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1.
p53 is a key regulator of apoptosis. p53 upregulated modulator of apoptosis (PUMA) is a critical mediator of p53‐dependent and independent apoptosis. The objective of this study was to evaluate the relationship of p53 and PUMA to the prognosis of MDS. Bone marrow biopsies of MDS patients at the time of diagnosis (n = 76) and at the time of transformation (n = 19) were included in the study group. The expression of p53 and PUMA was evaluated using immunohistochemistry. When compared to the control group, both p53 (p < 0.001) and PUMA (p = 0.012) expression levels were significantly higher in MDS group. In MDS group, there was a moderate positive correlation between p53 and PUMA expressions. PUMA expression was not correlated with event free and overall survival. However, overall survival was significantly lower in cases with p53 expression in more than 50% of the cells. There was an increase in PUMA expression in cases that showed transformation as compared to the initial diagnostic bone marrows but was not statistically significant. The correlation that existed between p53 and PUMA was lost in transformed cases. Our results showed that PUMA and p53 expressions are increased in MDS marrows compared to normal marrows. PUMA expression increases further during transformation while the expression of p53 is not significantly altered which suggests that PUMA alterations might be a late event during the evolution of MDS.  相似文献   
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Background

Refractory acute myeloid leukemia (AML) includes AML includes failure of disease to respond to standard induction chemotherapy, relapse within 6 months after first CR, and 2 or more relapses. The outcome of these patients is usually very poor; only a small proportion can be rescued by allogenic hematopoietic stem-cell transplantation (allo-HSCT). The aim of this study was to evaluate the efficacy and feasibility of allo-HSCT in patients with refractory AML.

Patients and Methods

We retrospectively analyzed the clinical outcome of 91 patients who were diagnosed with treatment-refractory AML at Hacettepe University Hospital between January 2002 and June 2018. Patients' disease status included refractory AML, defined as failure to respond to standard induction chemotherapy and relapse within 6 months after first complete remission.

Results

The median follow-up was 12 months (range, 0.5-184 months) for the entire group. Kaplan-Meier estimates of the 3-year overall survival for patients who underwent allo-HSCT and patients who received only salvage chemotherapy were 67% and 12%, respectively. Additionally, the Kaplan-Meier estimates of 5-year overall survival for patients who underwent allo-HSCT and patients who received only salvage chemotherapy were 44% and 4%, respectively (P < .001). Complete remission was obtained in 25 patients (83.3%) who underwent allo-HSCT; however, the disease of only 3 patients (3.8%) exhibited complete response after salvage chemotherapy.

Conclusion

Allo-HSCT is still the best-known treatment option with curative potential in patients with treatment-refractory AML. Therefore, all efforts should be made in an attempt to find a suitable matched donor in order to perform allo-HSCT.  相似文献   
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目的介绍并推广中国儿童与老年健康证据转化平台(Chinese Clearinghouse for Evidence Translation in Child & Aging Health,CCET)。方法分别成立儿童、老年健康顾问委员会,利用科学的评价量表评价筛选国内外相关的儿童、老年健康促进项目并由研究团队翻译转化。与兰州博阳软件工程有限公司合作,根据网站需呈现的内容与目标功能,共同规划设计网站框架与界面,初步建立站点。将转化的健康证据及其他信息资源(疾病基本情况、项目评价量表、研究报告标准等)上传使之在网站相应栏目中呈现,建立CCET网站,并通过微信和微博媒介定期传播儿童及老年健康最新进展、循证研究最新方法。结果CCET主要由儿童健康、老年健康、评价量表、报告标准、推广应用和老年抑郁症循证防治数据库6个版块组成。CCET儿童与老年健康促进项目由国内外专家采用科学的评价量表筛选和评价,转化的证据科学性强,目前已有相关研究机构和社区有意向参与CCET研究和应用转化项目。结论CCET致力于循证方法培训,建立国内健康干预项目的科学性和适用性评价系统,对国外证据转换后的后续干预项目培训,提升服务机构能力,以及综合干预课程研发。CCET信息全面、界面简单、用户友好,为促进我国儿童与老年健康提供证据支持。  相似文献   
6.

Background and purpose

Avascular necrosis (AVN) is a major cause of disability after treatment of developmental dysplasia of the hip (DDH), leading to femoral head deformity, acetabular dysplasia, and osteoarthritis in adult life. Type-II AVN is characterized by retarded growth in the lateral aspect of the physis or by premature lateral fusion, which produces a valgus deformity of the head on the neck of the femur. We investigated the effect of medial percutaneous hemi-epiphysiodesis as a novel technique in the treatment of late-diagnosed type-II AVN.

Patients and methods

9 patients (11 hips) with a diagnosis of type-II AVN who underwent medial percutaneous hemi-epiphysiodesis after the surgical treatment for DDH were included in the study. 10 patients (12 hips) with the same diagnosis but who did not undergo hemi-epiphysodesis were chosen as a control group. Preoperative and postoperative articulotrochanteric distances, head-shaft angles, CE (center-edge) angles, and physeal inclination angles were measured. The treatment group underwent medial hemi-epiphysodesis at a mean age of 8 years. The mean ages of the treatment group and the control group at final follow-up were 14 and 12 years respectively. The mean duration of follow-up was 5.7 years in the treatment group and 8.3 years in the control group.

Results

Preoperative articulotrochanteric distance, head-shaft angle, and functional outcome at the final follow-up assessment were similar in the 2 groups. However, preoperative and postoperative CE angles and physeal inclination angles differed significantly in the treatment group (p < 0.05). The final epiphyseal valgus angles were better in the treatment group than in the control group (p = 0.05). The treatment group improved after the operation.

Interpretation

Medial percutaneous epiphysiodesis performed through a mini-incision under fluoroscopic control is a worthwhile modality in terms of changing the valgus tilt of the femoral head.Avascular necrosis (AVN) of the proximal femoral epiphysis is an iatrogenic complication of treatment for developmental dysplasia of the hip (DDH) (Danielsson 2000, Dhar 2003, Domalzki and Synder 2004, Roposch et al.2013). A late abnormality that may be the manifestation of the lateral portion of the capital femoral growth plate in type-II AVN alters the morphology of hip joint (Kalamchi and MacEwen 1980). When a progressive valgus deformity occurs in a patient with type-II AVN, problems associated with hip dysplasia may follow (Siffert 1981, Campbell and Tarlos 1990, Kim et al. 2000, Wu et al. 2010, Herring 2014). Due to inadequate coverage, reduced contact area between acetabulum and femoral head leads to early secondary osteoarthritis (Aronson 1986, Inoue et al. 2000, Herring 2014).The treatment decision for type-II AVN is challenging. Procedures such as varus femoral osteotomy and redirectional acetabular osteotomy have been used with a view to preventing future degenerative disease. However, these procedures are technically difficult and may result in serious complications (Siebenrock et al. 2013). On the other hand, as the main pathology is the growth disturbance at the lateral aspect of the femoral head, some form of arrest of the medial portion of the growth plate may be more logical in the treatment of type-II AVN (Herring 2014). We analyzed the radiographic and clinical outcomes of 11 hips in 9 patients with late-diagnosed type-II AVN who underwent percutaneous hemi-epiphysiodesis of the femoral head.  相似文献   
7.
Upper gastrointestinal bleeding episodes from variceal structures are severe complications in patients with portal hypertension. Endoscopic sclerotherapy and variceal ligation are the treatment options preferred for upper variceal bleeding owing to extrahepatic portal hypertension due to portal vein thrombosis (PVT). Recurrent duodenal variceal bleeding in non-cirrhotic patients with diffuse porto-splenic vein thrombosis and subsequent portal cavernous transformation represent a clinical challenge if classic shunt surgery is not possible or suitable.In this study, we represent a case of recurrent bleeding of duodenal varices in a non-cirrhotic patient with cavernous transformation of the portal vein that was successfully treated with a collateral caval shunt operation.  相似文献   
8.
The genes encoding RAS family members are frequently mutated in juvenile myelomonocytic leukemia (JMML) and acute myeloid leukemia (AML). RAS proteins are difficult to target pharmacologically; therefore, targeting the downstream PI3K and RAF/MEK/ERK pathways represents a promising approach to treat RAS-addicted tumors. The p110α isoform of PI3K (encoded by Pik3ca) is an essential effector of oncogenic KRAS in murine lung tumors, but it is unknown whether p110α contributes to leukemia. To specifically examine the role of p110α in murine hematopoiesis and in leukemia, we conditionally deleted p110α in HSCs using the Cre-loxP system. Postnatal deletion of p110α resulted in mild anemia without affecting HSC self-renewal; however, deletion of p110α in mice with KRASG12D-associated JMML markedly delayed their death. Furthermore, the p110α-selective inhibitor BYL719 inhibited growth factor–independent KRASG12D BM colony formation and sensitized cells to a low dose of the MEK inhibitor MEK162. Furthermore, combined inhibition of p110α and MEK effectively reduced proliferation of RAS-mutated AML cell lines and disease in an AML murine xenograft model. Together, our data indicate that RAS-mutated myeloid leukemias are dependent on the PI3K isoform p110α, and combined pharmacologic inhibition of p110α and MEK could be an effective therapeutic strategy for JMML and AML.  相似文献   
9.
The aim of this study was to determine serotype distribution and investigate antimicrobial resistance patterns of Streptococcus pneumoniae in healthy Turkish children in the era of community-wide pneumococcal conjugate vaccine (PCV7). The study was conducted on 1,101 healthy children less than 18 years of age. Specimens were collected with nasopharyngeal swabs between April 2011 and June 2011. Penicillin and ceftriaxone susceptibilities were determined by E-test according to the 2008 Clinical Laboratory Standards Institute, and serotypes of the isolates were determined by Quellung reaction. The nasopharyngeal pneumococcal carriage rate was 21.9 % (241/1,101). Using the meningitis criteria of minimum inhibitory concentration values, 73 % of the isolates were resistant to penicillin and 47.7 % of them were resistant to ceftriaxone. Half of all pneumococcal isolates were serotyped as 19F (15.2 %), 6A (15.2 %), 23F (10.3 %), and 6B (9.3 %) and surprisingly, no serotype 19A was isolated. Serotype coverage rates of PCV7 and non-PCV7 were 46.2 and 53.8 %, respectively. The most common penicillin- and ceftriaxone-resistant serotypes were 6A, 6B, 14, 19F, and 23F. Penicillin- and ceftriaxone-resistant isolates were more prevalent in serotypes covered by PCV7 than the non-PCV7 serotypes. Conclusion: After the community-wide PCV7 vaccination, more non-PCV7 serotypes were isolated from the carriers compared to the time before PCV7 was used especially the serotype 6A, and the antimicrobial resistance of pneumococci was significantly increased.  相似文献   
10.
We investigated biofilms of two pathogens, Acinetobacter baumannii and Staphylococcus aureus, to characterize mechanisms by which the extracellular polymeric substance (EPS) found in biofilms can protect bacteria against tobramycin exposure. To do so, it is critical to study EPS-antibiotic interactions in a homogeneous environment without mass transfer limitations. Consequently, we developed a method to grow biofilms, harvest EPS, and then augment planktonic cultures with isolated EPS and tobramycin. We demonstrated that planktonic cultures respond differently to being treated with different types of EPS (A. baumannii versus S. aureus) in the presence of tobramycin. By harvesting EPS from the biofilms, we found that A. baumannii EPS acts as a “universal protector” by inhibiting tobramycin activity against bacterial cells regardless of species; S. aureus EPS did not show any protective ability in cell cultures. Adding Mg2+ or Ca2+ reduced the protective effect of A. baumannii EPS. Finally, when we selectively digested the proteins or DNA of the EPS, we found that the protective ability did not change, suggesting that neither has a significant role in protection. To the best of our knowledge, this is the first study that demonstrates how EPS protects pathogens against antibiotics in a homogeneous system without mass transfer limitations. Our results suggest that EPS protects biofilm communities, in part, by adsorbing antibiotics near the surface. This may limit antibiotic diffusion to the bottom of the biofilms but is not likely to be the only mechanism of protection.  相似文献   
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