RESUMO
BACKGROUND: Brain metastases (BMs) are the most serious complication of lung cancer, affecting the prognosis of lung cancer patients, and pose distinct clinical challenges. This study was designed to explore the prognostic factors related to lung cancer BM and the value of surgical resection in BMs from lung cancer. METHODS: A retrospective analysis was performed on 714 patients with lung cancer BMs screened between January 2010 and January 2018 at the Sun Yat-sen University Cancer Center. A 1:1 propensity score matching analysis was performed to reduce the potential bias between the surgery and the nonsurgery group. In both the raw and the propensity-score matched dataset, univariate and multivariate Cox proportional hazards regression analyses were used to evaluate risk factors for survival. RESULTS: After matching, 258 patients (129 surgery, 129 no surgery) were analyzed. Multivariate analyses after propensity score matching demonstrated that surgical resection was an independent protective factor for overall survival (OS), and older age, lower Karnofsky Performance Scale (KPS) score, and extracranial metastases were independent risk factors for worse OS. Patients without extracranial metastases, without synchronous BM and with a single BM had a better prognosis. CONCLUSIONS: The findings showed that surgical resection, age, KPS score, and extracranial metastases are independent prognostic factors for predicting the OS of patients with lung cancer BMs, and surgical resection for brain metastatic lesions could significantly improve the OS. However, only certain groups of patients with BMs can benefit from intracranial lesion resection, such as no extracranial metastases and metachronous metastases.
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Neoplasias Encefálicas , Neoplasias Pulmonares , Neoplasias Encefálicas/secundário , Estudos de Coortes , Humanos , Neoplasias Pulmonares/patologia , Prognóstico , Estudos RetrospectivosRESUMO
Protein tyrosine phosphatase non-receptor type 21 (PTPN21) has been recognised as a new tumour-associated protein that is implicated in diverse tumours. However, the correlation between PTPN21 and glioma remains unaddressed. This investigation focused on the relevance of PTPN21 in glioma. The Cancer Genome Atlas (TCGA) analysis identified PTPN21 as being up-regulated in glioma tissue. The elevation of PTP21 in glioma was validated by evaluating clinical specimen. Kaplan-Meier plot analysis revealed that a high PTPN21 level predicted poor survival rate in glioma patient. Silencing of PTPN21 produced remarkable anticancer effects in glioma cells including proliferation inhibition, cell cycle arrest, metastasis suppression and enhanced chemosensitivity. Mechanistic studies uncovered that PTPN21 contributes to mediation of the phosphatidyl-inositole-3 kinase (PI3K)/AKT pathway via the regulation of epidermal growth factor receptor (EGFR). Restraint of EGFR diminished PTPN21 overexpression-induced promoting effect on PI3K/AKT pathway. Reactivation of AKT reversed PTPN21 silencing-evoked antitumor effect. The tumorigenic potential of PTPN21-silenced glioma cells in vivo was markedly compromised. In summary, this study demonstrates that silencing of PTPN21 produces remarkable anticancer effects in glioma by restraining the EGFR/PI3K/AKT pathway.
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Glioma , Fosfatidilinositol 3-Quinases , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células , Receptores ErbB/genética , Receptores ErbB/metabolismo , Glioma/tratamento farmacológico , Glioma/genética , Glioma/metabolismo , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de SinaisRESUMO
Improving the chemotherapy resistance of temozolomide (TMZ) is of great significance in the treatment of glioblastoma multiforme (GBM). Long non-coding RNA just proximal to the X-inactive specific transcript (JPX) has been proven to be involved in cancer progression. However, the intrinsic significance and molecular mechanism by which JPX orchestrates GBM progression and TMZ chemotherapy resistance remain poorly understood. Here, JPX was found to be significantly elevated in GBM tissues and cell lines, and patients with high expressions of JPX showed significantly worse prognoses. Functional experiments revealed its carcinogenic roles in GBM cell proliferation, TMZ chemoresistance, anti-apoptosis, DNA damage repair, and aerobic glycolysis. Mechanistically, JPX formed a complex with phosphoinositide dependent kinase-1 (PDK1) messenger RNA (mRNA) and promoted its stability and expression. Furthermore, an RNA immunoprecipitation (RIP) experiment showed that JPX interacted with N6-methyladenosine (m6A) demethylase FTO alpha-ketoglutarate dependent dioxygenase (FTO) and enhanced FTO-mediated PDK1 mRNA demethylation. JPX exerted its GBM-promotion effects through the FTO/PDK1 axis. Taken together, these findings reveal the key role of JPX in promoting GBM aerobic glycolysis and TMZ chemoresistance in an m6A-dependent manner. Thus, it comprises a promising novel therapeutic target for GBM chemotherapy.
Assuntos
Antineoplásicos Alquilantes/farmacologia , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , RNA Longo não Codificante/metabolismo , Temozolomida/farmacologia , Adenosina/análogos & derivados , Adenosina/metabolismo , Aerobiose , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Desmetilação , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Glioblastoma/tratamento farmacológico , Glioblastoma/mortalidade , Glioblastoma/patologia , Glicólise , Humanos , Proteínas de Neoplasias/metabolismo , Prognóstico , RNA Mensageiro/metabolismoRESUMO
OBJECTIVE: The efficacy and safety of deep brain stimulation (DBS) under general anesthesia for the treatment of dystonia have not yet been confirmed with high level of evidence. This meta-analysis with pooled individual patient data aims to assess the clinical outcomes and identify the potential prognostic factors of dystonia patients who underwent general anesthesia DBS. METHODS: We searched PubMed, Web of Science, and Embase for articles describing patients with dystonia who underwent asleep DBS and had individual Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores. The relative improvement in BFMDRS scores was considered the primary outcome. Pearson correlation analyses and multivariate linear regression analysis were conducted to explore the prognostic factors. RESULTS: A total of 34 studies involving 341 patients were included. The mean postoperative improvement in BFMDRS-M (BFMDRS movement subscale) and BFMDRS-D (BFMDRS disability subscale) scores were 58.6±36.2% and 48.5±38.7% at the last follow-up visit, respectively, with a mean follow-up time of 22.4±27.6 months. Age at surgery and disease duration showed a negative correlation with the percent improvement of BFMDRS-M (%) at the last visit (r=-0.134, P=0.013; r=-0.165, P=0.006). In the stepwise multivariate regression, only disease duration remained a relevant factor. Additionally, the adverse events were acceptable. CONCLUSION: General anesthesia DBS is a safe, effective, and feasible option for dystonia patients in the long term. Shorter disease duration predicts better clinical outcomes.
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Estimulação Encefálica Profunda , Distonia , Distúrbios Distônicos , Anestesia Geral , Distonia/terapia , Distúrbios Distônicos/terapia , Globo Pálido , Humanos , Resultado do TratamentoRESUMO
INTRODUCTION: Total resection of meningiomas involving the major dural sinuses (MIMDS) is still challenging for neurosurgeons. Gamma knife radiosurgery (GKRS) was shown to have a high probability of tumor control. The current study evaluated the clinical outcomes of patients who underwent subtotal resection alone or in combination with postoperative GKRS for the treatment of WHO grade I MIMDS. METHODS: From January 2006 to December 2016, 204 patients with MIMDS underwent Simpson IV subtotal resection in Wuhan Union Hospital. In 151 patients, no additional treatment was performed, while the tumor remnant was treated with GKRS in 53 patients. All patients were monitored with regular MR follow-ups. We retrospectively reviewed the clinical data, radiological characteristics, and outcomes of these 204 patients. Progression-free survival (PFS) was determined by Kaplan-Meier analysis. Related factors were determined by univariate Cox regression analyses. RESULTS: The mean follow-up period was 75.5 months. The tumor recurrence/progression rates were 13.9% in the microsurgery group and 3.8% in the combined therapy group (p = 0.045). The 5- and 10- year progression-free survival (PFS) rates were 92.3 and 80.7%, respectively, in the microsurgery group and 100.0 and 88.5% in the combined therapy group. Treatment approach was found to be an independent prognostic factor for tumor recurrence/progression in the univariable analyses (p=0.04). CONCLUSIONS: Compared with microsurgery alone, targeted Simpson grade IV resection combined with early gamma knife treatment resulted in longer progression-free survival without increased complications for WHO grade I MIMDS.
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Cavidades Cranianas/cirurgia , Dura-Máter/cirurgia , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirurgia , Meningioma/radioterapia , Meningioma/cirurgia , Cuidados Pós-Operatórios , Radiocirurgia , Adolescente , Adulto , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Complicações Pós-Operatórias/etiologia , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Deep brain stimulation (DBS) is considered an effective and safe treatment for patients with primary Meige syndrome (MS). Both the subthalamic nucleus (STN) and globus pallidus pars internus (Gpi) have been shown to be optional targets for electrode implantation to improve clinical symptoms, but the relationship between clinical outcomes and target is still unclear. The current study aims to compare the clinical outcomes of DBS with different electrode targets for primary MS. MATERIALS AND METHODS: We performed a retrospective study to assess the clinical outcomes for 17 consecutive patients with primary MS in Wuhan Union Hospital from January 2016 to September 2019. Six patients were treated by Gpi-DBS and 11 patients were treated by STN-DBS. All patients were assessed before surgery and at the last follow-up after surgery. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) including the movement and disability scales was used to evaluate the dystonia severity of the eyes, the mouth, speech, and swallowing. The median follow-up duration was 30.1 ± 13.1 months (range 6 months-52 months). RESULTS: In our study, DBS improved the BFMDRS-M scores by 70.52 ± 7.45% and the BFMDRS-D scores by 70.51 ± 8.38% for patients with MS. STN-DBS and Gpi-DBS had similar effects not only on the BFMDRS-M and BFMDRS-D scores, but also on the subitems including eyes, mouth, speech, and swallowing. The stimulation voltage for the Gpi was significantly higher than that for the STN. The improvements were similar in the general anesthesia and local anesthesia groups (p > 0.05). CONCLUSION: The curative effects of STN-DBS and Gpi-DBS on patients with primary MS are similar. Both the STN and Gpi could be effective targets of DBS for primary MS.
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Estimulação Encefálica Profunda , Síndrome de Meige , Eletrodos , Globo Pálido , Humanos , Síndrome de Meige/terapia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A Gram-stain-negative, non-motile, coccus-shaped, catalase- and oxidase-positive, facultatively anaerobic and pink-pigmented bacterium, designated strain CQN31T, was isolated from sediment of Changqiaohai Lake, Yunnan Province, China. Growth occurred at 4-45 °C (optimum, 37 °C), at pH 6.5-9.5 (optimum, pH 8.0) and with 0-1â% (w/v) NaCl (optimum, 0â%). C18â:â1 ω7c/C18â:â1 ω6c and C16â:â0 were the predominant fatty acids. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), diphosphatidylglycerol (DPG), phosphatidyldimethylethanolamine (PME) and one unidentified aminolipid (AL) were the major polar lipids. The G+C content of the genomic DNA was 71.5â%. 16S rRNA gene sequence comparisons indicated that strain CQN31T shared 96.8â% similarity with Roseomonas wooponensis JCM 19527T and 95.9â% with R. terricola EM0302T. Digital DNA-DNA hybridization values between strain CQN31T and Roseomonas stagni DSM 19981T, R. rosea DSM 14916T and R. mucosa NCTC 13291T were 21.0, 19.4 and 19.8â%, respectively. Average amino acid identity and average nucleotide identity values between strain CQN31T and R. stagni DSM 19981T, R. rosea DSM 14916T and R. mucosa NCTC 13291T were 73.7, 63.4 and 61.9 %, and 79.2, 77.1 and 77.5%, respectively. Distinct morphological, physiological and genotypic differences from previously described taxa support the classification of strain CQN31T as a representative of a novel species in the genus Roseomonas, for which the name Roseomonas bella sp. nov. is proposed. The type strain is CQN31T (=KCTC 62447T=MCCC 1H00309T).
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Sedimentos Geológicos/microbiologia , Lagos/microbiologia , Methylobacteriaceae/classificação , Filogenia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Methylobacteriaceae/isolamento & purificação , Hibridização de Ácido Nucleico , Fosfolipídeos/química , Pigmentação , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
We aimed to develop a high-throughput deep DNA sequencing assay of cerebrospinal fluid (CSF) to identify clinically relevant oncogenic mutations that contribute to the development of glioblastoma (GBM) and serve as biomarkers to predict patients' responses to surgery. For this purpose, we recruited five patients diagnosed with highly suspicious GBM according to preoperative magnet resonance imaging. Subsequently, patients were histologically diagnosed with GBM. CSF was obtained through routine lumbar puncture, and plasma from peripheral blood was collected before surgery and 7 days after. Fresh tumor samples were collected using routine surgical procedures. Targeted deep sequencing was used to characterize the genomic landscape and identify mutational profile that differed between pre-surgical and post-surgical samples. Sequence analysis was designed to detect protein-coding exons, exon-intron boundaries, and the untranslated regions of 50 genes associated with cancers of the central nervous system. Circulating tumor DNAs (ctDNAs) were prepared from the CSF and plasma from peripheral blood. For comparison, DNA was isolated from fresh tumor tissues. Non-silent coding variants were detected in CSF and plasma ctDNAs, and the overall minor allele frequency (MAF) of the former corresponded to an earlier disease stage compared with that of plasma when the tumor burden was released (surgical removal). Gene mutation loads of GBMs significantly correlated with overall survival (OS, days) (Pearson correlationâ¯=â¯-0.95, Pâ¯=â¯0.01). We conclude that CSF ctDNAs better reflected the sequential mutational changes of driver genes compared with those of plasma ctDNAs. Deep sequencing of the CSF of patients with GBM may therefore serve as an alternative clinical assay to improve patients' outcomes.
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Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Glioblastoma/genética , Proteínas de Neoplasias/genética , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/líquido cefalorraquidiano , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/líquido cefalorraquidiano , Intervalo Livre de Doença , Feminino , Glioblastoma/sangue , Glioblastoma/líquido cefalorraquidiano , Glioblastoma/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/líquido cefalorraquidiano , Resultado do TratamentoRESUMO
PURPOSE: This paper examines the application of 3D printing technology in the endoscopic endonasal approach for the treatment of macroadenomas. METHODS: We have retrospectively analysed 20 patients who diagnosed with macroadenoma underwent endoscopic transsphenoidal surgery in Wuhan Union hospital from January 2017 to May 2017. Among the 20 patients, 10 patients received the service of 3D printing technology preoperatively. The data of 3D processing and clinical result were recorded for further evaluation. RESULTS: The 10 patients who received the service had a successful 3D printed model of their tumors, it shows the anatomy of sphenoid sinus, tumor location which were in good agreement with our intraoperative observations. The 10 patients who received the service had a less operation time (127.0 ± 15.53 vs. 143.40 ± 17.89), blood loss (159.90 ± 12.31 vs. 170.00 ± 29.06) and less postoperative complication rate (20% vs. 40%). the design time of the 3D images varies 2 h 10 min to 4 h 32 min. the printing time of the 3D models varies 10 h 12 min to 22 h 34 min. CONCLUSIONS: The use of 3D printing technology has unquestionable potential applications to endoscopic endonasal approach for macroadenomas, in particular reflecting the complicated anatomy of sphenoid sinus and tumor location. Owing to the advantages of 3D printing technology, it may help the patients get a good prognosis.
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Adenoma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Impressão Tridimensional , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Seio Esfenoidal/cirurgiaRESUMO
PURPOSE: To evaluate the incidence, type and risk factors of cement leakage (CL) with cement-augmented pedicle screw instrumentation (CAPSI) in degenerative lumbosacral disease. METHODS: Two hundred and two patients using a total of 950 cement-augmented screws were enrolled. CL was classified into three types: type S: leakage via segmental veins; type B: leakage via basivertebral veins; and type I: leakage via pedicle screw instrumentation to paravertebral soft tissue. The age, gender, operation stage (primary or later stage), body mass index, bone mineral density, the number and type of augmented screw, the position of the tip of screw (lateral or internal part of vertebral body), the position of screw (left or right side), the volume of bone cement, location of the augmented vertebra (lumbar or sacrum), the type of CL and complications were recorded. Binary logistic regression correlation was used to analyze risk factors of veins leakage (type S and type B). RESULTS: The CL was observed in 165 patients (81.68%) and 335 screws (35.26%), leakage types of S, B and I were seen in 255 (76.12%), 77 (22.99%), and 30 (8.96%) of screws, respectively. Besides, double or multiple routes of leakage were seen in 27 screws. Number of augmented screw was a risk factor for vein leakage (OR 0.58; 95% CI 0.44-0.77; P = 0.000). Furthermore, the doses of cement (OR 0.79; 95% CI 0.61-0.99; P = 0.038) and the position of screw (OR 0.39; 95% CI 0.29-0.53; P = 0.000) were identified as risk factors for type S, and the doses of bone cement (OR 0.37; 95% CI 0.25-0.54; P = 0.000) and the position of the tip of screw (OR 0.07; 95% CI 0.04-0.13; P = 0.000) were risk factors for type B. CONCLUSIONS: CAPSI bears a high risk of asymptomatic CL, with a higher rate of leakage into segmental veins and basivertebral veins. As is known, more augmented screws and larger doses of cement are risk factors for veins leakage (type S and type B), while the tip of screw approaching to the midline of the vertebral body is another risk factor to type B. Thus, the CL could be reduced by the amelioration of operative techniques and procedures. These slides can be retrieved under Electronic Supplementary Material.
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Cimentos Ósseos/efeitos adversos , Vértebras Lombares/cirurgia , Parafusos Pediculares , Complicações Pós-Operatórias/etiologia , Sacro/cirurgia , Doenças da Coluna Vertebral/cirurgia , Fusão Vertebral/instrumentação , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Resultado do TratamentoRESUMO
Both microscopic and endoscopic transsphenoidal surgery are effective approaches for nonfunctioning pituitary adenomas. The issue on the comparison of their efficacy and safety remains inconsistent. A thorough search of the literatures (PubMed, EMBASE, MEDLINE) were performed up to March 2017. Studies reporting outcomes of microscopic or endoscopic transsphenoidal surgery on nonfunctioning pituitary adenomas were included. A meta-analysis was performed focusing on the early stage and long term outcomes. The final search yielded 19 eligible studies enrolling 3847 patients, 389 of them underwent microscopic approach and 3458 of them with endoscopic approach. As to the early stage outcomes, the rate of gross tumor resection was significantly higher in the endoscopic group than that in microscopic group (73% versus 60%, P < 0.001). Meanwhile, endoscopic approach showed priority over microscopy on postoperative hypopituitarism (63% versus 65%, P < 0.001) and CSF leakage (3% versus 7%, P < 0.001). For the long term outcomes, the rate of visual improvement was significant higher in the endoscopic group than that in microscopic group (77% versus 50%, P < 0.001). However, there was no significant difference between the groups regarding the rate of permanent diabetic insipidus and meningitis. The endoscopic approach may be associated with higher rate of gross tumor movement and lower risk of postoperatively complications for treating nonfunctioning pituitary adenoma, when compared with microscopic approach. However, the confidence was shorted due to limited high quality evidence (largely randomized and controlled studies).
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Adenoma/cirurgia , Diabetes Insípido/diagnóstico , Endoscopia/métodos , Hipopituitarismo/diagnóstico , Meningite/diagnóstico , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/diagnóstico , Adenoma/patologia , Diabetes Insípido/etiologia , Diabetes Insípido/fisiopatologia , Feminino , Humanos , Hipopituitarismo/etiologia , Hipopituitarismo/fisiopatologia , Masculino , Meningite/etiologia , Meningite/fisiopatologia , Pessoa de Meia-Idade , Neoplasias Hipofisárias/patologia , Complicações Pós-Operatórias/fisiopatologia , Osso Esfenoide/cirurgia , Resultado do Tratamento , Acuidade VisualRESUMO
BACKGROUND/AIMS: Plastrum testudinis extracts (PTE) show osteoprotective effects on glucocorticoid-induced osteoporosis in vivo and in vitro. However, the underlying molecular mechanism of PTE in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is unclear. METHODS: BMSC proliferation was investigated using the Cell Counting Kit-8 assay. BMSC differentiation and osteogenic mineralization were assayed using alkaline phosphatase and Alizarin red staining, respectively. The mRNA expression levels of Let-7f-5p, Tnfr2, Traf2, Pi3k, Akt, ß-catenin, Gsk3ß, Runx2, and Ocn were measured using real time quantitative polymerase chain reaction. Protein levels of TNFR2, TRAF2, p-PI3K, p-AKT, p-ß-CATENIN, and p-GSK3ß were analyzed by western blotting. The functional relationship of Let-7f-5p and Tnfr2 was determined by luciferase reporter assays. RESULTS: The optimum concentration for PTE was 30 µg/ml. PTE significantly promoted BMSC osteogenic differentiation and mineralization after 7 and 14 days in culture, respectively. The combination of PTE and osteogenic induction exhibited significant synergy. PTE upregulated Let-7f-5p, ß-catenin, Runx2, and Ocn mRNA expression, and downregulated Tnfr2, Traf2, Pi3k, Akt, and Gsk3ß mRNA expression. PTE inhibited TNFR2, TRAF2, and p-ß-CATENIN protein expression, and promoted p-PI3K, p-AKT, and p-GSK3ß protein expression. In addition, Tnfr2 was a functional target of Let-7f-5p in 293T cells. CONCLUSIONS: Our results suggested that PTE may promote BMSC proliferation and osteogenic differentiation via a mechanism associated with the regulation of Let-7f-5p and the TNFR2/PI3K/AKT signaling pathway.
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Células da Medula Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/biossíntese , Osteogênese/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/biossíntese , Proteínas Proto-Oncogênicas c-akt/biossíntese , Receptores Tipo II do Fator de Necrose Tumoral/biossíntese , Transdução de Sinais/efeitos dos fármacos , Extratos de Tecidos/farmacologia , Animais , Células da Medula Óssea/citologia , Feminino , Células-Tronco Mesenquimais/citologia , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Surgical procedures are critical in making a conclusive histopathological diagnosis of primary central nervous system lymphoma (PCNSL), which typically presents contrast-enhancing lesions in magnetic resonance imaging (MRI). The fluorescein sodium-guided technique could enhance tumor visibility. We reported a series of patients with PCNSL underwent fluorescein sodium-guided surgical procedures. PATIENTS AND METHODS: 12 patients clinically considered brain tumors underwent fluorescein sodium-guided surgery in Sun Yat-sen University Cancer Center from March 2016 to July 2017. The age of 4 female and 8 male patients ranges from 39 to 62 years. In 4 patients, corticosteroid had been prescribed before surgery due to intracranial hypertension. After injection of low dose of sodium fluorescein (3-5 mg/kg), the lesions with strong fluorescence staining were identified as the target area for biopsy or resection. RESULTS: Based on the targeted tissues with bright and homogenous fluorescence staining, all 12 patients were conclusively diagnosed as B cell non-Hodgkin's lymphoma (diffuse large cell). The specificity of the specimens sent for frozen section was 86.4% (19/22). No fluorescein sodium associated side effects were observed. CONCLUSION: Fluorescein sodium guided surgery is an effective and safe tool in biopsy or tumor resection in patients suspicious for PCNSL with preoperative MRI presented contrast-enhanced homogenous lesions. Such technique might still be considered in those patients who have been pretreated with corticosteroid.
Assuntos
Neoplasias Encefálicas/cirurgia , Meios de Contraste , Fluoresceína , Biópsia Guiada por Imagem , Linfoma/cirurgia , Cirurgia Assistida por Computador , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Feminino , Humanos , Linfoma/diagnóstico por imagem , Linfoma/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Procedimentos NeurocirúrgicosRESUMO
Preoperative prognostic nutritional index (PNI) has been widely demonstrated to predict survival of patients with malignant tumors. Its utility in predicting outcomes in patients with high-grade gliomas (HGG) remains undefined. A retrospective study of 188 HGG patients was conducted. An optimal PNI cut-off value was applied to stratify patients into high PNI (≥52.55, n = 78) and low PNI (<52.55, n = 110) groups. Univariate and multivariate analysis was performed to identify prognostic factors associated with overall survival (OS) and progression free survival (PFS). The resulting prognostic models were externally validated using a demographic-matched cohort of 130 HGG patients. In the training set, PNI value was negatively correlated with age (p = 0.027) and tumor grade (p = 0.048). Both PFS (8.27 vs. 20.77 months, p < 0.001) and OS (13.57 vs. 33.23 months, p < 0.001) were significantly worse in the low PNI group. Strikingly, patients in high PNI group had a 52% decrease in the risk of tumor progression and 55% decrease of death relative to low PNI. Multivariate analysis further demonstrated PNI as an independent predictor for PFS (HR = 0.62, 95% CI 0.43-0.87) and OS (HR = 0.56, 95% CI 0.38-0.80). The PNI retained independent prognostic value in the validation set for both PFS (p = 0.013) and OS (p = 0.003). On subgroup analysis by tumor grade and treatment modalities, both PFS and OS were better for the patients with high PNI. The PNI is a potentially valuable preoperative marker for the survival of patients following HGG resection.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidade , Glioma/diagnóstico , Glioma/mortalidade , Avaliação Nutricional , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Neoplasias Encefálicas/cirurgia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Glioma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: Hyperprolactinemia has been associated with endothelial dysfunction and a wide range of cardiovascular risk factors, thus it can potentially lead to cardiac dysfunction. The present study was designed to interrogate our hypothesis that hyperprolactinemia can contribute to preclinical impaired left ventricular function. METHODS: Thirty-one prolactinoma patients and 60 healthy volunteers were prospectively recruited. Left ventricular function was evaluated using conventional two dimensions and M-mode echocardiography, as well as Doppler tissue imaging (DTI). RESULTS: The Tei index (0.45 ± 0.06 vs. 0.41 ± 0.03, P = .005) and ratio of transmitral and myocardial early diastolic velocities (E/Em; 6.30 ± 1.45 vs. 5.64 ± 0.69, P = .045) were significantly higher, and septal systolic velocity (Sm; 9.88 ± 1.45 vs. 11.58 ± 1.28 cm/s, P<.001) was significantly lower in prolactinoma patients. Furthermore, significant motional abnormalities were detected in regional segments of prolactinoma patients. Pearson's correlation analysis revealed that prolactin level was inversely associated with Sm (r = -0.373, P = .009) and late diastolic phase (Am; r = -0.293, P = .043). Moreover, inverse correlations between prolactin and partial left ventricular segment wall motion were found, including the basal (r = -0.363, P = .014), middle (r = -0.418, P = .004), and apical segment (r = -0.574, P<.001) of the posterior ventricular septum. Multivariate linear regression analysis revealed that prolactin (ß = -0.28, 95% confidence interval -0.011 to 0, P = .035), as a single factor, can significantly predict decreased Sm, independent of traditional vascular risk factors. CONCLUSION: Our results suggest that subclinical cardiac dysfunction occurs in untreated prolactinoma patients and is characterized by impaired systolic and diastolic function of the left ventricle, as well as regional segment motional abnormality. ABBREVIATIONS: A = transmitral late diastolic velocity Am = late diastolic phase Apo = apolipoprotein DTI = Doppler tissue imaging E = transmitral early diastolic velocity Em = myocardial early diastolic velocity FMD = flow-mediated dilation HOMA-IR = homeostasis model assessment of insulin resistance hsCRP = high-sensitivity C-reactive protein IMT = intima media thickness LDL-C = low-density lipoprotein cholesterol LV = left ventricular PPCM = postpartum cardiomyopathy Sm = septal systolic velocity.
Assuntos
Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/fisiopatologia , Prolactinoma/complicações , Prolactinoma/fisiopatologia , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Ecocardiografia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/diagnóstico , Prolactinoma/diagnóstico , Fatores de Risco , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
Recent studies have shown that circulating serotonin plays a potential role in bone metabolism. However, conflicting results have been reported for the relationship between serum serotonin concentrations and bone mineral density (BMD). We investigated whether the serum serotonin concentrations related to BMD in Chinese postmenopausal women. Serum serotonin and bone turnover concentrations of 117 premenopausal women and 262 asymptomatic postmenopausal women were analyzed by enzyme-linked immunosorbent assay. BMD at the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry. The relationship between serotonin and BMD was investigated. The postmenopausal women had lower mean serum serotonin concentrations compared to the premenopausal women. Serotonin concentrations were negatively associated with age, weight, BMI, fat mass, and ß-CTX concentrations in postmenopausal women. No significant correlations were found between serotonin and these parameters in premenopausal women. In postmenopausal women, age- and BMI-adjusted serotonin concentrations were positively correlated with BMD of the lumbar spine and femoral neck. Multiple regression analyses showed serum serotonin and ß-CTX were the predictors for lumbar spine BMD. Only serum serotonin was the determinant for femoral neck BMD. In conclusion, lower serum serotonin concentrations are linked to low lumbar spine and femoral neck BMD in postmenopausal women.
Assuntos
Densidade Óssea , Colágeno Tipo I/sangue , Fraturas Ósseas/sangue , Peptídeos/sangue , Pós-Menopausa/sangue , Serotonina/sangue , Absorciometria de Fóton , Tecido Adiposo , Adulto , Idoso , Povo Asiático , Biomarcadores/sangue , Índice de Massa Corporal , Peso Corporal , Remodelação Óssea , Estudos Transversais , Feminino , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/metabolismo , Colo do Fêmur/patologia , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/etnologia , Fraturas Ósseas/patologia , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/metabolismo , Vértebras Lombares/patologia , Pessoa de Meia-Idade , Pós-Menopausa/etnologia , Pré-Menopausa/sangue , Pré-Menopausa/etnologiaRESUMO
BACKGROUND: Burr hole craniostomy is a widely used method for the evacuation of CSDH. However it is not clear whether the irrigation during operation improves the prognosis or gives rise to additional complications instead. This retrospective cohort study was conducted to determine this issue. METHODS: Patients attending two medical centers in China who underwent burr hole drainage with irrigation (BHDI) or burr hole drainage without irrigation (BHD) for unilateral CSDH during January 2013 to December 2016 were included in this study. The patients' clinical information and follow-up data were retrospectively reviewed, and the radiologic findings were processed using the 3D Slicer software. The differences in outcomes were identified using t-test, chi-square test, or Fisher's exact test. RESULTS: A total of 151 patients comprising 63 patients in the BHD group and 88 patients in the BHDI group were included. Patients in the BHDI group had a higher volume of pneumocrania on the first postoperative day than that of patients in the BHD group (p < 0.05). No significant differences were observed between the two approaches in rates of rebleeding, recurrence and other complications (p > 0.05). CONCLUSIONS: Irrigation had no improvement in the long-term curative effect on CSDH, but it increased the risk of short-term complication in terms of pneumocrania. Therefore, this study suggests that irrigation is not an obligatory procedure during burr hole drainage.
Assuntos
Craniotomia/métodos , Drenagem/métodos , Hematoma Subdural Crônico/cirurgia , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Recidiva , Estudos Retrospectivos , Irrigação TerapêuticaRESUMO
BACKGROUND: Low-level expression of O(6) methylguanine-DNA-methyl transferase (MGMT) prolactinomas has been noted previously in case reports, although what modulates MGMT expression remains unclear. This study therefore aimed to delineate the factors regulating MGMT expression in prolactinomas. METHODS: We retrospectively reviewed 136 prolactinoma patients who were treated in our center between January 2000 and September 2013. Expression of MGMT, Ki-67, and p53 protein were examined by immunohistochemical staining, and MGMT promoter methylation evaluated with methylation-specific PCR. RESULTS: MGMT immunopositivity was <25 % in 106/136 tumor specimens (77.94 %). MGMT immunoexpression was positively correlated with age (r = 0.251, p = 0.003), but inversely correlated with p53 staining (r = -0.153, p = 0.021). Moreover, reduced MGMT expression was more frequent in atypical prolactinomas (p = 0.044). Methylated MGMT promoter was confirmed in 10/46 specimens (21.7 %), all of which had low level or absent MGMT staining. Both p53 protein (r = -0.33, p = 0.025) and promoter methylation (r = -0.331, p = 0.025) were negatively associated with MGMT expression. Multivariate logistic analysis indicated that age (odds ratio [OR] = 1.127. 95 % confidence interval [CI] 1.027-1.236, p = 0.012) and p53 (OR = 0.116. 95 % CI 0.018-0.761, p = 0.025) staining were independent determents of MGMT expression. CONCLUSIONS: The majority of prolactinomas, especially atypical prolactinomas, showed low-level or no MGMT immunoexpression, providing a rationale for the utility of temozolomide as an alternative to managing prolactinomas. In summary, epigenetic and transcriptional regulation are involved in silencing MGMT expression.
Assuntos
Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , O(6)-Metilguanina-DNA Metiltransferase/genética , Neoplasias Hipofisárias/genética , Prolactinoma/genética , Adolescente , Adulto , Idoso , Metilação de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , O(6)-Metilguanina-DNA Metiltransferase/metabolismo , Razão de Chances , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Prolactinoma/metabolismo , Prolactinoma/patologia , Regiões Promotoras Genéticas , Estudos Retrospectivos , Carga Tumoral , Proteína Supressora de Tumor p53/metabolismo , Adulto JovemRESUMO
BACKGROUND: According to some clinical studies, insufficient cement distribution (ID) in the fractured area and asymmetrical cement distribution around the fractured area were thought to be the reasons for unrelieved pain and recollapse after percutaneous vertebral augmentation (PVA) in the treatment of symptomatic osteoporotic vertebral compression fractures. METHODS: Finite element methods were used to investigate the biomechanical variance among three patterns of cement distribution (ID and sufficient cement distribution in the fractured area and asymmetrical cement distribution around the fractured area including upward [BU] and downward [BD] cement distribution). RESULTS: Compared with fractured vertebra before PVA, distribution of von Mises stress in the cancellous bone was transferred to be concentrated at the cancellous bone surrounding cement after PVA, whereas it was not changed in the cortical bone. Compared with sufficient cement distribution group, maximum von Mises stress in the cancellous bone and cortical bone and maximum displacement of augmented vertebra increased significantly in the ID group, whereas asymmetrical cement distribution around the fractured area in BU and BD groups mainly increased maximum von Mises stress in the cancellous bone significantly. Similar results could be seen in all loading conditions. CONCLUSIONS: ID in the fractured area may lead to unrelieved pain after PVA in the treatment of symptomatic osteoporotic vertebral compression fractures as maximum displacement of augmented vertebral body increased significantly. Both ID in the fractured area and asymmetrical cement distribution around the fractured area are more likely to induce recollapse of augmented vertebra because they increased maximum von Mises stress in the cancellous bone and cortical bone of augmented vertebra significantly.
Assuntos
Cimentos Ósseos , Fraturas por Compressão/terapia , Modelos Biológicos , Fraturas por Osteoporose/terapia , Fraturas da Coluna Vertebral/terapia , Fenômenos Biomecânicos , Análise de Elementos Finitos , Humanos , Imageamento TridimensionalRESUMO
OBJECTIVE: To establish a method of detecting spinal tuberculosis (TB) infection by enzyme-linked immunospot (ELlSPOT) assay and evaluate the value of CFP10/ESAT6 fusion protein for diagnosis of spinal TB. METHODS: Suspected spinal TB patients were prospectively recruited in two hospitals (First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine; Nanfang Hospital, Southern Medical University) from May 2012 to December 2013. Data on clinical characteristics of the patients and conventional laboratory results were collected. Compare and analyze the positive detection rate in spinal TB diagnosis by different methods including ELISPOT detection and conventional detection methods. RESULTS: 47 patients with spinal TB had available biopsy or surgical specimens for histopathological examination and 41 specimens had pathological features consistent with a diagnosis of TB infection. Among the spinal TB patients and non-TB disease patients,the overall sensitivity, specificity, positive predictive value, and negative predictive value of the ELISPOT assay in spinal TB diagnosis were 82.7%,87.2%,89.6%, and 79.1%,respectively; the 4 indexes of the PPD skin test were 61.5%, 46.2%, 60.4%, and 47.4%, respectively;those of the antibody detection were 55.8%, 61.5%, 65.9%, and 51.1%. The positive rate of ELISPOT was significantly higher than those of PPD skin test and antibody detection test (82.7% vs. 61.5%, Χ² =5.786, P=0.016; 82.7% vs. 55.8%, Χ² =8.847, P=0.003), but not significantly different from the positive rate of pathological examination (82.7% vs. 87.2%, Χ² =0.396, P=0.529). Moderate agreement was found between pathological examination and the ELISPOT assay (87.2%, Κ=0.498, P=0.001). CONCLUSION: With high sensitivity and specificity, the ELISPOT assay using CFP10/ESAT6 fusion protein as antigen is an effective technique for auxiliary diagnosis of spinal TB.