase-3, Caspase-9 and Cytochrome C. The oxidation factors (CAT and MDA protein contents) were observed by Chemical Colorimetric Analysis., Results: Nrf2 gene relative expression and protein contents increased with RU486 concentrations, and the above expression was the highest when the concentration of RU486 was 10(-7) mol/L, which was significantly higher than those in control and PQ exposure groups (P < 0.01 or P < 0.05). The relative gene expression and protein expression of IL-6 and TNF-α enhanced with the reduced concentrations of RU486, which were the lowest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.01 or P < 0.05), while the change of IL-10 content was the opposite. The relative expression of Caspase3, Caspase9 and Cytochrome C genes also increased with the reduced concentrations of RU486, which were the lowest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.01 or P < 0.05). The content of CAT enhanced with RU486 concentration, which was the highest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.05). But the change of MDA content was the contrary., Conclusion: Nrf2 expression induced by RU486 can promote the balance of oxidation-antioxidation system in A549 cells and inhibit the inflammation and apoptosis factors, which has a protective effect on A549 cell injury induced by PQ.

Objective: To investigate the method of establishing damaged endometrial stromal cells (ESC) model in vitro., Methods: (1) From June to December 2011 ESC from normal endometrim at proliferation phase (n = 8) and secretory phase (n = 8) were isolated, cultured and identified in vitro. (2) ESC was treated with different concentrations of mifepristone or withdrawal of mifepristone at different time point. The proliferation inhibition percent was measured by cell counting kit-8 (CCK-8). (3) 0 µmol/L(control group)and 60 µmol/L (experimental group) concentration of mifepristone was added into ESC for 48 hours, then withdrew of mifepristone, continued to be cultured for 48 hours. The morphological changes were observed and apoptosis of ESC in different menstrual cycle were detected by flow cytometry. The mRNA and protein level of vascular endothelial growth factor (VEGF), caspase-3, 8, and 9 were determined by one-step quantitative real-time PCR (Q-PCR) and western blot., Results: (1) ESC from 16 specimens of endometrium were all isolated and cultured successfully. (2) The proliferation inhibition rate of ESC was correlated with concentration and duration of mifepristone positively. The proliferation of ESC could be recovered at a range of time after withdrawal of mifepristone. However, when the concentration of mifepristone was 100 µmol/L, the growth of ESC recovered very hardly. (3) The damaged ESC spacing increased, the spindle shape and vacuolization in the cytoplasm were observed in experimental group; the rate of apoptosis of these damaged cells was significantly increased compared with control groups, which were (52 ± 12)% vs. (13 ± 5)% at the proliferative phase and (53 ± 6)% vs. (32 ± 3)% at the secretory phase (all P < 0.05). The relative mRNA level of VEGF was 0.52 ± 0.12 in experimental group and 1.00 ± 0.17 in control group at proliferation phase (P < 0.05). And the relative mRNA level of VEGF was 0.19 ± 0.03 in experimental group and 0.81 ± 0.07 in control group at secretory phase (P < 0.05). The relative level of VEGF protein in the experimental group were both decreased 1.98 and 2.79 folds at the proliferation phase and the secretory phase when compared with those in control group, respectively (P < 0.05). While the relative levels of caspase-3, 8, 9 mRNA were 5.62 ± 0.65, 5.41 ± 0.53, 7.22 ± 0.51 in the experimental group and 1.00 ± 0.44, 1.00 ± 0.21, 1.00 ± 0.32 in control group at the proliferative phase. In the mean time, the relative levels of caspase-3, 8, 9 mRNA were 10.22 ± 0.72, 25.3 ± 1.72, 9.48 ± 1.89 in experimental group and 1.42 ± 0.14, 1.14 ± 0.28, 1.16 ± 0.12 in control group at the secretory phase, respectively (P < 0.05). Compared with the control group, the levels of caspase protein in the experimental group were increased 2.04 and 1.60 folds in caspase-3, 4.23 and 1.49 folds in caspase-8, 2.65 and 3.5 folds in caspase-9 at the proliferative phase and at the secretory phase, respectively (P < 0.05)., Conclusion: The damaged model of ESC can be established after 48 hours by the withdrawal of 60 µmol/L mifepristone in treatment of ESC for 48 hours.

Objective: To evaluate the therapeutic effect and safety of pelvic methotrexate (MTX) injection via the posterior fornix for treatment of tubal pregnancy., Methods: Ninety-six patients with tubal pregnancy (mean age 21-40 years) were randomized into 3 groups for treatment with pelvic MTX injection via the posterior fornix+mifepristone+traditional Chinese medicine (experiment group), intramuscular MTX injection+mifepristone+traditional Chinese medicine (control group I), or mifepristone+traditional Chinese medicine (control group II). On days 4 and 7 of the treatment, blood β-HCG of the patients in different groups was detected, and in cases with continuous reduction of blood β-HCG or a reduction by over 15%, β-HCG was checked every week. One week after the treatment, the size of the mass was measured by B-mode ultrasound. The clearance time of β-HCG and the hospital stay of the patients were recorded., Results: Twenty-nine patients in the experimental group were treated successfully, with a cure rate of 90.6%, which was significantly higher than those in the two control groups (P<0.05). The clearance time of β-HCG and hospital stay were also much shorter in the experimental group (P<0.05)., Conclusion: Pelvic MTX injection via the posterior fornix is a convenient procedure associated with minimal complications and serves as a good alternative for treatment of tubal pregnancy.

Objective: To investigate the suitable mode of induced termination of pregnancy at second and third trimester for women with scarred uterus., Methods: A retrospective study was performed in 90 cases of second and third trimester pregnant women with scarred uterus, who requested termination of pregnancy due to medical indications in Beijing Obstetrics and Gynecology Hospital from September 2002 to June 2009. The indications of termination of pregnancy were fetal anomaly, serious pregnant complication and intrauterine fetal deaths. 72 second trimester pregnant women and 18 third trimester pregnant women were included in this study. The interval time of previous operation to this pregnancy were recorded. And it was < 2 years in 20 cases and ≥ 2 years in 70 cases. The patients with normal Hepatic function began to take mifepristone and had an allergic test of Ethacridine Lactate. The method of mifepristone combined with Ethacridine Lactate were adopted when the allergic test was negative (group A, 54 cases). The method of mifepristone combined with carboprost methylate suppositories were used in the patients who had a positive reaction to the allergic test of Ethacridine Lactate, or who failed to amniotomy to inject Ethacridine Lactate because of oligohydramnios or small gestational age (group B, 36 cases). Record the detail information of every patient. (1) Age, gestational weeks, gravidity and parity. (2) The mode of previous operation (inducing the scar of uterus), previous operation time and indication. (3) The mode of induced labor in this pregnancy, the interval time from administration to uterine contraction, delivery or not and the interval time from induction to delivery. (4) Postpartum hemorrhage, the successful rate of induce labor, placental retention ratio and rupture of uterus or not., Results: (1) It had no significant difference between group A and group B in age, gravidity, parity and the interval time of previous operation to this pregnancy (P > 0.05). But there was significant difference between two groups in gestational weeks of induction (16 weeks vs. 25 weeks, P < 0.01). (2) It had no significant difference between two groups in successful rate of induction and postpartum hemorrhage (P > 0.05), but the time from induction to regular uterine contraction and delivery in group B was significant shorter than that of group A (P < 0.01). The rate of delivery with 24 hours in group B was 94%. It was significant higher than that of group A (13%, P < 0.01). (3) The rate of retained placenta in group B (31%, 11/35) was significant higher than group A (10%, 5/52), but the ratio of residual of placenta and membranes in group A was significant higher than that of group B (54% vs. 34%). It was no significant difference in total rate of postpartum complication between two groups. Further analysis was done in relationship of complication and the time of previous operation. It was no significant difference between the over 2 years group and the less 2 years group in the incidence rate of complications including placental retention, residual of placenta and membranes, rupture of uterus, placental abruption and postpartum hemorrhage. (4) There was 1 case of uterine rupture in group B and 1 case of placental abruption in group A., Conclusions: Both of methods of mifepristone combined with carboprost methylate suppositories and the mifepristone combined with Ethacridine Lactate are feasible to induced second trimester and late trimester termination of pregnancy for women with scarred uterus. But sufficient preoperation preparation and the course of induction and labor careful monitoring must be done to prevent the uterine rupture.

Objective: To study the changes of DNA repair genes and enhanced anti-tumor effect of cisplatin induced by mifepristone in human ovarian cancer drug resistance cells., Methods: The alterations of cisplatin concentration producing 50% inhibition (IC50 ) in the COC1/DDP cell lines were examined by methyl thiazolyl tetrazolium (MTT) assay. RT-PCR and flow cytometry were used to analyze the changes of the mRNA of ERCC1, BRCA1, hMLH1 genes and cell cycle and apoptosis. Subcutaneous implantation of COC1/DDP was established in nude mice and the enhanced anti-tumor effect of cisplatin by mifepristone was observed in vivo., Results: Cisplatin IC50 values of COC1/DDP cell were decreased from (3.71 +/- 0.38) microg/ml to (3.18 +/- 0.46), (1.95 +/- 0.14), (0.64 +/- 0.18) microg/ml respectively when treated with 2.5, 5.0, 10.0 micromol/L mifepristone. Mifepristone could down-regulate the mRNA levels of ERCC1, BRCA1, hMLH1 genes and enhance G0/G1 phase block effect of cisplatin, and 2.5, 5.0, 10.0 micromol/L mifepristone combined with cisplatin increased rate of cell apoptosis from 0.08% to 5.11%, 9.13% and 12.24% respectively. The percentage of inhibition of xenograft tumor volume in combined treatment group was 70.1%, which was significantly different (P < 0.05)., Conclusion: By down-regulating ERCC1, BRCA1, hMLH1 genes, blocking G0/G1 phase, and increasing apoptosis rate, mifepristone could enhance anti-tumor effect of cisplatin.

Objective: To investigate the immunologic mechanism of low dose mifepristone as an anti-implantation contraceptive drug., Methods: Endometrial biopsies were obtained from fourteen normally cycling women during the receptive phase. Each endometrial tissue, divided into three equal parts, was assigned to three groups: control group, 65 nmol/L mifepristone group (group A) and 200 nmol/L mifepristone group (group B). Endometrial explants were cultured in vitro. The numbers of natural killer cells and the percentages of CD3- CD56+ CD16- subset and CD3- CD56+ CD16+ subset were analysed by immunohistochemistry and flow cytometry., Results: (1) The mean number of CD56+ NK cells in group A (148 +/- 11) and group B (150 +/- 12) were significantly higher when compared to the control group (121 +/- 7, P < 0.05). There was no significant difference between the two mifepristone-treated groups (P > 0.05). (2) The percentage of CD3- CD56+ Nk cells in group A (44 +/- 5)% and in group B (48 +/- 4)% were significantly higher when compared to the control group (35 +/- 3)% (P < 0.05), there was no significantly difference between the two mifepristone-treated groups (P > 0.05); The percentage of CD3- CD56+ CD16- subset in group A (42 +/- 5)% and in group B (45 +/- 5)% were significantly higher when compared to the control group (33 +/- 3)%, (P < 0.05), there was no significantly difference between the two mifepristone-treated groups (P > 0.05); the percentages of CD3- CD56+ CD16+ subset in three groups [(2.70 +/- 0.24)% (3.26 +/- 0.37)% and (2.33 +/- 0.29)%] were not significantly different (P > 0.05)., Conclusion: Low dose mifepristones increase the number of CD56+ NK cells and the percentage of CD3- CD56+ CD16- NK subset, which might result in the disturbance of human endometrial immuno-microenvironment during receptive phase and lead to implantation failure.

Objective: To explore the efficacy and safety of terminating biochemical pregnancy (the stage in which intrauterine or ectopic pregnancy cannot be confirmed) with mifepristone and misoprostol., Methods: Mifepristone (150 mg) combined with misoprostol (600 microg) 3 days later were given to 500 biochemical pregnancies (G(1)), 500 early clinical pregnancies (G(2)) and 500 clinical pregnancies (G(3)) which were classified according to amenorrhea days, serum human chorionic gonadotropin-beta subunit (beta-hCG) and vaginal B-ultrasonic examinations. All were observed for 6 hours after taking misoprostol and returned for assessment per week., Results: Expulsion of conceptus was G(1) 123 (24.6%, 123/500), G(2) 438 (87.6%, 438/500) and G(3) 467 (93.4%, 467/500). Failure rate was G(1) 6 (1.2%, 6/500), G(2) 24 (4.8%, 24/500) and G(3) 79 (15.8%, 79/500) for ongoing pregnancies, hospitalizations for suspected ectopic pregnancies and surgical intervention for heavy or long-time bleeding. Bleeding cases during the administration of mifepristone were G(1) 272 (54.4%, 272/500), G(2) 141 (28.2%, 141/500) and G(3) 87 (17.4%, 87/500); the mean bleeding days were G(1) (5.8 +/- 1.5), G(2) (9.0 +/- 2.9) and G(3) (14.3 +/- 5.9) days. Other side effects including abdominal pain, nausea, vomiting and diarrhea were low and light in each group, increasing with advancing gestational age. Menses recovery was 486 (97.2%, 486/500), 452 (90.4%, 452/500) and 433 (86.6%, 433/500) for each group on scheduled time. Satisfaction was 499 (99.8%, 499/500), 485 (97.0%, 485/500) and 369 (73.8%, 369/500) respectively., Conclusion: Mifepristone and misoprostol in combination is as safe, and effective for termination of biochemical pregnancies as ordinary medical abortion. It does not need to wait till ectopic pregnancy is excluded.

Objective: To study the clinical value of transcervical resection under hysteroscope in treatment of placental remnants., Methods: From March 2003 to April 2006, 14 cases of placental remnants were treated with transcervical resection under hysteroscope. They included 3 cases of term birth, and 11 cases of midtrimester induction of labor. Drug pretreatment was performed for those who had more than 80 U/L of blood beta-human chorionic gonadotropin (beta-hCG) level, including mifepristone (RU486), Chinese herbs and methotrexate (MTX). RU486 was taken orally at 25 mg, three times daily and misoprostol was given 600 microg at one dose on the third day. MTX was given by deep intramuscular injection at 1 mg/m(2) if beta-hCG was higher than 150 U/L. Bipolar evaporation was used in the operation with alternation of resection and forceps holder under ultrasonographic supervision. After operation a circular contraceptive device was placed followed by hormone periodic treatment such as estradiol valerate for 2 - 4 months., Results: Under the monitoring by ultrasonography, 14 operations were all performed smoothly. The follow-up was from 6 months to 2 years. Menstruations in almost all the cases were recovered, and 3 cases of those were pregnant and delivered smoothly 4, 6 and 7 months after operation., Conclusion: The transcervical resection under hysteroscope is useful in treatment of placental remnants with obvious effects, little trauma and few complications.

Objective: To evaluate the clinical effect and safety of combined use of methotrexate and mifepristone for treatment of ectopic pregnancy., Methods: By searching in the major databases of CNKI, CBMdisk and Pubmed according to the criteria of evidence-based medicine, we collected data of randomized controlled trials pertaining to combined use of methotrexate and mifepristone in the treatment of ectopic pregnancy., Results: Twenty-three randomized controlled trials involving totally 1 706 patients were collected according to the inclusion criteria, and meta-analysis of the data indicated that combined use of methotrexate and mifepristone can be of great value in the management of ectopic pregnancy in comparison with exclusive use of methotrexate [ combined odds ratio (OR) was 2.84 with 95%confidence interval [CI] (2.18, 3.69), Z=7.79, P<0.000 01]., Conclusion: The clinical evidence derived from the analysis suggests that the combination of methotrexate and mifepristone for ectopic pregnancy management can be effective with good safety security and minimal side effects, but still, this conclusion needs further verification by randomized, double-blind, and controlled trials with larger sample size and more rigorous trial design.

Objective: To select a safe, quick and effective method for terminating ectopic pregnancy (EP) with few adverse effects., Methods: Patients were divided into 2 groups. The observed group was treated with methotrexate (MTX, 50 mg/m2 for single dose intramuscular injection) plus RU 486 (600 mg taken orally in the morning with empty stomach, followed with fasting for 2 hrs) and Waiyun Zhuyu decoction (WZD, one dose a day for 7-10 days). The control group was only treated with MTX, with the same regimen as used in the observed group., Results: The curative rate, time for blood beta-HCG recovering, lump absorption time, and tube recanalization rate in the observed group were better than those in the control group (P < 0.01). CONCLUSION; The key links for successfully treating EP with conservative drug therpy are to diagnose the disease early and clearly, and to select indicative subject strictly. The scheme of single dose administration of MTX plus RU486 combined with WZD, with its high efficacy and few adverse reaction, may be used as the first choice for referential clinical drugs administration.

Objective: To observe the effects of mifepristone combined with methotrexate for conservative treatment of tubal ectopic pregnancy., Methods: A total of 102 cases of tubal ectopic pregnancy diagnosed at early stage were enrolled to receive oral mefepristone at the dose of 75 mg twice daily for 3 d and intramuscular injection with calcium leucovorin at 0.1 mg/kg 24 h after a single dose of methotrexate injection (1 mg/kg.b.w.). In the control group consisting of 86 similar cases, intramuscular injection with calcium leucovorin at 0.1 mg/kg was given 24 h after a single dose of methotrexate (1 mg/kg.b.w.)., Results: Ninety-four of the 102 cases ( 92.20%) receiving oral mifepristone combined with calcium leucovorin and methotrexate were cured, a curative rate significantly higher than that in the control group, where 70 cases (81.4%) were cured (P<0.05)., Conclusion: Mefepristone combined with methotrexate is safe and effective in the treatment of tubal ectopic pregnancy, without obvious side effects.

Objective: To assess the safety of mifepristone in combination with misoprotol for medical abortion., Method: Literatures on the safety of medical abortion were searched in 9 databases worldwide and 9 Chinese medical journals., Results: A total of 101 articles and 1364 women were collected. Severe side effects including allergic or hemorrhagic shock, arrhythmia, convulsion and newborn deformities were observed in 115 cases. A total of 1015 cases appeared vaginal bleeding, mild or moderate allergic reaction. Systematic review found the relative risks (95% confidence interval, CI) of bleeding, abdominal pain, fever and dizziness in the medical abortion population were 3.27 (1.14 - 9.38), 1.63 (1.14 - 2.34), 1.58 (1.03 - 2.44) and 1.36 (1.06 - 1.75), respectively. These were higher in the medical abortion population than that in the surgical abortion population. In addition, the duration of bleeding caused by medical abortion was longer than that caused by surgical abortion. Its weighted mean difference was 6.49 and 95% CI was 6.08 - 7.80., Conclusions: The incidence of side effects caused by this medical abortion was low. However, attention should be paid in clinical practice to the rare, but severe adverse events caused by this treatment. It is necessary to establish a comprehensive nationwide reporting system for these adverse events.

Objective: To investigate the effect of high dose mifepristone and high dose progesterone in the treatment of patients with endometrial carcinoma and to explore the possible mechanisms associating with them., Methods: Thirty untreated patients diagnosed as endometrial carcinoma through dilation and curettage of the uteri were divided into 3 groups at random. Each group was given medroxyprogesterone acetate (MPA), (500 mg/day) or mifepristone (MIF), (100 mg/day) or MIF (100 mg/day) + MPA (500 mg/day) for 5 days respectively. On the sixth day, hysterectomy was performed on these patients. The endometrial cancer specimen of post-hysterectomy was compared with the one of pre-administrating. The morphologic changes of the endometrial cancer cells were observed through light microscope. Immunohistochemistry assay (SP method) was applied to determine the localization and immunoreactive intensity of proliferating cell nuclear antigen (PCNA), estrogen receptor (ER), progesterone receptor (PR), B-cell leukemia lymphoma-2 (bcl-2), bcl-2 associated X protein (bax) and CD(44v6)., Results: Better differentiation degree and active excretion were observed in all of the post-hysterectomy endometrial specimen. In the same time, apoptosis of carcinoma cells was observed. The most significant changes were seen in the MIF + MPA group. In the MPA group, the pre-treatment and post-treatment expression of PR (2.9 +/- 1.1, 1.6 +/- 0.8), ER (2.8 +/- 0.9, 1.4 +/- 0.9), PCNA (0.84 +/- 0.10, 0.60 +/- 0.12), bcl-2 (0.236 +/- 0.089, 0.157 +/- 0.981) and CD(44v6) (4.6 +/- 1.8, 2.5 +/- 1.9) were all decreased (all P < 0.01); the expression of bax (0.20 +/- 0.10, 0.42 +/- 0.07) was increased (P < 0.01). In the MIF group, the expression of PR (3.4 +/- 1.0, 1.9 +/- 0.8), ER (2.7 +/- 0.9, 1.2 +/- 0.7), PCNA (0.80 +/- 0.15, 0.65 +/- 0.10), bcl-2 (0.214 +/- 0.097, 0.121 +/- 0.073) were all decreased (all P < 0.01); the expression of bax (0.21 +/- 0.05, 0.44 +/- 0.09) was increased (P < 0.01); no significant change in the expression of CD(44v6) (4.2 +/- 2.0, 4.3 +/- 1.7) was seen (P > 0.05). In the MIF + MPA group, the expression of PR (3.2 +/- 1.0, 0.8 +/- 0.8), ER (2.7 +/- 0.9, 0.7 +/- 0.9), PCNA (0.81 +/- 0.09, 0.25 +/- 0.09), bcl-2 (0.225 +/- 0.091, 0.066 +/- 0.009) and CD(44v6) (4.5 +/- 1.9, 2.7 +/- 1.6) were all decreased (all P < 0.01); the expression of bax (0.22 +/- 0.06, 0.59 +/- 0.09) was increased (P < 0.01); there were significant different expression of PCNA, ER, PR, bax and bcl-2 as compared with the MIF group and the MPA group, respectively (all P < 0.01). The expression of CD(44v6) was significantly different (P < 0.01) between the MIF + MPA group, and the MIF group, but not significantly different between the MIF + MPA group and the MPA group., Conclusions: The study indicates that high dose progesterone could inhibit the growth, promote apoptosis and inhibit metastasis of endometrial carcinoma, MIF could inhibit the growth and promote apoptosis, MIF + MPA could more strongly inhibit the growth, promote apoptosis and inhibit metastasis of endometrial carcinoma than MIF or MPA, and synergistic effect was observed on the expression of PCNA, ER, PR, bax and bcl-2.

Objective: To assess the efficacy and side-effects after treatment of 100 mg mifepristone and misoprostol in the luteal phase of the cycle., Methods: This study was carried out in seven family planning clinics in China, including 699 women who were exposed to unprotected intercourse more than five days earlier or having had more than one episode of unprotected intercourse in the same cycle. Mifepristone 100 mg was given on admission followed two days later by 400 micro g misoprostol orally in the luteal phase of the cycle., Results: One woman was lost to follow-up after taking mifepristone. After treatment 25 women (3.6%) were pregnant and 673 women had return of menstruation, among whom, 381 (56.6%) had the return of menstruation +/- 3 days of the expected day, 57 women (8.5%) had a delay of menstruation > 7 days. Pregnancy rate was related to the number of acts of intercourse before treatment, the difference was statistically significant (P < 0.05). The main side effects within a week after treatment were diarrhoea and abdominal pain (31.1%) as well as nausea and vomiting (20.4%)., Conclusion: The use of mifepristone with misoprostol during luteal phase provides an option for occasional use for preventing pregnancy.

Objective: To compare the effects of mifepristone of different doses on emergency contraception., Methods: 3,052 healthy women with regular menstrual cycle who visited the 10 family planning institutes and hospitals in Beijing, Shanghai, Shangdong, Sichuan, Tianjin, Guangdong, and Liaoning for emergency contraception within the period of 120 hours after a single act of unprotected sex were given a single dose of 10 mg or 25 mg mifepristone randomly and double-blindly. They were asked to record the vaginal hemorrhage that would occur and not to have unprotected sex until the next menstrual onset when they were followed up. The trial for a specific subject ended when she menstruated. If the menstruation was irregular or a specific subject failed to menstruate on time a blood or urine human chorionic gonadotropin (hCG) test was made. If the hCG test was negative, an appointment was made to follow up once one week later. If the hCG test was positive ultrasound examination was made to detect pregnancy. If the subject still failed to menstruate and the hCG test was still negative follow-up for this subject could be finished., Results: Twenty-two of the 3,052 subjects were lost to follow up. Among the remaining 3,030 women 1,516 were in the 10 mg group and 1 514 in the 25 mg group. Seventeen pregnancies occurred in each group, with a pregnancy rate of 1.1% for both groups. The relative risk of pregnancy of treatment of 25 mg mifepristone in comparison with treatment of 10 mg mifepristone was 1.0 (95% CI: 0.51-1.95). Both doses prevented about 85% approximately 86% of the anticipated pregnancy if no measure had been adopted. The pregnancy rate nearly doubled in the women who had unprotected sex after treatment of mifepristone. The efficacy of mifepristone decreased along with the delay of mifepristone administration. Side effects were uncommon and mild. Delay of 7 days or more in the onset of next menstruation occurred in 9%-10% of the women., Conclusion: Mifepristone of the dose of 10 mg is safe and effective for emergency contraception. Earlier administration is preferable, although the method can be used effectively up to five days after the unprotected sex.

Recently it was found that alpha1,3-fucosyltransferase (FUT9) was an essential enzyme involved in the synthesis of Le(X) oligosaccharide. In this article, the expression of FUT9 gene at different hormonal levels and the regulating mechanism of Le(X) synthesis in human endometrium were investigated by using RT-PCR Immuno histochemistry staining and Western blotting. FUT9 mRNA was detected with human endometrium, and the levels of mRNA in secretory endometrium and in proliferative endometrium from patients who had taken mifepristone before operation, were higher than tha t of proliferative endometrium (P<0.01). Le(X) antigen was mainly located on the surface of epithelium. The floating level of Le(X) antigen expression was similar to that of FUT9 gene. There were three (33 kD, 35 kD and 85 kD) LeX carrying proteins expressed in human endometrium, mifepristone treatment made 35 kD b and disappear. The results indicate that FUT9 gene is obviously expressed in human endometrium and can be upregulated by progesterone, and ovary hormones regulate the expression of Le(X) at the level of transcription.

Objective: To find out the optimal doses regimen of mifepristone with misoprostol for termination early pregnancy., Methods: A randomized comparative study in 1,621 women requesting medical abortion at < or = 49 days from 9 hospitals was conducted in Hebei, women were randomly divided into 2 groups by 2:1 ratio. Study group (n = 1,118) women took mifepristone 50 mg immediately, then 25 mg b. i. d(total amount of 300 mg), plus misoprostol 600 micrograms at 8:00 in the morning on 3th day, and plus misoprostol 200 micrograms respectively at 8:00 in the morning on 4th, 5th, 6th day. In control group (n = 494), mifepristone 50 mg immediately, then, 25 mg b. i. d (total amount of 150 mg), plus misoprostol 600 micrograms at 8:00 in the morning on 3th day., Results: In study group and control group, the complete abortion rate was 98.39% and 88.06% respectively, bleeding duration was (8.2 +/- 2.8) days and (12.3 +/- 3.9) days. There was no difference of side effects between the two groups., Conclusion: Mifepristone taken 300 mg plus misoprostol 1,200 micrograms orally for 6 days is an optimal dose regimen for termination of early pregnancy.

Objectives: To investigate the effectiveness and side-effects of different doses of mifepristone alone or in combination with anordrin given orally within 96 hours after unprotected intercourse as an emergency contraceptive., Methods: 2,400 cases of healthy women were recruited and allocated randomly in 4 groups: single dose of 25 mg mifepristone, 25 mg mifepristone plus 7.5 mg anordrin, 10 mg mifepristone plus 5 mg anordrin and 10 mg mifepristone alone. The efficacy rates of contraception were estimated according to Dixon method., Results: The total expected number of pregnancy was 171.9 for 2,387 subjects enrolled in the study. The number of observed pregnancies related to method failure was 32 cases. The contraceptive effectiveness rates for the above 4 groups were 80.9%, 85.3%, 90.6% and 67.3%, respectively. For the group received 10 mg mifepristone plus 5 mg anordrin, pregnancy rate was 0.7% which was significantly lower than that in 10 mg mifepristone alone group (2.2%, P < 0.05). The incidences of withdrawal bleeding were 9.2%, 4.9%, 3.4% and 6.7% for the 4 group respectively. Two groups received mifepristone in combination with anordrin showed significant lower incidence of withdrawal bleeding than those in mifepristone alone groups., Conclusion: Single oral administration of 25 mg mifepristone alone, and the combination of 10 mg mifepristone plus 5 mg anordrin were safe and effective treatment regimen for emergency contraception with no serious adverse reaction and disturbance on menstrual pattern.

Objective: To investigate the efficacy of three different low doses of mifepristone for emergency contraception, the side effects and the influence to the next menstruation., Methods: A randomized multicentre trial was conducted in Shanghai. 639 women with regular cycles and history of unprotected intercourse within 120 h of attendance were recruited, and they were randomly assigned to three groups. Group I (n = 214) mifepristone 50 mg was given, group II (n = 214) 25 mg and group III (n = 211) 10 mg., Results: There were eight pregnancies totally, 2 cases in group I, 1 in group II and 5 in group III. After correction for method failure there was only 1 pregnancy in each group and the contraceptive effectiveness rate were 93.4%, 93.3% and 93.8% respectively. The side effects of mifepristone were slight and tolerable and there was significant difference between the 50 mg group and the lower doses (25 mg and 10 mg) groups (P < 0.05) in women with no complaints. There were about 12%-14% women had a early onset of menses and about 25%-28% had a late one, but no significant differences were found among the 3 groups. The average days of delayed onset of next menstruation were significant longer in group I than that in group III (P < 0.05)., Conclusion: All the 3 doses of mifepristone could be used as an effective emergency contraception.

Objective: To compare the efficacy, side effects and the effect on next menstruation of levonorgestrel(LNG) to low dose mifepristone in emergency contraception., Methods: The study is a randomized double-blind multicenter comparative trial. The clients who have unprotected intercourse within 72 hours were allocated to one of the two study groups. In LNG group, 0.75 mg LNG was taken twice with 12 hours apart. In mifepristone (Mife-) group, single dose of 10 mg mifepristone was taken and a placebo 12 hours after. Follow-up visit was paid on the seventh day of the expected next menstruation to evaluate the contraceptive efficacy and to record side effects and menstruation. Contraceptive efficacy was calculated by Dixon's method., Results: The total valid subjects in LNG and Mife- group were 643 and 633, respectively. There were 20 and 9 pregnancies occurred respectively in each group. The failure rate was 3.1% and 1.4%. Contraceptive efficacy rate of preventing pregnancy was 59.2% and 79.7%, the difference was statistically significant (P < 0.05). The incidence of various side effects was less than 10.0% which were mild. There was no statistically difference between the two groups. The percentage of subjects who had their next menstruation before or after their expected menstruation 3 days in LNG group and Mife- group was 77.7% and 78.5% respectively. The menstrual period less than 7 days was 95.0% and 93.3%., Conclusion: Use of levonorgestrel or low dose mifepristone for emergency contraception is effective and safe.

Objective: To study the response of uterine leiomyoma to two different daily dosages of mifepristone., Methods: Prospective nonrandomized clinical trial on women with symptomatic uterine leiomyoma was conducted. Twenty-eight patients were treated with 10mg of mifepristone daily and fifteen patients with 20mg daily for 12 weeks, beginning on day 1 to 3 of the menstrual cycle. Volume changes of leiomyoma and uterus were measured with ultrasonography before treatment (as baseline) and monthly during the course of therapy. Blood samples for hemoglobin, liver and renal function were obtained monthly., Results: Ovarian acyclicity was induced in both groups of patients given different daily doses of mifepristone and dysmenorrhea and low abdominal pain disappeared. All symptoms and signs of anemia were resolved. The average hemoglobin level elevated 14-16g/L monthly. After 12 weeks of mifepristone treatment, the leiomyoma volume decreased to 41.4% of baseline in the 10mg daily dose group and 43.0% in the 20mg daily dose group. There was no significant difference between the two treatment groups; the side effects were similar., Conclusion: Mifepristone of 10mg daily is considered to be a more ideal dosage for treatment. Mifepristone therapy is indicated in larger fibroids, and/or as preoperative medication for severely anemic patients and in perimenopausal patients with symptomatic fibroids.

Objective: To compare use-effectiveness and side-effects of medical termination of early pregnancy by oral administration of separated doses of mifepristone 150 mg or single dose of mifepristone 200 mg followed by PG05 1 mg vaginally in 4500 healthy pregnant women with amenorrhea < or = 49 days in a phase I multicentre study., Methods: All subjects were recruited in 30 clinics after obtaining informed consents., Results: The complete, incomplete abortion and continuous pregnancy rates were 88.6%, 8.1%, 1.7% and 92.0%, 5.8%, 0.8% in single dose and separated doses groups, respectively. The efficacy of termination of early pregnancy by mifepristone 150 mg in separated doses was higher than that in single dose of mifepristone 200 mg when both in combination with PG05 1 mg (P < 0.01). One case of allergic rash was noted after administration of mifepristone. No severe side-effects were observed except bleeding problems. 65 cases received emergency vacuum aspiration and 7 of them received blood transfusion due to heavy bleeding. In addition, 2 cases of ectopic pregnancies required blood transfusion as heavy bleeding caused by exfetation disruption. There was no significant difference in to the time to start bleeding and the days of bleeding lasted between two treatment groups. However, there was a significant positive correlation (P < 0.001) between diameters of SAC and the days of bleeding lasted., Conclusions: Logistic regression analysis suggested that subject's age, gravidity and days of amenorrhea have significant effects on abortion efficacy. 75.2% of subjects are satisfactory in self-assessment of the treatment, and 81.8% of subjects will choose medical abortion method in case they need to terminate undesired early pregnancy in the future.

One thousand and thirty-five women in early pregnancy (< or = 49 days), who requested medical abortion were randomly allocated into 8 groups. Mifepristone and 15-methyt-PGF2 alpha vaginal suppository (PG05) and misoprostol oral (tablets) were given as the following 8 regimens: group 1 (n = 195): a single dose of mifepristone 200 mg + PG05 1 mg on the 3rd or 4th day; group 2 (n = 249): mifepristone 25 mg b.i.d. (total amount of 150mg) + PG05 1mg on the 3rd or 4th day; group 3 (n = 67): mifepristone 25 mg b.i.d. (total amount of 125mg) + PG05 1mg in the morning of the 3rd day; group 4 (n = 108): a single dose of mifepristone 200mg + misoprostol 600 micrograms on the 3rd day; group 5 (n = 199): a single dose of mifepristone 150mg + misoprostol 600 micrograms on the 3rd day; group 6 (n = 60): mifepristone 50 mg was given immediately, then 25 mg b.i.d. (total amount of 150mg + misoprostol 600 micrograms; group 7 (n = 123): mifepristone 50 mg in the morning and 25mg in the evening for two days (total amount of 150 mg) + misoprostol 600 micrograms; group 8 (n = 34): mifepristone 25 mg b.i.d. (total amount of 125mg) + misoprostol 400 micrograms. As a result, the complete abortion rate of each group was 92.8%, 95.2%, 92.5%, 93.5%, 87.4%, 98.4%, 92.7% and 94.1% successively. The rate of group 5 was significantly lower than that of group 2 and 6 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion was attempted in 316 healthy women in early pregnancy within 7 weeks with the RU486 alone (600mg in a single oral dose) or in combination with a PG (15-dl-methyl-PGF2 alpha-methyl-ester) 1 mg suppository. The result of using RU 486 alone in 204 women was complete abortion 65.2%, incomplete 3.4% and continued pregnancy 31.4%. While RU486 and PG in 112 women resulted in complete abortion 87.5%, incomplete 8.9% and continued pregnancy 3.6%. The complete abortion rate of RU486 and PG was significantly higher than that of the RU486 alone (P less than 0.01). In RU486 and PG group, the measured mean blood loss after complete abortion (52.0 ml) was much less than in the RU486 alone (177.4ml). The main side-effects were nausea vomiting and headache. The RU486 and PG is an effective and safe agent for termination of early pregnancy. However, it should be used only under close medical supervision.