Safety and effectiveness evaluation of a uterine direct visualization system in induced abortion. A multicenter clinical trial.

OBJECTIVES: While the decision of abortion is undeniably complex, there are situations where it becomes a necessary choice. In such circumstances, a secure abortion procedure is essential to safeguard the physical and mental well-being of women. A uterine direct visualization system was designed to fulfill the requirements and this study undertook an assessment of the system's safety and effectiveness within a medical facility setting. MATERIALS AND METHODS: Induced abortion requested women in 17 institutions across the country between December 2016 and February 2017 were enrolled. Subjects were separated to the study and control group randomly. Induced abortion was conducted by a uterine direct visualization system and an ultrasound-guided system in the study and control group, respectively. The clinical indexes collected during intra- and post-procedures were analyzed and compared between groups. RESULTS: Overall, 392 and 339 subjects were included in the study and control group, respectively. The baseline demographic and clinical characteristics were similar between two groups. Subjects in the study group had significant smaller number of uterine cavity entry (p < 0.001), less 2-h and 14-days postoperative bleeding (all p < 0.001), and less 14-days postoperative abdominal pain (p < 0.001). Significantly higher ratio of normal menstruation, in terms of incidence and duration after 60-days of operation, was observed in the study group (all p < 0.001). CONCLUSIONS: Induced abortion with uterine direct visualization system generate better outcome and less complication than the conventional ultrasound-guided abortion procedures.

Failure to reduce the risk of postoperative lower genital tract infection with perioperative antibiotic prophylaxis during induced abortion: a real-world study.

Objective: This study aimed to evaluate perioperative antibiotic use for induced abortion and its association with lower genital tract infections (LGTI) two weeks post-surgery in China. Methods: We conducted a prospective cohort study of women seeking induced abortion. We interviewed participants on the day of surgery and two weeks after, and evaluated preoperative tests, gynecological exams, perioperative antibiotic usage, postoperative vaginal microbiota, and LGTI diagnosis. Multivariate logistic regression was used to assess the association between the perioperative antibiotic use and LGTI risk. Results: We recruited 8,190 women undergoing induced abortion at 27 participating hospitals. Of these, 95% had gynecological exams, but over 80% lacked tests for vaginal microbiota, chlamydia, and gonorrhea. Approximately 20% of those examined had increased vaginal discharge and abnormal vaginal cleanliness. The positive rates for gram-positive rods, fungi, and trichomonas were 38.6, 2.4, and 0.3%, respectively. More than three-quarters (78.5%) of participants received antibiotics, mainly second-gen cephalosporins (36.8%) and nitroimidazoles (12.3%). LGTI rates two weeks post-surgery were 2.7% for antibiotic recipients and 3.1% for non-recipients, with no statistically significant difference (p > 0.05). Logistic regression showed no association between perioperative antibiotic use and LGTI risk (OR = 1.01, 95% CI 0.59-1.74). However, this risk increased with abnormal preoperative discharge tests (OR = 1.39, 95% CI 1.04-1.86). Conclusion: Most Chinese women undergoing induced abortion used perioperative antibiotics, but this did not significantly reduce LGTI risk. Instead, this risk was related to abnormal preoperative discharge tests. Standardization of perioperative antibiotic use for induced abortion is recommended, and prophylactic treatment in Chinese abortion services warrants further investigation.

Contraception, unintended pregnancy, and induced abortion within 24 months of delivery in China: a retrospective cohort study.

OBJECTIVE: To explore the prevalence of contraceptive use, unintended pregnancy, and induced abortions within 24 months postpartum in eastern, central, and western regions of China and in China overall. STUDY DESIGN: We conducted a retrospective cohort study and selected women who delivered a live birth between 12 and 24 months before the survey at 60 hospitals in eastern, central, and western regions of China. We used structured questionnaires for data collection and applied life-table analyses to estimate the prevalence of contraception, unintended pregnancy, and abortions. We used clustered log-rank tests to compare trends and rate differences at each time interval between/among regions. RESULTS: A total of 19,939 postpartum women were contacted, and 18,045 (90.5%) of them agreed to be interviewed. The 6-, 12-, and 24-month rates for modern contraceptive methods were 62.7% (95% confidence interval [CI] 58.9-66.4), 72.4% (95% CI 68.8-75.7), and 73.2% (95% CI 69.6-76.6), respectively. Condoms accounted for 79% of contraceptive initiators. The 6-, 12-, and 24-month rates were 1.4% (95% CI 1.2-1.7), 5.3% (95% CI 4.5--6.1), and 13.1% (95% CI 11.3-14.8) for unintended pregnancy; and 1.1% (95% CI 0.8-1.3), 4.0% (95% CI 3.4-4.6), and 10.4% (95% CI 8.9-11.8) for induced abortion, respectively. By 24 months postpartum, 3-quarters of unintended pregnancies ended in abortion. The 24-month rates of modern contraceptive methods (75.2% vs73.4%, 71.1%), unintended pregnancy (15.3% vs 11.1%, 12.6%), and induced abortion (11.8% vs 9.9%, 9.4%) were higher in the western region relative to the eastern or central regions. CONCLUSION: Postpartum contraception use was relatively high in China but dominated by less-effective methods, and these may contribute to higher risks of unintended pregnancy and induced abortion during the postpartum period. Use of long-acting reversible contraceptives and effective and reliable short-acting methods should thus be fostered in postpartum family planning services in China. IMPLICATIONS: A national postpartum family planning program is needed in China. Service providers should work on counselling postpartum women and their partners with respect to long-acting reversible contraceptive methods, and to effectively and reliably use short-acting methods during the postpartum period.

Safety and Efficacy of Combined Oral Contraceptive Ethinyl Estradiol/Drospirenone (YAZ) in Chinese Women: A Single-Arm, Open-Label, Multicenter, Post-Authorization Study.

INTRODUCTION: The study was conducted to assess the safety and efficacy of a combined oral contraceptive, YAZ, containing 3 mg drospirenone/20 µg ethinyl estradiol administered in a 24/4 regimen. METHODS: This was a single-arm, open-label, interventional, post-authorization safety surveillance study of YAZ across 6 treatment cycles. Primary objective was assessing its safety profile in Chinese women. Secondary objectives included assessing contraceptive efficacy, cycle control, and bleeding patterns among subjects with and without preceding abortion, along with efficacy in moderate acne vulgaris. Subgroup analyses included assessing efficacy in the dysmenorrhea group using a visual analog scale. All variables were analyzed by descriptive statistical methods. RESULTS: Of 1921 women treated with YAZ (mean age: 29.9 ± 5.5 years), 12.9% reported adverse drug reactions. Most frequently reported adverse events were nausea (2.6%), breast pain (2.3%), and breast swelling (1.3%). Unintended pregnancy rate (adjusted Pearl Index) was 0.3 (n = 2 pregnancies, 95% confidence interval 0.1-1.2). Incidence of overall withdrawal bleeding (cycle 2-cycle 5) was 93.3%-95.2%, of which 87.8%-95.1% in post-abortion subjects and 94.0%-95.3% in subjects without preceding abortion. Intra-cyclic bleeding (cycle 2-cycle 6) decreased in the overall population (from 14.9 to 5.5%), post-abortion subgroup (32.4% to 6.9%), and in subjects without preceding abortion (12.4% to 5.3%). Incidence of onset of withdrawal bleeding < 7 days among abnormal uterine bleeding patients at baseline was 85.2% and 87.2% at cycles 2 and 5, respectively, and incidence of intra-cyclic bleeding was 23.5% and 8.0% at cycles 1 and 6, respectively. Mean percent change in total acne lesion count from baseline to cycle 6 was - 79.9% ,and mean change in pain severity due to dysmenorrhea was - 31.2 mm at cycle 6 when compared with baseline. CONCLUSION: The 24/4 YAZ regimen showed good safety profile, contraceptive reliability, good cycle control along with subgroup of patients. Improvements in dysmenorrhea and acne were also observed. No events of venous thromboembolism/arterial thromboembolism were reported. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02710708; Center for Drug Evaluation (CDE), China Food and Drug Administration (CFDA) number: CTR20160203.

Clinical Efficacy and Safety of Stem Cell-Based Therapy in Treating Asherman Syndrome: A System Review and Meta-Analysis.

Asherman's Syndrome (AS) is an uncommon, acquired, and refractory gynecological disorder. Current treatment was still limited, and stem cell-based therapy has been proposed as a novel strategy for management of AS. Here, we conducted a meta-analysis of self-controlled clinical trials to assess the effectiveness and safety of stem cell-based therapy in Asherman syndrome patients who have failed in conventional treatment. We systematically searched PubMed, Embase, Cochrane, and Web of Science database (published up to October 3, 2020). Our main evaluation outcomes were menses improvement, endometrial thickness changes, pregnancy outcome, and side effects. All analyses were performed by using RevMan5.4 software. 427 studies were identified, eight of which were eligible and included in our analysis. Stem cell combined hormone therapy achieved a higher likelihood of improving menstruation (risk ratio [RR] 22.43, 95% CI: 8.03 to 62.68, P < 0.00001), an enhancement of pregnancy outcome (risk ratio [RR] 11.1, 95% CI: 3.58 to 34.38, P < 0.0001), and a mean increase of 3-month endometrial thickness (standardized mean difference [SMD] 2.43, 95% CI: 1.72 to 3.13, P < 0.00001). Subgroup analysis also indicated that 6-month and 9-month endometrial thickness increased significantly with the stem cell-based treatment. Moreover, no obvious and severe adverse reactions were observed during the process of stem cell therapy. There were 3 patients (3.57%) reported with lost appetite, mild gastritis, vomiting, or abdominal cramps, whereas, these symptoms relieved subsequently. This meta-analysis systematically reviewed and synthesized the outcomes of stem cell-based therapy in treating Asherman syndrome, which suggest that stem cell and hormone combination therapy was safe and more effective in improving menstruation duration, pregnancy outcome, and endometrial thickness. However, further trials with large sample sizes are needed to establish more solid evidence for administrating this therapy in clinic.

SDF-1/CXCR4 axis enhances the immunomodulation of human endometrial regenerative cells in alleviating experimental colitis.

Endometrial regenerative cells (ERCs) are a new type of mesenchymal-like stromal cells, and their therapeutic potential has been tested in a variety of disease models. SDF-1/CXCR4 axis plays a chemotaxis role in stem/stromal cell migration. The aim of the present study was to investigate the role of SDF-1/CXCR4 axis in the immunomodulation of ERCs on the experimental colitis. The immunomodulation of ERCs in the presence or absence of pretreatment of SDF-1 or AMD3100 was examined in both in vitro cell culture system and dextran sulphate sodium-induced colitis in mice. The results showed that SDF-1 increased the expression of CXCR4 on the surface of ERCs. As compared with normal ERCs, the SDF-1-treated, CXCR4 high-expressing ERCs more significantly suppressed dendritic cell population as well as stimulated both type 2 macrophages and regulatory T cells in vitro and in vivo. Meanwhile, SDF-1-pretreated ERCs increased the generation of anti-inflammatory factors (e.g., IL-4, IL-10) and decreased the pro-inflammatory factors (e.g., IL-6, TNF-α). In addition, SDF-1-pretreated CM-Dil-labeled ERCs were found to engraft to injured colon. Our results may suggest that an SDF-1-induced high level of CXCR4 expression enhances the immunomodulation of ERCs in alleviating experimental colitis in mice.

Human Endometrial Regenerative Cells Attenuate Bleomycin-Induced Pulmonary Fibrosis in Mice.

Endometrial regenerative cells (ERCs) have been recently evaluated as an attractive novel type of stem cell therapy. Previous studies have demonstrated that most ERCs accumulated in the lung after injection and are successfully used to treat diseases such as cardiac fibrosis. However, relevant studies of ERCs in idiopathic pulmonary fibrosis (IPF) have not been reported. The present study was designed to examine the effects of ERCs on bleomycin-induced pulmonary fibrosis. All IPF models in C57BL/6 mice were induced by administrating 5 mg/kg bleomycin in PBS intratracheally. ERCs were isolated from healthy female menstrual blood and were injected (1 million/mouse, i.v.) 24 hours after induction. Wet/dry weight ratio assay, hydroxyproline content, pathological and immunohistological changes, MDA content, T-SOD activity, cytokine profiles, and RT-qPCR analysis were assessed 2 weeks after disease induction. The results showed that ERC treatment significantly decreased the wet/dry ratio and reduced collagen deposition. Histological analyses, Masson staining, and hydroxyproline content analysis indicated that ERCs could reduce collagen fiber production. Immunohistochemical staining revealed lower expression of TGF-ß after ERC treatment. Furthermore, mice treated with ERCs had lower levels of IL-1ß and TNF-α, but a higher level of IL-10 in both the lung and serum. Gene expression analysis demonstrated that ERCs potently suppressed the proapoptotic gene Bax, while increasing the antiapoptotic gene Bcl-2 and antifibrosis genes HGF and MMP-9. Our results indicate that human ERCs protected the lung from pulmonary fibrosis in mice through immunosuppressive and antifibrosis effects. Moreover, these findings formed a foundation for the further use of ERCs in clinical treatment.

Prolongation of Cardiac Allograft Survival by Endometrial Regenerative Cells: Focusing on B-Cell Responses.

Endometrial regenerative cells (ERCs) have been recently evaluated as an attractive candidate source for emerging stem cell therapies in immunosuppression, but their role in immunoregulation is not fully understood. The present study was designed to investigate their effects, especially on B-cell responses in heart transplantation. In this study, ERCs were noninvasively obtained from menstrual blood. Heart transplantation was performed between C57BL/6 (H-2b ) donor mice and BALB/c (H-2d ) recipients. B-cell activation and antibody levels were determined using fluorescence-activated cell sorting, enzyme-linked immunosorbent assay and ELISpot. In this study, we demonstrated that ERCs negatively regulated B-cell maturation and activation in vitro without affecting their viability. ERC treatment prolonged cardiac allograft survival in mice, which was correlated with a decrease in IgM and IgG deposition and circulating antidonor antibodies, as well as with reduction in frequencies of antidonor antibody-secreting CD19+ B cells. In addition, upon ex vivo stimulation, B cells from ERC-treated heart transplant recipients had impaired proliferation capacity and produced less IgM and IgG antibody. Moreover, ERC treatment of mice receiving ovalbumin (OVA)-aluminum hydroxide vaccine resulted in significant lower numbers of anti-OVA IgG antibody-secreting splenic B cells and lower anti-OVA antibody titres. Our results indicate that therapeutic effects of ERCs may be attributed at least in part by their B-cell suppression and humoral response inhibition, suggesting the potential use of ERCs for attenuating antibody-mediated allograft rejection. Stem Cells Translational Medicine 2017;6:778-787.

Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice.

BACKGROUND: The endometrial regenerative cell (ERC) is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl4)-induced acute liver injury (ALI). METHODS: An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl4. Transplanted ERCs were intravenously injected (1 million/mouse) into mice 30 min after ALI induction. Liver function, pathological and immunohistological changes, cell tracking, immune cell populations and cytokine profiles were assessed 24 h after the CCl4 induction. RESULTS: ERC treatment effectively decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and improved hepatic histopathological abnormalities compared to the untreated ALI group. Immunohistochemical staining showed that over-expression of lymphocyte antigen 6 complex, locus G (Ly6G) was markedly inhibited, whereas expression of proliferating cell nuclear antigen (PCNA) was increased after ERC treatment. Furthermore, the frequency of CD4+ and CD8+ T cell populations in the spleen was significantly down-regulated, while the percentage of splenic CD4+CD25+FOXP3+ regulatory T cells (Tregs) was obviously up-regulated after ERC treatment. Moreover, splenic dendritic cells in ERC-treated mice exhibited dramatically decreased MHC-II expression. Cell tracking studies showed that transplanted PKH26-labeled ERCs engrafted to lung, spleen and injured liver. Compared to untreated controls, mice treated with ERCs had lower levels of IL-1ß, IL-6, and TNF-α but higher level of IL-10 in both serum and liver. CONCLUSIONS: Human ERCs protect the liver from acute injury in mice through hepatocyte proliferation promotion, as well as through anti-inflammatory and immunoregulatory effects.

Human endometrial regenerative cells attenuate renal ischemia reperfusion injury in mice.

BACKGROUND: Endometrial regenerative cells (ERCs) is an attractive novel type of adult mesenchymal stem cells that can be non-invasively obtained from menstrual blood and are easily replicated at a large scale without tumorigenesis. We have previously reported that ERCs exhibit unique immunoregulatory properties in experimental studies in vitro and in vivo. In this study, the protective effects of ERCs on renal ischemia-reperfusion injury (IRI) were examined. METHODS: Renal IRI in C57BL/6 mice was induced by clipping bilateral renal pedicles for 30 min, followed by reperfusion for 48 h. ERCs were isolated from healthy female menstrual blood, and were injected (1 million/mouse, i.v.) into mice 2 h prior to IRI induction. Renal function, pathological and immunohistological changes, cell populations and cytokine profiles were evaluated after 48 h of renal reperfusion. RESULTS: Here, we showed that as compared to untreated controls, administration of ERCs effectively prevented renal damage after IRI, indicated by better renal function and less pathological changes, which were associated with increased serum levels of IL-4, but decreased levels of TNF-α, IFN-γ and IL-6. Also, ERC-treated mice displayed significantly less splenic and renal CD4(+) and CD8(+) T cell populations, while the percentage of splenic CD4(+)CD25(+) regulatory T cells and infiltrating M2 macrophages in the kidneys were significantly increased in ERC-treated mice. CONCLUSIONS: This study demonstrates that the novel anti-inflammatory and immunoregulatory effects of ERCs are associated with attenuation of renal IRI, suggesting that the unique features of ERCs may make them a promising candidate for cell therapies in the treatment of ischemic acute kidney injury in patients.

Strained olefin enables triflic anhydride mediated direct dehydrative glycosylation.

For the first time, we demonstrated that Tf2O mediated direct dehydrative glycosylation was possible simply with strained olefins, and other typical bases were inhibitors of this reaction. We optimized the glycosylation conditions and found that typical benzyl protected 1-OH pyranosyl donors and certain alcohol acceptors were suitable for our glycosylation system. Furthermore, we found that complete 1,2-trans selectivity and a wider acceptor scope could be achieved with 2-O-Bz 3,4,6-tri-O-Bn pyranosyl donors.

1,2-Tans-1-dihydroxyboryl benzyl S-glycoside as glycosyl donor.

Activated by NBS, readily available 1,2-trans-1-dihydroxyboryl benzyl S-glycosides served as glycosyl donors and reacted with certain simple alcohol acceptors to produce pure 1,2-cis-O-glycosides in moderate yields. The boronic acid moiety was revealed essential in the glycosylation for product formation and good anomeric ratio. The preliminary model reactions suggested that glycosyl aryl boronic acids could be used for stereoselective glycosylation.

A novel strategy for preparing glycopeptide molecular probe using fluorous technology.

A novel and convenient strategy for iodine labeled glycopeptide molecular probe and purification was developed. The fluorine rich bi-functional coupling agent, 4-tris(2-perfluorohexylethyl)stannylbenzoate succinimidyl ester, was successfully synthesized via 5 steps starting from the fluorous Grignard reagent. It was purified by a simple and fast isolation using perfluorinated hexanes (FC-72). The "cold" iodine labeled yield for the coupling agent was as high as 92% within 15 min. The iodine-labeled product was only in organic fractions as we expected. It was shown that there was only one major peak in organic fractions according to HPLC. Finally, the iodine-labeled coupling agent was applied to label glycopeptide and afforded a high yield of 87% within 30 min.

Neoglycopeptide synthesis by suzuki-miyaura couplings between glycosyl aryl boronic acids and iodopeptides.

Suzuki-Miyaura coupling reaction was applied in the syntheses of neoglycopeptides. This work utilizes new type of glycosyl aryl boronic acid and readily accessible iodo amino acids/iodopeptides. Both carbohydrate and peptide moieties are unprotected and the final product could be isolated directly. The neoglyco amino acid and neoglycopeptide products feature an O-glycosyl biaryl linker between the carbohydrate and peptide moieties.

Direct glycosylation of bioactive small molecules with glycosyl iodide and strained olefin as acid scavenger.

A new strategy for diversity-oriented direct glycosylation of bioactive small molecules was developed. This reaction features (−)-ß-pinene as acid scavenger and work with glycosyl iodides under mild conditions. With the aid of RP-HPLC and chiral SFC separation techniques, the new direct glycosylation proved effective at gram scale on bioactive small molecules including AZD6244, podophyllotoxin, paclitaxel, and docetaxel. Interesting glycoside derivatives were efficiently created with good yields and 1,2-cis selectivity.

[Cognition and attitude of postpartum contraception among obstetricians in Tianjin area].

OBJECTIVE: Through analysed the questionnaire about postpartum contraception knowledge-attitude-practice (KAP) among obstetricians, to understand the postpartum contraceptive knowledge, idea, attitude and related factors among obstetricians. METHODS: From October 2013 to December 2013, 209 obstetricians of 10 different levels of the hospital of Tianjin area had been enrolled in this study, and KAP questionnaire was investigated. RESULTS: The knowledge of postpartum contraception among obstetricians was seriously lack, the total correct rate was 34.8%, the lowest score was 5 points, the highest was 80 points, the average score was 34.8±13.5, more than 60 points accounted for only 2.9% (6/209). 86.6% (181/209) obstetricians have thought it necessary to carry out postpartum contraceptive propaganda during pregnancy, and 97.6% (204/209) obstetricians have thought it necessary to develop postpartum contraception training. 92.8% (194/209) and 94.2% (197/209) obstetricians always informed that pay attention to contraception before discharge and postpartum visit, specific methods were not discussed. Obstetricians obtained relevant progress of contraceptive knowledge mainly through the daily medical work (92.8% , 194/209), hoped that approach postpartum contraception related knowlege through continuing education courses (77.5%, 162/209), special lectures in academic conference (72.2%, 151/209) and special training (67.5%, 141/209). CONCLUSIONS: (1) The postpartum contraception knowledge among obstetricians is seriously lack. (2) The obstetricians hold positive attitude towards the propaganda for postpartum contraceptive knowledge. (3) Postpartum contraception related education only provided before discharging and postpartum visit, and the content was simply inform that pay attention to contraception, specific methods are not discussed. (4) To explore the reason why postpartum contraception situation is not ideal, that's because insufficient attention and propaganda, obstetricians don't update the contraception knowledge, and be lack of knowledge on the efficient, long-acting reversible contraception methods, exaggerated the side effects and complications.

[The related study of first pregnancy women with Cu-IUD on copper content of blood serum and decidua, chorion tissues].

OBJECTIVE: Through determine the copper content of decidua, chorion and blood serum of first pregnancy women with Cu-IUD, we offer date for security of offspring. METHODS: March 2010 to December 2010, in family planning clinics of the general hospital of Tianjin medical university, we selected twenty-five first pregnancy women with Cu-IUD who intended to terminate pregnancy to be experimental group and twenty-five normal first pregnancy women who intended to terminate pregnancy to be control group, and determined the copper content of decidua, chorion and blood serum in experimental group and control group. RESULTS: The copper content of decidua, chorion and blood serum in experimental group is (0.91 ± 0.51) mg/kg, (0.72 ± 0.50) mg/kg, (0.79 ± 0.15) mg/L; the copper content of decidua, chorion and blood serum in control group is (0.57 ± 0.21) mg/kg, (0.46 ± 0.21) mg/kg, (0.71 ± 0.15) mg/L. The copper content of blood serum has no significant difference between experimental group and control group (P > 0.05). The copper content of decidua, chorion of experimental group is higher than control group (P < 0.05). CONCLUSION: Copper ion released from Cu-IUD only has an influence on the uterus tissues, but having no influence on the copper metabolism all over the body. The effects of high copper content of chorion in first pregnancy women with Cu-IUD on the offspring security will be researched further.