RESUMEN
Objective: The aim of the study is to assess the effect of maternal prolonged oxygen exposure during labor on fetal acid-base status, fetal heart rate tracings, and umbilical cord arterial metabolites. Design: The study was conducted as a secondary analysis. Settings: The study was set in three tertiary teaching hospitals in Beijing, China. Participants: Approximately 140 women in the latent phase of labor with no complications participated in the study. Intervention: Participants were randomly allocated in a 1:1 ratio to receive either 10 L of oxygen per minute in a tight-fitting simple facemask until delivery or room air only. Main outcome measures: The primary outcome was the umbilical cord arterial lactate. Results: Baseline demographics and labor outcomes were similar between the oxygen and room air groups; the time from randomization to delivery was 322 ± 147 min. There were no differences between the two groups in the umbilical cord arterial lactate (mean difference 0.3 mmol/L, 95% confidence interval -0.2 to 0.9), the number of participants with high-risk category II fetal heart rate tracings (relative risk 0.94, 95% confidence interval 0.68 to 1.32), or the duration of those high-risk tracings (mean difference 3.6 min, 95% confidence interval -9.3 to 16.4). Prolonged oxygen exposure significantly altered 91 umbilical cord arterial metabolites, and these alterations did not appear to be related to oxidative stress. Conclusion: Maternal prolonged oxygen exposure during labor did not affect either the umbilical cord arterial lactate or high-risk category II fetal heart rate tracings but might result in alterations to the umbilical cord arterial metabolic profile. Clinical trial registration: www.clinicaltrials.gov, identifier NCT03764696.
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Trabajo de Parto , Parto , Embarazo , Humanos , Femenino , Feto , Oxígeno , LactatosRESUMEN
Objective: To study patients' new treatment methods and mechanisms of repeated implantation failure. Design: A retrospective study. Setting: In vitro fertilization (IVF) unit in a Three-A hospital. Patients: Ninety-three patients with repeated implantation failure in IVF and embryo transfer. Interventions: the luteal phase support. Main outcome measures: According to whether human chorionic gonadotropin(HCG) was added, the two groups were divided into an observation group and a control group, and the clinical outcomes of the two groups were compared. Furthermore, 20 patients were selected for whole exome sequencing to investigate the mechanism. Results: The observation group's clinical pregnancy rate and live birth rate were significantly higher than those in the control group (P=0.004). Functional enrichment analysis showed that these genes were significantly enriched in embryo implantation or endometrial receptivity processes, such as microtubule-based movement, NABA CORE MATRISOME, superoxide anion generation, protein localization to vacuole, extracellular matrix organization, fertilization, microtubule-based transport, cell junction organization, microtubule cytoskeleton organization. Furthermore, variants detected in these pathway genes were missense mutations that affect the protein's biological activity but do not effectuate its inactivation. Conclusions: Adding HCG in the luteal phase might improve the clinical pregnancy and live birth rates in RIF patients. The potential pathogenesis of RIF genetic level may be caused by microtubule-based movement, extracellular matrix organization, and the Superoxide Anion generation pathway.
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Transferencia de Embrión , Superóxidos , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Transferencia de Embrión/métodos , Índice de Embarazo , Implantación del Embrión/genéticaRESUMEN
Mitochondrial DNA (mtDNA) mutations are often associated with incurable diseases and lead to detectable pathogenic variants in 1 out of 200 babies. Uncoupling of the inheritance of mtDNA and the nuclear genome by spindle transfer (ST) can potentially prevent the transmission of mtDNA mutations from mother to offspring. However, no well-established studies have critically assessed the safety of this technique. Here, using single-cell triple omics sequencing method, we systematically analyzed the genome (copy number variation), DNA methylome, and transcriptome of ST and control blastocysts. The results showed that, compared to that in control embryos, the percentage of aneuploid cells in ST embryos did not significantly change. The epiblast, primitive endoderm, and trophectoderm (TE) of ST blastocysts presented RNA expression profiles that were comparable to those of control blastocysts. However, the DNA demethylation process in TE cells of ST blastocysts was slightly slower than that in the control blastocysts. Collectively, our results suggest that ST seems generally safe for embryonic development, with a relatively minor delay in the DNA demethylation process at the blastocyst stage.
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Blastocisto , Variaciones en el Número de Copia de ADN , Aneuploidia , Blastocisto/metabolismo , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Desarrollo Embrionario/genética , Femenino , Humanos , EmbarazoRESUMEN
BACKGROUND: There are limited data to guide the duration and dose of oxygen supplementation for pregnant women undergoing labor. OBJECTIVE: To assess the effect of maternal long-duration high-concentration oxygen administration during labor on umbilical cord venous partial pressure of oxygen. STUDY DESIGN: This randomized clinical trial was conducted between January and October of 2021 in the obstetrics wards of 3 tertiary teaching hospitals in Beijing, China. Women undergoing the latent phase of labor with no existing medical conditions or obstetrical complications who were admitted for delivery were eligible. The women who met inclusion criteria with category I fetal heart rate tracings in labor were randomized in a 1:1 ratio to oxygen or room air. The oxygen group received 10 L of oxygen per minute by simple, tight-fitting face mask until delivery. The room-air group received room air only, without a face mask. The primary outcome was the umbilical cord venous partial pressure of oxygen. RESULTS: A total of 661 women were screened, and 521 were excluded; 140 participants with category I fetal heart rate tracings were enrolled and randomized to oxygen (N=70) or room air (N=70). A total of 135 women with valid paired umbilical cord venous and arterial gas values were included in the umbilical cord venous partial pressure of oxygen and arterial pH analyses. All 140 women were included in the fetal heart rate tracings analysis. Baseline characteristics were similar between the oxygen and room-air groups. The duration of oxygen exposure was approximately 322±147 minutes. There were no differences between the oxygen and room-air groups in the umbilical cord venous partial pressure of oxygen (mean difference, 1.1 mm Hg; 95% confidence interval, -1.0 to 3.2; P=.318) or the proportion of participants with category II fetal heart rate tracings (81.4% vs 78.6%; relative risk, 1.04; 95% confidence interval, 0.88-1.22; P=.672). However, the umbilical cord arterial pH was significantly lower in the oxygen group than in the room-air group (median, 7.23; interquartile range, 7.20-7.27 vs median 7.27; interquartile range, 7.20-7.30; P=.005). CONCLUSION: Maternal long-duration high-concentration oxygen administration during labor did not affect either the umbilical cord venous partial pressure of oxygen or fetal heart rate pattern distribution but resulted in a deterioration of the umbilical cord arterial pH at birth.
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Trabajo de Parto , Oxígeno , Análisis de los Gases de la Sangre , Femenino , Sangre Fetal , Humanos , Recién Nacido , Presión Parcial , Embarazo , Cordón UmbilicalRESUMEN
Mitochondrial diseases are a group of heterogeneous genetic metabolic diseases caused by mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) gene mutations. Mining the gene-disease association of mitochondrial diseases is helpful for understanding the pathogenesis of mitochondrial diseases, for carrying out early clinical diagnosis for related diseases, and for formulating better treatment strategies for mitochondrial diseases. This project researched the relationship between genes and mitochondrial diseases, combined the Malacards, Genecards, and MITOMAP disease databases to mine the knowledge on mitochondrial diseases and genes, used database integration and the sequencing method of the phenolyzer tool to integrate disease-related genes from different databases, and sorted the disease-related candidate genes. Finally, we screened 531 mitochondrial related diseases, extracted 26,723 genes directly or indirectly related to mitochondria, collected 24,602 variant sites on 1474 genes, and established a mitochondrial disease knowledge base (MitDisease) with a core of genes, diseases, and variants. This knowledge base is helpful for clinicians who want to combine the results of gene testing for diagnosis, to understand the occurrence and development of mitochondrial diseases, and to develop corresponding treatment methods.
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Bases de Datos Genéticas , Predisposición Genética a la Enfermedad , Bases del Conocimiento , Enfermedades Mitocondriales/genética , Minería de Datos/métodos , Sitios Genéticos , Humanos , Enfermedades Mitocondriales/patología , Fenotipo , Polimorfismo de Nucleótido SimpleRESUMEN
Oocytes reconstructed by spindle transfer (ST) are prone to chromosome abnormality, which is speculated to be caused by mechanical interference or premature activation, the mechanism is controversial. In this study, C57BL/6N oocytes were used as the model, and electrofusion ST was performed under normal conditions, Ca2+ free, and at room temperature, respectively. The effect of enucleation and electrofusion stimulation on MPF activity, spindle morphology, γ-tubulin localization and chromosome arrangement was compared. We found that electrofusion stimulation could induce premature chromosome separation and abnormal spindle morphology and assembly by decreasing the MPF activity, leading to premature activation, and thus resulting in chromosome abnormality in oocytes reconstructed via ST. Electrofusion stimulation was an independent factor of chromosome abnormality in oocytes reconstructed via ST, and was not related to enucleation, fusion status, temperature, or Ca2+. The electrofusion stimulation number should be minimized, with no more than 2 times being appropriate. As the electrofusion stimulation number increased, several typical abnormalities in chromosome arrangement and spindle assembly occurred. Although blastocyst culture could eliminate embryos with chromosomal abnormalities, it would significantly decrease the number of normal embryos and reduce the availability of embryos. The optimum operating condition for electrofusion ST was the 37°C group without Ca2+.
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Blastocisto/citología , Fusión Celular , Aberraciones Cromosómicas , Embrión de Mamíferos/citología , Oocitos/citología , Inducción de la Ovulación/métodos , Huso Acromático/fisiología , Animales , Blastocisto/metabolismo , Fenómenos Electromagnéticos , Embrión de Mamíferos/metabolismo , Desarrollo Embrionario , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Oocitos/metabolismoRESUMEN
BACKGROUND: Cervical cancer ranks as the fourth leading cause of death from cancer in women. Historically, women with metastatic or recurrent cervical cancer have had limited treatment options. New anti-angiogenesis therapies, such as vascular endothelial growth factor (VEGF) targeting agents, offer an alternative strategy to conventional chemotherapy; they act by inhibiting the growth of new blood vessels, thereby restricting tumour growth by blocking the blood supply. OBJECTIVES: To assess the benefits and harms of VEGF targeting agents in the management of persistent, recurrent, or metastatic cervical cancer. SEARCH METHODS: We performed searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, online registers of clinical trials, and abstracts of scientific meetings up until 27 May 2020. SELECTION CRITERIA: We examined randomised controlled trials (RCTs) that evaluated the use of VEGF targeting agents alone or in combination with conventional chemotherapy or other VEGF targeting agents. DATA COLLECTION AND ANALYSIS: Three review authors independently screened the results of search strategies, extracted data, assessed risk of bias, and analysed data according to the standard methods expected by Cochrane. The certainty of evidence was assessed via the GRADE approach. MAIN RESULTS: A total of 1634 records were identified. From these, we identified four studies with a total of 808 participants for inclusion. We also identified two studies that were awaiting classification and nine ongoing studies. Bevacizumab plus chemotherapy versus chemotherapy Treatment with bevacizumab plus chemotherapy may result in lower risk of death compared to chemotherapy alone (hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.62 to 0.95; 1 study, 452 participants; low-certainty evidence). However, there are probably more specific adverse events when compared to chemotherapy alone, including gastrointestinal perforations or fistulae (risk ratio (RR) 18.00, 95% CI 2.42 to 133.67; 1 study, 440 participants; moderate-certainty evidence); serious thromboembolic events (RR 4.5, 95% CI 1.55 to 13.08; 1 study, 440 participants; moderate-certainty evidence); and hypertension (RR 13.75, 95% CI 5.07 to 37.29; 1 study, 440 participants; moderate-certainty evidence). There may also be a higher incidence of serious haemorrhage (RR 5.00, 95% CI 1.11 to 22.56; 1 study, 440 participants; low-certainty evidence). In addition, the incidence of serious adverse events is probably higher (RR 1.44, 95% CI 1.16 to 1.79; 1 study, 439 participants; moderate-certainty evidence). The incremental cost-effectiveness ratio was USD 295,164 per quality-adjusted life-year (1 study, 452 participants; low-certainty evidence). Cediranib plus chemotherapy versus chemotherapy Treatment with cediranib plus chemotherapy may or may not result in similar risk of death when compared to chemotherapy alone (HR 0.94, 95% CI 0.53 to 1.65; 1 study, 69 participants; low-certainty evidence). We found very uncertain results for the incidences of specific adverse events, including gastrointestinal perforations or fistulae (RR 3.27, 95% CI 0.14 to 77.57; 1 study, 67 participants; very low-certainty evidence); serious haemorrhage (RR 5.45, 95% CI 0.27 to 109.49; 1 study, 67 participants; very low-certainty evidence); serious thromboembolic events (RR 3.41, 95% CI 0.14 to 80.59; 1 study, 60 participants; very low-certainty evidence); and serious hypertension (RR 0.36, 95% CI 0.02 to 8.62; 1 study, 67 participants; very low-certainty evidence). In addition, there may or may not be a similar incidence of serious adverse events compared to chemotherapy alone (RR 1.15, 95% CI 0.75 to 1.78; 1 study, 67 participants; low-certainty evidence). Apatinib plus chemotherapy or chemotherapy/brachytherapy versus chemotherapy or chemotherapy/brachytherapy Treatment with apatinib plus chemotherapy or chemotherapy/brachytherapy may or may not result in similar risk of death compared to chemotherapy alone or chemotherapy/brachytherapy alone (HR 0.90, 95% CI 0.51 to 1.60; 1 study, 52 participants; low-certainty evidence). However, hypertension events may occur at a higher incidence as compared to chemotherapy alone or chemotherapy/brachytherapy alone (RR 5.14, 95% CI 1.28 to 20.73; 1 study, 52 participants; low-certainty evidence). Pazopanib plus lapatinib versus lapatinib Treatment with pazopanib plus lapatinib may result in higher risk of death compared to lapatinib alone (HR 2.71, 95% CI 1.16 to 6.31; 1 study, 117 participants; low-certainty evidence). We found very uncertain results for the incidences of specific adverse events, including gastrointestinal perforations or fistulae (RR 2.00, 95% CI 0.19 to 21.59; 1 study, 152 participants; very low-certainty evidence); haemorrhage (RR 2.00, 95% CI 0.72 to 5.58; 1 study, 152 participants; very low-certainty evidence); and thromboembolic events (RR 3.00, 95% CI 0.12 to 72.50; 1 study, 152 participants; very low-certainty evidence). In addition, the incidence of hypertension events is probably higher (RR 12.00, 95% CI 2.94 to 49.01; 1 study, 152 participants; moderate-certainty evidence). There may or may not be a similar incidence of serious adverse events as compared to lapatinib alone (RR 1.45, 95% CI 0.94 to 2.26; 1 study, 152 participants; low-certainty evidence). Pazopanib versus lapatinib Treatment with pazopanib may or may not result in similar risk of death as compared to lapatinib (HR 0.96, 95% CI 0.67 to 1.38; 1 study, 152 participants; low-certainty evidence). We found very uncertain results for the incidences of specific adverse events, including gastrointestinal perforations or fistulae (RR 1.03, 95% CI 0.07 to 16.12; 1 study, 150 participants; very low-certainty evidence); haemorrhage (RR 1.03, 95% CI 0.31 to 3.40; 1 study, 150 participants; very low-certainty evidence); and thromboembolic events (RR 3.08, 95% CI 0.13 to 74.42; 1 study, 150 participants; very low-certainty evidence). In addition, the incidence of hypertension events is probably higher (RR 11.81, 95% CI 2.89 to 48.33; 1 study, 150 participants; moderate-certainty evidence). The risk of serious adverse events may or may not be similar as compared to lapatinib (RR 1.31, 95% CI 0.83 to 2.07; 1 study, 150 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: We found low-certainty evidence in favour of the use of bevacizumab plus chemotherapy. However, bevacizumab probably increases specific adverse events (gastrointestinal perforations or fistulae, thromboembolic events, hypertension) and serious adverse events. We found low-certainty evidence that does not support the use of cediranib plus chemotherapy, apatinib plus chemotherapy, apatinib plus chemotherapy/brachytherapy, or pazopanib monotherapy. We found low-certainty evidence suggesting that pazopanib plus lapatinib worsens outcomes. The VEGF inhibitors apatinib and pazopanib may increase the probability of hypertension events.
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Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/efectos adversos , Antineoplásicos/efectos adversos , Bevacizumab/efectos adversos , Bevacizumab/uso terapéutico , Sesgo , Braquiterapia/efectos adversos , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Intervalos de Confianza , Femenino , Fístula Gástrica/inducido químicamente , Hemorragia Gastrointestinal/inducido químicamente , Humanos , Hipertensión/inducido químicamente , Indazoles , Fístula Intestinal/inducido químicamente , Perforación Intestinal/inducido químicamente , Lapatinib/efectos adversos , Lapatinib/uso terapéutico , Persona de Mediana Edad , Recurrencia Local de Neoplasia/irrigación sanguínea , Recurrencia Local de Neoplasia/mortalidad , Supervivencia sin Progresión , Piridinas/efectos adversos , Piridinas/uso terapéutico , Pirimidinas/efectos adversos , Pirimidinas/uso terapéutico , Calidad de Vida , Quinazolinas/efectos adversos , Quinazolinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Tromboembolia/inducido químicamente , Neoplasias del Cuello Uterino/irrigación sanguínea , Neoplasias del Cuello Uterino/mortalidad , Adulto JovenRESUMEN
BACKGROUND: Despite the widespread use of oxygen (O2) in intrauterine resuscitation, the obstetric scientists' understanding of O2 therapy is full of contradictions. We tested the hypothesis that higher maternal arterial partial pressure of oxygen (PO2) is associated with higher umbilical cord venous PO2 (UvPO2). METHODS: This is a planned secondary analysis of a randomised controlled trial (RCT), 443 normal women were 1:1 randomly allocated to receive 2 L/min O2 or room air from the onset of second stage to delivery. We reported that maternal 2 L/min O2 exposure cannot affect the umbilical cord arterial pH or the fetal heart rate (FHR) pattern. In 217 non-random samples, we found 2 L/min O2 exposure increased the maternal arterial PO2 to the median 150 mmHg (hemoglobin would be saturated). The primary outcome for this analysis was UvPO2 in these non-random samples. RESULTS: There were no significant differences between the O2 group (N = 107) and the control group (N = 110) in the UvPO2 (median 30.2, interquartile 25.4-35.2 versus median 28.3, interquartile 23.4-35.3, mmHg, P = 0.379). There were also no significant differences between room air and different percentiles of O2 exposure duration (< 25th, ⧠25th < 50th, ⧠50th < 75th, ⧠75th percentile) in the UvPO2. CONCLUSIONS: Maternal O2 exposure at super-physiological levels (median arterial blood PO2 150 mmHg) in normal labor may not change the UvPO2. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02221440 , first posted in 20 August 2014.
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Sangre Fetal/química , Terapia por Inhalación de Oxígeno , Oxígeno/sangre , Oxígeno/metabolismo , Adulto , Arterias , Femenino , Humanos , Segundo Periodo del Trabajo de Parto , Oxígeno/fisiología , Presión Parcial , Embarazo , VenasRESUMEN
BACKGROUND: Chemotherapy-induced thrombocytopenia (CIT) is defined as a peripheral platelet count less than 100×109/L, with or without bleeding in cancer patients receiving myelosuppressive chemotherapy. CIT is a significant medical problem during chemotherapy, and it carries the risk of sub-optimal overall survival and bleeding. Alternative interventions to platelet transfusion are limited. Different stages of preclinical and clinical studies have examined the thrombopoietin receptor agonists (TPO-RAs) for CIT in patients with solid tumours. OBJECTIVES: To assess the effects of TPO-RAs to prevent and treat CIT in patients with solid tumours:(1) to prevent CIT in patients without thrombocytopenia before chemotherapy, (2) to prevent recurrence of CIT, and (3) to treat CIT in patients with thrombocytopenia during chemotherapy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, to 28 September 2017), MEDLINE (from 1950 to 28 September 2017), as well as online registers of ongoing trials (Clinical Trials, Chinese Clinical Trial Register, Australian New Zealand Clinical Trial Registry, WHO ICTRP Search Portal, International Standard Randomised Controlled Trial Number registry, GlaxoSmithKline Clinical Study Register, and Amgen Clinical Trials) and conference proceedings (American Society of Hematology, American Society of Clinical Oncology, European Hematology Association, European Society of Medical Oncology, and Conference Proceedings Citation Index-Science, from 2002 up to September 2017) for studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing TPO-RAs alone, or in combination with other drugs, to placebo, no treatment, other drugs, or another TPO-RAs for CIT in patients with solid tumours. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the results of the search strategies, extracted data, assessed risk of bias, and analysed data according to standard methodological methods expected by Cochrane. MAIN RESULTS: We identified six trials eligible for inclusion, of which two are ongoing, and one awaiting classification study. The three included trials were conducted at many different sites in Europe, America, and Asia. All of the three studies recruited adult and elder participants (no children were included) with solid tumours, and compared TPO-RAs with placebo. No studies compared TPO-RAs alone, or in combination with other drugs, to no treatment, or other drugs, or another TPO-RAs.We judged the overall risk of bias as high as we found a high risk for detection bias. We assessed the risk of bias arising from inadequate blinding of outcome assessors as high for number and severity of bleeding episodes (one of the primary outcomes).To prevent CIT: We included two trials (206 participants) comparing TPO-RAs (eltrombopag, multiple-dose oral administration with chemotherapy) with placebo. The use of TPO-RAs may make little or no difference to the all-cause mortality at 33 weeks of follow-up (RR 1.35, 95% CI 0.53 to 3.45; one trial, 26 participants; low quality of evidence). There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one bleeding episode of any severity (RR 0.62, 95% CI 0.22 to 1.78; two trials, 206 participants; very low quality of evidence). There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one severe/life-threatening bleeding episode (RR 0.36, 95% CI 0.06 to 2.06; two trials, 206 participants; very low quality of evidence). No studies were found that looked at overall survival (one of the primary outcomes), the number of treatment cycles with at least one bleeding episode, the number of days on which bleeding occurred, the amount of bleeding, or quality of life.To prevent recurrence of CIT: We included one trial (62 participants) comparing TPO-RAs (romiplostim, single-dose subcutaneous administration with chemotherapy) with placebo. There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one bleeding episode of any severity (RR 2.80, 95% CI 0.17 to 47.53; one trial, 62 participants; very low quality of evidence). There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one severe/life-threatening bleeding episode (no severe/life-threatening bleeding episodes; one trial, 62 participants; very low quality of evidence). No studies were found that looked at overall survival (one of the primary outcomes), the number of treatment cycles with at least one bleeding episode, the number of days on which bleeding occurred, the amount of bleeding, or quality of life. We found one ongoing study (expected recruitment 74 participants), it is planned to give TPO-RAs (romiplostim, subcutaneous administration with chemotherapy) to participants, but to date this trial has not reported any outcomes.To treat CIT: We found one ongoing study (expected recruitment 83 participants), which is planned to give TPO-RAs (eltrombopag, seven days orally) to participants when their platelet counts are less than 75×109/L during chemotherapy. This trial was originally planned to complete in March 2017, however, the completion date has passed and no results are reported.The one awaiting classification study included patients without thrombocytopenia before chemotherapy (to prevent CIT), patients with thrombocytopenia during chemotherapy (to prevent recurrence of CIT), and other patients during chemotherapy (uncertain whether CIT had happened). There was no evidence for a difference in the number of patients with at least one bleeding episode of any severity (RR 0.27, 95% CI 0.07 to 1.02; one trial, 75 participants). There was no evidence for a difference in the number of patients with at least one severe/life-threatening bleeding episode (RR 0.44, 95% CI 0.03 to 6.77; one trial, 75 participants). This study did not address overall survival or quality of life. AUTHORS' CONCLUSIONS: No certain conclusions can be drawn due to the lack of strong evidence in the review. The available weak evidence did not support the use of TPO-RAs for preventing CIT or preventing recurrence of CIT in patients with solid tumours. There was no evidence to support the use of TPO-RAs for treating CIT in patients with solid tumours.
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Antineoplásicos/efectos adversos , Benzoatos/administración & dosificación , Hidrazinas/administración & dosificación , Pirazoles/administración & dosificación , Receptores Fc/administración & dosificación , Receptores de Trombopoyetina/agonistas , Proteínas Recombinantes de Fusión/administración & dosificación , Trombocitopenia/tratamiento farmacológico , Trombocitopenia/prevención & control , Trombopoyetina/administración & dosificación , Adulto , Anciano , Humanos , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Trombocitopenia/inducido químicamente , Trombocitopenia/mortalidadRESUMEN
Molecular hydrogen (H2) has been previously reported playing an important role in ameliorating damage caused by acute radiation. In this study, we investigated the effects of H2 on the alterations induced by low-dose long-term radiation (LDLTR). All the mice in hydrogen-treated or radiation-only groups received 0.1 Gy, 0.5 Gy, 1.0 Gy, and 2.0 Gy whole-body gamma radiation, respectively. After the last time of radiation exposure, all the mice were employed for the determination of the body mass (BM) observation, forced swim test (FST), the open field test (OFT), the chromosome aberration (CA), the peripheral blood cells parameters analysis, the sperm abnormality (SA), the lymphocyte transformation test (LTT), and the histopathological studies. And significant differences between the treatment group and the radiation-only groups were observed, showing that H2 could diminish the detriment induced by LDLTR and suggesting the protective efficacy of H2 in multiple systems in mice against LDLTR.
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Sistema Hematopoyético/efectos de la radiación , Hidrógeno/farmacología , Linfocitos/efectos de la radiación , Traumatismos Experimentales por Radiación/prevención & control , Espermatozoides/efectos de la radiación , Bazo/efectos de la radiación , Animales , Conducta Animal/efectos de los fármacos , Conducta Animal/efectos de la radiación , Índice de Masa Corporal , Aberraciones Cromosómicas/efectos de los fármacos , Aberraciones Cromosómicas/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Sistema Hematopoyético/efectos de los fármacos , Linfocitos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Distribución Aleatoria , Espermatozoides/efectos de los fármacos , Bazo/citología , Bazo/efectos de los fármacos , Irradiación Corporal TotalRESUMEN
INTRODUCTION: Fallopian tube, which is normally discarded in surgical procedures, has proven to be a source of mesenchymal stem cells (MSCs) with increasing evidence. However, fallopian tube mucosa, which can be acquired via non-invasive procedures, is a previously unknown source of MSCs. In the present study, we explored the existence of MSCs in the human fallopian tube mucosa and also compared multipotent stem cells derived from fallopian tubes and fallopian tube mucosa according to their biological characteristics and therapeutic potential for treatment of autologous reproductive tract injury. METHODS: Cells isolated from human fallopian tubes and fallopian tube mucosa were expanded and characterised by flow cytometry. The proliferative capacity of both cell types was measured by performing colony-forming unit-fibroblast and Cell Counting Kit-8 assays. Both cell types underwent in vitro adipogenic, chondrogenic, and osteogenic differentiation. The expression of osteocyte-, adipocyte-, and chondrocyte-related genes in the differentiated cell lineages was assessed by reverse transcription-polymerase chain reaction. The secretion of growth factors and immunomodulatory cytokines by both cell types were measured by enzyme-linked immunosorbent assays. RESULTS: We found that MSCs existed in the fallopian tube mucosa. The comparison between human fallopian tube MSCs (hFTMSCs) and human fallopian tube mucosa MSCs (hFMMSCs) showed that hFTMSCs had a stronger proliferative capacity and shorter duplication time than hFMMSCs. Both cell types could be differentiated into adipocytes, osteoblasts, or chondrocytes in vitro. Real-time polymerase chain reaction analysis demonstrated that hFTMSCs displayed increased expression of osteogenic-specific genes compared with hFMMSCs, but the two types of cells showed no significant increase in the mRNA expression of adipogenic-specific or chondrogenic-specific genes. hFMMSCs and hFTMSCs robustly produced a variety of growth factors and immunomodulatory cytokines. CONCLUSIONS: Human fallopian tube mucosa is a novel source of multipotent cells. hFMMSCs demonstrated stronger proliferative capacity and superior secretion of growth factors and immunomodulatory cytokines than hFTMSCs, making the former a better source of stem cells for the treatment of autologous reproductive tract injury. Compared with fallopian tube, fallopian tube mucosa has more wide-ranging applications and can be used to carry out autologous transplantation.
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Trompas Uterinas/citología , Genitales/lesiones , Membrana Mucosa/citología , Células Madre Multipotentes/trasplante , Adipogénesis , Adulto , Condrogénesis , Citocinas/análisis , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Persona de Mediana Edad , Células Madre Multipotentes/citología , Células Madre Multipotentes/metabolismo , Osteogénesis , Trasplante AutólogoRESUMEN
OBJECTIVE: To assess the conclusiveness of Cochrane reviews in the field of gynaecological cancer. METHODS: The Cochrane Library was searched for reviews regarding gynaecological cancer published between 1 January 2000 and 1 November 2014. Data were extracted from each paper and the conclusiveness of each review was assessed. RESULTS: The study included 66 reviews, 41 (62.1%) of which were conclusive. Of these, 58 included randomized controlled trials (RCTs), 37 (63.8%) of which were conclusive. Conclusive reviews of RCTs included significantly more patients than inconclusive reviews, but there was no difference in the number of included studies. Of the eight reviews of nonrandomized studies, four (50.0%) were conclusive. The majority of reviews recognized the need for additional studies. CONCLUSIONS: In the field of gynaecological cancer, reviews are more likely to be conclusive when they include RCTs, as well as large numbers of patients.
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Neoplasias de los Genitales Femeninos , Periodismo Médico/normas , Femenino , HumanosRESUMEN
Background. Polycystic ovarian syndrome (PCOS) women undergoing in vitro fertilization and embryo transfer (IVF-ET) treatment always attain a low cumulative pregnancy rate disaccording with the satisfactory number of oocytes. Objective. We aim to evaluate the status of coagulation and fibrinolytic system in PCOS patients undergoing controlled ovarian hyperstimulation (COH) process. Method. Of the 97 women, 30 patients with PCOS composed the study group; 67 women of child-bearing age with normal endocrine function composed the control group. All participants underwent GnRH agonist standard long protocol, and plasma HCY, FVIII, FX, and D-dimer levels as well as hormone parameters were measured at day of full downregulation, hCG priming, and embryos transfer. Results. On day of full downregulation, FX levels were significantly higher in PCOS group (P < 0.01). On hCG priming day, FX and estrogen levels in PCOS group were higher than in the control group and FVIII levels were significantly lower on day of embryos transfer whereas FX and E2 levels were significantly higher in PCOS group. Conclusion. Hypercoagulable state during peri-implantation phase would probably lead to poor microcirculation of endometrium and be one of the most important disadvantages of successful implantation and subsequent clinical pregnancy.
RESUMEN
It is well known that most of the ionizing radiation-induced damage is caused by hydroxyl radicals (·OH) follows radiolysis of H2O. Molecular hydrogen (H2) has antioxidant activities by selectively reducing ·OH and peroxynitrite(ONOO-). We firstly hypothesized and demonstrated the radioprotective effect of H2 in vitro and in vivo, which was also repeated on different experimental animal models by different departments. A randomized, placebo-controlled study showed that consumption of hydrogen-rich water reduces the biological reaction to radiation-induced oxidative stress without compromising anti-tumor effects. These encouraging results suggested that H2 represents a potentially novel preventative strategy for radiation-induced oxidative injuries. H2 is explosive. Therefore, administration of hydrogen-rich solution (physiological saline/pure water/other solutions saturated with H2) may be more practical in daily life and more suitable for daily consumption. This review focuses on major scientific and clinical advances of hydrogen-rich solution/H2 as a new class of radioprotective agent.
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Hidrógeno/farmacología , Protectores contra Radiación/farmacología , Animales , Línea Celular , Sistema Libre de Células/efectos de los fármacos , Sistema Libre de Células/efectos de la radiación , Humanos , Hidrógeno/química , Radical Hidroxilo/química , Radical Hidroxilo/toxicidad , Masculino , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Radiación Ionizante , RatasRESUMEN
Advancements of diagnosis and treatment have substantially improved cancer survival rates in the last few decades. The increasing number of survivors focuses attention on long-term effects caused by cancer treatment and its impact on quality of life. Ovarian failure is one of the major sequelae of cytotoxic chemotherapy and/or radiotherapy in female children and reproductive-age women. Oncologists should address the patients about fertility preservation options before therapy. Embryo cryopreservation is the only well-established method for females in preserving fertility; however other strategies including ovarian suppression, ovarian transposition and cryopreservation of oocytes and ovarian tissue are still experimental. Patients need advice and to know which are the most practical options for them. This article reviews the available fertility preservation methods in women, and the related issues including normal physiology of the ovary, effect of anticancer therapy on fertility, role of the oncologist and ethics. We performed a MEDLINE search from 1971 to 2011 in a similar way as Jensen et al. 2011, using the following MeSH terms: antineoplastic agents; ovarian failure; premature; infertility, female; fertility preservation; child and cancer; reproductive technologies, assisted.
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Preservación de la Fertilidad/métodos , Infertilidad Femenina , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Criopreservación/métodos , Femenino , Humanos , Ovario/efectos de los fármacos , Ovario/efectos de la radiaciónRESUMEN
Molecular hydrogen (dihydrogen, H(2)) acts as a therapeutic antioxidant by selectively reducing hydroxyl radicals (â¢OH) and peroxynitrite (ONOO-). It has been well-known that ionising radiation (IR) causes oxidative damage and consequent apoptosis mainly due to the production of â¢OH that follows radiolysis of H(2)O. Our department reported the protective effect of H(2) in irradiated cells and mice for the first time, and this effect is well repeated by us and another laboratory in different experimental animal models. A randomised, placebo-controlled investigation also showed consumption of H(2) can improve the quality of life of patients treated with radiotherapy for liver tumours. These encouraging results suggested that H(2) has a potential as a radioprotective agent with efficacy and non-toxicity.
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Hidrógeno/química , Hidrógeno/uso terapéutico , Radical Hidroxilo/química , Neoplasias Hepáticas/prevención & control , Ácido Peroxinitroso/química , Protectores contra Radiación/química , Protectores contra Radiación/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Humanos , Hidrógeno/farmacología , Neoplasias Hepáticas/radioterapia , Protectores contra Radiación/farmacologíaRESUMEN
Recent studies suggest that mangiferin aglycone (norathyriol) has great potential as a novel radioprotector without any known toxic side effects. In this study, we assessed the protective effects of mangiferin aglycone against radiation-induced injuries on normal human intestinal epithelial cells (HIECs), while using mangiferin as a reference compound. The in vitro experiments showed that pretreatment of either mangiferin aglycone or mangiferin could inhibit cytotoxic effects of ionizing irradiation (IR) on HIECs. Cellular changes were estimated by measuring cell viability, clonogenic surviving rate, and apoptotic rate. Compared to mangiferin, we found mangiferin aglycone had greater radioprotective effects of mangiferin aglycone on HIECs. It has been demonstrated that the cytotoxicity of ionizing radiation relates to its capacity to induce DNA damage. In view of this, we monitored DNA double-strand breaks (DSBs) using γH2AX foci formation to test whether mangiferin aglycone and mangiferin could modulate genotoxic effects of radiation. It shows that mangiferin aglycone could eliminate 46.8% of the total DSBs of the cells exposed to 2 Gy IR, which is significantly better than mangiferin. Complementing earlier results from our group, it appears possible to conclude that mangiferin aglycone presents potential useful effects on IR-induced damage and may be a better radioprotective agent than mangiferin therapeutically.
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Células Epiteliales/efectos de los fármacos , Células Epiteliales/efectos de la radiación , Intestinos/citología , Xantonas/farmacología , Línea Celular , Daño del ADN/efectos de los fármacos , Daño del ADN/efectos de la radiación , Humanos , Radiación IonizanteRESUMEN
BACKGROUND: Radiation often causes depletion of immunocytes in tissues and blood, which results in immunosuppression. Molecular hydrogen (H2) has been shown in recent studies to have potential as a safe and effective radioprotective agent through scavenging free radicals. This study was designed to test the hypothesis that H2 could protect immunocytes from ionizing radiation (IR). MATERIAL/METHODS: H2 was dissolved in physiological saline or medium using an apparatus produced by our department. A 2-[6-(4'-hydroxy) phenoxy-3H-xanthen-3-on-9-yl] benzoate (HPF) probe was used to detect intracellular hydroxyl radicals (â¢OH). Cell apoptosis was evaluated by annexin V-FITC and Propidium iodide (PI) staining as well as the caspase 3 activity. Finally, we examined the hematological changes using an automatic Sysmex XE 2100 hematology analyzer. RESULTS: We demonstrated H2-rich medium pretreatment reduced â¢OH level in AHH-1 cells. We also showed H2 reduced radiation-induced apoptosis in thymocytes and splenocytes in living mice. Radiation-induced caspase 3 activation was also attenuated by H2 treatment. Finally, we found that H2 rescued the radiation-caused depletion of white blood cells (WBC) and platelets (PLT). CONCLUSIONS: This study suggests that H2 protected the immune system and alleviated the hematological injury induced by IR.
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Apoptosis/efectos de los fármacos , Citoprotección/efectos de los fármacos , Hidrógeno/farmacología , Linfocitos/patología , Protectores contra Radiación/farmacología , Cloruro de Sodio/farmacología , Animales , Apoptosis/efectos de la radiación , Caspasa 3/metabolismo , Células Cultivadas , Citoprotección/efectos de la radiación , Activación Enzimática/efectos de los fármacos , Activación Enzimática/efectos de la radiación , Rayos gamma , Humanos , Radical Hidroxilo/metabolismo , Linfocitos/efectos de los fármacos , Linfocitos/efectos de la radiación , Masculino , Ratones , Ratones Endogámicos BALB C , Bazo/efectos de los fármacos , Bazo/enzimología , Bazo/efectos de la radiaciónRESUMEN
BACKGROUND: Recent studies show that molecular hydrogen (dihydrogen, H2) has potential as an effective and safe radioprotective agent through reducing oxidative stress. The aim of this study was to investigate whether H2 is able to protect spermatogenesis and hematopoiesis from radiation-induced injuries. MATERIAL/METHODS: H2 was dissolved in physiological saline using an apparatus produced by our department. -60Co-gamma rays in the irradiation centre were used for irradiation. Spermatid head counts and histological analysis were used to evaluate spermatogenesis. Endogenous hematopoietic spleen colony formation (endoCFUs), bone marrow nucleated cells (BMNC) and peripheral blood (PB) leukocytes were used to evaluate hemopoiesis. RESULTS: This study demonstrates that treating mice with H2 before ionizing radiation (IR) can increase the spermatid head count and protect seminiferous epithelium from IR. This study also demonstrates that H2 could significantly increase the number of endoCFUs, BMNC and PB leukocyte. CONCLUSIONS: This study suggests that hydrogen-rich saline could partially protect spermatogenesis and hematopoiesis in irradiated mice.
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Hematopoyesis , Hidrógeno , Traumatismos por Radiación/prevención & control , Cloruro de Sodio , Espermatogénesis , Animales , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
Our recent studies suggest that H2 (hydrogen) has a potential as a novel radioprotector without known toxic side effects. The present study was designed to examine the underlying radioprotective mechanism of H2 and its protective role on irradiated germ cells. Produced by the Fenton reaction and radiolysis of H2O, hydroxyl radicals (â¢OH) were identified as the free radical species that were reduced by H2. We used a H2 microelectrode to dynamically detect H2 concentration in vivo, and found H2 significantly reduced in situ fluorescence intensity of hydroxyphenyl fluorescein; however, as we treated the mice with H2 after irradiation, the decrease is not significant. We found that pre-treatment of H2 to IR (ionizing radiation) significantly suppressed the reaction of â¢OH and the cellular macromolecules which caused lipid peroxidation, protein carbonyl and oxidatively damaged DNA. The radioprotective effect of H2 on male germ cells was supported by ameliorated apoptotic findings examined by morphological changes and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling) in testicular tissue, and by preserved viability of stem spermatogonia examined for testicular histological parameters, daily sperm production and sperm quality; we used WR-2721 [S-2-(3-aminopropylamino)ethyl phosphorothioic acid] as a reference compound. Our results represent the first in vivo evidence in support of a radioprotective role of H2 by neutralizing â¢OH in irradiated tissue with no side effects.