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Objective: To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations, and the association between BRCA2 pathogenic mutation and clinicopathological characteristics. Patient survivals were also examined. Methods: Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University, Chengdu, China from June 2014 to August 2021 were collected. A retrospective analysis of histopathological morphology, clinicopathological characteristics, and patient survivals was conducted. Results: The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene (DRG) in 73 cases (73/249, 29.3%), including 22 cases (8.8%) with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG. Among the 22 patients with BRCA2 pathogenic mutation, 14 patients (5.6%) harbored germline mutations and 8 patients (3.2%) somatic mutations. Their ages ranged from 48 to 91 years, with a median of 67 years. Seventeen patients (77.3%) had distant metastasis, including 16 cases with bone metastasis and 1 case with multiple metastases. Thirteen patients (59.1%) were castration-resistant prostate cancer. The histological type was mainly classical prostatic acinar adenocarcinoma, including 16 cases (72.7%) with intraductal carcinoma of the prostate (IDC-P). Six cases (27.3%) showed focal neuroendocrine differentiation. Perineural/vascular invasion and extraprostatic extension were seen in 11 cases (50.0%) and 8 cases (36.4%), respectively. The Gleason scores of 19 patients (86.4%) were≥8. IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.002). With a total follow-up time of 189 months, the median overall survival (OS) was 132.3 months. Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation (P=0.040). The OS of patients with BRCA2 germline pathogenic mutation did not significantly differ from that of patients with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.216). Conclusions: The presence of BRCA2 gene pathogenic mutation is common in the prostate cancers with high Gleason grade, advanced clinical stage, and castration resistance. IDC-P is more commonly noted in cases with BRCA2 germline pathogenic mutation than those without. Patients with DRG pathogenic mutation have shorter OS than those with no-DRG pathogenic mutation, but there is no significant association between BRCA2 pathogenic mutations and OS.
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Proteína BRCA2 , Mutación , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Proteína BRCA2/genética , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Pronóstico , Anciano de 80 o más Años , Neoplasias Óseas/genética , Neoplasias Óseas/secundario , Neoplasias Óseas/patologíaRESUMEN
OBJECTIVE: This study aimed to investigate the relationship between common clinical immune indicators, disability degree, and cognitive impairment in patients with neuromyelitis optica spectrum disorder (NMOSD). PATIENTS AND METHODS: We retrospectively analyzed lymphocyte subsets and routine parameters in the peripheral blood of 55 patients with NMOSD. We assessed the degree of disability using the Extended Disability Status Scale (EDSS). The Montreal Cognitive Assessment (MoCA) scores were used to assess cognitive function. In addition, we also determined the cytokine levels in 33 patients with NMOSD. The relationships of these immunological indicators with disability and cognitive impairment were assessed using correlation and multiple linear regression analyses. RESULTS: The results of the multiple linear regression analysis suggested that for patients with NMOSD, the neutrophil-lymphocyte ratio (NLR) (ß=0.072, p=0.034) and number of attacks (ß=0.131, p=0.03) were positively correlated with EDSS scores, whereas the number of attacks was positively correlated with MoCA scores. In addition, we also collected cytokine levels in 33 of these patients. The results of the study showed a positive correlation between IL-10 and EDSS scores and a negative correlation between IL-6 and MoCA scores. CONCLUSIONS: Our results show that these immune cells and cytokines are, to some extent, associated with the degree of disability and cognitive impairment in patients with NMOSD. Closely monitoring these indicators may allow detecting changes in patients' disease courses and predicting the severity of their disease. In clinical practice, this may facilitate early intervention and appropriate treatment decisions, which may improve the management of patient prognosis.
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Disfunción Cognitiva , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/complicaciones , Estudios Retrospectivos , Pronóstico , Citocinas , Disfunción Cognitiva/complicaciones , Acuaporina 4RESUMEN
Hereditary pulmonary alveolar proteinosis (hPAP) is a rare interstitial lung disease caused by mutation in CSF2RA/CSF2RB, characterized by the deposition of pulmonary surfactant due to the alveolar macrophage dysfunction. The whole lung lavage can effectively alleviate the symptoms but is associated with potential complications. Cell therapy is a novel approach with advances that provide a new therapeutic strategy for the treatment of hPAP.
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Proteinosis Alveolar Pulmonar , Surfactantes Pulmonares , Humanos , Proteinosis Alveolar Pulmonar/genética , Proteinosis Alveolar Pulmonar/terapia , Macrófagos Alveolares , Tratamiento Basado en Trasplante de Células y Tejidos , Mutación , Lavado BroncoalveolarRESUMEN
OBJECTIVE: To identify and characterize read-through RNAs and read-through circular RNAs (rt-circ-HS) derived from transcriptional read-through hypoxia inducible factor 1α (HIF1α) and small nuclear RNA activating complex polypeptide 1 (SNAPC1) the two adjacent genes located on chromosome 14q23, in renal carcinoma cells and renal carcinoma tissues, and to study the effects of rt-circ-HS on biological behavior of renal carcinoma cells and on regulation of HIF1α. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing were used to examine expression of read-through RNAs HIF1α-SNAPC1 and rt-circ-HS in different tumor cells. Tissue microarrays of 437 different types of renal cell carcinoma (RCC) were constructed, and chromogenic in situ hybridization (ISH) was used to investigate expression of rt-circ-HS in different RCC types. Small interference RNA (siRNA) and artificial overexpression plasmids were designed to examine the effects of rt-circ-HS on 786-O and A498 renal carcinoma cell proliferation, migration and invasiveness by cell counting kit 8 (CCK8), EdU incorporation and Transwell cell migration and invasion assays. RT-PCR and Western blot were used to exa-mine expression of HIF1α and SNAPC1 RNA and proteins after interference of rt-circ-HS with siRNA, respectively. The binding of rt-circ-HS with microRNA 539 (miR-539), and miR-539 with HIF1α 3' untranslated region (3' UTR), and the effects of these interactions were investigated by dual luciferase reporter gene assays. RESULTS: We discovered a novel 1 144 nt rt-circ-HS, which was derived from read-through RNA HIF1α-SNAPC1 and consisted of HIF1α exon 2-6 and SNAPC1 exon 2-4. Expression of rt-circ-HS was significantly upregulated in 786-O renal carcinoma cells. ISH showed that the overall positive expression rate of rt-circ-HS in RCC tissue samples was 67.5% (295/437), and the expression was different in different types of RCCs. Mechanistically, rt-circ-HS promoted renal carcinoma cell proliferation, migration and invasiveness by functioning as a competitive endogenous inhibitor of miR-539, which we found to be a potent post-transcriptional suppressor of HIF1α, thus promoting expression of HIF1α. CONCLUSION: The novel rt-circ-HS is highly expressed in different types of RCCs and acts as a competitive endogenous inhibitor of miR-539 to promote expression of its parental gene HIF1α and thus the proliferation, migration and invasion of renal cancer cells.
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Carcinoma de Células Renales , Subunidad alfa del Factor 1 Inducible por Hipoxia , Neoplasias Renales , MicroARNs , ARN Circular , Humanos , Carcinoma de Células Renales/patología , Proliferación Celular , Hipoxia , MicroARNs/genética , Invasividad Neoplásica/genética , ARN Circular/genética , ARN Circular/metabolismo , ARN Interferente Pequeño , Subunidad alfa del Factor 1 Inducible por Hipoxia/genéticaRESUMEN
Objective: To investigate the clinical and pathological features and prognosis of patients with microfocal prostate adenocarcinoma. Methods: Clinical and pathological data of the patients diagnosed with microfocal adenocarcinoma on prostate biopsy at the West China Hospital from 2013 to 2019 were collected. Microfocal adenocarcinoma was defined as follows: Gleason score of 3+3=6, total number of the cores ≥10, number of the positive cores ≤2, and proportion of the tumor in each positive core<50%. Clinicopathological parameters, treatment plans and follow-up data were collected. Pathological information of the biopsy and radical resection specimens was used to analyze the correlation between pathological parameters in the biopsy report and adverse pathological features of radical resection specimens, including increased Gleason score, capsule invasion, positive surgical margin and perineural invasion. Results: A total of 206 cases of microfocal adenocarcinoma were diagnosed on prostate biopsies from 2013 to 2019, accounting for 6.7% of all adenocarcinoma cases. There were 139 cases of 1 positive core and 67 cases of 2 positive cores. Patients with microfocal adenocarcinoma were younger than those with non-microfocal adenocarcinoma (69 years versus 71 years, P<0.001). Compared with patients with non-microfocal adenocarcinoma, the pre-biopsy total prostate specific antigen (tPSA) and free prostate specific antigen (fPSA) levels in patients with microfocal adenocarcinoma were both lower (11.2 µg/L2 versus 23.7 µg/L2; 1.4 µg/L2 versus 3.0 µg/L2, P<0.001), the fPSA/tPSA level was higher (12.9% versus 10.7%, P<0.05), the prostate volume was larger (38.9 mL versus 34.3 mL, P<0.05), and the PSA density was lower (0.3 µg/L2 versus 0.8 µg/L2, P<0.001). 130 patients underwent radical prostatectomy, 30 patients chose active monitoring, 31 patients chose endocrine or radiation therapy, and 15 patients were lost to follow-up. Three patients in the active surveillance group underwent radical prostatectomy for disease progression after 21-39 months observation. Biochemical relapses occurred in two patients in the radical prostatectomy group. The remaining patients have no disease progression or recurrence at present. Compared with radical prostatectomy specimens, Gleason score in the biopsy material was increased in 64/115 patients (55.7%). Among resection excision specimens, 14 cases (12.2%) had extraprostatic extension (EPE), 35 cases (30.4%) had perineural invasion, and 16 cases (13.9%) had a positive margin. Univariate and multivariate analyses showed that low fPSA/tPSA ratio and 2 positive cores were independent risk factors for Gleason score increase in the radical prostatectomy specimens. A low fPSA/tPSA ratio was an independent risk factor for perineural invasion. Low fPSA/tPSA ratio and low prostate volume were associated with a positive margin in radical prostatectomy specimens. Conclusions: In this study, patients diagnosed with microfocal adenocarcinoma on prostate biopsy account for a high proportion of the patients with increased Gleason score in the radical prostatectomy specimens, and there is a certain proportion of adverse pathological features in the radical specimens. Therefore, for the patients with only a small amount of low-grade adenocarcinoma found in biopsy, PSA levels and PSA density should be taken into consideration in treatment selection.
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Adenocarcinoma , Neoplasias de la Próstata , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Humanos , Masculino , Próstata/patología , Próstata/cirugía , Antígeno Prostático Específico , Prostatectomía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugíaRESUMEN
Objective: To use Meta analysis to understand the prevalence of the heritability of body mass index (BMI) in twins. Methods: All studies on the heritability of the twins' BMI published before December 31, 2020 were retrieved through the China National Knowledge Network, Wanfang, VIP, PubMed and Web of Science databases. The literature quality was evaluated by using Joanna Briggs Institute Critical Appraisal tools. Stata 16.0 was used to perform subgroup analysis on the outcome indicators (heritability, 95%CI) to explore the source of heterogeneity. The local weighted regression method was used to fit the trend of heritability with age. The publication bias test and the sensitivity analysis of included literatures were also performed by using Stata 16.0. Results: A total of 10 articles meeting the inclusion and exclusion criteria were included with 79 twins' independent estimates of heritability for BMI. Meta-analysis showed that the combined value of BMI heritability was 0.69 (95%CI: 0.65-0.71), the combined value of BMI (0.68, 95%CI: 0.65-0.70) in males was lower than that (0.70, 95%CI: 0.68-0.72) in females. The heritability of BMI (0.72, 95%CI: 0.68-0.76) in childhood and adolescence was higher than that (0.68, 95%CI: 0.66-0.70) in adulthood. The gender specific difference in BMI heritability in twins ≤18 years old was even greater, which was lower in males (0.68, 95%CI: 0.61-0.76) than in females (0.75, 95%CI: 0.69-0.81). The heritability increased with age in childhood, reached peak at about 18 years old, and then slowly decreased with age. Conclusions: The heritability of BMI varied with population characteristics, especially age and gender. In view of the high estimated value of BMI heritability in female children and adolescents, more attention should be paid to the start time of health intervention.
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Gemelos , Adolescente , Adulto , Índice de Masa Corporal , Niño , China/epidemiología , Femenino , Humanos , Masculino , Prevalencia , Factores Sexuales , Gemelos/genéticaRESUMEN
Objective: To quantitatively analyze the effects of population aging and other risk factors on the burden of atherosclerosis cardiovascular disease (ASCVD) in China from 1990 to 2019. Methods: Disability adjusted life years (DALY) and age-standardized rates obtained from the Global Burden of Disease Study 2019 (GBD2019) were used to describe the temporal trend of a burden on ASCVD. And a decomposition method established by Gupta was applied to quantify the burden related to population growth, aging, age-specific prevalence, and the severity of the disease. Results: In 2019, 61.00% of the burden of cardiovascular disease in China was caused by ASCVD. The DALY of ischemic heart disease increased by 133.66% compared with that in 1990, with 29.57% of the increase attributed to population growth, 108.74% due to population aging, and 8.87% due to the rise of age-specific prevalence and -13.53% benefited from changes in disease severity. The DALY of ischemic stroke increased by 138.64% compared with 1990, and the proportions attributable to the above four parts were 30.95%, 123.38%, 55.80%, and -71.49%, respectively. Hypertension remained the leading risk factor for ASCVD in 2019, followed by high LDL cholesterol. The age-standardized DALY rate attributable to drinking had the most significant increase (486.01%) from 1990, with an average annual growth of 10.93%. Conclusions: Aging population seems responsible for the main reason for the considerable increase in the burden of ASCVD in China. Still, the adverse trends of other avoidable risk factors, especially metabolic risk factors, can not be ignored.
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Aterosclerosis , Enfermedades Cardiovasculares , Personas con Discapacidad , Anciano , Aterosclerosis/epidemiología , Enfermedades Cardiovasculares/epidemiología , China/epidemiología , Costo de Enfermedad , Humanos , Años de Vida Ajustados por Calidad de Vida , Factores de RiesgoRESUMEN
Objective: To investigate the clinicopathological and molecular characteristics of the epithelioid glioblastoma (eGBM) with BRAF V600E mutation. Methods: Sixteen cases of eGBM with BRAF V600E mutation diagnosed at the West China Hospital of Sichuan University, China from 2012 to 2019 were collected. Their clinicopathological and molecular characteristics were analyzed. Results: The range of patients' age was from 7 to 61 years (median 31.5 years). There were 4 males and 12 females, with a male to female ratio of 1â¶3. Eleven cases were newly diagnosed eGBM and five cases had a previous history of astrocytomas. Most of the tumors were located in the cerebral hemisphere, often in the frontal lobe, with an average diameter of 4.6 cm (2.0-8.0 cm). The tumors were composed of relatively uniform, closely packed epithelioid cells, some showing discohesion, with distinct cell membrane, eosinophilic cytoplasm, eccentric nuclei, distinct nucleoli and mitotic activity. Palisaded/coagulative necrosis was seen in all cases. Glomerular microvascular proliferation was seen in most of the cases, while mono-or multi-nucleated tumor giant cells were seen in some cases. Focal sarcomatoid area was seen in 2 cases, and focal pleomorphic xanthoastrocytoma (PXA)-like area was seen in 3 cases. Immunohistochemistry showed variable positivity for GFAP, Olig2 and p53. The median Ki-67 index was 30% (10%-50%). Only one case lost ATRX protein expression. Sanger sequencing identified the BRAF V600E mutation in all sixteen patients. Five cases also had mutations in the TERT gene promoter. No IDH1 (R132) or IDH2 (R172) mutation was detected. Surgical resection of the tumors was performed for all patients, and 3 patients also received adjuvant radiotherapy and chemotherapy. Follow-up data were available for 15 patients, with a follow-up time of 1-89 months (median 10 months). Among the 15 patients, 7 patients died of disease and another 5 patients had recurrences. The overall survival time of the patients under 35 years of age was significantly longer than that of the patients aged 35 years or older (P=0.014), but their progression-free survival was not statistically different (P=0.232). Conclusions: eGBM with BRAF V600E mutation is more commonly detected in young women than other the populations (i.e. elderly or male). The epithelioid morphology should include rhabdoid meningioma, anaplastic PXA, atypical teratoid/rhabdoid tumor, metastatic tumors, and melanoma in its differential diagnosis. PXA-like area is observed in some eGBM cases, suggesting a relationship of these two types of tumor. eGBM is a high-grade malignant tumor and most of the cases show recurrences or deaths in a short-period time. The younger patients have a relatively better prognosis than the older ones.
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Astrocitoma , Neoplasias Encefálicas , Glioblastoma , Adolescente , Adulto , Anciano , Astrocitoma/genética , Neoplasias Encefálicas/genética , Niño , China , Femenino , Glioblastoma/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Adulto JovenRESUMEN
Objective: To preliminarily explore the treatment effect of nivolumab on Chinese non-small-cell lung cancer (NSCLC) patients with brain metastases, and further enrich the evidences of programmed death-ligand 1 (PD-1) monoclonal antibody in the treatment of NSCLC patients with brain metastases. Methods: The clinical and pathological data of 22 NSCLC patients with brain metastases treated with nivolumab were collected. The electronic imaging data were collected to confirm the treatment effect and time point of disease progression, and the survival data of the patients were obtained through follow-up. Results: Twenty-one patients were evaluated for the intracranial treatment effect. The intracerebral objective response rate (IORR) was 28.6%, the intracranial disease control rate (IDCR) was 47.6%. The median intracranial progression-free-survival (iPFS) of all the 22 patients was 5.2 months. Both the 1-year and 2-year survival rates were 56.7%. Conclusions: The treatment effect of PD-1 monoclonal antibody on NSCLC patients with brain metastases is similar as those without brain metastases.
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Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Nivolumab , Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Nivolumab/uso terapéutico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Objective: To investigate the efficacy and safety of rapamycin in children with tuberous sclerosis complex (TSC) associated renal disease. Methods: A prospective self-control study was conducted. The clinical data of 92 children diagnosed with tuberous sclerosis complex associated kidney disease at the People's Liberation Army General Hospital from January 2011 to January 2019 were collected. The long-term rapamycin treatment for all patients initiated at 1 mg/(m(2)·d), which was gradually adjusted to reach a blood concentration of 5-10 µg/L. The changes of the maximum diameter of renal lesions in children after rapamycin treatment were observed and analyzed with Wilcoxon test. Results: Ninety-two children, including 52 males and 40 females, who met the criteria were analyzed. Sixty patients had only renal angiomyolipoma(RAML), while 24 patients had only multiple renal cysts(MRC), and 8 patients had both lesions. The age of TSC diagnosis was 16.0 (7.0, 42.0) months, and the age of initial treatment with rapamycin was 63.5 (21.0, 103.0) months. The follow-up lasted for 12.0 (4.0, 23.0) months. Sequencing of TSC1 and TSC2 genes was performed in 54 children with TSC, including 3 patients (6%) with mutations in TSC1 gene and 51 patients (94%) with mutations in TSC2 gene. The maximum RAML diameter before treatment was 7.0 (4.0, 9.0) mm. The best effect reached at 3 months of treatment, with the diameter of 4.0 (0,7.0) mm. The maximum diameters at 6 months, 1 year and 1-2 years were 5.0 (0,9.8) mm, 5.0 (1.5, 8.5) mm, 5.5 (3.0, 9.0) mm, respectively, and were significantly different from the baseline (Z=-2.404,-2.350,-2.750,P=0.016,0.019,0.006, respectively). The maximum diameter after 2-3 years, and ≥3 years were 5.0 (3.9,7.0) mm and 6.0 (1.0, 11.0) mm, without significant difference from the baseline (Z=-0.856,-0.102,P=0.393,0.919, respectively).The maximum diameters of MRC after 3 months, 6 months, 1 year,1-2 years, 2-3 years, and ≥3 years were 11.0 (5.0, 14.0) mm,3.0 (0.0,11.0) mm,5.0 (0,21.0) mm,0 (0,14.0) mm,0 (0,10.0) mm, and 0 (0,18.3) mm, respectively, but were not significantly different rom the baseline (7.0 (5.0, 15.7) mm)(Z=-0.944,-1.214,-1.035,-1.896,-1.603,-1.214,P=0.345,0.225,0.301,0.058,0.109,0.225, respectively).Twenty-nine patients (32%) had oral ulcers during the entire treatment period, and no serious adverse reactions were observed. Conclusions: Rapamycin could decrease the diameter of TSC-related RAML, but could not inhibit the growth of cysts. It is well tolerated in the treatment of renal diseases associated with tuberous sclerosis complex.
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Angiomiolipoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Sirolimus/uso terapéutico , Esclerosis Tuberosa/complicaciones , Angiomiolipoma/etiología , Niño , China , Femenino , Humanos , Recién Nacido , Neoplasias Renales/etiología , Masculino , Estudios Prospectivos , Sirolimus/administración & dosificaciónRESUMEN
Objective: To investigate the clinical effects of first generation epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) compared with platinum-based chemotherapy as first-line therapy in advanced lung adenocarcinoma patients with uncommon EGFR mutations. Methods: Clinical data of 4 276 patients diagnosed as advanced lung adenocarcinoma (â ¢B/â £) underwent EGFR gene detection at the Affiliated Cancer Hospital of Zhengzhou University from January 2012 to February 2018 were collected and 99 cases with uncommon EGFR mutations were selected. The clinical pathological features, treatment outcomes, treatment options and prognosis after first-line treatment of the 99 cases were analysed and compared with other patients with common EGFR mutations. Results: The objective response rates of patients with uncommon EGFR mutations receiving EGFR-TKIs or platinum-based chemotherapy were 33.0% and 27.1%, respectively. The disease control rates were 76.5% and 87.5%, respectively. The progression-free survival (PFS) of patients treated with EGFR-TKIs was 7.2 months, significantly superior than 4.9 months of patients receiving chemotherapy (P=0.009). The overall survival of patients treated with EGFR-TKIs was 14.3 months, significantly worse than 20.7 months of patients receiving chemotherapy (P=0.034). Multivariate analysis showed that distant metastases (P=0.001) and smoking history (P=0.013) were independent prognostic factors for OS of lung adenocarcinoma patients with EGFR uncommon mutations. Conclusions: Compared with chemotherapy, the usage of first generation of EGFR-TKIs as first-line therapy can improve the short-term efficacy of advanced lung adenocarcinoma patients with EGFR uncommon mutations. However, platinum-based chemotherapy shows a longer overall survival.
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Adenocarcinoma del Pulmón/tratamiento farmacológico , Receptores ErbB/uso terapéutico , Genes erbB-1/efectos de los fármacos , Genes erbB-1/genética , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Adenocarcinoma del Pulmón/patología , Humanos , Neoplasias Pulmonares/patología , Mutación , Resultado del TratamientoRESUMEN
Objective: To investigate the status and prognostic significance of TERT and IDH1/2 genes mutations in diffusely infiltrating gliomas. Methods: Hot spot mutations of TERT and IDH1/2 genes were detected by DNA sequencing in 236 cases of gliomas at West China Hospital from 2012 to 2016, including pilocytic astrocytoma (WHO grade â , 16 cases), diffuse astrocytoma and oligodendroglioma (WHO grade â ¡, 89 cases), anaplastic astrocytoma and oligodendroglioma (WHO grade â ¢, 72 cases) and glioblastoma (WHO grade â £, 59 cases). The prognostic significance of TERT and IDH1/2 hot spot mutations was evaluated. Results: No IDH or TERT mutations were detected in pilocytic gliomas. TERT promoter mutation frequency was higher in patients aged ≥40 years(60.8%, 93/153) than in patients aged <40 years (32.8%, 22/67; P<0.01). TERT promoter mutation rate was also significantly higher in oligodendroglioma (87.5% , 56/64) than that in astrocytoma(37.8%, 59/156; P<0.01). Young age (<40 years), oligodendroglioma and IDH1 mutation were favorable prognostic factors for diffusely infiltrating astrocytic and oligodendroglial tumors. TERT mutation alone was not of prognostic significance. Diffusely infiltrating astrocytic and oligodendroglial tumors were divided into four molecular subtypes according to TERT and IDH1 mutation status: IDH(+ )/TERT(+ ), IDH(+ )/TERT(-), IDH(-)/TERT(-) and IDH(-)/TERT(+ ). There was significant prognostic difference among the 4 subtypes. Conclusions: Combined IDH and TERT gene mutation analysis may be useful for prognostic subgrouping. Notably, IDH1 wild-type cases can be further subdivided into TERT(+ ) or (-) subgroups with significant prognostic difference.
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Neoplasias Encefálicas/genética , Glioma/genética , Isocitrato Deshidrogenasa/genética , Mutación , Telomerasa/genética , Adulto , Anciano , Astrocitos , Astrocitoma/genética , Astrocitoma/mortalidad , Neoplasias Encefálicas/mortalidad , China , Glioblastoma/genética , Glioblastoma/mortalidad , Glioma/mortalidad , Humanos , Persona de Mediana Edad , Tasa de Mutación , Oligodendroglioma/genética , Oligodendroglioma/mortalidad , Pronóstico , Regiones Promotoras Genéticas , Análisis de Secuencia de ADNRESUMEN
Objective: To investigate the status of immunization of National Immunization Program (NIP) and its adverse reaction rate in children with tuberous sclerosis. Method: Questionnaire survey was adopted to identify the vaccination coverage and its adverse events; 72 cases of children with tuberous sclerosis and 78 normal controls (healthy children completing age-appropriate NIP) admitted to Chinese People's Liberation Army General Hospital from December 2014 to November 2015 were involved into this study. Result: The age-appropriate NIP coverage rate of tuberous sclerosis was 36%(26/72). The coverage rate of bacillus calmette-guerin (BCG), hepatitis B vaccine 1st to 3rd doses (HepB1-3), oral poliovaccine 1st dose (OPV1), diphtheria, pertussis and tetanus 1st dose (DPT1), DPT1-3, meningococcal polysaccharide vaccine group A (MPVA), measles amd rubella vaccine/measles vaccine 1st dose (MRV/MCV1), and Japanese encephalitis vaccine 1st dose (JEV1) were 100%(72 cases), 75%(51 cases), 97%(66 cases), 91%(62 cases), 82%(56 cases), 66%(45 cases), 69%(42 cases), and 61%(37 cases) respectively. The reasons why the children did not complete the vaccination plan were that parents were concerned about vaccination-induced seizures or seizures had not been controlled. Among 72 children with TSC, the rate of adverse events or suspected adverse events after vaccination was 17% (12 cases), which was higher than the normal control children (2 cases, 3%) (χ2=8.799, P<0.05). The main adverse events were seizure events, which accounted for 92%(11 cases). Conclusion: The age-appropriate NIP coverage rate among children with tuberous sclerosis is low. The high incidence of adverse events may be associated with a fact that there are some nervous system abnormalities in cases with tuberous sclerosis. TSC children vaccination is relatively safe, with no serious adverse events.
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Programas de Inmunización , Esclerosis Tuberosa , Vacunación/efectos adversos , Niño , Preescolar , Vacunas contra Hepatitis B , Humanos , Inmunización , Lactante , Sarampión , PadresRESUMEN
We investigated the clinical phenotypes and genetic mutations in Chinese children diagnosed with tuberous sclerosis complex (TSC). Sequencing of TSC1 and TSC2 genes was performed in 117 children with TSC and their parents. Association of TSC gene mutations with clinical manifestations was investigated. All gene mutations were heterozygous including in 16 patients (13.7%) with mutations in TSC1 gene and 101 patients (86.3%) with mutations in TSC2 gene. Among the 16 patients with TSC1 gene mutations, 15 different types of mutations were found, which included 5 novel mutations; all patients had skin manifestations and epilepsy. Among the 101 patients with TSC2 mutations, 85 different types of mutations were found, which included 25 novel mutations; 97 patients (96.0%) had skin manifestations; 97 (96.0%) had epilepsy; 74 (73.3%) had intellectual disability and 25 patients (24.8%) were autistic. The clinical phenotype of the 14 children with familial TSC was more severe than that of their parents.
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Esclerosis Tuberosa/genética , Proteínas Supresoras de Tumor/genética , Pueblo Asiatico/genética , Trastorno Autístico/genética , Niño , Preescolar , Epilepsia/genética , Femenino , Genotipo , Humanos , Discapacidad Intelectual/genética , Masculino , Mutación , Fenotipo , Esclerosis Tuberosa/etiología , Proteína 1 del Complejo de la Esclerosis Tuberosa , Proteína 2 del Complejo de la Esclerosis TuberosaRESUMEN
OBJECTIVE: To assess the efficacy and safety of mammalian target of rapamycin (mTOR) inhibitor rapamycin in treatment of children with cardiac rhabdomyoma, associated with tuberous sclerosis complex (TSC). METHOD: The clinical data of children with cardiac rhabdomyomas, who had received a diagnosis of TSC previously, were collected between September 2011 and November 2015 from Pediatric Department of the People's Liberation Army General Hospital.Patients in line with the inclusion criteria received long-term treatment with sirolimus.The starting doses of sirolimus was 1 mg/ (m(2)·d), and the plasma concentration was maintained at 5-10 µg/L.The size and number of cardiac rhabdomyomas were analyzed after treatment with rapamycin, and the efficacy and safety were assessed. The Wilcoxon test was used to analyze data. RESULT: All the 51 children met the inclusion and exclusion criteria, including 30 males and 21 females.The median age for rapamycin treatment was 15.0 months (7.0-35.0 months). Tumors disappeared in 26 (51%) children, decreased by more than 50%(including 50%) in 15 (29%) children, decreased by less than 50% in 5 (12%) children, and had no change or progressed in 4 (8%) children.The number of tumors decreased by 77(72%). The median maximum diameter of tumor was 8.7 (5.9-11.3) mm before treatment, 0.0 (0.0-4.0) mm after treatment, and the median decrease of tumor size were 6.7 (3.9-10.0) mm (Z=-8.817, P<0.01). The median disappearance time was 3.26 (2.92-5.37) months.Among different age groups, after treatment by rapamycin, the rate of tumor's disappearance was 50% (12/24) in 0-1 years group.Tumors disappeared in 10 of 16 patients in >1-3 years group and in 4 of 11 patients in >3 years group.The rate of tumor's disappearance was the highest after 3 months of treatment as compared with 6 and 12 months of treatment.Ten children had adverse event that was related to rapamycin.Canker sore was reported in one child and dyslipidemia was reported in 9 children. CONCLUSION: Rapamycin is efficacious and well tolerate in treatment of cardiac rhabdomyomas associate with TSC, and lead to a reduction in tumor size and number, in addition, significantly shorten the duration of cardiac rhabdomyoma.
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Neoplasias Cardíacas/tratamiento farmacológico , Rabdomioma/tratamiento farmacológico , Sirolimus/uso terapéutico , Esclerosis Tuberosa/tratamiento farmacológico , Preescolar , Femenino , Humanos , Lactante , MasculinoRESUMEN
17ß-Estradiol has been demonstrated to protect blood-brain barrier from disruption and attenuate brain injury in various conditions. The aim of this study was to investigate the effect of 17ß-estradiol on the blood-retina barrier (BRB) breakdown induced by intravitreous injection of vascular endothelial growth factor (VEGF), a significant mediator of vascular permeability. Intravitreous injection of VEGF was performed to initiate BRB breakdown in male rats with PBS in the contralateral eye as control. 2 doses of 17ß-estradiol and vehicle control were given to 3 groups of rats. The integrity of the BRB was quantified by Evans blue technique and assessed by fluorescent dyes in retinal sections and wholemounts. BRB breakdown was achieved by VEGF as retinal vascular permeability was increased compared with control eyes (14.66±4.09 vs. 4.94±1.20 µl/g/h, p<0.01). Vascular permeability in the 2 groups treated with 17ß-estradiol was reduced compared with control (14.66±4.09 vs. 10.26±3.67 vs. 7.37±2.22 µl/g/h, p<0.01). Rhodamine isothiocyanate (RhIC) extravasation in retinal sections and Evans blue-albumin complex leakage in retinal wholemounts were also decreased in the 2 treatment groups. These results suggest that 17ß-estradiol attenuates BRB breakdown induced by VEGF in male rats, which may provide a new role of 17ß-estradiol in ocular diseases.
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Barrera Hematorretinal/efectos de los fármacos , Barrera Hematorretinal/metabolismo , Estradiol/administración & dosificación , Estrógenos/administración & dosificación , Enfermedades de la Retina/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Permeabilidad Capilar/efectos de los fármacos , Humanos , Masculino , Ratas , Ratas Sprague-Dawley , Enfermedades de la Retina/metabolismoRESUMEN
OBJECTIVE: To study the clinical characteristics of post-traumatic endophthalmitis following open-globe injury and identify factors affecting its frequency in order to gain further knowledge about possible risk factors for the development of endophthalmitis. METHODS: All consecutive records of open globe injury cases (4968 eyes in 4865 inpatients) in 15 tertiary referral hospitals in China over 5 years (January 2001 to December 2005) were retrospectively reviewed. The information was collected from a standardised database of eye injuries from which a detailed analysis of factors influencing the incidence of endophthalmitis was performed. RESULTS: 173 eyes (one bilateral rupture of a male) removed within 24 h after trauma were excluded. It was observed that 571 eyes (571 patients) out of a total of 4795 eyes (4693 patients) developed endophthalmitis, and the rate of incidence was 11.91%. Laceration was an independent risk factor for open globe injury. Primary repair within 24 h, intraocular tissue prolapse and self-sealing of wounds seemed to impart protective effects against the development of endophthalmitis. However, gender, age, lens breach and posterior zone of wounds were not significant. Intravitreal antibiotic and corticosteroid therapy was administered to 53 eyes (9.28%), and vitrectomy was performed on 305 eyes (53.42%). At discharge or follow-up, the proportion (16.81%) of enucleation/evisceration of eyes with endophthalmitis was higher than that (8.71%) without endophthalmitis. CONCLUSIONS: Laceration was associatied with a significantly higher risk of endophthalmitis for open globe injuries. Early primary repair, intraocular tissue prolapse and self-sealing of wounds were independent protective factors against the development of endophthalmitis.
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Endoftalmitis/etiología , Lesiones Oculares Penetrantes/complicaciones , Adolescente , Adulto , Anciano , Niño , Preescolar , China/epidemiología , Endoftalmitis/epidemiología , Endoftalmitis/terapia , Enucleación del Ojo/estadística & datos numéricos , Lesiones Oculares Penetrantes/epidemiología , Lesiones Oculares Penetrantes/cirugía , Femenino , Humanos , Lactante , Laceraciones/complicaciones , Laceraciones/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
OBJECTIVES: To characterise West Australian cases of longitudinally extensive myelopathy (LEM). METHODS: Twenty six patients with LEM were identified from a cohort of 983 patients with demyelinating disease. Clinical and MRI data and AQP4-IgG results were reviewed. RESULTS: LEM cases were classified as conventional MS (CMS) 13, neuromyelitis optica (NMO) 7, and isolated LEM 6. LEM was the initial presentation in 13/26 cases. In CMS cases lesions were mainly in the lower cervical cord (C4-C7) whereas in NMO and isolated LEM they were more often thoracic and were longer. The severity of disability was highly variable but was greater in the NMO than the CMS group. Only one of 20 patients tested was seropositive for AQP4-IgG. CONCLUSION: LEM occurred as part of CMS or NMO or in isolation. Patients with LEM had highly heterogeneous clinical characteristics and a low rate of AQP4-IgG seropositivity.
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Bases de Datos Factuales , Enfermedades Desmielinizantes/epidemiología , Enfermedades de la Médula Espinal/epidemiología , Población Blanca/estadística & datos numéricos , Adulto , Acuaporina 4 , Australia/epidemiología , Áreas de Influencia de Salud , Enfermedades Desmielinizantes/inmunología , Enfermedades Desmielinizantes/patología , Evaluación de la Discapacidad , Femenino , Humanos , Inmunoglobulina G/inmunología , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Médula Espinal/patología , Enfermedades de la Médula Espinal/inmunología , Enfermedades de la Médula Espinal/patologíaRESUMEN
BACKGROUND: The diversity of multiple sclerosis (MS) and the nosology of the conventional form of MS (CMS), optic-spinal MS (OSMS) and neuromyelitis optica (NMO) have been subject to controversy. AIMS: The purpose of this study was to investigate whether the current Asian optic-spinal multiple sclerosis (OSMS) criteria could also apply in Western countries, and whether or not cerebrospinal fluid (CSF) and imaging features in the Western Australian patient population of demyelinating disease was similar to that found in Asia. METHODS: This study retrospectively reviewed 915 individual case notes with central nervous system demyelinating disease seen by two neurologists in Western Australia (WA). 842 cases had sufficient data to be included in the analysis. The patient population was predominantly Caucasian, representing approximately two-thirds of MS cases in WA. The mean duration of follow-up for the whole studied cohort was 12.5 years, with 136 patients (16.2%) being followed-up for more than 20 years. RESULTS: The study confirmed the relatively low frequency of OSMS as a proportion of total demyelinating disease occurring in western countries, with 31 OSMS (3.7%) cases in contrast to 703 CMS cases (83.5%). It is likely, however, that our retrospective classification significantly underestimated the proportion of OSMS cases when compared with prospectively classified Asian cohorts. There were 11 OSMS cases that could also be classified as NMO according to published diagnostic criteria. The remainder of the spectrum comprised clinically isolated syndromes such as 50 acute myelitis (AM, 5.9%), 42 optic neuritis (ON, 5%) and 16 "atypical" cases such as tumefactive MS and acute disseminated encephalomyelitis (1.9%). The clinical characteristics of OSMS in our study were compatible with so-called Asian MS in many respects: oligoclonal bands (OCBs) were less frequent in OSMS (29.4%) than in CMS (66.4%, p = 0.003); visual evoked potentials and spinal MRI abnormalities were more prevalent in OSMS (85% and 92.6%) than in CMS (71.4% and 85%); as were long spinal cord lesions in OSMS (22.2%) versus CMS (3.4%, p,0.001). Brain abnormalities were seen in 48.4% of OSMS patients and 96.2% of CMS patients (p = 0.001). OCBs were identified in 7% of acute myelitis, 14.3% of optic neuritis and 73.4% of primary progressive MS patients. CONCLUSIONS: This cross-sectional study presents the full spectrum of demyelinating disease in WA, which has a stable population representing 10% of the total Australian population and suggests that the current classifications of MS, OSMS or NMO, ON and AM share many clinical and laboratory features, such as female predominance, age at onset, duration of disease and CSF investigations (including OCBs and MRI). Moreover, characteristics of the WA population were similar to those reported in Asian patients.