32 results on '"X. X. Wu"'
Search Results
2. [Sequential infusion of anti-CD22 and anti-CD19 CAR-T cells in the treatment of relapsed / refractory childhood acute B lymphoblastic leukemia: two cases report]
- Author
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J, Zhang, X X, Wu, M Y, Li, B Q, Song, L L, Zhou, X, Kong, H Y, Qiu, and D P, Wu
- Subjects
T-Lymphocytes ,Antigens, CD19 ,Humans ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Child ,Immunotherapy, Adoptive - Published
- 2022
3. [Associations between pre-pregnancy body mass index and occurrence and clinical features of preeclampsia]
- Author
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L L, Wu, Y X, Chen, X N, Guan, J N, Tong, X X, Wu, and J M, Niu
- Subjects
Infant, Newborn ,Pregnancy Outcome ,Infant ,Overweight ,Weight Gain ,Body Mass Index ,Pregnancy Complications ,Pre-Eclampsia ,Pregnancy ,Risk Factors ,Humans ,Female ,Obesity ,Child - Published
- 2021
4. [Radiomics nomogram of MR: a prediction of cervical lymph node metastasis in laryngeal cancer]
- Author
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C L, Jia, Y, Cao, Q, Song, W B, Zhang, J J, Li, X X, Wu, P Y, Yu, Y K, Mou, N, Mao, and X C, Song
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Nomograms ,Lymphatic Metastasis ,Humans ,Lymph Nodes ,Laryngeal Neoplasms ,Retrospective Studies - Published
- 2020
5. Correlation between AT1R gene polymorphism and epilepsy secondary to cerebral infarction
- Author
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L-L, Song, Y-M, Wang, X-X, Wu, L-X, Zhu, F, Pan, and Y-M, Chen
- Subjects
Epilepsy ,Polymorphism, Genetic ,Genotype ,Humans ,Cerebral Infarction ,Middle Aged ,Alleles ,Receptor, Angiotensin, Type 1 - Abstract
To explore the correlation between angiotensin II type 1 receptor (AT1R) gene polymorphism and epilepsy secondary to cerebral infarction and its significance for the diagnosis of this disease.A total of 200 patients with epilepsy secondary to cerebral infarction were enrolled from our hospital as observation group, and 200 patients without epilepsy after cerebral infarction as control group. Genomic deoxyribonucleic acids (DNAs) were extracted from the peripheral blood of the subjects, and the polymorphic regions at AT1R gene loci rs380400, rs1799870, rs12721273, and rs55707609 were amplified via polymerase chain reaction (PCR) and sent to the company for sequencing. The concentration of farnesyl diphosphate synthase (FDPS) was determined using enzyme-linked immunosorbent assay (ELISA) kit, and activated partial thromboplastin time (APTT) and prothrombin time (PT) were measured in the Laboratory Department.There were no differences in the allele distributions at AT1R gene loci rs380400 (p=0.070), rs179987 (p=0.0.280), and rs55707609 (p=0.046), but in the allele distribution at rs12721273 (p=0.001) between control group and observation group, and observation group exhibited a significantly lower frequency of allele G in cerebral infarction patients than control group [153 (0.383) vs. 198 (0.495)]. The frequency of genotype GT at rs12721273 was lower [71 (0.355)] and that of genotype TT was evidently higher [88 (0.440)] in observation group (p=0.000). Control group showed a notably lower frequency of genotype AA [47 (0.235)] and a markedly higher frequency of genotype AT [110 (0.550)] at rs55707609 (p=0.000). Observation group exhibited a substantially lower frequency of recessive model AG+GG [128 (0.640)] (p=0.037), and a notably higher frequency of homozygous model AA [72 (0.360)] (p=0.048) at AT1R gene locus rs380400, a remarkably lower frequency of dominant model GG+GT [112 (0.560)] (p=0.002) at rs12721273, and a significantly lower frequency of recessive model AT+TT [126 (0.630)] (p=0.000) and a considerably lower frequency of heterozygous model AT [84 (0.420)] (p=0.026) at rs55707609. The frequencies of AT1R gene haplotypes ACGA (p=0.001), ACGT (p=0.045), ACTT (p=0.000), ATTT (p=0.048), GCTA (p=0.000), and GTGA (p=0.005) in observation group were distinctly higher than those in control group, and the frequencies of the haplotypes ACTA (p=0.000) and ATTA (p=0.029) were evidently lower than those in control group. The loci rs12721273 and rs1799870 showed a significant association (D'=0.783), and APTT was considerably correlated with genotype AG at rs380400 (p=0.042), PT with genotype CC at rs1799870 (p=0.002) and FDPS with genotype AA at rs55707609 (p=0.015).The polymorphisms of AT1R gene loci rs380400, rs1799870, rs12721273, and rs55707609 are correlated with the susceptibility to epilepsy secondary to cerebral infarction.
- Published
- 2020
6. KLF7 promotes macrophage activation by activating the NF-κB signaling pathway in epicardial adipose tissue in patients with coronary artery disease
- Author
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W-H, Huang, Y-J, Xue, Y-J, Zhou, X-G, Wu, X-X, Wu, X-X, Zhang, X-X, Dong, and Y-T, Wei
- Subjects
Adipose Tissue ,THP-1 Cells ,Macrophages ,Kruppel-Like Transcription Factors ,NF-kappa B ,Humans ,Coronary Artery Disease ,Macrophage Activation ,Middle Aged ,Cells, Cultured ,Signal Transduction - Abstract
Inflammatory accumulation in epicardial adipose tissue (EAT) may influence the formation and development of coronary artery disease (CAD). EAT macrophages exhibit M1 polarization and the secretion of a large number of inflammatory factors in CAD patients. Emerging data demonstrate that Krüppel-like factor-7 (KLF7), contributes to the regulation of adipocyte differentiation and the secretion of adipose tissue inflammation. However, the function of KLF7 in EAT inflammation still remains to be uncovered. This study aims to investigate the role of KLF7 in macrophage activation in EAT.The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in cell supernatant were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels were measured by Real Time-PCR. The protein expression level was detected by Western blot.The expression of inflammatory factors and KLF7 were markedly increased in CAD EAT than non-CAD EAT. KLF7 is highly expressed in human THP-1-derived macrophages induced by inflammatory stimuli, such as LPS. The knockdown of KLF7 inhibited the release of inflammatory factors and significantly decreased the expression of KLF7 in human THP-1-derived macrophages stimulated by LPS. Moreover, transfection with KLF7-siRNA caused the marked inhibition of LPS-induced phosphorylation of JNK-MAPKs and also suppressed the levels of p-p65 and inhibited the activation of p-IκBα.Taken together, these results indicate that KLF7 enhances macrophage activation, mediated by JNK-NF-κB signaling pathways in EAT. This suggests that KLF7 may be a potential therapeutic target for cardiovascular diseases such as CAD.
- Published
- 2020
7. Substrate Diversity of L-Threonic Acid Dehydrogenase Homologs
- Author
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Huang Hongyong, C F Zhang, X X Wu, Liu Yang, and X S Zhang
- Subjects
Threonic acid ,Agrobacterium ,Sequence Homology ,Dehydrogenase ,Reductase ,Biochemistry ,Gluconates ,Sugar acids ,Substrate Specificity ,03 medical and health sciences ,chemistry.chemical_compound ,Xylose metabolism ,Animals ,Humans ,Amino Acid Sequence ,chemistry.chemical_classification ,0303 health sciences ,Xylose ,Catabolism ,030302 biochemistry & molecular biology ,Cupriavidus ,Sugar Acids ,General Medicine ,Isoenzymes ,Metabolic pathway ,Alcohol Oxidoreductases ,Enzyme ,chemistry ,Oxidation-Reduction ,Metabolic Networks and Pathways - Abstract
Despite physiological importance of aldonic sugar acids for living organisms, little is known about metabolic pathways of these compounds. Here, we investigated the functional diversity of homologs of L-threonic acid dehydrogenase (ThrDH; UniProt ID: Q0KBC7), an enzyme composed of two NAD-binding domains (PF14833 and PF03446). Ten ThrDH homologs with different genomic context were studied; seven new enzymatic activities were identified, such as (R)-pantoate dehydrogenase, L-altronic acid dehydrogenase, 6-deoxy-L-talonate dehydrogenase, L-idonic acid dehydrogenase, D-xylonic acid dehydrogenase, D-gluconic acid dehydrogenase, and 2-hydroxy-3-oxopantoate reductase activities. Two associated metabolic pathways were identified: L-idonic acid dehydrogenase was found to be involved in the degradation of L-idonic acid through oxidation/decarboxylation in Agrobacterium radiobacter K84, while 2-hydroxy-3-oxopantoate reductase was found to participate in D-glucarate catabolism through dehydration/cleavage in Ralstonia metallidurans CH34.
- Published
- 2020
8. [Clinical outcomes of hematopoietic stem cell transplantation for angioimmunoblastic T-cell lymphoma]
- Author
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L M, Xu, N N, Li, Z, Wang, X X, Wu, Y J, Dong, X R, Fu, Y, Liu, L D, Hu, X F, Li, Y N, Wang, Y M, Wu, H Y, Ren, M Z, Zhang, M H, Wang, Y H, Li, and W R, Huang
- Subjects
Adult ,Male ,Hematopoietic Stem Cell Transplantation ,造血干细胞移植 ,Lymphoma, T-Cell, Angioimmunoblastic ,Graft vs Host Disease ,Middle Aged ,Survival analysis ,Lymphoma, T-Cell ,Transplantation, Autologous ,生存率分析 ,论著 ,Treatment Outcome ,淋巴瘤,T细胞,血管免疫母细胞性 ,Humans ,Transplantation, Homologous ,Female ,Retrospective Studies - Abstract
目的 分析造血干细胞移植(HSCT)治疗血管免疫母细胞性T细胞淋巴瘤(AITL)的临床疗效。 方法 回顾性分析2007年6月至2017年6月期间在国内八所医院接受HSCT的AITL患者。 结果 共有19例患者纳入本研究,其中男13例,女6例,中位年龄50(32~60)岁;自体造血干细胞移植(auto-HSCT)12例,异基因造血干细胞移植(allo-HSCT)7例(均为同胞全相合供者,其中2例为auto-HSCT后复发患者)。auto-HSCT组移植前疾病处于完全缓解(CR)、部分缓解(PR)状态者分别为5例、7例;allo-HSCT组患者移植前疾病处于PR、疾病进展(PD)状态者分别为2例、3例。失访2例(均为auto-HSCT组),中位随访时间46.5(1~100)个月。allo-HSCT组3例患者发生急性移植物抗宿主病(GVHD)(Ⅰ度2例,Ⅱ度1例),5例发生慢性GVHD(局限型2例,广泛型3例)。auto-HSCT组死亡4例(原发病复发死亡3例),allo-HSCT组死亡3例(移植相关死亡2例,原发病复发死亡1例)。auto-HSCT组(10例)、allo-HSCT组(7例)的3年总生存率分别为56%(95%CI 32%~100%)、57%(95%CI 30%~100%)(P=0.979);3年累积无进展生存率分别为34%(95%CI 14%~85%)、57%(95%CI 30%~100%)(P=0.451)。 结论 auto-HSCT和allo-HSCT均是AITL的有效治疗方法。
- Published
- 2020
9. [A multicenter survey of the accessibility of essential medicines for children in China]
- Author
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Y, Dai, Z P, Li, H, Xu, L, Zhu, Y Q, Zhu, H, Cheng, Z B, Chen, Q Z, Huang, L, Lei, R Q, Li, G, Li, Y, Li, M, Liao, Q H, Lu, X P, Shi, H J, Sun, T L, Shi, X X, Wu, Z S, Wang, J, Xu, G, Zhao, G Y, Zhang, and C, Chen
- Subjects
China ,Cross-Sectional Studies ,Pharmaceutical Preparations ,Drugs, Generic ,Humans ,Child ,Pediatrics ,Drug Costs - Published
- 2020
10. [Evaluation of clinical outcomes of allogeneic hematopoietic stem cell transplantation for relapsed/refractory peripheral T-cell lymphoma with chemoresistance]
- Author
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L, Wang, N N, Li, Z, Wang, X X, Wu, Y J, Dong, X R, Fu, Y, Liu, L D, Hu, X F, Li, Y N, Wang, Y M, Wu, H Y, Ren, M Z, Zhang, M H, Wang, Y H, Li, D H, Liu, and W R, Huang
- Subjects
Drug Resistance, Neoplasm ,Hematopoietic Stem Cell Transplantation ,Graft vs Host Disease ,Humans ,Lymphoma, T-Cell, Peripheral ,Neoplasm Recurrence, Local ,Retrospective Studies - Published
- 2019
11. [The technique and efficacy of complete resection of mesogastrium above the pancreas by the right approach in laparoscopic assisted distal gastrectomy for radical gastrectomy]
- Author
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J, Min, K, Qian, X X, Wu, Z W, Wang, and W, Zhang
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Gastrectomy ,Stomach Neoplasms ,Humans ,Lymph Node Excision ,Laparoscopy ,Mesentery ,Retrospective Studies - Published
- 2018
12. [Association between single nucleotide polymorphism of BARD1 gene and BRCA1 gene mutation in epithelial ovarian cancer]
- Author
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W L, Liu, J Z, Zhao, Z Z, Wang, B, Dong, Y Y, Hou, X X, Wu, and Y J, Guo
- Subjects
Ovarian Neoplasms ,Genotype ,BRCA1 Protein ,Tumor Suppressor Proteins ,Ubiquitin-Protein Ligases ,Genes, BRCA1 ,High-Throughput Nucleotide Sequencing ,Carcinoma, Ovarian Epithelial ,Polymorphism, Single Nucleotide ,Mutation ,Humans ,Female ,Genetic Predisposition to Disease ,Neoplasms, Glandular and Epithelial ,Age of Onset - Published
- 2017
13. Identification of a new HLA-A allele, HLA-A*02:07:09, in a Chinese non-Hodgkin lymphoma patient
- Author
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B-J, Wang, M-R, Huo, D, Li, Y-H, Gao, and X-X, Wu
- Subjects
Base Sequence ,Genotype ,Histocompatibility Testing ,Lymphoma, Non-Hodgkin ,Gene Expression ,Exons ,Sequence Analysis, DNA ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Tissue Donors ,Asian People ,HLA-A2 Antigen ,Humans ,Codon ,Sequence Alignment ,Alleles - Abstract
HLA-A*02:07:09 is different from HLA-A*02:07:01 by a single nucleotide substitution at position 244.
- Published
- 2017
14. [Clinical significance and distribution of BRCA genes mutation in sporadic high grade serous ovarian cancer]
- Author
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W L, Liu, Z Z, Wang, J Z, Zhao, Y Y, Hou, X X, Wu, W, Li, B, Dong, T T, Tong, and Y J, Guo
- Subjects
Adult ,BRCA2 Protein ,Ovarian Neoplasms ,BRCA1 Protein ,Genes, BRCA2 ,Genes, BRCA1 ,Proteins ,Carcinoma, Ovarian Epithelial ,Middle Aged ,Cystadenocarcinoma, Serous ,WAP Four-Disulfide Core Domain Protein 2 ,CA-125 Antigen ,Mutation ,Biomarkers, Tumor ,Humans ,Female ,Neoplasms, Glandular and Epithelial - Published
- 2017
15. Critical genes of hepatocellular carcinoma revealed by network and module analysis of RNA-seq data
- Author
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M-R, Yang, Y, Zhang, X-X, Wu, and W, Chen
- Subjects
Carcinoma, Hepatocellular ,Liver Neoplasms ,Humans ,RNA ,Protein Interaction Maps ,Prognosis ,Nucleophosmin ,Biomarkers ,Genes, Neoplasm - Abstract
RNA-seq data of hepatocellular carcinoma (HCC) was analyzed to identify critical genes related to the pathogenesis and prognosis.Three RNA-seq datasets of HCC (GSE69164, GSE63863 and GSE55758) were downloaded from Gene Expression Omnibus (GEO), while another dataset including 54 HCC cases with survival time was obtained from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) were identified by significant analysis of microarrays (SAM) method using package samr of R. As followed, we constructed a protein-protein interaction (PPI) network based on the information in Human Protein Reference Database (HPRD). Modules in the PPI network were identified with MCODE method using plugin clusterViz of CytoScape. Gene Ontology (GO) enrichment analysis and pathway enrichment analysis were performed with DAVID. The difference in survival curves was analyzed with Kaplan-Meier (K-M) method using package survival.A total of 2572 DEGs were identified in the 3 datasets from GEO (GSE69164, GSE63863 and GSE55758). The PPI network was constructed including 660 nodes and 1008 edges, and 4 modules were disclosed in the network. Module A (containing 244 DEGs) was found to related to HCC closely, which genes were involved in transcription factor binding, protein metabolism as well as regulation of apoptosis. Nine hub genes were identified in the module A, including PRKCA, YWHAZ, KRT18, NDRG1, HSPA1A, HSP90AA1, HSF1, IKGKB and UBE21. The network provides the protein-protein interaction of these critical genes, which were implicated in the pathogenesis of HCC. Survival analysis showed that there is a significant difference between two groups classified by the genes in module A. Further Univariate Cox regression analysis showed that 72 genes were associated with survival time significantly, such as NPM1, PRKDC, SPARC, HMGA1, COL1A1 and COL1A2.Nine critical genes related to the pathogenesis and 72 potential prognostic markers were revealed in HCC by the network and module analysis of RNA-seq data. These findings could improve the understanding of the pathogenesis and provide valuable information to further investigate the prognostic markers of HCC.
- Published
- 2016
16. Annexin A5 anticoagulant activity in children with systemic lupus erythematosus and the association with antibodies to domain I of beta 2-glycoprotein I
- Author
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D M, Wahezi, N T, Ilowite, X X, Wu, L, Pelkmans, B, Laat, L E, Schanberg, J H, Rand, J, Winsor, Promovendi CD, Biochemie, and RS: CARIM School for Cardiovascular Diseases
- Subjects
Male ,Adolescent ,medicine.drug_class ,Immunoglobulin G ,Article ,pediatric lupus ,Young Adult ,Rheumatology ,Antiphospholipid syndrome ,immune system diseases ,medicine ,Beta 2-Glycoprotein I ,Humans ,Lupus Erythematosus, Systemic ,Prospective Studies ,skin and connective tissue diseases ,Child ,beta 2-glycoprotein I ,Lupus anticoagulant ,Lupus erythematosus ,biology ,business.industry ,Anticoagulant ,annexin A5 ,medicine.disease ,Lupus Coagulation Inhibitor ,Immunology ,Multivariate Analysis ,biology.protein ,Antibodies, Antiphospholipid ,Female ,Antibody ,Annexin A5 ,business ,Follow-Up Studies - Abstract
Children with systemic lupus erythematosus (SLE) have a high prevalence of antiphospholipid (aPL) antibodies and are at increased risk for aPL-related thrombosis. We investigated the association between annexin A5 anticoagulant activity and antibodies to the domain I portion of β2-glycoprotein I (anti-DI antibodies), and propose a potential mechanism for the pathogenesis of aPL-related thrombosis. Using samples from 183 children with SLE collected during the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we examined resistance to the anticoagulant effects of annexin A5, using the annexin A5 resistance (A5R) assay, and evaluated for anti-DI IgG antibodies. Children with SLE had higher frequency of anti-D1 antibodies ( p = 0.014) and significantly reduced A5R compared to pediatric controls: mean A5R = 172 ± 30% versus 242 ± 32% ( p
- Published
- 2013
17. Universality analysis of the existence of substantia nigra 'swallow tail' appearance of non-Parkinson patients in 3T SWI
- Author
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P, Gao, P-Y, Zhou, P-Q, Wang, G-B, Zhang, J-Z, Liu, F, Xu, F, Yang, X-X, Wu, and G, Li
- Subjects
Male ,Substantia Nigra ,Humans ,Female ,Parkinson Disease ,Middle Aged ,Magnetic Resonance Imaging ,Sensitivity and Specificity ,Aged - Abstract
To use the 3.0T susceptibility-weighted imaging (SWI) for universality analysis of the "swallow tail" appearance in the substantia nigra of non-Parkinson disease and discuss its lack of the value of imaging diagnosis of Parkinson disease (PD).Take 3.0TMR SWI in 60 PD patients (Group PD) and non-PD volunteers (Group N-PD), on the map of range analyze morphology and number of "swallow tail" appearance in substantia nigra of N-PD group volunteers, and compare the performance image of the corresponding region of the patients in the PD group.After, 15 patients with lesions in the brain stem and significant motion artifacts were excluded. Forty-nine cases of group N-PD (96.08%) had typical "swallow tail" appearance in the bilateral or unilateral substantia nigra compacta posterolateral. All 54 patients with group PD (100%) lacked the "drop" rear elliptical high signal.On the 3.0T SWI range map, the "swallow tail" appearance is ubiquitous in the substantia nigra of patients with non-PD. The deficiency of the signs has high sensitivity and specificity for PD diagnosis.
- Published
- 2016
18. Visualization of nigrosomes-1 in 3T MR susceptibility weighted imaging and its absence in diagnosing Parkinson's disease
- Author
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P, Gao, P-Y, Zhou, G, Li, G-B, Zhang, P-Q, Wang, J-Z, Liu, F, Xu, F, Yang, and X-X, Wu
- Subjects
Male ,Substantia Nigra ,Diffusion Magnetic Resonance Imaging ,Case-Control Studies ,Humans ,Female ,Parkinson Disease ,Signal Processing, Computer-Assisted ,Middle Aged ,Sensitivity and Specificity ,Aged - Abstract
To assess the imaging features of nigrosomes-1 in the substantia nigra through 3T MR susceptibility weighted imaging (SWI) and its disease-specific changes for the diagnosis of Parkinson's disease (PD).A total of 116 subjects were included in this study and allocated into 3 groups: 54 patients diagnosed with PD were assigned to the PD group, 51 age- and sex-matched volunteers without PD served as the control N-PD group, and 11 clinically suspected PD patients were allocated to the undiagnosed (UD) group. All patients received 3.0T superconducting MRI scanning on xxx. The images were analyzed and compared to assess the ability of nigrosomes-1 signals to depict PD pathology.The signals of nigrosomes-1 were strong, droplet-like or oval in shape, and were found in 49 patients from the N-PD group (96.08%), on both sides of the SN (47 cases) and unilaterally (2 cases). In contrast, these signals were absent in all 54 cases from the PD group, and were undetected in 7 out of 11 cases in the UD group, 7 cases without the "drop" and 1 case with narrow strips of hyperintensity were clinically proven to PD, 2 cases with the typical hyperintensity were clinically proven to Parkinson's plus syndrome, 2 cases with slightly wider strip of hyperintensity were less sensitive to the drug levodopa.The absence of typical droplet-like or oval-shaped nigrosomes-1 signals in 3.0T MR SWI may prove useful in identifying PD and Parkinson's syndrome with high sensitivity and specificity.
- Published
- 2015
19. PRESBYOPIA OPTOMETRY METHOD BASED ON DIOPTER REGULATION AND CHARGE COUPLE DEVICE IMAGING TECHNOLOGY
- Author
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Q, Zhao, X X, Wu, J, Zhou, X, Wang, R F, Liu, and J, Gao
- Subjects
Diagnostic Imaging ,Microcomputers ,Humans ,Presbyopia ,Eye ,Optometry - Abstract
With the development of photoelectric technology and single-chip microcomputer technology, objective optometry, also known as automatic optometry, is becoming precise. This paper proposed a presbyopia optometry method based on diopter regulation and Charge Couple Device (CCD) imaging technology and, in the meantime, designed a light path that could measure the system. This method projects a test figure to the eye ground and then the reflected image from the eye ground is detected by CCD. The image is then automatically identified by computer and the far point and near point diopters are determined to calculate lens parameter. This is a fully automatic objective optometry method which eliminates subjective factors of the tested subject. Furthermore, it can acquire the lens parameter of presbyopia accurately and quickly and can be used to measure the lens parameter of hyperopia, myopia and astigmatism.
- Published
- 2015
20. Autologous bone marrow mixed with HLA-haploidentical allogeneic marrow transplantation for treatment of patients with malignant blood diseases
- Author
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S. F. Xu, Yunlong Liu, C. B. Wang, Y. M. Wei, J. Z. Lu, X. X. Wu, Y. L. Wang, J. T. Zhong, H. Bai, W. M. Da, J. M. Chen, Qiang Zhang, and M. J. Ji
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Human leukocyte antigen ,Transplantation, Autologous ,Mice ,HLA Antigens ,Acute lymphocytic leukemia ,Animals ,Humans ,Transplantation, Homologous ,Medicine ,Bone Marrow Transplantation ,Transplantation ,business.industry ,Marrow transplantation ,Histocompatibility Testing ,Hematology ,medicine.disease ,Autologous bone ,Histocompatibility ,Lymphoma ,Treatment Outcome ,Hematologic Neoplasms ,Immunology ,Female ,business - Abstract
We have previously demonstrated that syngeneic marrow mixed with H-2 haploidentical marrow transplantation could provide not only protection against graft-versus-host disease (GVHD) but also anti-leukemic (GVL) effects in mice. In the present studies, we report clinical observations using autologous marrow mixed with HLA-haploidentical allogeneic marrow transplantation for treatment of patients with malignant blood diseases. Sixteen cases, including 12 with acute leukemia and four with advanced malignant lymphoma, were treated by autologous marrow, which was purged in vitro by hyperthemia (42.5 degrees C for 70 min) following incubation for 5 days with interleukin 2 (IL-2) in liquid culture and mixed with HLA haploidentical marrow cells from their sibling or parent. Acute GVHD was not observed in any patient after transplantation. Hematological rescue in the clinical setting was demonstrated in all cases but one who died early from hepatic veno-occlusive disease (VOD). Five cases who were transplanted at the time of CR2 or CR3 and in advanced phase of lymphoma, relapsed 4 to 7 months after transplantation. The relapse rate was 31.3%. None of eight patients who received allogeneic BMT within 2 h after ABMT relapsed with median follow-up of 12 months and two of them died from procedure-related complications. Seven cases are still alive and disease-free with a median follow-up of 12 months. Mixed chimerism was found in 3/6 cases, who had different sex donors, by analysis of sex chromosomes. These results show that mixed transplantation is a safe, effective and new approach to treating patients with malignant tumors. In order to detect the effects of GVL, studies are now in progress in our clinic.
- Published
- 1997
21. Monoclonal antibody to tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) induces apoptosis in primary renal cell carcinoma cells in vitro and inhibits tumor growth in vivo
- Author
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X. X. Wu, Vivian R. Albert, Y. Zeng, Michele Fiscella, Yoshiyuki Kakehi, Osamu Shimada, and Robin Humphreys
- Subjects
Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Programmed cell death ,Cell Survival ,Cell ,Cell Culture Techniques ,Mice, Nude ,Apoptosis ,Mice, SCID ,Biology ,urologic and male genital diseases ,Receptors, Tumor Necrosis Factor ,TNF-Related Apoptosis-Inducing Ligand ,Mice ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Enzyme Inhibitors ,Receptor ,Carcinoma, Renal Cell ,Cell Membrane ,Antibodies, Monoclonal ,Cell cycle ,Caspase Inhibitors ,Xenograft Model Antitumor Assays ,Kidney Neoplasms ,Receptors, TNF-Related Apoptosis-Inducing Ligand ,medicine.anatomical_structure ,Oncology ,Cell culture ,Caspases ,Monoclonal ,Cancer research ,Tumor necrosis factor alpha - Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in a variety of tumor cells through two of its receptors: TRAIL-R1 and TRAIL-R2. We investigate the susceptibility of human renal cell carcinoma (RCC) cells to TRM-1 and HGS-ETR2, 2 human monoclonal agonistic antibodies specific for TRAIL-R1 and TRAIL-R2, respectively. HGS-ETR2 effectively induced apoptotic cell death in 10 of 11 cell cultures, including 2 human RCC cell lines and 9 human primary RCC cell cultures, with a more pronounced effect after preincubation with anti-human IgG Fc. In contrast, TRM-1 was effective in only 1 primary RCC cell culture. The increased effectiveness of HGS-ETR2 for inducing cell death might have been affected by differences in the cell-surface expression of the 2 TRAIL receptors, namely that TRAIL-R2 but not TRAIL-R1 was frequently expressed in most of the RCC cells tested. The activities of caspase-9, -8, -6, and -3 were increased with HGS-ETR2-induced apoptosis, and cell death could be blocked by specific caspase inhibitors for caspase-9, -8, and -3, and the general caspase inhibitor. In vivo administration of HGS-ETR2 with or without cross-linker significantly suppressed tumor growth of subcutaneously inoculated human RCC xenografts in immunodeficient mice. These results suggest the potential utility of TRAIL-R2 antibody as a novel therapeutic agent in RCC.
- Published
- 2006
22. Enhancement of arsenic trioxide-induced apoptosis in renal cell carcinoma cells by L-buthionine sulfoximine
- Author
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X X, Wu, O, Ogawa, and Y, Kakehi
- Subjects
Apoptosis ,Drug Synergism ,Oxides ,Vinblastine ,Glutathione ,Arsenicals ,Kidney Neoplasms ,Arsenic Trioxide ,Doxorubicin ,Caspases ,Antineoplastic Combined Chemotherapy Protocols ,Tumor Cells, Cultured ,Humans ,Fluorouracil ,Buthionine Sulfoximine ,Carcinoma, Renal Cell ,Oxidation-Reduction ,Cell Division ,Glutathione Transferase - Abstract
Arsenic trioxide (As2O3) induces clinical remission in acute promyelocytic leukemic patients and apoptosis in various tumor cells in vitro. To develop As2O3-based combination chemotherapy for renal cell carcinoma (RCC), we investigated the cytotoxic effects of As2O3 in combination with chemotherapeutic agents or L-buthionine sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor. Cytotoxicity and synergy were assessed by the MTT assay and isobolographic analysis, respectively. Apoptosis was monitored by Hoechst 33342 staining, flow cytometrical analysis, and DNA fragmentation assay. Treatment of ACHN cells with As2O3 in combination with adriamycin, vinblastine, or 5-fluorouracil induced an antagonistic effect. However, combination treatment with As2O3 and BSO resulted in a synergistic cytotoxic effect. Synergy was also obtained in Caki-1, Caki-2, NC65 cells and freshly derived RCC cells from 6 patients. Simultaneous treatment of ACHN cells with As2O3 and BSO caused significantly more cytotoxicity than the As2O3 first BSO second or the reverse treatment. We further explored the mechanisms underlying this synergistic effect and found that the synergistic cytotoxicity of As2O3 and BSO was realized by inducing apoptosis. This combination markedly decreased intracellular GSH content and GSH-S-transferase (GST) activity. However, neither the intracellular GSH nor GST was decreased by As2O3 with adriamycin, vinblastine, or 5-fluorouracil. Furthermore, the GSH-increasing agents N-acetylcysteine and lipoic acid significantly inhibited the combined cytotoxicity of As2O3 and BSO. These findings indicate that BSO sensitizes RCC cells to As2O3-induced apoptosis through the down-regulation of the intracellular GSH redox system, suggesting the potential application of a combination of As2O3 and BSO for the treatment of RCC.
- Published
- 2004
23. [A case of strongyloidiasis]
- Author
-
Z X, Zheng and X X, Wu
- Subjects
Male ,Strongyloidiasis ,Humans ,Aged - Published
- 2003
24. Detection of circulating cancer cells by reverse transcription-polymerase chain reaction for uroplakin II in peripheral blood of patients with urothelial cancer
- Author
-
J J, Lu, Y, Kakehi, T, Takahashi, X X, Wu, T, Yuasa, T, Yoshiki, Y, Okada, T, Terachi, and O, Ogawa
- Subjects
Adult ,Aged, 80 and over ,Male ,Carcinoma, Transitional Cell ,Urologic Neoplasms ,Reverse Transcriptase Polymerase Chain Reaction ,Membrane Proteins ,Middle Aged ,Neoplastic Cells, Circulating ,Sensitivity and Specificity ,Kidney Neoplasms ,Urinary Bladder Neoplasms ,Lymphatic Metastasis ,Uroplakin II ,Biomarkers, Tumor ,Carcinoma, Squamous Cell ,Humans ,Female ,RNA, Messenger ,Neoplasm Metastasis ,Carcinoma, Renal Cell ,Aged - Abstract
Few attempts have been made at the molecular detection of urothelial cancer cells in the blood or lymph nodes mainly because of an absence of good candidate molecular or genetic changes specific to urothelial cancer or urothelium. In 1990, however, genes that encode urothelium-specific transmembrane proteins, uroplakins (UPs), were cloned. We have established a method of detecting circulating cancer cells in peripheral blood of patients with transitional cell carcinoma by nested reverse transcription-PCR assay for UP II. UP II mRNA-positive cells were detected in 3 (10.3%) of 29 patients with superficial cancers (pTa-1N0M0), 4 (28.6%) of 14 patients with muscularly invasive cancers (pT2-4N0M0), 2 (40.0%) of 5 loco-regional node-positive patients (pN1-2M0), and 6 (75.0%) of 8 patients with distant metastases. Positive rates, therefore, increased with tumor extension (P = 0.0033, Kruskal-Wallis test). Furthermore, sequential blood sampling was performed in three patients with metastases during and after systemic chemotherapy, and UP-II-positive cells were found to have disappeared in two patients who responded well to the systemic chemotherapy. These results suggest that our nested reverse transcription-PCR assay for UP II is highly specific and might be used as a tumor marker for molecular staging of urothelial cancers, although the sensitivity is not so optimal.
- Published
- 2000
25. Enhancement of Fas-mediated apoptosis in renal cell carcinoma cells by adriamycin
- Author
-
X X, Wu, Y, Mizutani, Y, Kakehi, O, Yoshida, and O, Ogawa
- Subjects
Antimetabolites, Antineoplastic ,Time Factors ,Antineoplastic Agents ,Vinblastine ,Interferon-gamma ,Lymphocytes, Tumor-Infiltrating ,Proto-Oncogene Proteins ,Tumor Cells, Cultured ,Humans ,Drug Interactions ,fas Receptor ,Carcinoma, Renal Cell ,Epirubicin ,Fluorescent Dyes ,bcl-2-Associated X Protein ,Antibiotics, Antineoplastic ,Dose-Response Relationship, Drug ,Caspase 3 ,Interferon-alpha ,Antineoplastic Agents, Phytogenic ,Immunohistochemistry ,Acridine Orange ,Kidney Neoplasms ,Proto-Oncogene Proteins c-bcl-2 ,Doxorubicin ,Caspases ,Fluorouracil ,Tumor Suppressor Protein p53 - Abstract
Anti-Fas monoclonal antibody (mAb) kills Fas-expressing cells by apoptosis. Several anticancer agents also mediate apoptosis and may share common intracellular pathways leading to apoptosis with Fas. Thus, we reasoned that combination treatment of drug-resistant cells with anti-Fas mAb and drugs might overcome their resistance. We investigated whether anticancer agents enhance Fas-mediated apoptosis and cytotoxicity against renal cell carcinoma (RCC) cells. Treatment of ACHN RCC cells with anti-Fas mAb in combination with 5-fluorouracil, vinblastine, IFN-alpha, or IFN-gamma did not overcome resistance to these agents. However, combination treatment with anti-Fas mAb and Adriamycin (ADR) resulted in a synergistic cytotoxic effect. Furthermore, synergy was also obtained even when the exposure time was shortened from 24 h to 8 or 2 h. Synergy was also achieved in four other RCC cell lines and five freshly derived human RCC cells. Treatment with anti-Fas mAb in combination with epirubicin or pirarubicin also resulted in a synergistic cytotoxic effect on ACHN cells. Similar results were achieved with a combination of humanized anti-Fas mAb and ADR. Incubation of ACHN cells with ADR augmented the expression of Fas and p53, but not Bcl-2, Bax, or caspase-3. However, the activity of caspase-3 itself was apparently enhanced after treatment with ADR alone or combined treatment with anti-Fas mAb. The synergy obtained in cytotoxicity with anti-Fas mAb and ADR was also achieved in apoptosis. Exposure of ACHN cells and freshly derived RCC cells to ADR enhanced their susceptibility to lysis by peripheral blood lymphocytes and tumor-infiltrating lymphocytes. This study demonstrates that combination treatment of RCC cells with anti-Fas mAb and ADR might overcome their resistance. The sensitization required a low concentration of ADR and a short exposure time, thus supporting the potential in vivo application of a combination of ADR and anti-Fas mAb or immunotherapy in the treatment of ADR- and/or immunotherapy-resistant RCC.
- Published
- 2000
26. Antibody-mediated disruption of the annexin-V antithrombotic shield: a new mechanism for thrombosis in the antiphospholipid syndrome
- Author
-
J H, Rand and X X, Wu
- Subjects
Animals ,Humans ,Thrombosis ,Annexin A5 ,Antiphospholipid Syndrome - Published
- 1999
27. A possible solution to the paradox of the 'lupus anticoagulant': antiphospholipid antibodies accelerate thrombin generation by inhibiting annexin-V
- Author
-
J H, Rand, X X, Wu, and P, Giesen
- Subjects
Lupus Coagulation Inhibitor ,Antibodies, Antiphospholipid ,Thrombin ,Humans ,Annexin A5 ,Antiphospholipid Syndrome - Published
- 1999
28. Chemoimmunosensitization of the T24 human bladder cancer line to Fas-mediated cytotoxicity and apoptosis by cisplatin and 5-fluorouracil
- Author
-
T Shirasaka, X X Wu, Osamu Yoshida, B Bonavida, and Y Mizutani
- Subjects
inorganic chemicals ,Cytotoxicity, Immunologic ,Cancer Research ,medicine.medical_treatment ,Antineoplastic Agents ,Apoptosis ,Tumor Cells, Cultured ,Medicine ,Cytotoxic T cell ,Humans ,fas Receptor ,Cytotoxicity ,neoplasms ,Cisplatin ,Bladder cancer ,business.industry ,Cancer ,Antibodies, Monoclonal ,Drug Synergism ,General Medicine ,Immunotherapy ,medicine.disease ,female genital diseases and pregnancy complications ,Cell killing ,Oncology ,Urinary Bladder Neoplasms ,Drug Resistance, Neoplasm ,Immunology ,Cancer research ,Drug Therapy, Combination ,Fluorouracil ,business ,medicine.drug - Abstract
Previous studies have demonstrated that cisplatin (CDDP) sensitizes bladder cancer cells to Fas-mediated cytotoxicity and that CDDP also enhances the cytotoxic effect of 5-fluorouracil (5-FU). These agents mediate apoptosis and may share common intracellular pathways leading to cell killing. We reasoned that combination treatment with CDDP, 5-FU and anti-Fas monoclonal antibody (mAb) might overcome the drug-resistance. We investigated whether CDDP, 5-FU and anti-Fas mAb synergize in cytotoxicity and apoptosis against the T24 bladder cancer line. Cytotoxicity was monitored by a one day microculture tetrazolium dye assay. Treatment of T24 cells with anti-Fas mAb in combination with CDDP or 5-FU resulted in a synergistic cytotoxic effect. In addition, combination treatment of T24 cells with CDDP, 5-FU and anti-Fas mAb further enhanced the synergistic cytotoxicity achieved by two agents. The synergy achieved in cytotoxicity with CDDP, 5-FU and anti-Fas mAb was also achieved in apoptosis. The current study demonstrates that combination treatment of bladder cancer cells with CDDP, 5-FU and anti-Fas mAb overcomes their resistance. In addition, the sensitization required low concentrations of CDDP and 5-FU, and thus supporting the potential in vivo application of combination of CDDP, 5-FU and immunotherapy in the treatment of drug-resistant bladder cancer.
- Published
- 1999
29. [Expression of major histocompatibility complex antigens and adhesion molecules on renal cell carcinoma cells, and effect of interferon-alpha and/or cimetidine on the expression]
- Author
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X X, Wu, Y, Mizutani, Y, Kakehi, E, Nakamura, K, Mitsumori, T, Takahashi, T, Terachi, Y, Okada, and O, Yoshida
- Subjects
Cytotoxicity, Immunologic ,Adjuvants, Immunologic ,Histocompatibility Antigens Class I ,Tumor Cells, Cultured ,Humans ,Interferon-alpha ,Antineoplastic Agents ,Cimetidine ,Intercellular Adhesion Molecule-1 ,Carcinoma, Renal Cell ,Kidney Neoplasms ,T-Lymphocytes, Cytotoxic - Abstract
Recently the combined therapy with interferon-alpha (IFN-alpha) and cimetidine has been reported to be effective against advanced renal cell carcinoma (RCC). IFN-alpha and cimetidine have an antitumor effect partly due to enhancement of cytotoxic activity of lymphocytes against cancer cells. We examined the expression of major histocompatibility complex (MHC) antigens and adhesion molecules on 4 fresh RCC cells and 5 RCC cultured cell lines, which have an important role in recognition and killing of cytotoxic lymphocytes against cancer cells. The effect of treatment with IFN-alpha and/or cimetidine on the expression of MHC antigens and adhesion molecules on RCC cells was also investigated. MHC class I and leukocyte function-associated antigen-3 (LFA-3) were expressed on all RCC cells, but not MHC class II. Intercellular adhesion molecule-1 (ICAM-1) and B7 were expressed on 6 and 5 of 8 RCC cells, respectively. IFN-alpha significantly augmented the expression of MHC class I in 6 of 9 RCC cells, ICAM-1 in 1 and LFA-3 in 2 of 8 RCC cells. However, IFN-alpha did not affect the expression of MHC class II and B7. On the other hand, cimetidine enhanced the expression of LFA-3 in 2 of 8 RCC cells, but not MHC antigens, ICAM-1 or B7. The combination of IFN-alpha and cimetidine did not show a synergistic enhancing effect on the expression of MHC antigens, ICAM-1, LFA-3 or B7. These results suggest that IFN-alpha augments the sensitivity of RCC cells to lysis by cytotoxic lymphocytes partly due to the enhancement of expression of MHC class I, ICAM-1 and LFA-3 on RCC cells, and that cimetidine also augments the susceptibility of RCC cells to lymphocytes by the enhanced expression of LFA-3 on RCC cells.
- Published
- 1998
30. Antiphospholipid antibodies accelerate plasma coagulation by inhibiting annexin-V binding to phospholipids: a 'lupus procoagulant' phenomenon
- Author
-
J H, Rand, X X, Wu, H A, Andree, J B, Ross, E, Rusinova, M G, Gascon-Lema, C, Calandri, and P C, Harpel
- Subjects
Blood Platelets ,Lipid Bilayers ,Phosphatidylserines ,Thromboplastin ,Immunoglobulin G ,Lupus Coagulation Inhibitor ,Antibodies, Antiphospholipid ,Prothrombin Time ,Humans ,Indicators and Reagents ,Partial Thromboplastin Time ,Annexin A5 ,Blood Coagulation ,Fluorescein-5-isothiocyanate ,Phospholipids ,Fluorescent Dyes - Abstract
The antiphospholipid syndrome is a thrombophilic condition marked by antibodies that recognize anionic phospholipid-protein cofactor complexes. We recently reported that exposure to IgG fractions from antiphospholipid patients reduces the level of annexin-V, a phospholipid-binding anticoagulant protein, on cultured trophoblasts and endothelial cells and accelerates coagulation of plasma exposed to these cells. Therefore, we asked whether antiphospholipid antibodies might directly reduce annexin-V binding to noncellular phospholipid substrates. Using ellipsometry, we found that antiphospholipid IgGs reduce the quantity of annexin-V bound to phospholipid bilayers; this reduction is dependent on the presence of beta2-glycoprotein I. Also, exposure to plasmas containing antiphospholipid antibodies reduces annexin-V binding to phosphatidyl serine-coated microtiter plates, frozen thawed washed platelets, activated partial thromboplastin time (aPTT) reagent and prothrombin time reagent and reduces the anticoagulant effect of the protein. These studies show that antiphospholipid antibodies interfere with the binding of annexin-V to anionic phospholipid and with its anticoagulant activity. This acceleration of coagulation, due to reduced binding of annexin V, stands in marked contrast to the "lupus anticoagulant effect" previously described in these patients. These results are the first direct demonstration of the displacement of annexin-V and the consequent acceleration of coagulation on noncellular phospholipid surfaces by antiphospholipid antibodies.
- Published
- 1998
31. The significance of subendothelial von Willebrand factor
- Author
-
J H, Rand, R W, Glanville, X X, Wu, J M, Ross, M, Zangari, R E, Gordon, E, Schwartz, and B J, Potter
- Subjects
Blood Platelets ,Binding Sites ,von Willebrand Factor ,Animals ,Humans ,Endothelium, Vascular ,Extracellular Matrix - Abstract
von Willebrand factor (vWf) serves to bridge between receptors on the platelet cytoplasmic membrane and the extracellular matrix. In addition to circulating in plasma, vWf is deposited into the extracellular matrix of the subendothelium where it is associated with type VI collagen microfibrils, but not with the elastin-associated microfibrils which are present in the deepest portion of the subendothelium at the zone of the internal elastic lamina. The reaction of platelets to type VI collagen in flow systems is qualitatively different from the shear rate dependent adhesion and aggregation response which is observed with fibrillar type I collagen, exhibiting a response only at low shear rates. The adhesion response to type VI collagen is dependent upon vWf, GP Ib and the GP IIb-IIIa complex. Platelets exposed to purified fibrillin-containing elastin-associated microfibrils adhere and aggregate at low shear rates; this response appears to involve GP IIb-IIIa but not GP Ib. The data are consistent with the hypothesis that type VI collagen is a physiologically relevant binding site for vWf in subendothelium.
- Published
- 1997
32. [Dig-DNA probe for etiologic diagnosis in tuberculosis patients]
- Author
-
S N, Wei, P, Yang, and X X, Wu
- Subjects
DNA, Bacterial ,Base Sequence ,Molecular Sequence Data ,Sputum ,Humans ,Mycobacterium tuberculosis ,DNA Probes ,Sensitivity and Specificity ,Tuberculosis, Pulmonary - Abstract
We have detected the sputa DNA with nonradioactive probe which is labelled to the specific sequence DNA, 31bp-188bp, by dig-11-dUTP. It showed that both the Sensitivity and specificity are satisfactory. The positive rate of the 80 specimens are 56.25%, and the 30 positive specimens of sputum culture are all positive when detected by the Dig-DNA probe.
- Published
- 1993
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