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PURPOSE: Here, we compared endometrioma recurrence rates in patients who have undergone a laparoscopic cystectomy and treated with a gonadotropin-releasing hormone agonist (GnRHa) alone or a GnRHa combined with a levonogestrel intrauterine system (LND-IUS). METHODS: We enrolled endometrioma patients who underwent laparoscopic cyst enucleation and divided them into two groups according to postoperative management: GnRHa alone and GnRHa in combination with LND-IUS. We compared preoperative history, perioperative parameters, postoperative endometrioma recurrence, and symptoms between these two groups. RESULTS: A total of 320 patients were included in the final analysis. With a median 84.6 months of follow-up, we detected significant differences between the two groups with respect to age at surgery (31.6 ± 4.8 vs. 37.6 ± 4.2 years, χ2 = 1.978, p < 0.001), gravida (0 vs. 2, χ2 = 4.391, p < 0.001), parity (0 vs. 1, χ2 = 0.035, p < 0.001), body mass index (21.0 ± 2.5 vs. 21.9 ± 2.4, χ2 = 0.0096, p = 0.009), r-AFS score (48 vs. 64, χ2 = 4.888, p = 0.001), and operation time (60 vs. 75 min, χ2 = 9.119, p = 0.003). Patients treated with both GnRHa and LND-IUS achieved significantly less endometrioma recurrence (23.6 vs. 11.5%, χ2 = 5.202, p = 0.023) and higher rates of pain remission (92.1 vs. 100%, χ2 = 6.511, p = 0.011), while those with GnRHa alone suffered more recurrent and painful symptoms (χ2 = 9.280, p = 0.026). Multivariate analysis using a Cox regression demonstrated that combined GnRHa and LNG-IUS treatment correlated with a decreased endometrioma recurrence rate after laparoscopic cystectomy (RR 0.369, 95% CI 0.182-0.749, p = 0.006). CONCLUSIONS: Combination treatment of GnRHa and LNG-IUS exhibited superior pain relief and recurrence prevention among endometrioma patients after fertility-sparing surgery. Thus, combination treatment is a preferable long-term option for patients without intent for pregnancy in the near future.
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Anticoncepcionais Femininos/administração & dosagem , Endometriose/cirurgia , Hormônio Liberador de Gonadotropina/administração & dosagem , Dispositivos Intrauterinos Medicados , Levanogestrel/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Adulto , Terapia Combinada , Anticoncepcionais Femininos/uso terapêutico , Endometriose/patologia , Feminino , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Levanogestrel/uso terapêutico , Recidiva Local de Neoplasia/patologia , Período Pós-Operatório , Prevenção Secundária , Resultado do TratamentoRESUMO
STUDY QUESTION: What are the oncofertility outcomes of young women (≤40 years old) with bilateral serous borderline ovarian tumors (SBOTs) after fertility-sparing surgery? SUMMARY ANSWER: Fertility preservation with the bilateral ovarian cystectomy procedure is feasible for bilateral SBOTs, with an acceptable oncological outcome and worthwhile pregnancy rates. WHAT IS KNOWN ALREADY: Fertility-sparing approaches are becoming the standard management of young patients with unilateral SBOTs and other borderline histological subtypes. However, there is a paucity of evidence to dictate the best management in bilateral SBOTs. STUDY DESIGN, SIZE, DURATION: This was a retrospective observational study performed at the Peking Union Medical College Hospital in Beijing, China, between January 1999 and January 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ninety-four women (≤40 years old) with pathologically confirmed bilateral SBOTs were included. Following preoperative counseling, patients self-selected into one of three treatment modalities: bilateral ovarian cystectomy (n = 48), unilateral adnexectomy plus contralateral cystectomy (UAC; n = 31), and radical surgery (n = 15). Univariate and multivariate analyses were used to determine the clinical and pathological features associated with disease-free survival and reproductive outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: During the median follow-up of 64 months (range, 4-243 months), 61 patients (65%) developed relapse, including 3 (20%) in the radical group, 26 (84%) in the UAC group and 32 (67%) in the bilateral cystectomy group. In the multivariate analyses, preoperative CA-125>300 U/mL, fertility preservation and micropapillary pattern were independently associated with adverse disease-free survival (P = 0.001, 0.03 and 0.026, respectively). Fourteen patients (15%) experienced invasive recurrence, and three (3%) died of progressive disease. The micropapillary pattern was significantly associated with invasive evolution risk (P = 0.006). Of the 49 patients who attempted to conceive, 23 (47%) achieved 27 pregnancies (24 spontaneous and three after IVF-ET), resulting in 19 live births. There was no significant difference in disease-free survival (P = 0.13) or pregnancy rate (41 vs. 50%, P = 0.56) between the UAC and bilateral procedures. LIMITATIONS, REASONS FOR CAUTION: As a retrospective study conducted in a referral center, inherent biases exist. The nonrandom allocation to treatment groups and relatively small number of patients attempt to conceive might limit the statistical power of our findings. Only 41 patients (43.6%) received complete staging during their initial surgeries, so an underestimation bias in terms of the FIGO stage and extraovarian implants might have occurred. WIDER IMPLICATIONS OF THE FINDINGS: The ultraconservative bilateral ovarian cystectomy procedure should be proposed in bilateral SBOTs when technically feasible. Invasive evolution occurs frequently in these women, and intense follow-up and oncofertility counseling are warranted, especially for those with micropapillary patterns. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.
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Preservação da Fertilidade , Neoplasias Ovarianas , Adulto , China , Feminino , Humanos , Recidiva Local de Neoplasia , Neoplasias Ovarianas/cirurgia , Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVE: To study the relationship between the clinic-pathological features and pain symptoms in patients with endometriotic cyst (EM). METHODS: The medical data of symptoms, laparoscopy and pathology examination in 416 patients with endometriosis were studied retrospectively. All cases were divided into two groups on the existence of ovarian endometrioma, including 338 patients in cyst group and 78 cases in non-cyst group. The relationship between clinical symptoms and location and type of endometrioma was studied. RESULTS: (1) Serum CA125 level: the level of CA125 were (61 ± 39) kU/L in cyst group (28 ± 24) kU/L in non-cyst group, which reached statistical difference (P < 0.01). (2) Pathological features: among 338 cases, 34.0% of cyst were on left side (115/338), 26.3% were right side (89/338), and 39.6% were on both side (134/338). And 95.8% (324/338) of cases were combined with the other type of endometriosis, which were 48.5% (164/338) with peritoneal endometriosis, 47.3% (160/338) with deep infiltrating endometriosis (DIE). In cystic patients, the incidences of endometriosis lesion were 13.9% (47/338) on the uterine surface, 38.5% (130/338) on obstruction of cul-de sac, 40.5% (137/338) on utero-sacral ligament of DIE, which were significantly higher than 5.1%, (4/78), 9.0% (7/78) and 28.2% (22/78) in noncyst group. (3) Pain symptom: the incidence and degree of dysmenorrhea and dyschezia had no statistical difference between two groups (P > 0.05), and the incidence of chronic pelvic pain (CPP) of 24.6% (83/338) and dyspareunia of 29.9% (101/338) in the cyst group were significantly lower than 35.9% (28/78) and 44.9% (35/78) in non-cyst group (P < 0.05). The incidence of dysmenorrheal was 85.1% (114/134) in cases with bilateral cyst, which was higher than 74.0% (151/204) in cases with single cyst. The incidence of dysmenorrheal and dyschezia in moderate-severe adhesion was 89.0% (138/155) and 18.7% (29/155), which was significantly higher than 68.8% (126/183) and 8.2% (15/183) in mild adhesion. In the patients cyst existed with DIE, the risk of dysmenorrheal, CPP, dyspareunia, and dyschezia were obviously raised (OR respectively was 5.17, 3.01, 3.05, 2.75). CONCLUSIONS: The endometriotic cyst often co-exists with other type of endometriotic lesions. Ovarian endometrioma was associated with lesion localized on uterine surface, cul-de-sac, sacrum ligament. The risk of all the pain symptoms would be raised when the endometriotic cyst co-exit with the DIE lesions. So the treatment for DIE lesions was as same important as the endometriotic lesions in order to relieve pain symptoms and delay the relapse.
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Endometriose/patologia , Endometriose/fisiopatologia , Cistos Ovarianos/patologia , Cistos Ovarianos/fisiopatologia , Dor/fisiopatologia , Adulto , Dismenorreia/epidemiologia , Dismenorreia/fisiopatologia , Dispareunia/epidemiologia , Dispareunia/fisiopatologia , Endometriose/cirurgia , Feminino , Humanos , Laparoscopia , Cistos Ovarianos/cirurgia , Dor/epidemiologia , Medição da Dor , Dor Pélvica/epidemiologia , Dor Pélvica/fisiopatologia , Estudos RetrospectivosRESUMO
BACKGROUND: When ovarian endometrioma coexist with adenomyosis, the risk of postoperative recurrence increased. How is the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) on symptomatic recurrence for those patients was unknown. METHODS: This study retrospectively analyzed 119 women with coexistent endometrioma and diffuse adenomyosis who received laparoscopic excision of pelvic endometriosis from January 2009 to April 2013. Women were categorized into two groups: intervention group with LNG-IUS and control group with expectant observation after surgery. Data were compared in terms of preoperative history, laboratory and intraoperative findings, and clinical outcomes during follow-up, including pain regression, changes in uterine volume and recurrence. RESULTS: During a median 79 months (range, 6-107) of follow-up, patients with LNG-IUS experienced a significantly lower symptomatic recurrence of either ovarian endometrioma or dysmenorrhea (11.1% vs. 31.1%, p = 0.013), compared with women under expectant observation by Kaplan-Meier survival analysis (χ2 = 5.448, p = 0.020) and Cox univariate assessment (hazard ratio of 0.336, 95% confidence interval 0.128-0.885, p = 0.027). Patients treated with LNG-IUS demonstrated a more prominent reduction in uterine volume (-14.1 ± 20.9 vs. 8.7 ± 48.8, p = 0.003) and higher percentage of complete pain remission (95.6% vs. 86.5%). For multivariate analysis, use of LNG-IUS (aHR 0.159, 95%CI 0.033-0.760, p = 0.021) and severity of dysmenorrhea (aHR 4.238, 95%CI 1.191-15.082, p = 0.026) were two independent factors associated with overall recurrence. CONCLUSION: Postoperative insertion of LNG-IUS may prevent recurrence in symptomatic women with comorbidity of ovarian endometrioma and diffuse adenomyosis.
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Adenomiose , Endometriose , Dispositivos Intrauterinos Medicados , Humanos , Feminino , Endometriose/complicações , Endometriose/cirurgia , Endometriose/tratamento farmacológico , Levanogestrel/uso terapêutico , Dismenorreia/prevenção & controle , Estudos Retrospectivos , Seguimentos , Adenomiose/complicações , Adenomiose/cirurgia , Estudos de Casos e ControlesRESUMO
OBJECTIVES: To compare operative characteristics, postoperative residue, recurrence, and pregnancy outcome between laparoscopic myomectomy (LM) and transabdominal myomectomy (TAM), and investigate the favourable surgical approach in women with uterine myomas. METHODS: From Jan 2008 to Dec 2008, 313 women undergoing LM and 148 women undergoing TAM were studied retrospectively in Peking Union Medical College Hospital. The patients' general information, including the largest diameter, mean numbers and weights of excised myomas, peri-operative characteristics (operating time, blood loss, and hemoglobin decrease), and residue, recurrence of myoma, and pregnancy outcome were compared and analyzed. RESULTS: The largest diameter, mean numbers and mean weight of myomas removed were larger in TAM group [(7.6 ± 3.0) cm, (5.6 ± 5.5), (308 ± 364) g, respectively] than those in LM group [(6.8 ± 2.0) cm, (2.4 ± 2.1), (140 ± 109) g, respectively; P < 0.01]. While the extension of operating time [(89 ± 32) versus (74 ± 35) min], increased blood loss [(239 ± 251) versus (149 ± 252) ml] and hemoglobin decrease [(22 ± 14) versus (15 ± 12) g/L], and longer hospital stay [(6.4 ± 1.6) versus (4.4 ± 1.3) d] were observed in TAM group when compared with those in LM group (P < 0.01). However, the residue rate of LM and TAM was 2.6% versus 1.4% respectively (P = 0.5130); the recurrence rate of LM and TAM was 11.1% versus 12.3% (P > 0.05); the pregnancy rate of LM and TAM was 49.2% versus 9/13 separately, the difference was not statistically significant (P = 0.2330). The number of myomas removed was the significant risk factors associated with recurrence (OR = 2.805, 95%CI: 1.192 - 6.601, P = 0.0180). No uterine rupture occurred during pregnancy. CONCLUSIONS: Both LM and TAM are effective surgical approaches for the patients with leiomyoma who desire to pregnancy, or to retain the integrity of their uteruses. Most of uterine myoma could be treated through laparoscopy. The residue rate of LM is higher than that of TAM. However, the short term recurrence rates of LM and TAM are similar. Multiple myomas is the risk factor associated with recurrence after myomectomy. The pregnancy rates are comparable between LM and TAM groups.
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Procedimentos Cirúrgicos em Ginecologia/métodos , Laparoscopia , Leiomioma/cirurgia , Neoplasias Uterinas/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Leiomioma/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Neoplasia Residual , Período Pós-Operatório , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Uterinas/patologiaRESUMO
OBJECTIVE: To investigate the expression of transforming growth factor (TGF)-ß and Smad pathway expressed in adhesion peritoneums in patients with endometriosis (EM). METHODS: From Dec. 2009 to Mar. 2010, 11 patients with EM [including 3 patients treated by gonadotropin releasing hormone agonist (GnRH-a) treatment] underwent laparoscopy surgery in Peking Union Medical College Hospital. In the mean time, 9 patients with benign ovarian tumor without EM and peritoneum adhesion were chosen as control. Peritoneum from lateral peritoneal cavity, adjacent from lesion and grossly normal was obtained during surgery. Microstructure of peritoneums was observed by HE staining and Masson staining. The expression of TGF-ß1, TGF-ß3, Smad 3 and Smad 7 in peritoneums were measured by immunohistochemistry staining and real-time PCR. The effect of GnRH-a on expressions of these markers were also analyzed. RESULTS: (1) Microstructures of peritoneum: enlargement of nucleus of peritoneal mesothelial cells, thickening of connective tissue, distributive disorder of fiber, increasing numbers of fibroblast and inflammatory cells in EM were significantly different from those in control group. (2) The expression of TGF-ß1 and 3 in peritoneum were 0.170 ± 0.020 and 0.110 ± 0.010 in EM group, which were significantly higher than 0.070 ± 0.010 and 0.050 ± 0.020 in control group. TGF-ß1 was downregulated to 0.130 ± 0.030 and TGF-ß3 was upregulated to 0.490 ± 0.090 by GnRH-a. (3) The expression of Smad 3 and 7 were 0.140 ± 0.020 and 0.110 ± 0.020 in peritoneum in EM group, which were significantly higher than 0.024 ± 0.004 and 0.014 ± 0.007 in control group. GnRH-a could upregualted the expression of smad 7 (0.040 ± 0.020), however, but no significant effect was observed on regulating Smad3 expression. CONCLUSIONS: The changes of microstructure and the alteration of TGF-ß/Smad expression in peritoneum of endometriosis were observed. GnRH-a could regulate the expression of TGF-ß and Smad.
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Endometriose/metabolismo , Peritônio/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Células Epiteliais/metabolismo , Epitélio/metabolismo , Feminino , Fibroblastos/metabolismo , Humanos , Cavidade Peritoneal , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Regulação para CimaRESUMO
OBJECTIVE: To investigate strategies of diagnosis and treatment of ureter endometriosis. METHODS: From 1983 to 2010, the cases registered in Peking Union Medical College Hospital and confirmed as ureter endometriosis by surgery were enrolled in this study. Clinical manifestations, pre-operative examinations, surgical categories and routes, surgical and pathological findings, post-operative medical treatment, relapse and relating factors were collected and studied. RESULTS: Totally 46 patients with ureter endometriosis underwent one or two surgeries. Forty-eight per cent (22/46) of patients were not be diagnosed with ureter endometriosis pre-operatively, and 46% (21/46) only presented dysmenorrhea or even no symptoms. Ureterolysis (72%, 33/46) and laparotomy (63%, 29/46) were the most common surgical category and surgical approach. There were 64% (25/39) of patients had left ureter involved and 80% (37/46) had extrinsic ureter endometriosis. Fifteen per cent (7/46) of patients had relapsed disease with median recurrent time of 24 months (13-49 months), and they all received second surgeries. Logistic regression analysis showed that only gonadotropin releasing hormone analogue agents were related with recurrence when compared with those patients without medical treatment post-operatively significantly (OR=23.2, 95%CI: 2.4-221.7, P=0.002). CONCLUSIONS: Ureter endometriosis was related with reproductive tract endometriosis. It has insidious process resulting in difficulty for early diagnosis. It's important to treat pelvic deep infiltrating endometriosis and ovarian endometrioma to prevent ureter from further involvement. Post-operative treatment of pelvic endometriosis is the key point of preventing relapse of ureter endometriosis.
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Endometriose/cirurgia , Ureter/cirurgia , Doenças Ureterais/cirurgia , Adulto , Dismenorreia/etiologia , Dismenorreia/terapia , Endometriose/diagnóstico , Endometriose/patologia , Feminino , Seguimentos , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Laparoscopia , Pessoa de Meia-Idade , Doenças Ovarianas/patologia , Doenças Ovarianas/cirurgia , Estudos Retrospectivos , Prevenção Secundária , Resultado do Tratamento , Ultrassonografia , Ureter/patologia , Doenças Ureterais/diagnóstico , Doenças Ureterais/patologiaRESUMO
Objective: To investigate the difference of clinical features and outcomes between EM patients with and without AM after following up for at least 6 years after surgery. Methods: We retrospectively analyzed 358 EM patients who had a minimum of 6 years follow-up after laparoscopic cystectomy, which was performed by one single doctor at Peking Union Medical College Hospital from January 2009 to April 2013. All women were divided into AM group and non-AM group and analysis was performed in preoperative characteristics, surgical findings and postoperative outcomes during follow-up. Results: A total of 358 EM patients were recruited, of which 142 (39.7%) were in the AM group and the rest 216 (60.3%) in the non-AM group. Between the two group, the mean age was 34.6 vs. 32.2 years (P < 0.001). The mean operating time in the AM and non-AM group was 73.2 vs. 61.9 min (P < 0.001). According to the revised AFS classification, the mean score of the two group were 60.3 vs. 45.5 (P < 0.001). At the end of the follow-up, though the AM group was with higher rate of disease relapse, yet no significant difference was found between the two groups in statistical comparison (34/142 [23.9%] vs. 34/216 [15.7%], P = 0.053). With a minimum follow-up of 6 years after laparoscopic cystectomy, failed and successful pregnancy were seen in 107/142(75.4%) and 35/142 (24.6%) patients in the AM group vs. 114/216(52.8%) and 102/216 (47.2%) patients in the non-AM group (P < 0.05). As for the successfully pregnant patients, live births, including spontaneous pregnancy and IVF-ET, were seen in 34/35 (97.1) vs. 99/102 (97.1) patients between AM and non-AM groups, while others ended in spontaneous abortion. No significant associations were found between the two groups in infertility, leiomyoma presence, the size of ovarian endometrioma, type of deep infiltrating endometriosis (DIE) or type of recurrence (P > 0.05). Conclusion: Compared with non-AM group, EM patients with concurrent AM may have higher age, longer mean operating time and higher mean AFS score. In terms of fertility outcomes, patients in the AM group were with lower likelihood of pregnancy after surgery during the long-time follow-up.
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OBJECTIVE: To investigate the relationship between the distribution of nerve fibers in multiple endometriosis lesions and pelvic pain. METHODS: From Sept. 2007 to Sept. 2008, 120 endometriosis patients treated in Peking Union Hospital were enrolled in this study, which including 19 cases with stage I, 29 cases with stage II, 44 cases with stage III and 28 cases with stage IV. The pain symptom was evaluated by visual analogue scales (VAS) score and nerve fibers in multiple endometriosis lesions were detected by immunohistochemical staining. RESULTS: The number of nerve fibers in multiple endometriosis lesions were (29.74+/-17.33)/mm2 in uterosacral ligament, (24.53+/-13.34)/mm2 in vaginal septum, (17.09+/-10.09)/mm2 in uterus rectum crux, (6.77+/-4.21)/mm2 in peritoneal endometriosis lesions, (0.07+/-0.25)/mm2 in endometriosis ovarian cyst wall. The number of nerve fibers in uterosacral ligament was mostly correlated with the degree of pain (r=0.56). The nerve fibers of uterus rectum crux and vaginal septum were correlated with defecation pain (r=0.58 and 0.41) and dyspareunia (r=0.82 and 0.67), which were significantly higher than those in endometriosis leision in peritoneum and ovary. There was no significant different number of nerve fibers among different stage disease (P>0.05). CONCLUSION: There was significantly different distribution of nerve fibers in multiple endometriosis lesions, which was correlated with dysmenorrhea, anus pain, dyspareunia and chronic pelvic pain, not with clinical staging.
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Endometriose/patologia , Fibras Nervosas/patologia , Dor/patologia , Útero/inervação , Vagina/inervação , Adulto , Endometriose/fisiopatologia , Feminino , Humanos , Imuno-Histoquímica , Laparoscopia , Ligamentos/inervação , Ligamentos/patologia , Dor/etiologia , Dor/fisiopatologia , Dor Pélvica/etiologia , Dor Pélvica/patologia , Dor Pélvica/fisiopatologia , Peritônio/inervação , Peritônio/patologia , Reto/inervação , Reto/patologia , Índice de Gravidade de Doença , Útero/patologia , Vagina/patologiaRESUMO
Hypoxic preconditioning has been shown to improve hypoxic tolerance in mice, accompanied by the downregulation of DNA methyltransferases (DNMTs) in the brain. However, the roles played by DNMTs in the multiple neuroprotective mechanisms associated with hypoxic preconditioning remain poorly understood. This study aimed to establish an in vitro model of hypoxic preconditioning, using a cultured mouse hippocampal neuronal cell line (HT22 cells), to examine the effects of DNMTs on the endogenous neuroprotective mechanisms that occur during hypoxic preconditioning. HT22 cells were divided into a control group, which received no exposure to hypoxia, a hypoxia group, which was exposed to hypoxia once, and a hypoxic preconditioning group, which was exposed to four cycles of hypoxia. To test the ability of hypoxic preadaptation to induce hypoxic tolerance, cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethonyphenol)-2-(4-sulfophenyl)-2H-tetrazolium assay. Cell viability improved in the hypoxic preconditioning group compared with that in the hypoxia group. The effects of hypoxic preconditioning on the cell cycle and apoptosis in HT22 cells were examined by western blot assay and flow cytometry. Compared with the hypoxia group, the expression levels of caspase-3 and spectrin, which are markers of early apoptosis and S-phase arrest, respectively, noticeably reduced in the hypoxic preconditioning group. Finally, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and western blot assay were used to investigate the changes in DNMT expression and activity during hypoxic preconditioning. The results showed that compared with the control group, hypoxic preconditioning downregulated the expression levels of DNMT3A and DNMT3B mRNA and protein in HT22 cells and decreased the activities of total DNMTs and DNMT3B. In conclusion, hypoxic preconditioning may exert anti-hypoxic neuroprotective effects, maintaining HT22 cell viability and inhibiting cell apoptosis. These neuroprotective mechanisms may be associated with the inhibition of DNMT3A and DNMT3B.
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INTRODUCTION: Ovarian endometriosis is the most common type of endometriosis (EM), affecting more than 40% of women with EM. Currently, surgical intervention is still controversial in infertile patients with ovarian endometriosis, especially in those with stage III-IV EM. Very few studies have been done to analyze long-term pregnancy results in patients with endometrioma more than 5 years after surgery. Therefore, the aim of this study was to explore the pregnancy outcomes and the related factors in patients with endometrioma and stage III-IV endometriosis during a long-term follow-up postoperatively. METHODS: We collected 347 patients with ovarian endometriosis, which included 59 infertile patients with stage III-IV endometriosis who had a minimum of 5 years of postoperative follow-up after undergoing laparoscopic excision of ovarian endometriomas performed by a single doctor at the Peking Union Medical College Hospital from January 2009 to April 2013. RESULTS: A total of 59 infertile patients were recruited. The mean age was 31.8 ± 3.6 years. The mean size of the endometriomas was 6.8 ± 3.3 cm. Before surgery, dysmenorrhea was present in 88.1% (52/59) of the cases, while chronic pelvic pain was reported in nine cases (15.3%). A total of 20.3% (12/59) of cases were concurrent with leiomyoma, 52.5% (31/59) with deep infiltrating endometriosis (DIE), and 39.0% (23/59) with adenomyosis. During laparoscopy, 21 cases were diagnosed as stage III (35.6%) and 38 as stage IV (64.4%) EM according to the revised American Fertility Society (AFS) classification. After laparoscopic cystectomy, 38 (64.4%) patients became successfully pregnant by the 5th year. All the patients were divided into two groups according to the postoperative pregnancy outcomes. In univariate analysis, the higher mean age and concurrent diagnosis of adenomyosis were seen to be related to poor postoperative pregnancy outcomes (p < 0.05). In multivariate analysis, however, the mean age, chronic pelvic pain (CPP), and adenomyosis were independent risk factors of pregnancy outcomes between the two groups (p < 0.05). With a minimum follow-up of 6 years, 23.7% (14/59) of recurrence was observed in the entire study cohort. CONCLUSION: Infertile patients with endometrioma and stage III-IV EM may have lower pregnancy rates after laparoscopic cystectomy if they are older and present with CPP and adenomyosis. Our data showed a lower rate of recurrence but a higher rate of pregnancy after surgery.
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Cistectomia/efeitos adversos , Endometriose/complicações , Endometriose/cirurgia , Infertilidade Feminina/etiologia , Laparoscopia/efeitos adversos , Recidiva Local de Neoplasia/etiologia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/cirurgia , Adulto , Estudos de Coortes , Feminino , Seguimentos , Humanos , Gravidez , Taxa de GravidezRESUMO
A finite element method based on ABAQUS is employed to examine the correlation between the microstructure and the elastic response of planar Cayley treelike fiber networks. It is found that the elastic modulus of the fiber network decreases drastically with the fiber length, following the power law. The power law of elastic modulus G' vs the correlation length xi obtained from this simulation has an exponent of -1.71, which is close to the exponent of -1.5 for a single-domain network of agar gels. On the other hand, the experimental results from multidomain networks give rise to a power law index of -0.49. The difference between -1.5 and -0.49 can be attributed to the multidomain structure, which weakens the structure of the overall system and therefore suppresses the increase in G'. In addition, when the aspect ratio of the fiber is smaller than 20, the radius of the fiber cross-section has a great impact on the network elasticity, while, when the aspect ratio is larger than 20, it has almost no effect on the elastic property of the network. The stress distribution in the network is uniform due to the symmetrical network structure. This study provides a general understanding of the correlation between microscopic structure and the macroscopic properties of soft functional materials.
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OBJECTIVE: To explore the risk factors for the recurrence of endometrioma and the risk factors for the recurrence of endometriosis-related pain after long-term follow-up. METHODS: This study retrospectively analyzed 358 women with endometriomas who had a minimum of 5-years follow up after laparoscopic endometrioma excision, which was performed at Peking Union Medical College Hospital from January 2009 to April 2013. All women were divided into recurrence group and nonrecurrence group. Analysis was performed with regard to preoperative history, laboratory analysis, findings during surgery, and symptoms during follow-up, including improvement and recurrence. RESULTS: The cumulative incidence rates of recurrence from 5 to 10 years after surgery were 15.4, 16.8, 19.3, 22.5, 22.5, and 22.5%, respectively. Significant differences were found between two groups in terms of age at surgery (RR: 0.764, 95% CI: 0.615-0.949, p = 0.015), duration of dysmenorrhea (RR: 1.120, 95% CI: 1.054-1.190, p < 0.001), presence of adenomyosis (RR: 1.629, 95% CI: 1.008-2.630, p = 0.046), CA125 level (RR: 1.856, 95% CI: 1.072-3.214, p = 0.021) and severity of dysmenorrhea. The severity of dysmenorrhea (RR: 1.711, 95% CI: 1.175-2.493, p = 0.005) and postoperative pregnancy (RR: 0.649, 95% CI: 0.460-0.914, p = 0.013) were significantly correlated with endometrioma recurrence in the multivariate analysis. No significant associations were found between the recurrence rate and gravida, parity, body mass index, infertility, leiomyoma presence, the size of ovarian endometrioma, the presence of deep infiltrating endometriosis, disease stage or postoperative medication. CONCLUSIONS: The severity of dysmenorrhea and postoperative pregnancy were independent risk factors for the recurrence of ovarian endometriomas after surgery during the long-time follow up.
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Endometriose/epidemiologia , Doenças Ovarianas/epidemiologia , Adulto , Dismenorreia/epidemiologia , Endometriose/cirurgia , Feminino , Seguimentos , Humanos , Doenças Ovarianas/cirurgia , Recidiva , Fatores de RiscoRESUMO
BACKGROUND: Endometriosis is a challenging disease with symptoms such as dysmenorrhea and infertility. However, its etiology is still vague and there is still no effective markers or treatment. This study aimed to profile the circular RNAs (circRNAs) expressed in eutopic endometrium from patients with ovarian endometriosis and explore potential clues to the pathogenesis of endometriosis, providing an evidence for clinical diagnosis and treatment. METHODS: A total of 63 clinical samples, including control endometrium (n = 22) and eutopic endometrium (n = 41), were collected from Peking Union Medical College Hospital between May 1, 2016, and December 31, 2016. Of them, four samples in each group were used for circRNA microarray. Then, four upregulated circRNAs were screened out for quantitative real-time polymerase chain reaction (qRT-PCR) validation. After that, bioinformatics analysis was performed to predict miRNAs targeted by validated circRNAs and investigate the circRNA-miRNA-mRNA interactions. RESULTS: Among 88 differentially expressed circRNAs, 11 were upregulated and 77 were downregulated in eutopic endometrium of patients with endometriosis. qRT-PCR validation results for two upregulated circRNAs (circ_0004712 and circ_0002198) matched the microarray results. The area under the receiver operating characteristic curve of circ_0002198 for distinguishing ovarian endometriosis was 0.846 (95% confidence interval [CI]: 0.752-0.939; P < 0.001) while that of circ_0004712 was 0.704 (95% CI: 0.571-0.837; P = 0.008). On the basis of target prediction, we depicted the molecular interactions between the identified circRNAs and their dominant target miRNAs, as well as constructed a circRNA-miRNA-mRNA network. CONCLUSIONS: This study provides evidence that circRNAs are differentially expressed between eutopic and normal endometrium, which suggests that circRNAs are candidate factors in the activation of endometriosis. circ_0002198 and circ_0004712 may be potential novel biomarkers for the diagnosis of ovarian endometriosis.
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Biomarcadores/análise , Endometriose/genética , RNA/análise , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Controle de Qualidade , RNA Circular , Reação em Cadeia da Polimerase em Tempo Real , Adulto JovemRESUMO
BACKGROUND: In addition to neurons, all components of the neurovascular unit (NVU), such as glial, endothelial, and basal membranes, are destroyed during traumatic brain injury (TBI). Previous studies have shown that excessive stimulation of calpain is crucial for cerebral injury after traumatic insult. The objective of this study was to investigate whether calpain activation participated in NVU disruption and edema formation in a mouse model of controlled cortical impact (CCI). METHODS: One hundred and eight mice were divided into three groups: the sham group, the control group, and the MDL28170 group. MDL28170 (20 mg/kg), an efficient calpain inhibitor, was administered intraperitoneally at 5 min, 3 h, and 6 h after experimental CCI. We then measured neurobehavioral deficits, calpain activity, inflammatory mediator levels, blood-brain barrier (BBB) disruption, and NVU deficits using electron microscopy and histopathological analysis at 6 h and 24 h after CCI. RESULTS: The MDL28170 treatment significantly reduced the extent of both cerebral contusion (MDL28170 vs. vehicle group, 16.90 ± 1.01 mmÎ and 17.20 ± 1.17 mmÎ vs. 9.30 ± 1.05 mmÎ and 9.90 ± 1.17 mmÎ, both P < 0.001) and edema (MDL28170 vs. vehicle group, 80.76 ± 1.25% and 82.00 ± 1.84% vs. 82.55 ± 1.32% and 83.64 ± 1.25%, both P < 0.05), improved neurological scores (MDL28170 vs. vehicle group, 7.50 ± 0.45 and 6.33 ± 0.38 vs. 12.33 ± 0.48 and 11.67 ± 0.48, both P < 0.001), and attenuated NVU damage resulting (including tight junction (TJ), basement membrane, BBB, and neuron) from CCI at 6 h and 24 h. Moreover, MDL28170 markedly downregulated nuclear factor-κB-related inflammation (tumor necrosis factor-α [TNF-α]: MDL28170 vs. vehicle group, 1.15 ± 0.07 and 1.62 ± 0.08 vs. 1.59 ± 0.10 and 2.18 ± 0.10, both P < 0.001; inducible nitric oxide synthase: MDL28170 vs. vehicle group, 4.51 ± 0.23 vs. 6.23 ± 0.12, P < 0.001 at 24 h; intracellular adhesion molecule-1: MDL28170 vs. vehicle group, 1.45 ± 0.13 vs. 1.70 ± 0.12, P < 0.01 at 24 h) and lessened both myeloperoxidase activity (MDL28170 vs. vehicle group, 0.016 ± 0.001 and 0.016 ± 0.001 vs. 0.024 ± 0.001 and 0.023 ± 0.001, P < 0.001 and 0.01, respectively) and matrix metalloproteinase-9 (MMP-9) levels (MDL28170 vs. vehicle group, 0.87 ± 0.13 and 1.10 ± 0.10 vs. 1.17 ± 0.13 and 1.25 ± 0.12, P < 0.001 and 0.05, respectively) at 6 h and 24 h after CCI. CONCLUSIONS: These findings demonstrate that MDL28170 can protect the structure of the NVU by inhibiting the inflammatory cascade, reducing the expression of MMP-9, and supporting the integrity of TJ during acute TBI.
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Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Calpaína/antagonistas & inibidores , Calpaína/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , NF-kappa B/metabolismo , Animais , Dipeptídeos/uso terapêutico , Modelos Animais de Doenças , Glicoproteínas/uso terapêutico , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Peroxidase/antagonistas & inibidores , Peroxidase/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Quenching effect of the photoluminescence of 1,2,4,5-tetrakis(4-pyridylvinyl)benzene in the presence of CdS colloids stabilized by inverse micelles was observed. The observed regularities of luminescence quenching by the quenchers of different size were studied. An increase in the two-photon absorption cross section (6.5 times higher) and in the two-photon-induced fluorescence intensity was observed for the composite solution when pumped by 740-nm laser irradiation. The results are in accord with theoretical prediction of enhancement of third-order optical nonlinearity of quantum-confined semiconductor.
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BACKGROUND: Adenomyosis (AM) has impaired contraction. This study aimed to explore the expression of potassium channels related to contraction in myometrial smooth muscle cells (MSMCs) of AM. METHODS: Uterine tissue samples from 22 patients (cases) with histologically conï¬rmed AM and 12 (controls) with cervical intraepithelial neoplasia were collected for both immunohistochemistry and real-time polymerase chain reaction to detect the expression of large conductance calcium- and voltage-sensitive K + channel (BKCa)-α/ß subunits, voltage-gated potassium channel (Kv) 4.2, and Kv4.3. Student's t-test was used to compare the expression. RESULTS: The BKCa-α/ß subunits, Kv4.2, and Kv4.3 were located in smooth muscle cells, glandular epithelium, and stromal cells. However, BKCa-ß subunit expression in endometrial glands of the controls was weak, and Kv4.3 was almost undetectable in the controls. The expression of BKCa-α messenger RNA (mRNA) (0.62 ± 0.19-fold decrease, P < 0.05) and Kv4.3 mRNA (0.67 ± 0.20-fold decrease, P < 0.05) decreased significantly in the MSMCs of the control group compared with the AM group. However, there were no significant differences in BKCa-ß subunit mRNA or Kv4.2 mRNA. CONCLUSIONS: The BKCa-α mRNA and the Kv4.3 mRNA are expressed significantly higher in AM than those in the control group, that might cause the abnormal uterus smooth muscle contractility, change the microcirculation of uterus to accumulate the inflammatory factors, impair the endometrium further, and aggravate the pain.
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Adenomiose/metabolismo , Miócitos de Músculo Liso/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Neoplasias Uterinas/metabolismo , Adulto , Feminino , Humanos , Imuno-Histoquímica , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Canais de Potássio Shal/metabolismo , Contração Uterina/fisiologia , Útero/metabolismoRESUMO
In this report, the binding interaction of chromium(VI), as Cr2O7(2-), with humic acid was studied by using UV-visible absorption, fluorescence spectroscopy, and molecular modeling method. The fluorescence spectral data indicated that the binding interaction existed between Cr2O7(2-) and humic acid and the order of magnitude of binding constants were 10(3). The rise in temperature caused a decrease in the values of the binding constant of humic acid with Cr2O7(2-). Thermodynamic analysis presented that multi-intermolecular forces including hydrogen bonding, hydrophobic, and electrostatic forces were involved in the binding process at pH 6.5. The spectral data also indicated that Cr2O7(2-) affected the aromatic ring structures in humic acid. Furthermore, the molecular modeling analysis indicated that a lot of reactive groups and binding cavities in HA played a key role in its binding with Cr2O7(2-).
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Endometriosis has critical implications for women's quality of life. However, an overview of the current knowledge of this issue is limited. The objective of this systematic review was to determine the extent of endometriosis and its treatment upon women's health-related quality of life (HRQoL). PubMed, Embase, PsycoINFO, CINAHL and the Cochrane Clinical Trials were searched up to May 2012, and only studies using standardized instruments to evaluate HRQoL in women with endometriosis were selected. Our electronic searches identified 591 citations, of which 39 studies satisfied the inclusion criteria including nine qualitative studies and 30 treatment-related studies. Findings showed that endometriosis impaired women's HRQoL. Pain was strongly related to a poor HRQoL, and medical or surgical treatment could partially restore this impairment. No conclusive evidence was available on whether endometriosis imposed an additional impairment in HRQoL per se, apart from the decrease caused by chronic pelvic pain, or on the superiority of various hormonal suppression agents. The impacts of disease extent, duration and fertility status upon HRQoL were inconsistent. In summary, HRQoL was impaired in women with endometriosis, and medical or surgical treatment to alleviate pain could partially restore this impairment.
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AUXIN BINDING PROTEIN 1 (ABP1) has long been proposed as an auxin receptor to regulate cell expansion. The embryo lethality of ABP1-null mutants demonstrates its fundamental role in plant development, but also hinders investigation of its involvement in post-embryonic processes and its mode of action. By taking advantage of weak alleles and inducible systems, several recent studies have revealed a role for ABP1 in organ development, cell polarization, and shape formation. In addition to its role in the regulation of auxin-induced gene expression, ABP1 has now been shown to modulate non-transcriptional auxin responses. ABP1 is required for activating two antagonizing ROP GTPase signaling pathways involved in cytoskeletal reorganization and cell shape formation, and participates in the regulation of clathrin-mediated endocytosis to subsequently affect PIN protein distribution. These exciting discoveries provide indisputable evidence for the auxin-induced signaling pathways that are downstream of ABP1 function, and suggest intriguing mechanisms for ABP1-mediated polar cell expansion and spatial coordination in response to auxin.