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1.
Apolipoprotein E (ApoE) is a constituent of many types of lipoproteins that play a role in metabolism of cholesterol and lipids in the body as well as in the brain. ApoE is synthesised in astrocytes and microglia and enter to neurons through LDL, LRP and VLDL receptors. Recently it was shown that ApoE is also produced in neurons. ApoE has a role in modulating learning and memory, structural plasticity, mobilization of cholesterol in repair, growth and maintenance of myelin and neuronal membranes during development and aging, and cell death after ischemic, convulsive, or other type of brain injury. The aim of this research was to investigate the possible association of ApoE gene polymorphism with the development of resistance to pharmacological therapy in patients with partial complex seizures with or without secondary generalization. In this prospective matched-pair controlled study, 60 patients with cryptogenic epilepsy with complex partial seizures, with or without secondary generalization, who have been suffering for five or more years, were studied. The first group comprised 30 patients refractory to the current therapy, while the second group consisted of patients with well-controlled seizures. The refractory and non-refractory groups of patients differed significantly in their phenotypes. Phenotype E3/4 was six times more frequent in refractory group than among non-refractory group. The lack of response was shown to be significantly associated with the presence of epsilon4 allele. This study provided evidence that the presence of epsilon4 allele is more often associated with a lack of response to current antiepileptic drugs as compared to epsilon2 and epsilon3 alleles.  相似文献   

2.
Biomarkers which can identify Diffuse Large B-Cell Lymphoma (DLBCL) likely to be refractory to first-line therapy are essential for selecting this population prior to therapy initiation to offer alternate therapeutic options that can improve prognosis. We tested the ability of a CT-based radiomics approach with machine learning to predict Primary Treatment Failure (PTF)-DLBCL from initial imaging evaluation. Twenty-six refractory patients were matched to 26 non-refractory patients, yielding 180 lymph nodes for analysis. Manual 3D delineation of the total node volume was performed by two independent readers to test the reproducibility. Then, 1218 hand-crafted radiomic features were extracted. The Random Forests machine learning approach was used as a classifier for constructing the prediction models. Seventy percent of the nodes were randomly assigned to a training set and the remaining 30% were assigned to an independent test set. The final model was tested on the dataset from the 2 readers, showing a mean accuracy, sensitivity and specificity of 73%, 62% and 82%, respectively, for distinguishing between refractory and non-refractory patients. The area under the receiver operating characteristic curve (AUC) was 0.83 and 0.79 for the two readers. We conclude that machine learning CT-based radiomics analysis is able to identify a priori PTF-DLBCL with a good accuracy.  相似文献   

3.
目的分析烧伤病房患者不同创面金葡菌的分布及耐药性,为临床合理选用抗菌药提供依据。方法对2006年1月至2013年12月间中国人民解放军第八五医院烧伤病房患者创面分离出金葡菌,采用K—B纸片扩散法进行药物敏感试验。分析金葡菌的耐药性,并对难愈性创面、非难愈性创面的耐甲氧西林金葡菌(MRSA)与甲氧西林敏感金葡菌(MSSA)的耐药性进行对比分析。结果分离出金葡菌112株,其中难愈性创面有70株MRSA和17株MSSA来自难愈性创面,16株MRSA和9株MSSA来自非难愈性创面。金葡菌对青霉素、红霉素、克林霉素的耐药率较高(分别为94.64%、81.25%和74.11%),对复方新诺明、呋喃妥因的耐药率较低(分别为16.07%和1.79%),对万古霉素、利奈唑烷的耐药率为0。MRSA的耐药率高于MSSA。来源于难愈性创面与非难愈性创面的MRSA仅在对利福平的耐药率上有明显差异,而来源于两创面的MSSA的耐药率无明显差异。结论创面金葡菌中MRSA的构成比高,难愈性创面MRSA耐药严重,应积极防控创面MRSA感染和扩散。  相似文献   

4.
The clinical importance of erythroid predominance in bone marrow of patients with acute myeloid leukemia (AML) is controversial. These cases represent a heterogeneous group of diseases that historically have been classified into different categories. We studied 313 AML patients and specifically compared the clinical, cytogenetic, and molecular features of cases of AML with erythroid predominance, arbitrarily defined as ≥50% erythroid precursors, to AML cases without erythroid predominance. We also assessed 51 patients with a high-grade myelodysplastic syndrome (MDS), refractory anemia with excess blasts (RAEB). All neoplasms were classified according to the World Health Organization classification. With the exception of therapy-related AML/MDS, the presence of erythroid predominance in variously classified categories of AML was associated with a survival advantage. In addition, AML with erythroid predominance had a lower frequency of cytogenetic abnormalities as well as a lower frequency of mutations involving NPM1, NRAS and FLT3 as compared with AML without erythroid predominance. We conclude that the clinical, cytogenetic, and molecular features of AML with erythroid predominance in the non-therapy-related setting are much closer to those of a high-grade myelodysplastic syndrome than they are to other types of AML.  相似文献   

5.
《Cytotherapy》2022,24(7):676-685
BackgroundChronic inflammatory demyelinating polyneuropathy (CIDP), stiff-person syndrome (SPS), neuromyelitis optica spectrum disorders (NMOSD) and severe refractory myasthenia gravis (MG) are immune-mediated neurological diseases that severely affect patients’ functionality and quality of life, with a considerable percentage undergoing relapse or not responding to conventional treatment options. Autologous hematopoietic stem cell transplantation (auto-HSCT) has emerged as a potential second-line treatment alternative.MethodsWe performed a literature review in PubMed/Medline, EMBASE, Web of Science and Cochrane Library from inception to September 2021 of reported cases and studies of CIDP, SPS, NMOSD and MG that underwent HSCT as a treatment option.ResultsA total of 173 patients who underwent HSCT were found, including 32 patients described in case reports and 60 in a phase 2 clinical trial with CIDP, 29 patients with SPS, 42 patients with NMOSD and 10 patients with refractory MG. Complete remission was documented in 68/92 patients with CIDP, 13/29 with SPS and 10/10 with MG. From the NMOSD cases, 24/42 were relapse-free at last follow-up, with 13/33 having negative anti-AQ4 antibodies after HSCT. From all the included studies, only 8/173 patients received an allogeneic HSCT, 4/8 after a failed auto-HSCT. All showed clinical improvement and disease remission.ConclusionHSCT has the potential to induce long-term remission in patients with CIDP, NMOSD, SPS or MG with adequate safety and tolerability. Collaboration between centers is needed to implement larger, homogeneous prospective studies, focusing on immunological correlates of favorable long-term response.  相似文献   

6.
目的:研究128 层螺旋CT 在透析患者上肢CT 血管成像中的临床应用价值。方法:回顾性分析30 例患者的64 层CT 图像 (64 层组)与39 例患者128 层CT 图像(128 层组),对扫描数据进行三维重建后比较两组患者的动脉分支级别、血管边缘、静脉干 扰评分及瘘口显示情况的差异。结果:128 层组前臂与手部动脉分支级别显示评分高于64 层组,差异有统计学意义(P<0.05);128 层组肩部、上臂及前臂的血管边缘光滑度显示评分高于64 层组,差异有统计学意义(P<0.05)。结论:128 层螺旋CT 在透析患者上 肢血管成像中血管、内瘘口以及流入流出道等细节方面显示效果更理想。  相似文献   

7.
Gliomas are the most common brain tumors in adults and account for more than half of all brain tumors. Despite intensive clinical investigations, average survival for the patients harboring the malignancy has not been significantly improved. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), shown to have potent and cancer-selective killing activity, has drawn considerable attention as a promising anti-cancer therapy. In an attempt to develop TRAIL as an anti-cancer therapy for gliomas, tumor suppressor activity of TRAIL was assessed using human glioma cell lines such as U373MG, U343MG, U87MG and LN18. U343MG, U87MG and LN18 cells were susceptible to TRAIL; however, U373MG cells were completely refractory to TRAIL. Resistance to the applied therapies is a key issue in cancer treatment; thus, various combination treatments were evaluated using U373MG cells to identify a better regimen. Unlike Doxorubicin, Etoposide, Actinomycin D and Wortmannin, a proteasome inhibitor MG132 significantly enhanced TRAIL-induced apoptosis. Similarly, other proteasome inhibitors, including Lactacystin, Proteasome inhibitor I and Velcade (Bortezomib), also enhanced apoptotic activity of TRAIL. Among these proteasome inhibitors, Velcade, the only approved drug, was as effective as MG132 in enhancing TRAIL-induced apoptosis. Both Velcade and MG132 increased the protein levels of DR5, a TRAIL receptor known to be up-regulated by p53, in U373MG cells where p53 is mutated. Our data indicate that proteasome inhibitors up-regulate DR5 in a p53-independent manner and a combination therapy comprising TRAIL and Velcade become a better treatment regimen for gliomas.  相似文献   

8.
目的:探讨红藤养胃汤治疗胃癌的疗效及对血清胃癌相关抗原(MG7-Ag)、骨桥蛋白(OPN)、组织多肽特异性抗原(TPS)水平的影响。方法:选择2015年2月至2017年1月在我院进行胃癌治疗的86例患者,将其随机均分为观察组和对照组,每组43例。对照组患者给予奥美拉唑治疗,观察组患者在对照组基础上给予红藤养胃汤疗,比较两组患者的临床疗效,治疗前后血清MG7-Ag、TPS、OPN水平变化及不良反应的发生情况。结果:治疗后,观察组总有效率显著高于对照组,血清MG7-Ag、TPS、OPN水平均显著低于对照组,差异均具有统计学意义(P0.05),且恶心呕吐、发热及白细胞减少等不良反应的发生率显著低于对照组(P0.05)。结论:红藤养胃汤可显著提高胃癌患者的临床疗效,减少不良反应,有效降低患者血清MG7-Ag、TPS、OPN水平。  相似文献   

9.
Objectives: To examine whether antibiotics are indicated in treating uncomplicated acute sinusitis and, if so, whether newer and more expensive antibiotics with broad spectra of antimicrobial activity are more effective than amoxycillin or folate inhibitors. Design: Meta-analysis of randomised trials. Setting: Outpatient clinics. Subjects: 2717 patients with acute sinusitis or acute exacerbation of chronic sinusitis from 27 trials. Interventions: Any antibiotic versus placebo; amoxycillin or folate inhibitors versus newer, more expensive antibiotics. Main outcome measurements: Clinical failures and cures. Results: Compared with placebo, antibiotics decreased the incidence of clinical failures by half (risk ratio 0.54 (95% confidence interval 0.37 to 0.79)). Risk of clinical failure among 1553 randomised patients was not meaningfully decreased with more expensive antibiotics as compared with amoxycillin (risk ratio 0.86 (0.62 to 1.19); risk difference 0.9 fewer failures per 100 patients (1.4 more failures to 3.1 fewer failures per 100 patients)). The results were similar for other antibiotics versus folate inhibitors (risk ratio 1.01 (0.52 to 1.97)), but data were sparse (n=410) and of low quality. Conclusions: Amoxycillin and folate inhibitors are essentially as effective as more expensive antibiotics for the initial treatment of uncomplicated acute sinusitis. Small differences in efficacy may exist, but are unlikely to be clinically important.

Key messages

  • A major question in managing acute sinusitis is whether antibiotics should be used, and if so which drugs should be chosen
  • In a comprehensive meta-analysis we evaluated evidence from randomised controlled trials comparing, firstly, antibiotics against placebo and, secondly, amoxycillin and folate inhibitors against newer, more expensive antibiotics
  • Antibiotics were significantly more efficacious than placebo in achieving cure of clinical symptoms, but over two thirds of placebo patients showed spontaneous resolution or improvement of symptoms
  • Amoxycillin and folate inhibitors had overall similar efficacy compared with newer antibiotics
  • The current evidence does not justify the use of expensive, broad spectrum antibiotics in the community for treating uncomplicated acute sinusitis
  相似文献   

10.
《Endocrine practice》2014,20(3):252-260
ObjectiveDetermine the relationship between mean glucose (MG), as assessed by continuous glucose monitoring (CGM), and hemoglobin A1c (A1C) in insulin-requiring adults in a clinical practice setting and examine the persistence of this relationship over time.MethodsIn this retrospective record review in a diabetes practice, a linear regression model was developed using data sets from all patients with ≥ 1 available download of a Dexcom SevenPlus CGM device in which there was > 50% utilization in the 60 days prior to a laboratory A1C. Persistence of the MG to A1C relationship was examined in patients with ≥ 2 data sets available.ResultsA total of 139 patients had ≥ 1 data set available for evaluation, and 101 patients had ≥ 2 data sets (range, 2 to 6; total, 279). The slope of the MG versus A1C curve was 19.5 mg/dL for each 1% change in A1C, with an intercept of 17.7 mg/dL. Although 88% of the measured MG values were within 15% of the A1C-predicted MG, there was substantial variation in individuals, with differences as large as ± 26%. The MG to A1C (MG:A1C) ratio, which is a measure of glycation, was normally distributed, with a median of 21.6. Spearman correlation coefficients for the MG:A1C ratio on repeated measures ranged from 0.52 to 0.73, demonstrating persistence.ConclusionThe relationship between MG and A1C is linear in a population but can vary between individuals. The MG:A1C ratio was normally distributed, tended to persist in individuals over time, and thus could be useful to identify apparent high and low glycators. Glycemic goals may need to be modified in such patients. (Endocr Pract. 2014;20:252-260)  相似文献   

11.
Methylated guanine damage at O6 position (i.e. O6MG) is dangerous due to its mutagenic and carcinogenic character that often gives rise to G:C-A:T mutation. However, the reason for this mutagenicity is not known precisely and has been a matter of controversy. Further, although it is known that O6-alkylguanine-DNA alkyltransferase (AGT) repairs O6MG paired with cytosine in DNA, the complete mechanism of target recognition and repair is not known completely. All these aspects of DNA damage and repair have been addressed here by employing high level density functional theory in gas phase and aqueous medium. It is found that the actual cause of O6MG mediated mutation may arise due to the fact that DNA polymerases incorporate thymine opposite to O6MG, misreading the resulting O6MG:T complex as an A:T base pair due to their analogous binding energies and structural alignments. It is further revealed that AGT mediated nucleotide flipping occurs in two successive steps. The intercalation of the finger residue Arg128 into the DNA double helix and its interaction with the O6MG:C base pair followed by rotation of the O6MG nucleotide are found to be crucial for the damage recognition and nucleotide flipping.  相似文献   

12.
13.
Aim: To determine the diagnostic efficiency of 3D Eletrical Impedance Tomography (EIT) compared to Mammography (MG) and Ultrasonography (USG) in imaging the breast. Materials and Methods: A group of 88 patients presenting with various breast complaints was examined using combined Mammography and Ultrasonography (MG & USG) or either of these modalities alone. The same patients were then examined using the 3D EIT imaging system "MEIK". The findings were then compared. The sensitivity of these modalities for this group of patients were later determined and statistically analysed. Results: Of the total of 88 patients, 59 findings were "suspicious" by any of the 3 modalities alone or by their combination. EIT had a sensitivity of 77.8 % compared to MG with a sensitivity of 83.3 % and USG with a sensitivity of 94.4 % regarding cases of fibrocystic mastitis. For cases involving cysts, EIT had 100 % sensitivity which was the same as that for USG compared to MG with a sensitivity of only 81 %. Among cases of fibroadenoma, EIT had a sensitivity of just 68.8 % compared to MG with a sensitivity of 87.5 % and USG with a sensitivity of 75 %. Finally among cases of carcinoma, EIT had a sensitivity of 75 % compared to the sensitivity of 100 % of MG and USG in our group of patients. The study revealed that there was no overall significant difference in sensitivity between MG-USG (p = 0.219) and MG-EIT (p = 0.779) and USG-EIT (p = 0.169). However, in regard to identifying cysts there was significant difference in the sensitivity of MG compared to USG & EIT suggesting that EIT has a role in these cases. Conclusion: Electrical impedance could be used as an adjunct to Mammography and Ultrasonography for breast cancer detection. However, the differentiation of malignant from benign lesions based on impedance measurements needs further investigation. Multifrequency electrical impedance imaging appears the most promising for detecting breast malignancies but methodological improvements need to be made to realise its potential.  相似文献   

14.
目的:分析循环滤泡辅助性T(c Tfh)细胞亚型与重症肌无力(MG)患者临床特点之间的关系。方法:横断面研究30例MG患者外周血c Tfh细胞各个亚型百分比和临床特点之间的关系。c Tfh细胞亚型的百分比是通过流式细胞术获取的。MG患者的临床特点包括性别、年龄、病程、胸腺情况、美国重症肌无力协会(MGFA)分型和重症肌无力量化(QMG)评分。结果:CD4~+CXCR5~+ICOS~+、CD4~+CXCR5~+PD-1~+和CD4~+CXCR5~+CXCR3-CCR6~+(Th17样)c Tfh细胞亚型百分比与QMG评分之间存在正相关关系;全身型重症肌无力(GMG)患者在CD4~+CXCR5~+ICOS~+、CD4~+CXCR5~+PD-1~+和Th17样c Tfh细胞亚型百分比要高于眼肌型重症肌无力(OMG)患者,OMG患者在CD4~+CXCR5~+CXCR3-CCR6-(Th2样)c Tfh亚型细胞百分比要高于GMG患者。c Tfh细胞各个亚型百分比与MG患者的性别、年龄、病程、胸腺情况均无显著相关性。结论:CD4~+CXCR5~+ICOS~+、CD4~+CXCR5~+PD-1~+和Th17样c Tfh细胞亚型百分比与MG病情严重性间存在正相关关系,提示c Tfh细胞与MG之间的密切关系。  相似文献   

15.
OBJECTIVE: To correlate the cytomorphologic spectrum of giant cell tumor of tendon sheath (GCTTS) with clinical and histologic findings and determine key features helpful in preoperative diagnosis. STUDY DESIGN: Retrospective analysis was done on 48 cases diagnosed cytologically over 9 years. Cases were divided into 2 groups: in group 1 cytology and histology were available (12), and in group 2 cytology alone was available (36). Cytomorphologic features were correlated with clinical and histologic findings. RESULTS: Patients ranged in age from 11 to 60 years, with more women. Small joint involvement was seen in all cases except 1, with upper limb involvement in most cases. Recurrence occurred in 3 cases. Aspiration smears in all cases showed high cellularity, multinucleated osteoclastic type of giant cells and stromal cells. Other features seen less frequently were cytoplasmic granules and vacuoles, nuclear grooves, inclusions, budding, focal mild pleomorphism, hemosiderin-laden macrophages and foam cells. Mitosis and necrosis were absent. Cytologic features were classified as constant when present in all cases and variable when present occasionally. CONCLUSION: The constant cytologic features when combined with clinical and radiologic details are sufficiently distinctive of GCTTS. Fine needle aspiration cytology can be used in early, accurate preoperative diagnosis.  相似文献   

16.
Finding new uses for existing drugs, or drug repositioning, has been used as a strategy for decades to get drugs to more patients. As the ability to measure molecules in high-throughput ways has improved over the past decade, it is logical that such data might be useful for enabling drug repositioning through computational methods. Many computational predictions for new indications have been borne out in cellular model systems, though extensive animal model and clinical trial-based validation are still pending. In this review, we show that computational methods for drug repositioning can be classified in two axes: drug based, where discovery initiates from the chemical perspective, or disease based, where discovery initiates from the clinical perspective of disease or its pathology. Newer algorithms for computational drug repositioning will likely span these two axes, will take advantage of newer types of molecular measurements, and will certainly play a role in reducing the global burden of disease.  相似文献   

17.
目的:研究连续性血液净化联合血液灌流技术治疗糖尿病肾病合并难治性心衰患者的临床效果。方法:选择我院收治的60例糖尿病肾病合并难治性心衰患者为研究对象,按入院先后顺序随机分为对照组和观察组,每组各30例患者,对照组患者给予常规对症治疗,而观察组患者在常规对症治疗的基础上应用连续性血液净化联合血液灌流技术,比较两组患者的肾、心功能变化和治疗效果。结果:治疗后,观察组的总有效率、好转率及1年存活率均明显高于对照组(P0.05)。对照组患者的肾、心功能指标均较治疗前显著改善(除Scr、E/A),而观察组的各项肾、心功能指标均较治疗前明显改善,且均明显优于对照组,差异均具有统计学意义(P0.05)。结论:连续性血液净化联合血液灌流技术治疗糖尿病肾病合并难治性心衰较常规药物对症治疗更有效。  相似文献   

18.
目的:研究对比阿立哌唑与利培酮治疗难治性精神分裂症(简称难治性精分症)的临床疗效。方法:选择2012年6月至2015年5月在我院接受治疗的难治性精分症患者108例进行研究。根据数字法随机将患者分成观察组及对照组各54例,观察组给予阿立哌唑治疗,对照组给予利培酮治疗,8周后对比两组治疗后的总体疗效,不良反应情况,以及不同时期阴性与阳性症状量表(PANSS)评分值。结果:观察组治疗后的总有效率92.59%,显著高于照组的77.78%(P0.05)。两组治疗1周后~治疗8周后的阳性症状、阴性症状、一般病理及PANSS总分均分别显著低于治疗前的水平(P0.05),且观察组治疗1周后~治疗8周后的阴性症状及PANSS总分均分别显著低于对照组(P0.05)。观察组治疗后的不良反应总发生率为33.33%,显著低于对照组的64.81%(P0.05)。结论:阿立哌唑较利培酮治疗难治性精分症可获得更好的疗效及安全性,建议可在临床进一步研究和推广应用。  相似文献   

19.
MG7-Ag is a human gastric-carcinoma-associated antigen with a high specificity. So far it is remained unclear whether MG7-Ag is correlated with the in vivo cellular immune response of patients with gastric cancer. In this study, we detected the expression of the T cell receptor (TCR) repertoire of T cell subpopulations and cytokines in tumor-infiltrating lymphocytes (TIL), peripheral blood lymphocytes (PBL), and residue benign mucosal lymphocytes (NML) of patients with gastric cancer using semiquantitative RT-PCR. Our data showed that the expanded clones in CD8(+) NML and TIL and CD4+ NML and PBL in MG7-Ag-positive patients were significantly fewer than those of MG7-Ag-negative patients (p = 0.0360; p = 0.0026; p = 0.0065 p = 0.0109, respectively). The levels of IL-8 in CD8(+) TIL and TNF in CD4(+) TIL from the MG7-Ag-positive group were significantly higher than those from the MG7-Ag-negative group (p = 0.0302; p = 0.0177, respectively). Taken together, the results demonstrated a weaker T cell immune response and more proinflammatory cytokine secretion in MG7-Ag-positive patients with gastric cancer than in MG7-Ag-negative ones. This likely contributes to the poor prognosis in MG7-Ag-positive gastric-cancer patients.  相似文献   

20.
《Endocrine practice》2009,15(2):128-133
ObjectiveTo present pathologic and radiographic features of 3 patients with adrenocortical neoplasms—2 with uncertain malignant potential and 1 adenoma with areas of myelolipomatous and lipomatous metaplasia.MethodsWe describe 3 patients who had adrenocortical neoplasms with foci of myelolipomatous and lipomatous metaplasia. For each patient, the clinical and pathologic data are reviewed.ResultsAll 3 patients were women, with a mean age at presentation of 58 years. The lesion size averaged 6.8 cm (range, 3.9 to 11.0), and the mean gland weight was 128.8 g (range, 32.5 to 249). Two patients showed imaging findings compatible with adrenal myelolipoma. Pathologically, 2 of the lesions were classified as adrenocortical neoplasms of uncertain malignant potential, and 1 lesion was classified as an adrenocortical adenoma. All 3 lesions contained myelolipomatous foci throughout the neoplasm, and 2 of the tumors contained several pure lipomatous foci.ConclusionAdrenocortical neoplasms, including those associated with an uncertain malignant potential, may be associated with areas of myelolipomatous and lipomatous metaplasia. Imaging studies may result in a false diagnosis of a benign adrenal myelolipoma and potential undertreatment in such patients. (Endocr Pract. 2009;15:128-133)  相似文献   

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