TRIM28-Mediated Excessive Oxidative Stress Induces Cellular Senescence in Granulosa Cells and Contributes to Premature Ovarian Insufficiency In Vitro and In Vivo.

Premature ovarian insufficiency (POI) is a clinical syndrome of ovarian dysfunction characterized by the abnormal alteration of hormone levels such as FSH and E2. POI causes infertility, severe daily life disturbances, and long-term health risks. However, the underlying mechanism remains largely unknown. In this study, we found that POI is associated with the cellular senescence of ovarian granulosa cells, and TRIM28 mediates oxidative stress (OS)-induced cellular senescence in granulosa cells. Mechanistically, OS causes a decrease in TRIM28 protein levels in KGN cells. Subsequently, it triggers an increase in the levels of autophagy marker proteins ATG5 and LC3B-II, and the downregulation of P62. Abnormal autophagy induces an increase in the levels of cellular senescence markers γ-H2A.X, P16, and P21, provoking cellular senescence in vitro. The overexpression of ovarian TRIM28 through a microinjection of lentivirus attenuated autophagy, cellular senescence, and follicular atresia in the ovaries of POI mice and improved mouse fertility in vivo. Our study highlights the triggers for POI, where the reduction of TRIM28, which is regulated by reactive oxygen species, causes follicular atresia and POI via triggering autophagy and inducing granulosa cell senescence. Shedding light on TRIM28 may represent a potential intervention strategy for POI.

Progestin and adipoQ receptor 7 (PAQR7) mediate the anti-apoptotic effect of P4 on human granulosa cells and its deficiency reduces ovarian function in female mice.

PURPOSE: PAQR7 plays a key role in cell apoptosis as a progesterone membrane receptor. The physiological mechanism of PAQR7 in ovarian function and its anti-apoptotic action in mammals remain poorly understood. METHODS: We first added 0.2 µM aminoglutethimide (AG), an inhibitor of endogenous progesterone (P4) secretion, and transfected siPAQR7 co-incubated with P4 in human KGN cells to identify granulosa cell apoptosis, respectively. Additionally, we used Paqr7 knockout (PAQR7 KO) mice to assess the role of PAQR7 in the ovary. RESULTS: The PAQR7 deficiency significantly increased apoptosis of KGN cells, and this significant difference disappeared following P4 supplementation. The Paqr7-/- female mice showed a prolonged estrous cycle, reduced follicular growth, increased the number of atresia follicles, and decreased the concentrations of E2 and AMH. The litters, litter sizes, and spontaneous ovulation in the Paqr7-/- mice were significantly decreased compared with the Paqr7+/+ mice. In addition, we also found low expression of PAQR7 in GCs from human follicular fluids of patients diagnosed with decreased ovarian reserve (DOR) and ovaries of mice with a DOR-like phenotype, respectively. CONCLUSIONS: The present study has identified that PAQR7 is involved in mouse ovarian function and fertilization potential. One possible mechanism is mediating the anti-apoptotic effect of P4 on GC apoptosis via the BCL-2/BAX/CASPASE-3 signaling pathway. The mechanism underlying the effect of PAQR7 on ovarian development and aging remains to be identified.

The emerging role of lysine succinylation in ovarian aging.

BACKGROUND: Ovarian aging is a process of decline in its reserve leading to ovary dysfunction and even reduced health quality in offspring. However, aging-related molecular pathways in the ovary remain obscure. Lysine succinylation (Ksuc), a newly post-translational modification (PTM), has been found to be broadly conserved in both eukaryotic and prokaryotic cells, and associated with multiple pathophysiological processes. There are no relevant reports revealing a link between the molecular mechanisms of ovarian aging and Ksuc. METHODS: The level of Ksuc in ovaries of aged and premature ovarian insufficiency (POI) mice were detected by immunoblotting and immunohistochemical. To further explore the role of Ksuc in ovarian aging, using in vitro mouse ovary tissue culture and an in vivo mouse model with changed Ksuc level. RESULTS: Increased Ksuc in ovaries of aged and POI mice and distribution of Ksuc in various types of mice ovarian cells and the high level of Ksuc in granulosa cells (GCs) were revealed. Histological assessments and hormone levels analyses showed that the high Ksuc level down-regulated the ovarian index and the anti-Müllerian hormone (AMH) and estrogen levels, and increased follicular atresia. Moreover, in the high Ksuc groups, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) intensities and the expression of Cleaved-caspase-3 increased and the expression of B-cell lymphoma-2 (Bcl-2) decreased together with positively-expressed P21, an aging-related marker. These results suggest that ovarian aging is likely associated with alteration in Ksuc. CONCLUSION: The present study has identified Ksuc in mouse ovary and found that high Ksuc level most likely contributes to ovarian aging which is expected further investigation to provide new information for delaying physiological ovarian aging and treating pathological ovarian aging.

Effect of inactivated COVID-19 vaccination on pregnancy outcomes following frozen-thawed embryo transfer: A retrospective cohort study.

OBJECTIVE: To investigate the effect of inactivated coronavirus disease 2019 (COVID-19) vaccination on frozen-thawed embryo transfer (FET) outcomes. METHODS: This retrospective cohort study enrolled 1,210 patients undergoing FET cycles in a single university-affiliated hospital between July 1, 2021, and May 1, 2022. Of them, 387 women with two full doses of inactivated SARS-CoV-2 vaccines (CoronaVac or BBIBP-CorV) after oocyte retrieval were assigned to the vaccinated group, while 823 were unvaccinated as controls. Propensity score matching and multiple regression analysis were applied to control for baseline and cycle characteristics (19 covariates in total). RESULTS: There were 265 patients in each group after matching. The rates of clinical pregnancy (58.5% vs. 60.8%; P = 0.595) and live birth (44.4% vs. 48.8%; P = 0.693) were similar between vaccinated and unvaccinated patients, with adjusted odds ratios of 0.89 (95% confidence interval [CI] 0.61-1.29) and 1.31 (95% CI 0.37-4.56), respectively. Consistently, no significant differences were found in serum human chorionic gonadotropin levels as well as biochemical pregnancy, biochemical pregnancy loss, and embryo implantation rates. Based on the time interval from vaccination to FET, vaccinated patients were further subdivided into two categories of ≤2 months and >2 months, and the outcomes remained comparable. CONCLUSION: Our study showed that inactivated COVID-19 vaccination in women did not have measurable detrimental impact on implantation performance and live birth outcome during FET treatment cycles. This finding denies the impairment of endometrial receptivity and trophoblast function by vaccine-induced antibodies at the clinical level.

Proteomics analysis reveals the defense priming effect of chitosan oligosaccharides in Arabidopsis-Pst DC3000 interaction.

Chitosan oligosaccharides (COS) worked effectively in multiple plant-pathogen interactions as plant immunity regulator, however, due to the complexity of the COS-induced immune signaling network, the topic requires further investigation. In the present study, quantitative analysis of proteins was performed to investigate the underlying mechanism of COS induced resistance to Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) in Arabidopsis thaliana. 4303 proteins were successfully quantified, 186, 217 and 207 proteins were differently regulated in mock + Pst, COS, and COS + Pst treated plants, respectively, compared with mock plants. From detailed functional and hierarchical clustering analysis, a priming effect of COS on plant immune system by pre-regulated the key proteins related to signaling transduction, defense response, cell wall biosynthesis and modification, plant growth and development, gene transcription and translation, which confers enhanced resistance when Pst DC3000 infection in Arabidopsis. Moreover, RACK1B which has the potential to be the key kinase receptor for COS signals was found out by protein-protein interaction network analysis of COS responsive proteins. In conclusion, COS treatment enable plant to fine-tuning its defense mechanisms for a more rapid and stronger response to future pathogen attacks, which obviously enhances plants defensive capacity that makes COS worked effectively in multiple plant-pathogen interactions.

Left ventricular remodeling in patients with acute type B aortic dissection after thoracic endovascular aortic repair: Short- and mid-term outcomes.

BACKGROUND: Left ventricular (LV) remodeling remains unknown in patients with acute Type B aortic dissection (aTBAD) after thoracic endovascular aortic repair (TEVAR) during follow-up. METHODS: Between May 2004 and January 2016, 163 consecutive patients (136 males, mean preoperative age: 51.06 ±â€¯10.79 years) with aTBAD underwent TEVAR. A linear mixed model was used to evaluate risk factor influencing on LV remodeling and investigate longitudinal changes in LV thickness, diameter, volume, function and mass at preoperation, postoperation, short- and mid-term follow-up. RESULTS: Median follow-up time was 48.0 months (quartiles 1-3, 31-84 months, maximum 147 months). LV thickness and mass followed a continuous downward trend over time. Interventricular septal thickness at end-diastole significantly decreased at mid-term follow-up (time, p < 0.001: preoperative 11.59 ±â€¯0.14 mm vs mid-term 10.82 ±â€¯0.15 mm, p < 0.001; postoperative 11.40 ±â€¯0.14 mm vs mid-term 10.82 ±â€¯0.15 mm, p = 0.006). LV posterior wall thickness at end-diastole was markedly reduced at mid-term follow-up (time, p < 0.001: preoperative 10.89 ±â€¯0.11 mm vs mid-term 10.02 ±â€¯0.11 mm, p < 0.001; postoperative 10.78 ±â€¯0.13 mm vs mid-term 10.02 ±â€¯0.11 mm, p < 0.001; short-term 10.56 ±â€¯0.15 mm vs mid-term 10.02 ±â€¯0.11 mm, p = 0.021). LV mass index markedly decreased during follow-up (time, p = 0.001: preoperative 129.60 ±â€¯3.55 g/m2 vs short-term 119.26 ±â€¯3.19 g/m2, p = 0.009; preoperative 129.60 ±â€¯3.55 g/m2 vs mid-term 115.79 ±â€¯3.62 g/m2, p = 0.003). LV function was improved, but not significantly so, during follow-up. Strict blood pressure control had no influence on LV remodeling. True lumen followed a continuous enlargement trend in terms of proximal thoracic aorta and celiac trunk level during follow-up. CONCLUSIONS: TEVAR can reverse LV remodeling and LV hypertrophy in patients with aTBAD during follow-up.

Effects of chitosan nanoparticles on seed germination and seedling growth of wheat (Triticum aestivum L.).

To investigate the effect and mechanism of chitosan nanoparticles (CSNPs) on the germination and seedling growth of wheat (Triticum aestivum L.), we conducted systematic research on the impact of different concentrations (1-100 µg/mL) of CSNPs and chitosan (CS). The result of energy-dispersive spectroscopy (EDS) and confocal laser scanning microscopy (CLSM) showed that adsorption of CSNPs on the surface of wheat seeds was higher than that of CS. CSNPs had growth promoting effect at a lower concentration (5 µg/mL) compared with CS (50 µg/mL). In addition, the application of 5 µg/mL CSNPs induced the auxin-related gene expression, accelerated indole-3-acetic acid (IAA) biosynthesis and transport, and reduced IAA oxidase activity resulting in the increase of IAA concentration in wheat shoots and roots. The results suggest that CSNPs have positive effect on seed germination and seedling growth of wheat at a lower concentration than CS due to higher adsorption on the surface of wheat seeds.

Effects of Calcium Alginate Submicroparticles on Seed Germination and Seedling Growth of Wheat (Triticum aestivum L.).

Calcium alginate (CaAlg) submicroparticles have a potential application in agricultural delivery systems. This study investigated the effects of CaAlg submicroparticles on seed germination and seedling growth of wheat. CaAlg submicroparticles with a Z-average diameter of around 250.4 nm and a measured zeta potential value of about -25.4 mV were prepared and characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM) and energy dispersive X-ray spectrometer (EDS). After this, the effects of the concentration of CaAlg submicroparticles (10⁻500 µg/mL) on germination percentage, seedling length, the number of adventitious roots, chlorophyll content and soluble protein content were evaluated. The results demonstrated a significant increase in the level of germination percentage (9.0%), seedling index (50.3%), adventitious roots (27.5%), seedling length (17.0%), chlorophyll (8.7%) and soluble protein contents (4.5%) at a concentration of 100 µg/mL. However, an inhibitory effect was observed at a concentration of 500 µg/mL. The SEM examination showed that CaAlg submicroparticles could be successfully adsorbed onto the surface of the wheat seed. Further studies proved that CaAlg submicroparticles at a concentration of 100 µg/mL promoted the expression of indole-3-acetic acid (IAA)-related genes (YUCCA9, AUX1, ARF and UGT) in wheat, which resulted in an increase of 69% and 21% in IAA concentration in wheat roots and shoots, respectively.

Increased SCF in Follicular Fluid and Granulosa Cells Positively Correlates With Oocyte Maturation, Fertilization, and Embryo Quality in Humans.

Stem cell factor (SCF), which is derived from granulosa cells (GCs), plays a key role in the process of follicular development and oocyte maturation. The present study aimed to explore whether the levels of SCF in follicular fluid (FF) and GCs can be used as a potential marker for predicting oocyte developmental potential. Follicular fluid and GC samples from 150 female patients undergoing intracytoplasmic sperm injection were collected in this study. The SCF concentrations in FFs and SCF messenger RNA (mRNA) in GCs were evaluated by using enzyme-linked immunosorbent assay and real-time polymerase chain reaction, respectively. The results showed that the levels of SCF protein and mRNA were significantly associated with oocyte maturation, normal fertilization, cleavage, and embryo quality. Moreover, the levels of SCF protein and mRNA in pregnancy group were also higher than those in the nonpregnancy group. The cutoff value of SCF in FF for predicting high-quality embryo was 1.346, with a sensitivity of 57.8% and a specificity of 72.4%, and the cutoff value of SCF in GCs for predicting high-quality embryo was 6.650, with a sensitivity of 64.4% and a specificity of 78.1%. In conclusion, our results showed a positive and statistically significant relationship between SCF level and oocyte maturation, normal fertilization, cleavage, embryo quality, and clinical pregnancy. Therefore, the levels of SCF in FF and GCs might be considered as a new marker for predicting oocyte developmental potential.

Overexpression of microRNA-122 re-sensitizes 5-FU-resistant colon cancer cells to 5-FU through the inhibition of PKM2 in vitro and in vivo.

5-Fluorouracil (5-FU) is one of the most commonly used anticancer drugs in the treatment of colon cancer. However, acquired chemoresistance is becoming one of the major challenges for patients with advanced stages of colon cancer. Currently, the mechanisms underlying cancer cell resistance to 5-FU are not fully understood. MicroRNAs (miRNA) have been suggested to play important roles in tumorigenesis and drug resistance in colon cancer. In this study, we generated 5-FU-resistant colon cancer cell lines from which we found that miR-122 was downregulated in 5-FU-resistant cells compared with sensitive cells. Meanwhile, the glucose metabolism is significantly upregulated in 5-FU-resistant cells. We report that PKM2 is a direct target of miR-122 in colon cancer cell. Importantly, overexpression of miR-122 in 5-FU-resistant cells resensitizes 5-FU resistance through the inhibition of PKM2 both in vitro and in vivo. In summary, these findings reveal that the dysregulated glucose metabolism contributes to 5-FU resistance, and glycolysis inhibition by miR-122 might be a promising therapeutic strategy to overcome 5-FU resistance.

Influence of interleukin-28B polymorphism on progression to hepatitis virus-induced hepatocellular carcinoma.

Genetic variation of interleukin-28B (IL-28B) rs12979860 T/C polymorphism is associated with the immune response to interferon (IFN) therapy, which is applied in the treatment of chronic viral hepatitis induced by hepatitis B virus (HBV) and hepatitis C virus (HCV). These chronic liver diseases could progress to end-stage liver diseases, such as hepatocellular carcinoma (HCC). The aim of this study was to clarify whether there exists a causal association between IL-28B rs12979860 T/C polymorphism and development of HCC. In a meta-analysis of six studies with 850 cases and 811 controls, we summarized the data on the association between IL-28B rs12979860 T/C polymorphism and HCC risk and calculated ORs and 95 % CIs to estimate the association strength. We observed that IL-28B rs12979860 T/C polymorphism was positively associated with overall HCC risk (TT vs. CC: OR = 2.38; 95 %, 1.60-3.55; TT vs CT + CC: OR = 1.79; 95 %, 1.23-2.60). In the stratified analysis by ethnicity, the robust association retained in Caucasians with higher risk among TT carriers relative to the CC carriers. A similar trend was found in the studies of healthy controls when data were stratified by source of controls. The combined data suggest that IL-28B rs12979860 T/C polymorphism seems to augment the risk of developing HCC, especially in Caucasians.

Low expression of prolyl hydroxylase 2 is associated with tumor grade and poor prognosis in patients with colorectal cancer.

Previous studies have indicated that prolyl hydroxylases (PHDs) function as tumor suppressors in human colorectal cancer (CRC), but their clinical and prognostic significance is uncertain. Expressions of PHD1, PHD2, PHD3 and hypoxia-inducible factor (HIF)-1α were detected using immunohistochemistry in an independent CRC cohort of 93 specimens represented on a tissue microarray (TMA). PHD expression levels were correlated with clinicopathological features, patient survival and presumed corresponding HIF-1α expression. Pearson χ(2) test was used to compare clinicopathological features with protein expressions. Survival was estimated by Kaplan-Meier analysis. Cox regression analysis was performed for multivariate analysis of prognostic factors. Of the TMA, 47, 68 and 51 from 93 specimens had low expressions of PHD1, PHD2 and PHD3, respectively. HIF-1α was positively expressed in 75 specimens. Low expression of PHD2 correlated with the high-grade group and a terrible overall survival (P = 0.017 and P = 0.032). Patients who had early stage CRC with low PHD2 expression had a poorer survival (P = 0.015), whereas patients with advanced-stage disease did not demonstrate such a difference (P = 0.691). Besides, PHD2 was uncorrelated with HIF-1α expression. The present study indicated that low expression of PHD2 in CRC predicts poor survival independent of HIF-1α, specifically for patients who have early stage tumors.

Synergistic antitumor effect of dichloroacetate in combination with 5-fluorouracil in colorectal cancer.

Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been recently demonstrated as a promising nontoxic antineoplastic agent that promotes apoptosis of cancer cells. In the present study, we aimed to investigate the antitumor effect of DCA combined with 5-Fluorouracil (5-FU) on colorectal cancer (CRC) cells. Four human CRC cell lines were treated with DCA or 5-FU, or a combination of DCA and 5-FU. The cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The interaction between DCA and 5-FU was evaluated by the median effect principle. Immunocytochemistry with bromodeoxyuridine (BrdU) was carried out to determine the proliferation of CRC cells. Cell cycle and apoptosis were measured by flow cytometry, and the expression of apoptosis-related molecules was assessed by western blot. Our results demonstrated that DCA inhibited the viability of CRC cells and had synergistic antiproliferation in combination with 5-FU. Moreover, compared with 5-FU alone, the apoptosis of CRC cells treated with DCA and 5-FU was enhanced and demonstrated with the changes of Bcl-2, Bax, and caspase-3 proteins. Our results suggest that DCA has a synergistic antitumor effect with 5-FU on CRC cell lines in vitro.

[Effects of cryoablation on the bronchi of normal pigs].

OBJECTIVE: To investigate the effects of cryoablation on different bronchi of normal pigs and provide experimental bases for the potential clinical application of this technique. METHODS: Six normal pigs were divided into two groups and subjected to percutaneous cryoablation of the lung tissues. Three pigs were sacrificed on day 3 (group A) and another 3 on day 28 (group B) after the ablation, and the morphology and volume of the ablated areas and the pathological changes in different bronchi. RESULTS: In group A, examination of the biopsy samples taken 3 days after the ablation revealed significantly greater maximal longitudinal (t=9.789, P=0.000) and transverse (t=3.253, P=0.023) diameters of the area of freezing damage than those observed immediately after the cryoablation. The diameters of the freezing damage area in group B were significantly smaller than those in group A (t=7.227, P=0.000; t=6.006, P=0.001). The freezing damages to the bronchi worsened with the reduction of the bronchial lumen; the damages to the major bronchi and the second-order bronchi were relatively slight, which also showed better recovery 28 days after the ablation. CONCLUSION: CT-guided percutaneous cryoablation does not produce serious effects on the major bronchi and the second-order bronchus, and can be a minimally invasive therapy for lung tumors with good tolerance and safety.

[Neonatal outcomes of pregnancy resulting from in vitro fertilization and embryo transfer: analysis of 1274 cases].

OBJECTIVE: To evaluate the neonatal outcomes of pregnancies resulting from in vitro fertilization and embryo transfer (IVF-ET) in relation to the occurrence of congenital malformations of the neonates. METHODS: A total of 1274 infants born after IVF-ET were reviewed. The neonatal outcome was evaluated based on gestational weeks, body weight, congenital malformations, manner of spermatization, maternal age and multiple gestation. RESULTS: IVF-ET resulted in 930 deliveries, giving birth to a total of 1274 newborns. Spontaneous delivery occurred in 115 cases (12.37%), with preterm birth in 224 cases (24.09%). Among these newborns, 363 (28.49%) had very low born weight (VLBW), 13 (1.02%) had congenital malformations, and neonatal mortality occurred in 15 cases (1.18%). CONCLUSION: IVF increases the risks of twin pregnancies, preterm birth and VLBW, but does not increase the rate of congenital malformations and neonatal mortality. Intracytoplasmic sperm injection (ICSI) is at higher risk of congenital malformations. Maternal age and twin pregnancies are not associated with congenital malformations. IVF can be safe for treatment of infertility.

[Clinical application of gonadotropin-releasing hormone antagonist in Chinese women undergoing controlled ovarian hyperstimulation for in vitro fertilization and embryo transfer].

OBJECTIVE: To analyze the clinical characteristics and cycle outcome of Chinese women with gonadotropin-releasing hormone (GnRH) antagonist treatment during controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET). METHODS: A retrospective review was conducted in patients who completed 54 consecutive cycles of IVF-ET with GnRH antagonist treatment for luteinizing hormone (LH) surge prevention. Descriptive statistics were recorded for the patients' age, GnRH treatment duration (days) and dose, timing and duration of GnRH antagonist treatment, serum E2 and LH level on the day of antagonist use and hCG injection, number of oocytes retrieved, and clinical pregnancy rate. RESULTS: The clinical pregnancy rate was 46.2% per ET cycle for GnRH antagonist group and 56.8% in GnRH agonist group, showing no significant difference between the two protocols. The age of the patients with GnRH antagonist averaged 35.7-/+3.8 years. Gn and GnRH antagonist treatment lasted for 8.5-/+1.6 and 4.5-/+1.1 days, respectively. On the day of ovulation triggered by hCG, the serum estradiol level was 1616.7-/+721.1 pg/ml, and a mean of 7.4-/+4.6 oocytes was collected per retrieval. The number of the embryos transferred was 2.4-/+0.6, with an implantation rate of 27.7%, resulting in a clinical pregnancy rate of 50.0% in the fixed protocol (antagonist initiation on day 4 or 5 of stimulation) and 37.5% in the flexible protocol (antagonist treatment initiated for a follicle of 12-15 mm, on day 6 to 9 of stimulation). CONCLUSIONS: GnRH antagonists treatment results in good outcomes and can be safe, short, convenient and effective for Chinese women undergoing COH for IVF. GnRH antagonist treatment can be initiated on day 4 to 9 of Gn stimulation to obtain comparable pregnancy rate.

[Comparison of clinical outcomes of four protocols for frozen-thawed embryo transfer cycle].

OBJECTIVE: To compare the clinical outcome of 4 protocols of frozen-thawed embryo transfer cycle to select the optimal endometrial preparation method for frozen-thawed embryos transfer. METHODS: A retrospective analysis of the 4 clinical protocols was conducted including natural cycle, down-regulated hormone replacement treatment (HRT) cycle, hMG cycle and natural cycle+hCG in endometrial preparation for 419 frozen-thawed embryos transfer cycle, and the clinical pregnancy rate, implantation rate, early abortion rate, ectopic pregnancy rate , ongoing pregnancy rate and delivery rate were compared between the 4 protocols. RESULTS: There was no significant difference between the 4 groups with different clinical protocols in age, duration of infertility, reason of infertility, number of embryo transferred and endometrial thickness. The 4 protocols differed little in the implantation rate, clinical pregnancy rate, biochemical pregnancy rate, early abortion rate, ectopic pregnancy rate, ongoing pregnancy rate and delivery rate in the four clinical protocols. CONCLUSION: The 4 clinical protocols for frozen-thawed embryos transfer all have favorable clinical outcome, and choice of a specific protocol should be made according to the a comprehensive consideration of the individual conditions of the patient.

[Combined use of methotrexate and mifepristone for ectopic pregnancy management: a meta- analysis].

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.