Objective Malignant neoplasms represent a major public health threat to women of child-bearing age(WCBA)worldwide,with incidence rates significantly higher than those in men of comparable age.However,systematic research remains lacking regarding the long-term evolution patterns of WCBA-specific cancer disease burden and their socioeconomic determinants across extended timeframes.This study aims to comprehensively evaluate the disease burden and spatiotemporal trends of 30 cancer types among global WCBA from 1990 to 2021,providing scientific evidence for developing targeted precision prevention and control strategies for female malignancies.Methods A cross-sectional design was adopted in this study,and the data from the Global Burden of Disease Study(GBD)2021 on the incidence,prevalence,and disability-adjusted life-years(DALYs)of 30 cancers among WCBA from 1990 to 2021 were extracted.Stratification was performed by age groups(15 to 29 and 30 to 49 years old)and socio-demographic index(SDI).Incidence rates,DALYs rates,and their estimated annual percentage change(EAPC)with 95%CI were calculated.Spearman correlation analysis and restricted cubic spline(RCS)models were applied to fit the non-linear relationship between disease burden and SDI(significance level P<0.05).Results In 2021,the 3 leading cancers by incidence among global WCBA were breast cancer(28.81/100 000,95%UI:26.84 to 30.94),cervical cancer(15.77/100 000,95%UI:14.40 to 17.23),and ovarian cancer(4.40/100 000,95%UI:3.86 to 4.88).From 1990 to 2021,the incidence of colorectal cancer demonstrated a significant upward trend(EAPC=0.48,95%CI:0.42 to 0.55,P<0.05),whereas the burden of stomach cancer(EAPC=-2.01,95%CI:-2.07 to-1.95,P<0.05)and leukemia(EAPC=-0.90,95%CI:-0.97 to-0.83,P<0.05)declined significantly.RCS fitting revealed significant non-linear correlations between disease burden of tracheal,bronchial,and lung cancer and SDI(P for non-linearity<0.05),with the incidence peaking at an SDI of approximately 0.8.Age-stratified analysis indicated that the 15 to 29 years age group was predominantly affected by leukemia and central nervous system tumors,while the burden in the 30 to 49 years age group concentrated on breast cancer,cervical cancer,and colorectal cancer.Conclusion Between 1990 and 2021,the overall cancer burden among global WCBA remained substantial,with significant evolutionary shifts in the disease spectrum.Cancer incidences demonstrate close associations with socio-economic development levels,characterized by high incidence in high-SDI regions coupled with low DALYs.This study provides macro-level data support for developing intervention strategies that integrate cancer prevention and control with reproductive health management.Countermeasures Health policymakers are recommended to implement stratified precision prevention and control policies based on age and regional SDI levels:for the 15-to 29-years-old population,priority should be given to promoting HPV vaccination and implementing fertility preservation measures during antineoplastic therapy;for those aged 30 to 49 years,coverage of combined breast and cervical cancer screening should be expanded,and early intervention for metabolic-related tumors such as colorectal cancer should be incorporated into workplace and community health management systems.
Background:Malignant neoplasm is one of the leading durden of diseases worldwide, particularly among women of child-bearing age (WCBA) with a significant higher incidence rate than their male counterparts. This study aimed to assess the burden and trend of cancers among WCBA from 1990 to 2021. Methods: This study retrieved data from the Global Burden of Disease Study (GBD) 2021 on the incidence, prevalence, and disability adjusted life-years (DALYs) of 30 cancers among WCBA from 1990 to 2021. Estimated annual percentage changes (EAPC) and percentage change, by age and socio-demographic index (SDI), were calculated to quantify the temporal trends. Spearman correlation analysis was used to examine the correlation between burdens and SDI. Results: Our results showed that breast, cervical, ovarian, colon/rectum, thyroid, uterine, tracheal/bronchus/lung, brain/central nervous system (CNS), stomach, non-Hodgkin lymphoma, leukemia, and malignant skin melanoma had the highest global incidence rates respectively among WCBA in 2021. From 1990 to 2021, the incidence and prevalence rates of colon/rectum, thyroid, and brain/CNS cancers showed an upward trend, while the burdens of stomach cancer and leukemia significantly declined. In terms of SDI regions, the high and high-middle SDI regions had higher DALYs rstes of colon/rectum, brain/CNS, tracheal/bronchus/lung, and melanoma, the middle SDI regions had higher DALYs rstes of stomach cancer and leukemia, and the low SDI regions had higher DALYs rstes of thyroid cancers and non-Hodgkin lymphoma. Age distribution analysis indicated that the burden of major cancers increased with age, peaking in the 45 to 49 age group. Conclusion: This study reveals the global and regional distribution characteristics of cancer burden among WCBA and highlights the important impact of socio-economic factors on cancer burden. The findings provide a scientific basis for developing cancer prevention and control strategies, especially in high burden regions and specific age groups.
There is a considerable proportion of false positive results when the result of preimplantation genetic testing for aneuploidy is chromosomal mosaicism. The aim of this study was to assess the concordance among clinical trophectoderm biopsy, second trophectoderm biopsy, and inner cell mass biopsy in mosaic human embryos with segmental deletion and evaluate a modified biopsy protocol. This retrospective study included 100 pretested blastocysts, which were classified as segmental deletion mosaics with one to two chromosomes were affected, donated by 84 couples in a single, high-volume fertility center in Beijing China. Re-biopsy was taken from the inner cell mass and two symmetrical trophectoderm sites near the inner cell mass in each embryo. Samples from the inner cell mass and one of the two trophectoderm were prepared for modified protocol, which isolated portions into single cells, the cells with normal morphology were collected and cell debris were removed. Re-biopsy samples were analyzed by next-generation sequencing. Main outcome measures were concordance between clinical biopsy and blastocyst, and segmental mosaicism in modified protocol. Only six (6.5
ObjectiveThe 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.DesignThe study was conducted as a secondary analysis.Setting(s)The study was set in three tertiary teaching hospitals in Beijing, China.ParticipantsApproximately 140 women in the latent phase of labor with no complications participated in the study.InterventionParticipants 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 measuresThe primary outcome was the umbilical cord arterial lactate.ResultsBaseline 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.ConclusionMaternal 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 registrationwww.clinicaltrials.gov, identifier NCT03764696.
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.
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.
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.
目的 探究妊娠晚期合并心功能衰竭患者的分娩期处理策略.方法 回顾性分析2007年12月至2018年12月间我院心脏外科与妇产科联合治疗的23例妊娠晚期合并心功能衰竭(心功能Ⅲ~Ⅳ级)患者的临床资料,探讨心功能衰竭孕妇的分娩处理及临床急救策略.结果 23例孕妇均以全身麻醉剖宫产术作为结束妊娠的方式.17例患者单纯行剖宫产术,顺利度过围产期,另择期行心脏手术或进行内科治疗.6例患者在剖宫产过程中出现心脏停搏或心室颤动,紧急插管,行外周型体外膜肺氧合转机并辅助循环:2例患者转机2h内心脏恢复自主跳动;1例患者转机6h心脏出现自主跳动;3例患者虽有自主心跳但室颤反复发作,其中2例剖宫产术后第3天分别行心脏瓣膜置换和室间隔封堵,1例严重心肌病患者体外膜肺撤机困难,转机12 d后死于肺部感染.结论 心脏病患者妊娠晚期发生心功能衰竭是导致孕产妇死亡的主要原因之一,加强孕期保健及多学科合作,及时终止妊娠,可改善患者的预后.
目的 探讨难治性产后出血围产期急症子宫切除术的原因、时机、术后并发症及孕产妇结局.方法 回顾性分析2016年7月至2019年12月本院收治的因难治性产后出血行急诊子宫切除术19例患者的临床资料.结果 19例患者平均年龄(33.4±4.2)岁,平均孕次(2.8±12)次,平均孕周(36.4±44)周.子宫切除术原因为胎盘因素7例,宫缩乏力为5例,宫缩乏力合并边缘性胎盘产前出血2例,软产道损伤形成大血肿2例,羊水栓塞2例,晚期产后出血合并感染1例.子宫切除术前平均出血量(4 697.2±1 868.5)ml,平均血红蛋白(56.3±21.7) g/L.除1例羊水栓塞患者死亡外,18例患者痊愈出院.结论 围产期急症子宫切除是治疗难治性产后出血的重要措施,胎盘异常及宫缩乏力是两大主要原因.
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.
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+.
目的 总结胚胎植入前遗传学诊断(PGD)治疗的特点及规律,为临床应用提供参考. 方法 收集2017年1月至2019年1月在解放军总医院第六医学中心妇产科生殖中心就诊并完成IVF/ICSI助孕周期及PGD的50对夫妇为研究对象,其中40例为夫妻之一携带染色体结构异常者,10例为单基因病家族史、夫妻一方或双方为致病基因携带者.对患者的临床资料进行回顾性分析;采用囊胚活检术获得胚胎细胞,单细胞全基因组扩增后,采用二代测序技术(NGS)检测胚胎染色体拷贝数.选择染色体平衡、无单基因病发病风险的胚胎,行单囊胚移植.妊娠后在孕中期(18~22 W)进行羊水穿刺,产前诊断,对胎儿进行核型分析及基因检测. 结果 50例行PGD的患者进行了62个促排卵周期,获得218个囊胚,全部采用囊胚活检技术,活检成功率100%.40例染色体病患者共6个病种,获得可移植的囊胚39枚,60%的患者获得可移植囊胚;移植20人,临床妊娠12人,妊娠率60.0%(12/20),流产2人,获得10例健康婴儿.10例单基因疾病患者共7个病种,共获得24个可移植囊胚,100%的患者获得了可移植囊胚;移植9人,临床妊娠5人,妊娠率55.6%(5/9),1例孕24 W自然流产,1例目前孕30 W,共获得3名健康婴儿.孕中期产前诊断,胎儿染色体核型均正常,单基因病家系胎儿基因型与PGD结果相符. 结论 NGS技术可以有效筛查出携带染色体病和单基因病的囊胚,避免移植此类囊胚,阻断遗传病的传递.PGD技术是解决遗传病高危患者生育问题的有效措施.
Maternal oxygen (O2) inhalation therapy is widely used for intrauterine fetal resuscitation.However, the research results were inconsistent in the effects of maternal O2 administration on fetal oxygenation.There were only four randomized controlled trials (RCTs) of O2 inhalation during labor showed that O2 inhalation therapy did not improve the fetal acid-base metabolism state or even increased the risk of fetal acidosis.Several studies showed that O2 inhalation therapy triggered maternal-fetal oxidative stress, and several studies found hyperoxia-induced vasoconstriction.This article reviewed the controversy of maternal O2 administration on mother and fetus during labor.
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effectiveness and safety of angiogenesis inhibitors in the management of persistent, recurrent and metastatic cervical cancer.
目的 探讨胚胎植入前遗传学筛查( PGS)在高龄和复发性流产(RSA)患者中的应用价值.方法 选择91例行PGS治疗的高龄和RSA患者作为研究对象,用单细胞全基因组扩增( WGA)结合二代测序技术( NGS)对胚胎23对染色体进行筛查,选择染色体正常的胚胎进行移植,观察其临床结局.结果 行PGS检测的526枚胚胎,染色体异常率为67.49% (355/526),其中RSA患者染色体异常率为65.96% (217/329),临床妊娠率(CPR)为56.00% (28/50);高龄患者染色体异常率为72.84% (177/243),CPR为57.14% (16/28).结论 高龄和RSA患者胚胎异常率较高,通过PGS可改善其妊娠结局.
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.
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 ofH2on 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 thatH2could diminish the detriment induced by LDLTR and suggesting the protective efficacy ofH2in multiple systems in mice against LDLTR.
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.