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1.
Br J Ophthalmol ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519547

RESUMO

BACKGROUND: Bestrophin-1 (BEST1) gene is associated with a wide range of ocular phenotypes, collectively termed as bestrophinopathy. The aim of the current study was to identify the mutation spectrum of BEST1 in a large cohort of Chinese patients with bestrophinopathy. METHODS: Patients clinically suspected of bestrophinopathy were screened using multigene panel testing. All BEST1 variants were confirmed by Sanger sequencing, and validated in the families. FINDINGS: A total of 92 patients (Best vitelliform macular dystrophy (BVMD)=77; autosomal recessive bestrophinopathy (ARB)=15) from 58 unrelated families of Chinese origin and their available family members (n=65) were recruited. Overall, 39 distinct disease-causing BEST1 variants were identified, including 13 novel variants, and two reported variants but novel for ARB. Of them, 14 were associated with ARB, 23 with BVMD and two (c.604C>T and c.898G>A) with both BVMD and ARB. Most mutations associated with BVMD were missense (97.78%), while ARB was associated with more complex mutations, including missense (88.46%), splicing effect (3.85%), and frameshifts (15.38%). BEST1 hotspots were c.898G>A and c.584C>T among BVMD and ARB patients, respectively. Hot regions were located in exons 8, 2 and 6 in BVMD patients, and in exons 5 and 7 in ARB patients. The overall penetrance of BEST1 in our cohort was 71.30%, no de novo mutations were identified. CONCLUSION: This is the largest study to date that provides major population-based data of the BEST1 mutation spectrum in China. Our results can serve as a well-founded reference for genetic counselling for patients with bestrophinopathy of Chinese origin.

2.
Ophthalmology ; 126(11): 1549-1556, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31054281

RESUMO

PURPOSE: To characterize the genetic landscape of patients with suspected retinitis pigmentosa (RP) in the Chinese population. DESIGN: Cohort study. PARTICIPANTS: A total of 1243 patients of Chinese origin with clinically suspected RP and their available family members (n = 2701) were recruited. METHODS: All patients and available family members were screened using multigene panel testing (including 586 eye disease-associated genes), followed by clinical variant interpretation. MAIN OUTCOME MEASURES: Diagnostic yield, the 17 most commonly implicated genes, age at onset, de novo mutations, and clinical usefulness of genetic testing. RESULTS: Overall, 72.08% of patients received a molecular diagnosis, and the 17 top genes covered 75.63% of diagnostic cases. Diagnostic yield was higher among patients in the early-onset subgroup (≤5 years old, 79.58%) than in the childhood or adolescence-onset subgroup (6-16 years old, 73.74%) and late-onset subgroup (≥17 years old, 65.99%). Moreover, different genes associated with different onset ages and subgroups with different onset ages showed a diverse mutation spectrum. Only 11 de novo mutations (3.18%) were identified. Furthermore, 16.84% of the patients who received a molecular diagnosis had refinement of the initial clinical diagnoses, and the remaining 83.16% received definite genetic subtypes of RP. CONCLUSIONS: This large cohort study provides population-based data of the genome landscape of patients with suspected RP in China. The diagnostic yield was significantly higher than that in previous studies, and the mutation spectrum is completely different with other populations. Genetic testing improves the chance to establish a precise diagnosis, identifies features not previously determined, and allows a more accurate refinement of risk to family members. Our results not only expand the existing genotypic spectrum but also serve as an efficient reference for the design of panel-based genetic diagnostic testing and genetic counseling for patients with suspected RP in China.

3.
Spine (Phila Pa 1976) ; 43(6): E348-E356, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28742761

RESUMO

STUDY DESIGN: Prospective trial. OBJECTIVE: To establish an individualized navigation template for safe and accurate insertion of lower cervical anterior transpedicular screw (ATPS) based on a three-dimensional (3D) printing technique. SUMMARY OF BACKGROUND DATA: Conventional screw insertion manually under fluoroscopy easily leading to deviation of ATPS screw channel, cervical instrumentation procedures demand the need for a precise technique for screw placement. METHODS: Twenty adult cervical spine specimens (10 men and 10 women, with a mean age of 50.29 ±â€Š6.98) were selected for computed tomography pre- and postoperatively. A 3D lower cervical spine model was reconstructed using Mimics software to measure the screw-related parameters and generate a reverse template with optimal screw channel as well as a prototype using 3D printing. Assisted by the navigation template, bilateral ATPS were inserted into the cadavers. RESULTS: The mean outer width and height of pedicle were 5.31 ±â€Š1.23 and 6.78 ±â€Š1.10 mm, respectively. The average length, sagittal, and axial angles of the optimal screw channel obtained through the optimal entry point were 36.34 ±â€Š4.39 mm, 40.67°â€Š±â€Š5.10°, and 93.7°â€Š±â€Š7.96°, respectively. The adjustable safe ranges of sagittal and axial angles were 3.89°â€Š±â€Š1.13° and 5.64°â€Š±â€Š0.97°, respectively. The axial and sagittal accuracies of the 200 screws were 99.5% and 97%, respectively. The average deviations of the actual entry point and the preset opening in the X, Y, and Z axes were 0.39 ±â€Š0.43, 0.21 ±â€Š0.41, and 0.29 ±â€Š0.14 mm, respectively (P > 0.05). CONCLUSION: An individualized ATPS navigation template was developed using Mimics software and 3D printing prototyping, based on computed tomography, for highly accurate screw insertion. LEVEL OF EVIDENCE: 4.


Assuntos
Parafusos Ósseos , Vértebras Cervicais/cirurgia , Pescoço/cirurgia , Impressão Tridimensional , Adulto , Idoso , Cadáver , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Software , Tomografia Computadorizada por Raios X/métodos
4.
Zhongguo Gu Shang ; 29(3): 248-51, 2016 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-27149795

RESUMO

OBJECTIVE: To evaluate the clinical effects of iliolumbar fixation for the sacrum fractures of Denis type II. METHODS: The clinical data of 86 patients with sacrum fracture of Denis type II treated by iliolumbar fixation from January 2008 to January 2012 were retrospectively analyzed. There were 55 males and 31 females, aged from 17 to 55 years old with an average of 39.1 years. Among them, 73 cases complicated with pelvis fracture and 13 cases with acetabular fracture; 37 cases with sacral neurological symptoms and 49 cases without sacral neurological symptoms. Fracture healing time, nerve function, clinical function and complications were observed in the patients. RESULTS: In 86 cases, 6 cases were out of followed-up and 80 cases were followed up from 24 to 71 months with an average of 36 months. The mean fracture healing time was 13 weeks (ranged, 10 to 38 weeks). According to Gibbons scoring to evaluate the neurological function, preoperative nerve rehabilitation, lower limbs feeling, lower limbs activity,bladder and rectum function,total score respectively were 0.62 +/- 0.04, 1.54 +/- 0.35, 1.12 +/- 0.18, 0.23 +/- 0.01, 3.46 +/- 0.47 and postoperative respectively were 0.82 +/- 0.12, 0.36 +/- 0.04, 0.05 +/- 0.01, 0.03 +/- 0.01, 1.25 +/- 0.22, there were statistically significant differences between preoperative and postoperative (P < 0.05). According to Majeed scoring to evaluate the clinical function, postoperative pain, standing, sitting, sexual life, work ability, total score respectively were 22.54 +/- 4.02, 27.93 +/- 5.46, 8.47 +/- 3.61, 2.54 +/- 1.33, 16.46 +/- 4.34, 81.32 +/- 8.73, 60 cases got excellent results, 17 good, 3 fair. The main complications including fracture nonunion of 5 cases,deep incision infection of 1 case, and screw prominence resulting uncomfortable of 8 cases. CONCLUSION: Iliolumbar fixation has the advantages of stable fixation, satisfactory functional rehabilitation, less complications, and is a good method in treating sacrum fracture of Denis type II.


Assuntos
Sacro/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Adolescente , Adulto , Parafusos Ósseos , Feminino , Fixação Interna de Fraturas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sacro/lesões , Resultado do Tratamento , Adulto Jovem
5.
Neural Regen Res ; 10(8): 1286-91, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26487857

RESUMO

In this study, we investigated the effect of an antibody against E3 ubiquitin ligase seven in absentia homolog 1 (SIAH-1) in PC12 cells. 1-Methyl-4-phenylpyridinium (MPP(+)) treatment increased α-synuclein, E1 and SIAH-1 protein levels in PC12 cells, and it reduced cell viability; however, there was no significant change in light chain 3 expression. Treatment with an SIAH-1 antibody decreased mRNA expression levels of α-synuclein, light chain 3 and SIAH-1, but increased E1 mRNA expression. It also increased cell viability. Combined treatment with MPP(+) and rapamycin reduced SIAH-1 and α-synuclein levels. Treatment with SIAH-1 antibody alone diminished α-synuclein immunoreactivity in PC12 cells, and reduced the colocalization of α-synuclein and light chain 3. These findings suggest that the SIAH-1 antibody reduces the monoubiquitination and aggregation of α-synuclein, promoting its degradation by the ubiquitin-proteasome pathway. Consequently, SIAH-1 may be a potential new therapeutic target for Parkinson's disease.

6.
Int J Clin Exp Pathol ; 8(10): 12885-92, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26722480

RESUMO

Seven in absentia homolog (SIAH) is a ubiquitin ligase that monoubiquitinates α-synuclein. Lewy bodies are characteristically rich in monoubiquitinated α-synuclein. We aimed to determine the effect of siRNA-SIAH1 on α-synuclein autophagy and UPS degradation in SH-SY5Y. SIAH1 expression was measured with real-time quantitative PCR and Western Blot. Cell proliferation was measured by CCK-8 assay; cell apoptosis assayed by flow cytometry. Relative protein expressions were measured by Western Blot. mRNA levels of relative protein were measured by real-time quantitative PCR. The expression of α-synuclein, LC3-II and SIAH1 were observed by confocal microscopy. We found: (1) Transfection efficiency of SIAH1-siRNA into SH-SY5 measured approximately 89% by flow cytometry. (2) siRNA silencing of SIAH1 promoted cellular proliferation and suppressed apoptosis. (3) Protein and mRNA expression of α-synuclein, LC3-II and p53 decreased after SIAH1 knockdown. E1 protein and mRNA levels increased after SIAH1 siRNA. These data show silencing SIAH1 increased cell proliferation and inhibited apoptosis in SH-SY5Y neuroblastoma cells. SIAH1 knockdown enhanced the clearance of non-aggregated α-synuclein by UPS. SIAH1 is a potential target for treatment of Parkinson's disease.


Assuntos
Apoptose/genética , Proliferação de Células/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Nucleares/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , alfa-Sinucleína/metabolismo , Linhagem Celular Tumoral , Inativação Gênica , Humanos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Nucleares/genética , Ubiquitina-Proteína Ligases/genética
7.
Zhonghua Yan Ke Za Zhi ; 47(1): 27-34, 2011 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-21418924

RESUMO

OBJECTIVE: To investigate the characteristics of fundus fluorescein angiography (FFA) in metastatic choroidal carcinomas and determine the value of FFA in differentiating metastatic choroidal carcinomas from primary choroidal melanomas. METHODS: It was a retrospective case series. The retrospective analysis of clinical data and FFA findings was performed in 23 eyes of 22 patients with metastatic choroidal carcinomas and 31 eyes of 31 patients with primary choroidal melanomas as the control. RESULTS: Ocular fundus findings of metastatic choroidal carcinomas were divided into three types: solitary flat (tumor thickness less than 3 mm), solitary elevated (tumor thickness more than 3 mm) or diffuse type. FFA of the three types showed hypofluorescence during the arterial phase and progressive hyperfluorescence during the subsequent phases. The border of the lesions revealed retinal capillary dilation during the arteriovenous phase and persistent pinpoint leakage throughout the angiogram. Retinal capillary dilation and pinpoint leakage were more frequently presented in the solitary flat type. Simultaneous visualization of retinal and tumor circulation (the so called double circulation) was more frequently presented in the solitary elevated type. Pinpoint leakage could be detected in 17 (73.91%) eyes of metastatic choroidal carcinomas and in 5 (16.13%) eyes of primary choroidal melanomas. The difference between the visibility of pinpoint leakage in metastatic choroidal carcinomas and primary choroidal melanomas was statistically significant (P = 0.0000). When pinpoint leakage of FFA was used to differentiate metastatic choroidal carcinomas from primary choroidal melanomas, the sensitivity, specificity, accuracy, positive and negative predictive values were 73.91%, 83.87%, 79.63%, 77.27%, 81.25% respectively. CONCLUSIONS: FFA is helpful for the diagnosis of metastatic choroidal carcinomas. Pinpoint leakage on the border of lesions has some value in differentiating metastatic choroidal carcinomas from primary choroidal melanomas.


Assuntos
Carcinoma/diagnóstico por imagem , Neoplasias da Coroide/diagnóstico por imagem , Melanoma/diagnóstico por imagem , Adolescente , Adulto , Idoso , Neoplasias da Coroide/secundário , Diagnóstico Diferencial , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Radiografia , Estudos Retrospectivos , Adulto Jovem
8.
Zhonghua Yan Ke Za Zhi ; 44(4): 321-6, 2008 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-18844018

RESUMO

OBJECTIVE: To describe clinical phenotype in a Chinese family with Best vitelliform macular dystrophy (BVMD) and to identify the mutation of the VMD2 gene in this family. METHODS: It was a retrospective case analysis. Five patients (10 eyes) were diagnosed as BVMD by the fundus photography, EOG, fluorescein angiography (FFA) and optical coherence tomography (OCT). Their clinical data were analyzed retrospectively. Molecular genetic analysis was performed on DNA extracted from peripheral leucocytes of all patients and 2 unaffected family members. Exon 1 to 11 of the VMD2 gene were amplified by polymerase chain reaction for direct sequencing. RESULTS: The pedigree showed an autosomal dominant inheritance. Ten eyes from 5 patients were classified into Stage 0, II a, II b, III and IV with different clinical manifestations. Direct sequencing of all affected members revealed a T-->G transition at codon 301, producing Asp301Glu mutation of VMD2 gene. CONCLUSIONS: Asp301Glu mutation of the VMD2 gene is found in a Chinese family with BVMD. The phenotype of BVMD in this family belongs to geographic type. Molecular genetic approach may be useful for the proper diagnosis of BVMD.


Assuntos
Canais de Cloreto/genética , Proteínas do Olho/genética , Degeneração Macular/genética , Adolescente , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Bestrofinas , Criança , Códon , Éxons , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Estudos Retrospectivos , Análise de Sequência , Adulto Jovem
10.
Zhonghua Yan Ke Za Zhi ; 43(12): 1089-92, 2007 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-18331678

RESUMO

OBJECTIVE: To investigate the clinical features of Best vitelliform macular dystrophy (BVMD) in Chinese patients. METHODS: Ten consecutive patients (20 eyes) were diagnosed as BVMD by the fundus photography, EOG, fluorescein angiography (FFA) and optical coherence tomography (OCT). Their clinical data were analyzed retrospectively. RESULTS: Of the twenty eyes from ten patients, three eyes from three patients (age range 9-18 years, mean 12.33+/-4.93 years) in Stage II, two eyes from two patients (age range 9-18, mean 13.50+/-6.36 years) in Stage IIa, four eyes from two patients (age range 11-29 years, mean 20.00+/-10.39 years) in Stage III and eleven from six patients (age range 9-44 years, mean 27.09+/-14.02 years) in Stage IV were found at their first presentation to our hospital. OCT scan showed the broadening of the outer-retina-choroid-complex signal with the retinal elevation in Stage II. The moderately reflective material which represents the vitelliform material may accumulate forming a conical mound that would elevate the retinal sensory layer in Stage IIa. In 'pseudohypopon' or atrophy phase there may be a large volume of serous retinal detachment. If a fibrous macular or foveal atrophy was seen in the fundus photograph, the thinning of the outer-retina-choroid-complex signal with serous retinal detachment may be shown by OCT. CONCLUSIONS: The present observation is a first study on the clinical findings of Chinese BVMD patients. It supports the hypothesis that the yellowish material is located under the RPE. Long term evaluation with more patients should be done to acknowledge more characteristics of BVMD in Chinese patients.


Assuntos
Degeneração Macular/diagnóstico por imagem , Adolescente , Adulto , Criança , Feminino , Angiofluoresceinografia , Humanos , Masculino , Radiografia , Tomografia de Coerência Óptica , Adulto Jovem
11.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 31(3): 363-6, 2006 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-16859125

RESUMO

OBJECTIVE: To determine the expression of Smad4 and TGF-beta1 in bladder transitional cell carcinoma (BTCC), and to understand the mechanism of invasion, angiogenesis, and metastasis of BTCC. METHODS: The expressions of Smad4 and TGF-beta1 in samples of 42 human bladder carcinoma and 12 normal bladder mucosa tissues were determined with standard immunohistochemical analysis. We also analyzed the relationship among the expressions of Smad4 and TGF-beta1 and invasion, angiogenesis, and metastasis of BTCC, and the correlation between Smad4 and TGF-beta1. RESULTS: The positive rate of Smad4 in BTCC was significantly lower than those in normal bladder mucosa tissues (33.3% vs 83.3%, P < 0.01). The expressions of Smad4 in poorly differentiated, invasive, recurrent, or with lymph node metastasis of BTCCs were lower than those in well differentiated, superficial, nonrecurrent, or without lymph node metastasis ones (P <0.05). The positive rate of TGF-beta1 in BTCC was significantly lower than that in normal bladder mucosa tissues (64.3% vs 100%, P <0.01), which was positively correlated to that of Smad4 (P = 0.000). CONCLUSION: The expressions of Smad4 and TGF-beta1 in BTCC decrease with the increase in clinical stage, poor pathological grade, and the recurrence and metastasis of BTCC.


Assuntos
Carcinoma de Células de Transição/metabolismo , Proteína Smad4/biossíntese , Fator de Crescimento Transformador beta/biossíntese , Neoplasias da Bexiga Urinária/metabolismo , Adulto , Idoso , Carcinoma de Células de Transição/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Proteína Smad4/genética , Fator de Crescimento Transformador beta/genética , Neoplasias da Bexiga Urinária/patologia
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