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1.
Cancer Med ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31994344

RESUMO

BACKGROUND: Septicemia is an important cause of treatment-related mortality and treatment failure in pediatric acute lymphoblastic leukemia (ALL) in developing countries. A multicenter CCCG-ALL-2015 study was conducted in China and factors associated with septicemia and mortality were studied. METHODS: Patients participated in CCCG-ALL-2015 study from January 2015 to December 2017 were included. Patients with documented septicemia were identified from the Data Center and additional data were collected. RESULTS: A total of 4080 patients were recruited in the study and 527 patients with septicemia were identified (12.9%, 95% CI 11.9%-13.9%). The intermediate risk (IR)/high risk (HR) group had significantly higher incidence of septicemia as compared with low risk (LR) group, 17.1% vs 9.1% (OR 2.07, 95% CI 1.71-2.49, P < .001). Induction phase was the period with majority of septicemia episodes happened, 66.8% in LR and 56.1% in IR/HR groups. Gram-positive bacteria accounted for 54.1%, gram-negative bacteria 44.5%, and fungus 1.4% of positive cultures. Multidrug-resistant organisms were detected in 20.5% of all organisms. The mortality rate after septicemia was 3.4% (95% CI 1.9%-4.9%). Multiple logistic regression identified female gender, comorbid complications, and fungal infection as risk factors associated with mortality. Gram-negative septicemia was associated with higher mortality, 4.9% vs 1.4% (OR 0.28, 95% CI 0.09-0.88, P = .02). There was marked variation in the incidence of septicemia among the 18 centers, from 4.8% to 29.1%. CONCLUSION: Overall the incidence and pattern of septicemia in this multicenter study in China was similar to the reports of western countries. The septicemia-related mortality rate was low. There was marked variation in the incidence of septicemia among the centers.

2.
JAMA Oncol ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31944221

RESUMO

Importance: A randomized clinical trial is needed to determine whether the second-generation Abl-tyrosine kinase inhibitor dasatinib is more effective than the first-generation inhibitor imatinib mesylate for childhood Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL). Objective: To determine whether dasatinib given at a daily dosage of 80 mg/m2 is more effective than imatinib mesylate at a daily dosage of 300 mg/m2 to improve event-free survival of children with Philadelphia chromosome-positive ALL in the context of intensive chemotherapy without prophylactic cranial irradiation. Design, Setting, and Participants: This open-label, phase 3 randomized clinical trial was conducted at 20 hospitals in China. Enrollment occurred from January 1, 2015, through September 18, 2018, and randomization was stopped on October 4, 2018, when the early stopping criterion of the trial was met. Patients aged 0 to 18 years were recruited. Of the 225 patients with the diagnosis, 35 declined participation and 1 died before treatment, leaving 189 patients available for analysis. Data were analyzed from January 1 through August 4, 2019. Interventions: Patients were randomized to receive daily dasatinib (n = 92) or imatinib (n = 97) continuously for the entire duration of ALL therapy from the time of diagnosis made during remission induction to the end of continuation therapy. Main Outcomes and Measures: The primary outcome was event-free survival, analyzed based on intention to treat. The secondary outcomes were relapse, death due to toxic effects, and overall survival. Results: Among the 189 participants (136 male [72.0%]; median age, 7.8 [interquartile range (IQR), 5.2-11.3] years) and a median follow-up of 26.4 (IQR, 16.3-34.1) months, the 4-year event-free survival and overall survival rates were 71.0% (95% CI, 56.2%-89.6%) and 88.4% (95% CI, 81.3%-96.1%), respectively, in the dasatinib group and 48.9% (95% CI, 32.0%-74.5%; P = .005, log-rank test) and 69.2% (95% CI, 55.6%-86.2%; P = .04, log-rank test), respectively, in the imatinib group. The 4-year cumulative risk of any relapse was 19.8% (95% CI, 4.2%-35.4%) in the dasatinib group and 34.4% (95% CI, 15.6%-53.2%) in the imatinib group (P = .01, Gray test), whereas the 4-year cumulative risk of an isolated central nervous system relapse was 2.7% (95% CI, 0.0%-8.1%) in the dasatinib group and 8.4% (95% CI, 1.2%-15.6%) in the imatinib group (P = .06, Gray test). There were no significant differences in the frequency of severe toxic effects between the 2 treatment groups. Conclusions and Relevance: Intensive chemotherapy including dasatinib at a dosage of 80 mg/m2 per day yielded superior results in the treatment of Philadelphia chromosome-positive ALL compared with imatinib mesylate at a dosage of 300 mg/m2 per day and provided excellent control of central nervous system leukemia without the use of prophylactic cranial irradiation. Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IPR-14005706.

3.
Blood ; 135(1): 41-55, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31697823

RESUMO

To study the mechanisms of relapse in acute lymphoblastic leukemia (ALL), we performed whole-genome sequencing of 103 diagnosis-relapse-germline trios and ultra-deep sequencing of 208 serial samples in 16 patients. Relapse-specific somatic alterations were enriched in 12 genes (NR3C1, NR3C2, TP53, NT5C2, FPGS, CREBBP, MSH2, MSH6, PMS2, WHSC1, PRPS1, and PRPS2) involved in drug response. Their prevalence was 17% in very early relapse (<9 months from diagnosis), 65% in early relapse (9-36 months), and 32% in late relapse (>36 months) groups. Convergent evolution, in which multiple subclones harbor mutations in the same drug resistance gene, was observed in 6 relapses and confirmed by single-cell sequencing in 1 case. Mathematical modeling and mutational signature analysis indicated that early relapse resistance acquisition was frequently a 2-step process in which a persistent clone survived initial therapy and later acquired bona fide resistance mutations during therapy. In contrast, very early relapses arose from preexisting resistant clone(s). Two novel relapse-specific mutational signatures, one of which was caused by thiopurine treatment based on in vitro drug exposure experiments, were identified in early and late relapses but were absent from 2540 pan-cancer diagnosis samples and 129 non-ALL relapses. The novel signatures were detected in 27% of relapsed ALLs and were responsible for 46% of acquired resistance mutations in NT5C2, PRPS1, NR3C1, and TP53. These results suggest that chemotherapy-induced drug resistance mutations facilitate a subset of pediatric ALL relapses.

4.
BMC Pregnancy Childbirth ; 19(1): 487, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823750

RESUMO

BACKGROUND: Previous studies have shown that among women with polycystic ovary syndrome who have difficulties conceiving, frozen-embryo transfer resulted in increased live birth rates and decreased ovarian hyperstimulation syndrome risk than did fresh-embryo transfer. In the present retrospective analysis, we sought to determine the effect of body mass index (BMI) on pregnancy and perinatal outcomes in women with PCOS undergoing FET. METHODS: Women with PCOS (n = 1556) undergoing FET were divided into groups based on weight, with those with normal weight having a BMI of 18.5-24.9 kg/m2,those who were overweight having a BMI of 25-29.9 kg/m2, and those who were obese having a BMI ≥30 kg/m2. Both pregnancy and perinatal outcomes were compared among these groups. RESULTS: The normal-weight, overweight, or obese groups exhibited similar pregnancy outcomes, including clinical pregnancy rate, miscarriage rate, ongoing pregnancy rate and live birth rate. In singletons, birth characteristics regarding newborn gender, gestational age, birthweight and length at birth were comparable between the three groups. For adverse neonatal outcomes, the three groups showed no significant differences on the rates of low birthweight, very low birthweight, preterm birth, and very preterm birth after adjustment. In addition, the obstetric complications and the frequencies of live-birth defects were also comparable between the three groups except that overweight and obese women were more likely than women of normal weight to have delivered via cesarean section. CONCLUSION: BMI did not affect the pregnancy or perinatal outcomes in women with PCOS undergoing FET.

5.
Drug Des Devel Ther ; 13: 3867-3877, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814708

RESUMO

Objective: Frozen-thawed embryo transfer enables surplus embryos derived from IVF or IVF-ICSI treatment to be stored and transferred in subsequent cycles into a more "physiologic environment". This study aimed to investigate the clinical effect of letrozole use or hMG stimulation on pregnancy and neonatal outcomes in ovulatory patients undergoing FET. Methods: This study includes a total of 5901 FET cycles with letrozole use (n = 1569), HMG (n =1827) or letrozole + HMG (n = 2505). In the letrozole group, 2.5 mg of letrozole was administered on menstrual cycle day 3 to 5 for 3 days for patients, and then follicle growth was monitored beginning on day 10. If the follicular diameter was ≥14 mm on the 10th day, no other ovarian stimulation drugs were needed. If the follicular diameter was <14 mm on the 10th day, 150 IU human menopausal gonadotropin (hMG) was added to stimulate follicle growth every two days (hMG + letrozole group). In hMG stimulation group, a total of 150 IU of hMG was injected every two days to stimulate development of follicles from cycle day 10 to 12. Results: Compared with the patients undergoing hMG stimulation, the group receiving letrozole or letrozole+HMG stimulation exhibits significantly higher clinical pregnancy rates per transfer (hMG: 47.02% vs letrozole: 52.07% vs letrozole+HMG: 52.26%) and implantation rates (hMG: 31.76% vs letrozole: 34.36% vs letrozole+HMG: 34.24%). In addition, the letrozole group was associated with a statistically significantly lower incidence of miscarriage (hMG: 14.78% vs letrozole: 10.53% vs letrozole+HMG: 14.13%) and ectopic pregnancies (hMG: 1.83% vs letrozole: 0.97% vs letrozole+HMG: 1.58%) than the letrozole + HMG and HMG groups. Neonatal outcomes are similar among the three groups. Conclusion: Our data demonstrate that the letrozole use may improve clinical pregnancy outcomes and decrease the risk of ectopic pregnancies and miscarriage in ovulatory patients who receive FET cycles.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31649624

RESUMO

Background: Prior studies have shown that patients with a >10% estradiol (E2) rise after trigger had more oocytes retrieved than plateauing or decreasing E2 responders. However, multiple follicles develop at different stages of maturation during controlled ovarian stimulation (COS) and may exhibit different responses to trigger. The association between the magnitude of E2 increase and oocyte retrieval outcomes is still unclear. Methods: This was a retrospective cohort study of 2,898 women undergoing their first COS cycles with normal response from January 2014 to December 2017 at a tertiary-care academic medical center. Patients were categorized into five groups according to the percentage increase in E2 levels before and after dual trigger: <10.0%, 10.0-19.9%, 20.0-29.9%, 30.0-39.9%, and ≥40.0%. Univariable and multivariable linear regression analysis were performed to explore the association between E2 increase and oocyte/mature oocyte yield, while logistic regression was used to assess its effect on low oocyte/mature oocyte yield (<10th percentile). Results: The post-trigger E2 increase was negatively associated with both oocyte yield (P-trend < 0.001, adjusted P-trend = 0.033) and mature oocyte yield (P-trend < 0.001, adjusted P-trend = 0.002). Compared with a <10.0% E2 increase after trigger, patients with a ≥40.0% rise had fewer mature oocyte yield [adjusted mean absolute difference [MD] = -5.2, 95% confidence interval [CI]: -8.2--1.8] and higher risk of low mature oocyte yield (adjusted odds ratio [OR] = 1.64, 95% CI: 1.04-2.60), whereas no statistical significance was found in oocyte yield (adjusted MD = -2.7, 95% CI: -6.1-0.8) and low oocyte yield (adjusted OR = 1.48, 95% CI: 0.96-2.28). In addition, the rates of implantation, positive pregnancy test, clinical pregnancy, ongoing pregnancy, pregnancy loss, and live birth were comparable among the 1,942 frozen embryo transfer cycles with embryos originating from different groups of E2 increase (all P > 0.05). Conclusions: A higher E2 rise after dual trigger is independently associated with a lower oocyte and mature oocyte yield in normal responders. Further studies are needed to explore the efficacy of individualized time interval from trigger to oocyte retrieval based on the magnitude of E2 increase after trigger.

7.
Drug Des Devel Ther ; 13: 2553-2563, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440037

RESUMO

Purpose: Dydrogesterone (DYG) has been demonstrated to be an alternative progestin in the progestin-primed ovarian stimulation (PPOS) protocol with comparable oocyte retrieval and pregnancy outcomes. However, its safety regarding neonatal outcomes and congenital malformations is still unclear. Patients and methods: This retrospective cohort study included 3556 live-born infants after in vitro fertilization and vitrified embryo transfer cycles using the DYG + human menopausal gonadotropin (hMG) protocol (n=1429) or gonadotropin-releasing hormone (GnRH)-agonist short protocol (n=2127) from January 2014 to December 2017. Newborn information was gathered from standardized follow-up questionnaires and/or access to medical records within 7 days after birth. Associations between ovarian stimulation protocols and outcome measures were analyzed by binary logistic regression after adjusting for confounding factors. Results: In both singletons and twins, birth characteristics regarding mode of delivery, newborn gender, gestational age, birthweight, length at birth and Z-scores were comparable between the two protocols. For adverse neonatal outcomes, the two protocols showed no significant differences on the rates of low birthweight, very low birthweight, preterm birth, very preterm birth, small-for-gestational age, large-for-gestational age and early neonatal death after adjustment. Furthermore, the incidence of major congenital malformations in the DYG + hMG protocol (1.12%) was similar to that in the GnRH-agonist short protocol (1.08%), with the adjusted odds ratio of 0.98 (95% confidence interval [CI]: 0.40-2.39) and 0.90 (95% CI: 0.33-2.41) in singletons and twins, respectively. Conclusion: Our data suggested that compared with the conventional GnRH-agonist short protocol, application of DYG in the PPOS protocol was a safe option for the newborn population without compromising neonatal outcomes or increasing congenital malformation risks.

8.
Biomed Pharmacother ; 115: 108913, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31054507

RESUMO

Suppressor of cytokine signaling 3 (SOCS3) has been characterized as one of the most crucial negative regulator in the JAK2/STAT3 signaling pathway. However, there are few studies on the relationship between SOCS3 and pediatric acute lymphoblastic leukemia (ALL). This study analyzes the influence of SOCS3 expression on the risk and the progression of pediatric ALL and the underlying mechanism. The levels of SOCS3, p-JAK2, p-STAT3, SOCS3 methylation, CD4+CD25+CD127lowTreg were detected by PCR, laser confocal microscopy, western blot, bisulfite sequencing and flow cytometry at different progression of ALL. We found that the SOCS3 expression level at initial diagnosis (DG) of ALL patients was significantly lower than that of healthy controls (HC), while the expression of SOCS3 methylation was opposite. The expression of SOCS3 and SOCS3 methylation were returned to normal in the complete remission (CR) stage, and there were no difference between resistance, relapse and initial diagnosis. The expression of SOCS3 decreased and weakened the inhibition of pSTAT3 expression in DG, resistance and relapse groups. The levels of Treg cells in ALL children were significantly higher than those in the HC children. There was a positive correlation between the expression level of STAT3 and the expression level of Treg cells in children with ALL, while that was negatively correlated with the expression levels of Treg cells. Compared with high-level of SOCS3, the low-level of SOCS3 patients had more high risk factors, as higher WBC counts, LDH level and much more poor prognostic genes. SOCS3 methylation leads to low-expression of SOCS3, which can lead to continuous activation of JAK/STAT3 and increased expression of Treg cells, which in turn affects the anti-tumor immunological effect of the body. Taken together, our data show that monitoring the level of SOCS3 can contribute to the understanding of the state of illness and evaluate the risk of progression of ALL.


Assuntos
Janus Quinase 2/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Regiões Promotoras Genéticas , Fator de Transcrição STAT3/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/genética , Estudos de Casos e Controles , Criança , Metilação de DNA , Feminino , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Transdução de Sinais , Linfócitos T Reguladores/metabolismo , Resultado do Tratamento
9.
Reprod Biomed Online ; 38(6): 892-900, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30954432

RESUMO

RESEARCH QUESTION: What are the live birth rates and neonatal outcomes following cleavage-stage embryo transfer and blastocyst transfer in a freeze-all treatment scenario? DESIGN: This was a retrospective cohort study. All good-quality embryos were frozen on the third day; the remaining embryos were grown on until they reached blastocyst stage and then frozen. Between 2007 and 2016, 11,801 patients underwent cleavage-stage embryo transfer and 1009 patients underwent blastocyst transfer in the first treatment cycle using the freeze-all strategy. The live birth rate and neonatal outcomes were evaluated. RESULTS: The live birth rate in the first frozen embryo transfer cycle was higher following blastocyst transfer than following cleavage-stage transfer (69.1% versus 55.5%, P < 0.01), but there was no difference in live birth rate in the second frozen embryo transfer cycle between blastocyst transfer and cleavage-stage transfer (45.2% versus 52.7%, P > 0.05). Similarly, no difference was found in the cumulative live birth rate for the first complete IVF cycle (71.1% versus 69.2%, P > 0.05). Blastocyst transfer gave a higher risk of preterm singleton delivery than did cleavage-stage transfer. However, there was no difference in the risk of early preterm delivery, low birth weight, very low birth weight, high birth weight and very high birth weight between the two groups. CONCLUSIONS: There is no evidence to support the superiority of blastocyst transfer compared with cleavage-stage transfer in a freeze-all treatment scenario. There may be a higher risk of preterm singleton delivery following blastocyst transfer than following cleavage-stage transfer but further studies are needed to verify this.

10.
Arch Dis Child ; 104(6): 522-529, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30705079

RESUMO

OBJECTIVES: Before 2003, most children with acute lymphoblastic leukaemia (ALL) abandoned treatment, with only approximately 30% treated in China. With the development of national insurance for underprivileged patients, we assessed the current frequency and causes of treatment abandonment among patients with ALL who were enrolled in the Chinese Children's Cancer Group ALL protocol between 2015 and 2016. METHODS: Demographic, clinical and laboratory data on patients who abandoned treatment, as well as economic and sociocultural data of their families were collected and analysed. General health-related statistics were retrieved from publicly accessible databanks maintained by the Chinese government. RESULTS: At a median follow-up of 119 weeks, 83 (3.1%, 95% CI 2.5% to 3.8%) of the 2641 patients abandoned treatment. Factors independently associated with abandonment included standard/high-risk ALL (OR 2.62, 95% CI 1.43 to 4.77), presence of minimal residual disease at the end of remission induction (OR 3.57, 95% CI 1.90 to 6.74) and low-income economic region (OR 3.7, 95% CI 1.89 to 7.05). According to the family members, economic constraints (50.6%, p=0.0001) were the main reason for treatment abandonment, followed by the belief of incurability, severe side effects and concern over late complications. CONCLUSIONS: The rate of ALL treatment abandonment has been greatly reduced in China. Standard/high-risk ALL, residence in a low-income region and economic difficulties were associated with treatment abandonment. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-IPR-14005706, pre-results.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , China , Feminino , Seguimentos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasia Residual , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Indução de Remissão , Estudos Retrospectivos , Fatores Socioeconômicos
11.
BMC Womens Health ; 19(1): 14, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30658623

RESUMO

BACKGROUND: Cesarean scar endometriosis (CSE) is the most common type of abdominal wall endometriosis (AWE). The aim of this study was to systematically identify the clinical features of CSE and recommend precautionary measures. METHODS: A large, retrospective study was undertaken with CSE patients treated surgically at our hospital between January 2005 and December 2017. RESULTS: A total of 198 CSE patients were enrolled, with a mean age of 32.0 ± 4.0 years. The main complaint of the patients was abdominal mass (98.5%), followed by cyclic pain (86.9%). The latency period of CSE was 31.6 ± 23.9 months, and the duration between the onset of symptoms and this surgery was 28.3 ± 25.0 months. A majority (80.8%, n = 160) of the patients had undergone a Pfannenstiel incision, and a minority (19.2%, n = 38) a vertical midline incision. The latency period of CSE in the case of a Pfannenstiel incision was significantly shorter than that in the case of a vertical midline incision (24.0 vs 33.0 months, P = 0.006). A total of 187 (94.4%) patients had a single endometrioma, 11 (5.6%) patients had multiple endometriomas, and the 11 multiple-endometrioma patients had all undergone a Pfannenstiel incision. Lesions of endometrioma were common in corner sites, after either incision: 142/171 (83.0%) in Pfannenstiel incision scars and 32/38 (84.2%) in vertical incision scars. CONCLUSIONS: The findings of this study indicate that the Pfannenstiel incision carries a higher risk of CSE than the vertical midline incision. Thorough cleaning at the conclusion of CS, particularly of both corner sites of the adipose layer and the fascia layer, is strongly recommended for CSE prevention. Further studies might provide additional recommendations.


Assuntos
Parede Abdominal/patologia , Cesárea/efeitos adversos , Cicatriz/patologia , Endometriose/patologia , Parede Abdominal/cirurgia , Adulto , Cicatriz/etiologia , Endometriose/cirurgia , Feminino , Humanos , Obesidade/complicações , Dor/etiologia , Estudos Retrospectivos , Fatores de Risco
12.
Medicine (Baltimore) ; 97(34): e11906, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30142796

RESUMO

Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation regimen for in vitro fertilization (IVF), with the advantages of an oral administration route and more control over preovulatory luteinizing hormone (LH) levels. Assessing the safety of this novel regimen is an important premise for its routine practice.We conducted a large retrospective cohort study for infants born between August 2014 and April 2017 from IVF and embryo transfer cycles after either PPOS and the conventional gonadotropin-releasing hormone-agonist (GnRH-a) short protocol at our center. Around 1589 live-born infants were finally enrolled, corresponding to 1258 frozen-thawed (FET) cycles, which led to 855 live-born infants from PPOS (659 FET cycles) and 734 live-born infants from the short protocol (599 FET cycles).Birth characteristics regarding gestational age, birth weight and length, infant sex, and early neonatal death were comparable between the 2 groups. The incidence of live-birth defects in the PPOS group (1.52%) was similar to that in the short protocol group (1.63%) and was not statistically significant. For birth defects, the risk significantly increased for multiple births, and the adjusted odds ratio was 3.14 (95% confidence interval [CI]: 1.25-7.88). No associations were found between congenital birth defects and maternal age, body mass index (BMI), the duration of infertility, method of insemination, infant sex, embryo stage at transfer, the number of embryos transferred or ovarian stimulation regimen.Our study shows that the neonatal outcomes and risk of congenital malformations were similar between the PPOS and conventional GnRH-a short protocol. However, multiple pregnancy led to a higher likelihood of birth defects.


Assuntos
Hormônio Liberador de Gonadotropina/agonistas , Indução da Ovulação/métodos , Progestinas/administração & dosagem , Administração Oral , Adulto , Transferência Embrionária , Feminino , Fertilização In Vitro , Humanos , Lactente , Recém-Nascido , Nascimento Vivo , Idade Materna , Gravidez , Taxa de Gravidez , Progestinas/farmacologia , Estudos Retrospectivos
13.
Arch Gynecol Obstet ; 298(4): 833-840, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30135993

RESUMO

PURPOSE: To explore the risk of birth defects among children born after vitrified blastocyst transfers and those born after fresh and vitrified cleavage-stage embryo transfers. METHODS: A retrospective cohort study was conducted including infants born after fresh and vitrified day 3 embryo transfers and those born after vitrified day 5 or 6 blastocyst transfers from January 2005 through December 2016. The outcome measures included any birth defect, multiple birth defects and 13 individual categories of birth defects. RESULTS: Any birth defect occurred in 1.15% of infants born after fresh day 3 embryo transfers, 1.75% of infants born after vitrified day 3 embryo transfers, 1.60% of infants born after vitrified day 5 blastocyst transfers and 1.10% of infants born after vitrified day 6 blastocyst transfers. There was no difference in the risk of birth defects between vitrified blastocyst-stage transfers and vitrified cleavage-stage transfers (including day 5 vs. day 3 and day 6 vs. day 3) among all births or in only singletons or twins. For infants born after cleavage-stage embryo transfers at day 3, there was no difference in the risk of birth defects between fresh embryo transfers and vitrified embryo transfers among all births or in only singletons or twins. CONCLUSIONS: Transfer of vitrified day 5 or 6 blastocysts does not increase the risk of birth defects compared with vitrified day 3 embryos. However, randomized control trials and follow-up studies of the long-term outcome of children born after blastocyst-stage transfers are needed to confirm the clinical safety of extending embryo culture to the blastocyst stage.


Assuntos
Anormalidades Congênitas/etiologia , Transferência Embrionária/efeitos adversos , Vitrificação , Adulto , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(6): 1647-1651, 2017 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-29262891

RESUMO

OBJECTIVE: To explore clinical characteristics and outcome of deep vein thrombosis(DVT) in children with acute lymphoblastic leukemia (ALL). METHODS: A tatol of 266 patients were diagnosed as ALL from January 1, 2010 to May 31, 2016. The clinical data of 12 cases of patients with DVT were retrospectively analyzed, 183 cases diagnosed before January 1, 2015 were received chemotherapy with the scheme of SCMC-05. The other cases were treated by the scheme of CCCG. All the patients received central venous catheter. RESULTS: The DVT happened in 12 cases including 10 cases of limb DVT and 2 cases of intacranial venous sinus thrombosis. The DVT mostly occured in intermediate risk ALL patients, the infection and coagulopathy existed in most patients. They were treated with low molecular heparin(LWHP), among them 5 cases were given extubation; the thrombus disappeared in 6 cases after 1 week; the intracranial venous sinus thrombosis in 1 case did not obviously improved after 6 months of treatment. The ALL children with DVT were treated with LWHP when using L-ASP, as a result no thrombuses happened. CONCLUSION: Centralvenous catheter and chemotherapeutic drugs were the major cause of DVT. Abnormal coagulation, infection, and risk stratification are another risk factors for thrombosis. ALL children thrombosis are benefited from LWHP prevention when using L-ASP again.


Assuntos
Anticoagulantes/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Tromboembolia Venosa/complicações , Criança , Heparina , Humanos , Estudos Retrospectivos , Fatores de Risco , Trombose , Tromboembolia Venosa/tratamento farmacológico , Trombose Venosa
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(5): 1367-1372, 2017 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-29070109

RESUMO

Obejective: To investigate the expression level of suppressor of cytokine signaling SOCS3 mRNA in children's acute lymphoblastic leukemia(ALL); to analyze the relationship between the expresion level of SOCS3 mRNA and disease status and risks of ALL, and to explore the application of SOCS3 mRNA in evaluation of ALL disease status, risk and target therapy. METHODS: The expression levels of SOCS3 mRNA in bone marrow mononuclear cells from 45 cases of newly diagnosed ALL at initial diganosis and induction remission and 13 normal children as controls were detected by SYBR Green fluorescence quantitative PCR; the correlation of SOCS3 mRNA expression level with risk and clinical characteristics of ALL was analyzed by means of statistical method; the immunofluorescence histochemistry method and laser confocal microscopy were used to detect the sites and expression level of SOCS3 mRNA in bone marrow samples of ALL patients. RESULTS: The SOCS3 mRNA expression level at initial diagnosis of 45 ALL patients was significantly lower than that of normal controls (P<0.05), and that in induction remission of 45 patients was not significant different from normal controls (P<0.05); the SOCS3 mRNA expression level at initial diagnosis of patients with standasd and high risk was higher than that of patients with low risk (P<0.05). The 45 patients were divided into high expression and low expression groups according to SOCS3 mRNA expression level at initial diagnosis by median method, comparison of clinical characteristics in 2 groups was found that the SOCS3 mRNA high expression group had even more higher leukocyte count in peripheral blood, even more higher LDH level and much more poor prognostic genes; in addition, the high expression group showed more higher risk in comparison between 2 group. CONCLUSION: The SOCS3 mRNA expression is down-regulated at initial diagnosis, while recovered to normal level after induction remission of disease, thus the SOCS3 can be used as an indicator for evaluation of disease status. The high expression of SOCS3 mRNA up-regulates the disease risk, therefore the SOCS3 mRNA can be used as a factor for evaluation of ALL risk. The treatment of ALL via regulation of SOCS3 mRNA expression level maybe can become a new way. The regulation of SOCS3 mRNA expression level maybe can become a new way for treatment of ALL.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Medula Óssea , Criança , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , RNA Mensageiro , Risco , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteínas Supressoras da Sinalização de Citocina
16.
Pediatr Blood Cancer ; 64(4)2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27781387

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous disease with major diagnostic and therapeutic difficulties. A large-scale multicenter study of pediatric HLH is still lacking in China. PROCEDURE: The Histiocytosis Study Group of the Chinese Pediatric Society conducted this retrospective study in 2014. A total of 323 patients diagnosed with HLH between 2011 and 2013 from 12 hospitals were registered. RESULTS: The median age at diagnosis was 2.2 years (range, 0-14.6 years), with a peak age of HLH onset at 0 to 3 years (63%). Mutations in HLH-related genes were found in 27.9% (24/86) patients who underwent genetic testing. PRF1, UNC13D, STXBP2 and LYST were the predominant genes involved. Sixteen patients (66.7%) presented with only monoallelic mutations in one gene. Epstein-Barr virus (EBV) infection was the major condition related to HLH, which was documented in 74.4% (201/270) of the patients who underwent EBV detection. Of 252 evaluable patients, 64.7% (163) achieved non-active disease at the eighth week and patients treated with a protocol containing etoposide presented higher remission rates (75.6% vs. 46.8%, P < 0.001). In multivariate analysis, a younger age at diagnosis (<12 months), platelet count less than 80×109 /L, central nervous system involvement, and initial treatment using a protocol without etoposide (not HLH-94/04) were independent prognostic factors indicating resistant disease. DISCUSSION: This study first multicenter assessment of HLH in China shows some different features in Chinese children with HLH compared with those in western countries, including older age, vulnerability to EBV infection, and a high proportion of patients with single monoallelic genetic mutations.


Assuntos
Biomarcadores/metabolismo , Linfo-Histiocitose Hemofagocítica/patologia , Adolescente , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/genética , Masculino , Proteínas de Membrana/genética , Proteínas Munc18/genética , Mutação/genética , Perforina/genética , Prognóstico , Estudos Retrospectivos , Proteínas de Transporte Vesicular/genética
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(2): 546-50, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-27151027

RESUMO

OBJECTIVE: To explore the clinical diagnostic value and significance of hepciden level by detecting the expression of serum hepcidin before and after treatment of infant iron deficiency anemia (IDA) with or without vitamin D deficiency. METHODS: A total of 60 cases of infamt IDA were divided into A and B groups, the group A consisted of 20 IDA infants with vitamin D deficiency, group B consisted of 48 IDA infants without vitamin D deficiency and the control group included 26 healthy infants. Blood examination including HGB, MCV, MCH and MCHC was performed by hematological analyzer, the level of serum ferritin was assayed by chemiluminescence immunoassay, the levels of hepcidin and 25- (OH) D were assayed by ELISA. RESULTS: The levels of serum hepcidin in group A, B and control group before treatment were (29.16 ± 7.50), (27.11 ± 7.10) and (29.25 ± 8.39) ng/ml, respectively (P > 0.05). The level of serum hepcidin in group A and B after treatments was significantly higher than that in control group [ (36.21 ± 5.68) ng/ml vs (29.25 ± 8.39) ng/ml, P < 0.01; (34.16 ± 4.54) ng/ml vs (29.25 ± 8.39) ng/ml, P < 0.01]; but there were no significantly difference between group A and B (P > 0.05). The serum ferritin positively correlated with hepcidin in group B both before and after treatments (r = 0.352 and 0.367, P < 0.05, P < 0.05). CONCLUSION: The level of serum hepcidin has an important significance in poccess of evaluatng for therapeutic effect in infant iron deficiency anemia, but the interference effect of vitamin D deficience should be eliminated when the expression level of hepcidin is applicated for diagnosis and differential diagnosis.


Assuntos
Anemia Ferropriva/diagnóstico , Hepcidinas/sangue , Deficiência de Vitamina D/sangue , Estudos de Casos e Controles , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Humanos , Lactente
18.
Medicine (Baltimore) ; 95(9): e2939, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26945402

RESUMO

Ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation is a current challenge for patients with polycystic ovarian syndrome (PCOS). Our previous studies indicated that progestin can prevent premature luteinizing hormone (LH) surge or moderate/severe OHSS in the general subfertile population, both in the follicular-phase and luteal-phase ovarian stimulation but it is unclear if this is true for patients with PCOS. The aim of the article was to analyze cycle characteristics and endocrinological profiles using human menopausal gonadotropin (hMG) in combination with medroxyprogesterone acetate (MPA) for PCOS patients who are undergoing IVF/intracytoplasmic sperm injection (ICSI) treatments and investigate the subsequently pregnancy outcomes of frozen embryo transfer (FET). In the randomized prospective controlled study, 120 PCOS patients undergoing IVF/ICSI were recruited and randomly classified into 2 groups according to the ovarian stimulation protocols: hMG and MPA (group A, n = 60) or short protocol (group B, n = 60). In the study group, hMG (150-225IU) and MPA (10 mg/d) were administered simultaneously beginning on cycle day 3. Ovulation was cotriggered by a gonadotropinreleasing hormone (GnRH) agonist (0.1 mg) and hCG (1000IU) when dominant follicles matured. A short protocol was used as a control. The primary end-point was the ongoing pregnancy rate per transfer and incidence of OHSS. Doses of hMG administrated in group A are significantly higher than those in the controls. LH suppression persisted during ovarian stimulation and no incidence of premature LH surge was seen in both groups. The fertilization rate and the ongoing pregnant rate in the study group were higher than that in the control. The number of oocytes retrieved, mature oocytes, clinical pregnancy rates per transfer, implantation rates, and cumulative pregnancy rates per patient were comparable between the 2 groups. The incidence of OHSS was low between the 2 groups, with no significant difference. The study showed that MPA has the advantages of an oral administration route, easy access, more control over LH levels. A possible reduction in the incidence of moderate or severe OHSS with the MPA protocol should be viewed with caution as the data is small. Large randomized trials with adequate sample size remain necessary.


Assuntos
Fertilização In Vitro/métodos , Acetato de Medroxiprogesterona/farmacologia , Menotropinas/farmacologia , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/fisiopatologia , Administração Oral , Adulto , Estudos Cross-Over , Método Duplo-Cego , Transferência Embrionária/métodos , Feminino , Fertilização/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Hormônio Luteinizante/metabolismo , Acetato de Medroxiprogesterona/administração & dosagem , Menotropinas/administração & dosagem , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Gravidez , Resultado da Gravidez , Estudos Prospectivos , Injeções de Esperma Intracitoplásmicas
19.
Biochem Biophys Res Commun ; 471(1): 260-5, 2016 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-26850853

RESUMO

Heterogeneous nuclear ribonucleoprotein K (hnRNP K), an evolutionarily conserved protein, is involved in several important cellular processes that are relevant to cell proliferation, differentiation, apoptosis, and cancer development. However, details of hnRNP K expression during mammalian oogenesis and preimplantation embryo development are lacking. The present study investigates the expression and cellular localization of K protein in the mouse ovaries and preimplantation embryos using immunostaining. We demonstrate, for the first time, that hnRNP K is abundantly expressed in the nuclei of mouse oocytes in primordial, primary and secondary follicles. In germ vesicle (GV)-stage oocytes, hnRNP K accumulates in the germinal vesicle in a spot distribution manner. After germinal vesicle breakdown, speckled hnRNP K is diffusely distributed in the cytoplasm. However, after fertilization, the K protein relocates into the female and male pronucleus and persists in the blastomere nuclei. Localization of K protein in the human ovary and ovarian granulosa cell tumor (GCT) was also investigated. Overall, this study provides important morphological evidence to better understand the possible roles of hnRNP K in mammalian oogenesis and early embryo development.


Assuntos
Blastocisto/metabolismo , Desenvolvimento Embrionário/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/metabolismo , Oogênese/fisiologia , Ovário/metabolismo , Animais , Células Cultivadas , Feminino , Camundongos , Camundongos Endogâmicos ICR , Ribonucleoproteínas Nucleares Pequenas , Distribuição Tecidual
20.
J Mech Behav Biomed Mater ; 60: 203-211, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26807774

RESUMO

The branching system plays an important role in maintaining the survival of palm trees. Due to the nature of monocots, no additional vascular bundles can be added in the palm tree tissue as it ages. Therefore, the changing of the cross-sectional area in the palm branch creates a graded distribution in the mechanical properties of the tissue. In the present work, this graded distribution in the tissue mechanical properties from sheath to petiole were studied with a multi-scale modeling approach. Then, the entire palm branch was reconstructed and analyzed using finite element methods. The variation of the elastic modulus can lower the level of mechanical stress in the sheath and also allow the branch to have smaller values of pressure on the other branches. Under impact loading, the enhanced frictional dissipation at the surfaces of adjacent branches benefits from the large Poisson׳s ratio of the sheath tissue. These findings can help to link the wind resistance ability of palm trees to their graded materials distribution in the branching system.


Assuntos
Arecaceae/fisiologia , Módulo de Elasticidade , Estresse Mecânico , Árvores/fisiologia
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