RESUMO
OBJECTIVE: Thyrotropin-secreting adenoma (TSHoma) is a rare type of pituitary adenoma, occurring in one per million people. Little is known about TSHoma. We summarized the demographic, clinical and hormonal characteristics of TSHoma based on a single-centre experience. Moreover, we explored the predictive value of postoperative thyroid function for long-term remission. DESIGN, PATIENTS AND MEASUREMENTS: We retrospectively analysed 63 patients who were diagnosed as TSHoma and surgically treated at our hospital from January 2015 to June 2021. The preoperative clinical characteristics were analysed and compared between remission and nonremission groups. Thyroid function was measured at 1 day, 1 month, 3 months, 6 months, 12 months and over 12 months after surgery to determine whether they could predict long-term remission. RESULTS: The male to female ratio for TSHoma was 1.25. The mean age at diagnosis was 45 ± 12 years. Clinical presentation was varied, presenting with hyperthyroidism (68.25%), space-occupying effect (15.87%), amenorrhea (7.14% of female patients) and nonsymptoms (22.22%). 88.14% of patients achieved postoperative endocrinological remission. Larger tumour size and tumour invasion into cavernous sinus and suprasellar with chiasmal compression were strong predictors of lower rates of endocrinological remission. Postoperative thyroid function at 3 months was a viable diagnostic predictor for postoperative remission, especially for FT4 level with a 20.65 pmol/L cutoff. CONCLUSIONS: Tumour size and extent are major prognostic factors for remission. Postoperative thyroid function at 3 months could be used as a clinical prediction tool for long-term endocrinological remission.
Assuntos
Adenoma , Neoplasias Hipofisárias , Tireotropina , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Tireotropina/sangue , Tireotropina/metabolismo , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/diagnóstico , Adenoma/cirurgia , Adenoma/metabolismo , Adenoma/diagnóstico , Indução de Remissão , Período Pós-Operatório , Resultado do TratamentoRESUMO
High energy consumption is the main obstacle of melting/vitrification technology for the disposal of municipal solid waste incineration fly ash (MSWIFA) for industrial applications. To reduce energy consumption and lower operating costs, oxygen enrichment melting was proposed and studied in this work. This research was conducted in a pilot-scale melting furnace, and three melting conditions were compared and discussed. The results showed that 66% of natural gas was saved and the operating cost was reduced by 55% when oxygen enrichment technology was applied to MSWIFA melting. When coal was used as the fuel with the oxygen enrichment melting technology, the operating cost was even lower at 66.39 dollar/ton of fly ash. Because MSWIFA was a Ca-rich material, the relatively high content of Si and Al in the coal fly ash promoted the formation of vitrificated slag, leading to a reduction in the overall pollution toxicity index (OPTI) of MSWIFA by 99.98%. Meanwhile, SO2, HCl, and secondary fly ash were the main pollutants during MSWIFA melting, and when coal was used as the fuel, the emissions of SO2 and HCl could be reduced and the OPTI of secondary fly ash was suppressed. These results suggested that to obtain the lowest operating cost and reduce secondary pollution during MSWIFA melting, the best option consisted of oxygen enrichment technology with coal as the fuel.
Assuntos
Metais Pesados , Eliminação de Resíduos , Cinza de Carvão , Resíduos Sólidos/análise , Gás Natural , Oxigênio , Incineração , Metais Pesados/análise , Carbono , Material ParticuladoRESUMO
Acromegaly is characterized by hypersecretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), accompanied by a compromise in the perception of wellness. The Patient-Assessed Acromegaly Symptom Questionnaire (PASQ) is relevant to assessing signs and symptoms but is mainly used to evaluate the efficacy of a pharmacological intervention. To explore the perioperative variation in symptom severity, the divergence between subgroups stratified according to clinical outcomes or treatment modalities, and the interaction between symptom scores and clinical indices, we prospectively recruited 106 patients with acromegaly from 2016 to 2018. Oral glucose tolerance and GH tests were performed, and PASQ was administered before treatment and 6 months postoperatively. Patients were divided into active (n = 49) and remission (n = 57) groups according to postoperative GH and IGF-1 levels. PASQ scores and GH and IGF-1 levels decreased significantly postoperatively in both groups. A significantly higher preoperative headache score and greater extent of decrease in arthralgia were seen in the active and remission groups, respectively. No significant variation in PASQ scores was found between patients receiving surgery alone and those receiving preoperative somatostatin analogs. Preoperative fasting GH (GH0) levels were positively correlated with preoperative excessive perspiration. Further regression analyses validated the variation in GH0 as a noteworthy determinant of the extent of change in soft-tissue swelling, excessive perspiration, fatigue, and total PASQ scores. Patient-reported symptoms were substantially alleviated after surgery, independent of endocrine remission or use of preoperative somatostatin. A GH level decrease was a notable coefficient for PASQ scores.
Assuntos
Acromegalia , Hormônio do Crescimento Humano , Humanos , Acromegalia/diagnóstico , Acromegalia/cirurgia , Acromegalia/tratamento farmacológico , Fator de Crescimento Insulin-Like I/metabolismo , Seguimentos , Autorrelato , Hormônio do Crescimento Humano/uso terapêutico , Hormônio do Crescimento , Somatostatina/uso terapêuticoRESUMO
Mortality in coronavirus disease 2019 (COVID-19) patients has been linked to the presence of a "cytokine storm" induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which involves elevated levels of circulating cytokines and immune-cell hyperactivation. Targeting cytokines during the management of COVID-19 patients has the potential to improve survival rates and reduce mortality. Although cytokine blockers and immune-host modulators are currently being tested in severely ill COVID-19 patients to cope with the overwhelming systemic inflammation, there is not too many successful cases, thus finding new cytokine blockers to attenuate the cytokine storm syndrome is meaningful. In this paper, we significantly attenuated the inflammatory responses induced by mouse hepatitis viruses A59 and SARS-CoV-2 through a soluble DR5-Fc (sDR5-Fc) chimeric protein that blocked the TNF-related apoptosis-inducing ligand-death receptor 5 (TRAIL-DR5) interaction. Our findings indicates that blocking the TRAIL-DR5 pathway through the sDR5-Fc chimeric protein is a promising strategy to treat COVID-19 severe patients requiring intensive care unit admission or with chronic metabolic diseases.
Assuntos
Tratamento Farmacológico da COVID-19 , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/imunologia , SARS-CoV-2 , Animais , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/prevenção & controle , Citocinas/metabolismo , Camundongos , Proteínas Recombinantes de Fusão/genéticaRESUMO
OBJECTIVE: Cushing disease is a potentially fatal endocrine disorder caused by adrenocorticotropin (ACTH)-secreting microadenomas in the pituitary gland. Accurate detection and localization of the adenomas is the key to clinical treatment. This study analysed the value of contrast-enhanced Sampling Perfection with Application-optimized Contrasts using different flip angle Evolutions (SPACE) sequence in magnetic resonance imaging (MRI) assessment of ACTH-secreting pituitary microadenomas. DESIGN AND PATIENTS: We carried out a retrospective study in which 45 patients with ACTH-secreting pituitary microadenomas were enrolled. Dynamic contrast-enhanced (DCE) coronal T1-SE sequence was performed. A contrast-enhanced coronal SPACE sequence was added immediately after DCE MRI finished. Two independent observers assessed the tumour existence and location, then the results were compared with surgical findings. RESULTS: Twenty-four lesions (53.3%) were detected by the DCE T1-SE sequence alone, while 35 lesions (80.0%) were detected with the addition of contrast-enhanced SPACE sequence. The sensitivity (58.5% vs. 85.3%; p < .05) and best diagnostic accuracy (62.0% vs. 84.4%; p < .05) were significantly better for addition with SPACE sequence than DCE-SE images alone in detection of ACTH-secreting pituitary microadenomas. For lesions <5 mm, the detected numbers were 4 (16.6%) versus 10 (27.8%) by DCE T1-SE sequence and combined DCE T1-SE with SPACE sequence. CONCLUSIONS: A combination of contrast-enhanced SPACE with DCE T1-SE sequence could improve the detection of ACTH-secreting pituitary microadenomas. Contrast-enhanced SPACE sequence could be a supplementary sequence for imaging of ACTH-secreting pituitary adenomas when T1-SE sequence provides negative or equivocal findings.
Assuntos
Adenoma , Neoplasias Hipofisárias , Adenoma/diagnóstico por imagem , Adenoma/patologia , Hormônio Adrenocorticotrópico , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias Hipofisárias/cirurgia , Estudos RetrospectivosRESUMO
Pituitary adenoma (PA) is one of the most common intracranial neoplasms. Several genetic predisposing factors for PA have been identified, but they account for a small portion of cases. In this study, we sought to identify the PA genetic risk factors by focusing on causative mutations for PAs. Among the 4 affected and 17 asymptomatic members from one family with familial PA, whole-exome sequencing identified cosegregation of the PA phenotype with the heterozygous missense mutation c.4136G>T (p.Arg1379Leu) in cadherin-related 23 (CDH23). This mutation causes an amino acid substitution in the calcium-binding motif of the extracellular cadherin (EC) domains of CDH23 and is predicted to impair cell-cell adhesion. Genomic screening in a total of 12 families with familial PA (20 individuals), 125 individuals with sporadic PA, and 260 control individuals showed that 33% of the families with familial PA (4/12) and 12% of individuals with sporadic PA (15/125) harbored functional CDH23 variants. In contrast, 0.8% of the healthy control individuals (2/260) carried functional CDH23 variants. Gene-based analysis also revealed a significant association between CDH23 genotype and PA (p = 5.54 × 10-7). Moreover, PA individuals who did not harbor functional CDH23 variants displayed tumors that were larger in size (p = 0.005) and more invasive (p < 0.001). Therefore, mutations in CDH23 are linked with familial and sporadic PA and could play important roles in the pathogenesis of PA.
Assuntos
Caderinas/genética , Mutação em Linhagem Germinativa , Neoplasias Hipofisárias/genética , Sequência de Aminoácidos , Proteínas Relacionadas a Caderinas , Estudos de Casos e Controles , Adesão Celular , Genômica , Heterozigoto , Humanos , Linhagem , Fenótipo , Conformação Proteica , Fatores de RiscoRESUMO
USP8, one member of deubiquitinating enzymes (DUBs) families, maintains the ubiquitination level of EGFR and regulates the downstream signaling pathways. The deregulation of USP8 has been implicated in many human diseases, especially in cancer. Therefore, USP8 has been identified as a promising target for drug design. Herein, via high throughput screening based on Ubiquitin-rhodamine-110 (Ubiquitin-Rho-110) fluorometric activity assay, we discovered a novel inhibitor DC-U43. By structure optimization, DC-U43-10 reached a half-maximal inhibitory concentration (IC50) value of 2.6 ± 1.1 µM and exhibited 10-fold selectivity against USP7. The binding between DC-U43-10 and USP8 was validated by surface plasmon resonance (SPR) assay with a KD value of 10.5 ± 3.7 µM. It also inhibited the colony formation of H1975 cells. Hence, DC-U43-10 represents a kind of USP8 inhibitors with novel scaffold and has broad prospects for being a probe for USP8-related academic and clinical research.
Assuntos
Complexos Endossomais de Distribuição Requeridos para Transporte/antagonistas & inibidores , Ensaios de Triagem em Larga Escala/métodos , Ubiquitina Tiolesterase/antagonistas & inibidores , Endopeptidases , Humanos , Simulação de Acoplamento Molecular , Transdução de Sinais , Espectrometria de Fluorescência/métodos , Ressonância de Plasmônio de Superfície , UbiquitinaçãoRESUMO
OBJECTIVE: The primary aim of this study was to investigate the value of multidisciplinary team (MDT) management in treating patients with Cushing's disease (CD). The secondary aim was to assess the concordance of bilateral inferior petrosal sinus sampling (BIPSS) lateralization with intraoperative observations. METHODS: The authors recruited 124 consecutive patients (128 procedures) who had undergone endoscopic endonasal resection of adrenocorticotropic hormone-secreting pituitary adenomas from May 2014 to April 2018 and assessed their clinical characteristics, surgical outcomes, and adjuvant therapies. The criteria for surgical remission were normalized serum and urinary cortisol levels, which could be suppressed by a low-dose dexamethasone suppression test at 3-months' follow-up without adjuvant treatment. RESULTS: The remission rates of the 113 patients with long-term follow-up (20.3 ± 12.2 months) were 83.2% after surgery alone and 91.2% after adjuvant therapy. The surgical remission rates of macroadenomas, MRI-visible microadenomas, and MRI-negative tumors were 66.7% (12/18), 89.3% (67/75), and 75% (15/20), respectively (p = 0.039). The surgical remission rates had a trend of improvement during the study period (87.5% in 2017-2018 vs 76.5% in 2014, p = 0.517). Multivariate regression analysis showed that a history of previous pituitary surgery (OR 0.300, 95% CI 0.100-0.903; p = 0.032) and MRI-visible microadenoma (OR 3.048, 95% CI 1.030-9.019; p = 0.044) were independent factors influencing surgical remission. The recurrence rate was 3.2% after a mean of 18 months after surgery. The remission rate of postoperative MDT management in patients with persistent disease was higher than non-MDT management (66.7% vs 0%, p = 0.033). In cases with preoperative BIPSS lateralization, 84.6% (44/52) were concordant with intraoperative findings. CONCLUSIONS: MRI-visible microadenoma and primary surgery were independent predictors of surgical remission in CD. The MDT management strategy helps to achieve a better overall outcome. BIPSS may help to lateralize the tumor in MRI-negative/equivocal microadenomas.
Assuntos
Gerenciamento Clínico , Relações Interprofissionais , Equipe de Assistência ao Paciente , Hipersecreção Hipofisária de ACTH/epidemiologia , Hipersecreção Hipofisária de ACTH/cirurgia , Adulto , Quimioterapia Adjuvante/métodos , China/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neuroendoscopia/métodos , Hipersecreção Hipofisária de ACTH/diagnóstico , Resultado do TratamentoRESUMO
BACKGROUND: We aim to study surgical technique and analyze the related factors affecting tumor total removal and postoperative endocrinological remission for endoscopic endonasal pituitary adenomas surgery. METHODS: We retrospectively analyzed 178 endoscopic endonasal pituitary adenomas surgery from March 2011 to May 2014. Endonasal approach included the routine transnasal-sphenoidal approach, transnasal- maxillary sinus approach in four cases and transnasal-clivus approach in one case. RESULTS: According to postoperative imaging data and endocrine examination results, total removal was achieved in 129 patients (72.5%), and endocrinological remission was achieved in 38 patients with functional adenomas (44.1%). Statistical analysis of the clinical data showed that total removal rate was much closely related to tumor volume (P = 0.006), and tumor invasiveness (P < 0.001). CONCLUSIONS: In this study, we found tumor sizes and invasion of cavernous sinus were related to total removal rate and endocrinological remission rate; the direction and degree of tumor invasion, and the surgeon's experience were the key influence factors of the endocrinological remission rate for invasive functional pituitary adenomas.
Assuntos
Adenoma/cirurgia , Endoscopia/métodos , Neoplasias Hipofisárias/cirurgia , Adolescente , Adulto , Idoso , Seio Cavernoso/patologia , Feminino , Humanos , Curva de Aprendizado , Masculino , Pessoa de Meia-Idade , Neurocirurgiões , Neoplasias Hipofisárias/diagnóstico , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: It is a common view that consistency and blood supply of pituitary adenoma (PA) can influence the surgical effect. The aim of this study was to determine whether MRI signal intensity (SI) was correlated to the consistency or blood supply of pituitary macroadenoma. METHODS: Forty eight pituitary macroadenoma patients were underwent preoperative MRI, including precontrast and contrast-enhanced (CE) T1-spin echo (T1-SE) imaging, CE-sampling perfection with application-optimized contrasts by using different flip angle evolutions (SPACE) imaging, and perfusion-weighted imaging (PWI). The tumor consistency and blood supply were determined by neurosurgeons. The expression of collagen IV and MIB-1 was detected with immunohistology. The correlation of the relative SI (rSI) values (tumor to normal frontal white matter SI) and PWI data to the tumor consistency, blood supply, and the expression level of collagen IV and MIB-1 was statistically studied by Kruskal-Wallis rank test (K-W test). RESULTS: A significant correlation was observed between the tumor consistency and the rSI on precontrast T1-SE imaging (P = 0.004) but not on CE T1-SE and CE SPACE imaging. The expression of collagen IV was also significantly associated with rSI on T1-SE imaging (P = 0.010). The blood supply was correlated with the relative CBV (rCBV) (P = 0.030). In addition, the expression of MIB-1 was correlated with rSI of CE T1-SE imaging (P = 0.007). CONCLUSION: Our results suggest that T1-SE imaging may be a simple and useful method for predicting consistency of PA. CBV value can provide helpful information for assessing the blood supply of pituitary macroadenoma.
Assuntos
Adenoma/diagnóstico por imagem , Imageamento por Ressonância Magnética , Imagem de Perfusão , Neoplasias Hipofisárias/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
INTRODUCTION: The difficulty of predicting the efficacy of somatostatin analogs (SSA) is not fully resolved. Here, we quantitatively evaluated the predictive value of relative signal intensity (rSI) on T1- and T2-weighted magnetic resonance imaging (MRI) for the short-term efficacy (3 months) of SSA therapy in patients with active acromegaly and assessed the correlation between MRI rSI and expression of somatostatin receptors (SSTR). METHODS: This was a retrospective review of prospectively recorded data. Ninety-two newly diagnosed patients (37 males and 55 females) with active acromegaly were recruited. All patients were treated with pre-surgical SSA, followed by reassessment and transspenoidal surgery. rSI values were generated by calculating the ratio of SI in the tumor to the SI of normal frontal white matter. The Youden indices were calculated to determine the optimal cutoff of rSI to determine the efficacy of SSA. The correlation between rSI and expression of SSTR2/5 was analyzed by the Spearman rank correlation coefficient. RESULTS: T2 rSI was strongly correlated with biochemical sensitivity to SSA. The cutoff value of T2 rSI to distinguish biochemical sensitivity was 1.205, with a positive predictive value (PPV) of 81.5 % and a negative predictive value (NPV) of 77.3 %. No correlation was found between MRI and tumor size sensitivity. Moreover, T2 rSI was negatively correlated with the expression of SSTR5. CONCLUSION: T2 rSI correlates with the expression of SSTR5 and quantitatively predicts the biochemical efficacy of SSA in acromegaly.
Assuntos
Acromegalia/diagnóstico por imagem , Acromegalia/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico por imagem , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Somatostatina/administração & dosagem , Acromegalia/cirurgia , Adulto , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
Predicting the efficacy of long-acting somatostatin analogues (SSA) remains a challenge. We aim to quantitatively evaluate the predictive value of the octreotide suppression test (OST) in short-term efficacy of SSA in active acromegaly. Sixty-seven newly diagnosed acromegaly patients were assessed with OST. Subsequently, all patients were treated with long-acting SSA for 3 months, followed by reassessment. Nine parameters were tested, including GHn (the nadir GH during OST), ΔGH1 (= [GH0h-GHn]/GH0h, GH0h was the baseline GH during OST), ΔGH2 (= [GHm-GHn]/GHm, GHm was the mean GH on day curve), AUC(0-6h) (the GH area under the curve during OST) , ΔAUC1 (= [GH0h-AUC(0-6h)]/GH0h), ΔAUC2 (=[GHm-AUC(0-6h)]/GHm), AUC(m-6h) (the GH AUC during OST where GHm was used instead of GH0h), ΔAUC1' (=[GH0h-AUC(m-6h)]/GH0h) and ΔAUC2' (=[GHm-AUC(m-6h)]/GHm). The Youden indices were calculated to determine the optimal cutoffs to predict the short-term efficacy of SSA. ΔGH2 more than 86.83%, ΔAUC2 more than -57.48% and ΔAUC2' more than -57.98% provided the best predictors of a good GH response (sensitivity 93.8%, specificity 85.7%). ΔGH2 more than 90.51% provided the best predictor of a good tumor size response (sensitivity 84.8%, specificity 87.5%). The percentage fall of GHn (ΔGH) was a better predictive parameter than GHn. OST showed higher efficiency in predicting the efficacy of octreotide LAR than lanreotide SR. In conclusion, OST is a valid tool to predict both GH and tumor size response to short-term efficacy of SSA in acromegaly, especially for octreotide LAR. GHm is better to be used as basal GH than GH0 during OST.
Assuntos
Acromegalia/diagnóstico , Acromegalia/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Técnicas de Diagnóstico Endócrino , Octreotida/farmacologia , Somatostatina/análogos & derivados , Acromegalia/etiologia , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/tratamento farmacológico , Adulto , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
Hsf4b, a key regulator of postnatal lens development, is subjected to posttranslational modifications including phosphorylation. However, the phosphorylation sites in Hsf4b and their biological effects on the transcription activity of Hsf4b are poorly understood. Here we examined 17 potential phosphorylation residues in Hsf4b with alanine-scanning assays and found that a T472A mutation diminished Hsf4b-mediated expression of Hsp25 and alphaB-crystallin. In contrast, the phosphomimetic mutation of T472D enhanced their expression. Further investigation demonstrated that Hsf4b could interact with nuclear-transporter importin beta-1 and Hsc70 via amino acids 246-320 and 320-493, respectively. T472A mutation reduced Hsf4bs interaction with importin beta-1, while enhancing its interaction with Hsc7O, resulting in Hsf4b cytosolic re-localization, protein instability and transcription activity attenuation. At the upstream, MEK6 was found to interact with Hsf4b and enhance Hsf4b's nuclear translocation and transcription activity, probably by phosphorylation at sites such as T472. Taken together, our results suggest that phosphotylation of Hsf4b at T472 by protein kinases such as MEI(6 regulates Hsf4b interaction with the importin V I -Hsc7O complex, resulting in blockade of its nuclear translocation and transcriptional activity of Hsf4b.
Assuntos
Núcleo Celular/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Treonina/genética , Treonina/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Linhagem Celular , Núcleo Celular/genética , Expressão Gênica , Células HEK293 , Proteínas de Choque Térmico HSC70/genética , Proteínas de Choque Térmico HSC70/metabolismo , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico HSP27/metabolismo , Fatores de Transcrição de Choque Térmico , Proteínas de Choque Térmico , Humanos , Chaperonas Moleculares , Mutação/genética , Fosforilação , Transporte Proteico , Transcrição Gênica , Cadeia B de alfa-Cristalina/genética , Cadeia B de alfa-Cristalina/metabolismo , beta Carioferinas/genética , beta Carioferinas/metabolismoRESUMO
PURPOSE: The aim of this study is to determine if contrast enhanced (CE) sampling perfection with application-optimized contrasts using different flip-angle evolutions (SPACE) images can provide clearer pituitary adenoma margin than conventional CE T1-weighted spin echo (T1-SE) sequence for cavernous sinus (CS) invasion evaluation. METHODS: 21 healthy volunteers were preformed with SPACE scans before and after administration of gadopentetate dimeglumine at different time points (1, 7 and 13 min). Signal intensity (SI) of regions of interest was plotted in SI/time curves for bilateral CS, pituitary and temporal lobe. 35 patients with pituitary adenoma (≥1 cm) were performed CE T1-SE and CE SPACE scans. Two observers made the visual assessment of the tumor margin delineation and CS invasion evaluation on both SPACE and T1-SE images. Surgical findings were compared with the invasion assessment results. RESULTS: At 1, 7 and 13 min after enhancement, SI of left CS increased 6.7, 9.5 and 11.2% respectively compared with unenhanced images (all p < 0.05). Right CS increased 7.2, 9.3 and 11.3% (all p < 0.05%). Within pituitary, a decline (6.3%, p < 0.05) of SI was measured at 1 min after enhancement. CE SPACE performed superior to those of CE T1-SE sequence in visual assessment of tumor edge (assessment score, 1.66 ± 0.42 vs. 1.23 ± 0.65, p < 0.05), as well as the specificity (86.8 vs. 66.0%, p < 0.05) and accuracy (85.7 vs. 68.6%, p < 0.05) for CS invasion evaluation. CONCLUSION: CE SPACE could provide better contrast of pituitary adenoma with surrounding CS and clear demonstration of tumor edge for CS invasion evaluation than conventional CE T1-SE sequence.
Assuntos
Adenoma/diagnóstico , Seio Cavernoso/patologia , Imageamento por Ressonância Magnética/métodos , Neoplasias Hipofisárias/diagnóstico , Adenoma/patologia , Adulto , Meios de Contraste , Feminino , Gadolínio DTPA , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/patologia , Sensibilidade e Especificidade , Adulto JovemRESUMO
OBJECTIVE: The clinical benefit of surgery for treatment of deep-seated cerebral cavernous malformations (CCMs) is still a matter of debate. Although the surgical removal of CCMs is widely accepted, the benefits of reducing the rate of haemorrhage must be balanced against the risk of peri-operative morbidity. Here, we provide a systematic review and meta-analysis of the clinical benefits of surgery for treating deeply localised CCMs. METHODS: A comprehensive search of PubMed and Embase was conducted to identify relevant studies. The rate and a 95% confidence interval (CI) were used to measure the risk of haemorrhage and adverse outcomes. RESULTS: A total of 34 cohort studies reporting surgeries on CCMs were included in our analysis. Overall, the average post-surgical haemorrhage rate was 1.0% (95% CI: 0.7-1.4%). Nine per cent (95% CI: 6.9-11.3%) of the patients developed adverse events at follow-up following the surgical resection of deep-seated CCMs. The percentage of transient neural defects following surgical resection was 34.6% (95% CI: 29.4-39.9%). The proportions of transient focal neurological defect before and after the year 2006 were 44.9% (95% CI: 34.1-55.8%) and 30.3% (95% CI: 25.1-35.9%), respectively. CONCLUSIONS: Our meta-analysis demonstrates post-surgical haemorrhage rate and complications related to surgeries on deep-seated CCMs. The post-surgical haemorrhage rate was low with a relatively high rate of post-surgical complications.
Assuntos
Hemorragia Cerebral/etiologia , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Hemorragia Cerebral/epidemiologia , Hemangioma Cavernoso do Sistema Nervoso Central/epidemiologia , Humanos , Procedimentos Neurocirúrgicos/efeitos adversosRESUMO
OBJECTIVE: To explore the chemopreventive effect of curcumin on DMH induced colorectal carcinogenesis and the underlining mechanism. METHODS: Totally 40 Wistar rats were divided into the model group and the curcumin group by random digit table, 20 in each group. Meanwhile, a normal control group was set up (n =10). A colorectal cancer model was induced by subcutaneously injecting 20 mg/kg DMH. The tumor incidence and the inhibition rate were calculated. The effect of curcumin on the expression of peroxisome proliferator-activated receptor gamma (PPARγ) in rat colon mucosal tissues was observed using immunohistochemistry and Western blot. HT 29 cell line were cultured and divided into a control group, the curcumin + GW9662 (2-chloro-5-nitro-N-4-phenylbenzamide) intervention group, and the curcumin group. The inhibition of different concentrations curcumin on HT29 cell line was detected using MTT. The expression of curcumin on PPARy was also detected using Western blot. RESULTS: The tumor incidence was 80. 00% (12/15 cases) in the model group, obviously higher than that of the curcumin group (58. 82%, 10/17 cases, P <0. 05). The inhibition rate of curcumin on DMH induced colorected carcinoma reached 26. 46%. Compared with the normal control group, the expression of PPARγ protein was significantly increased in the curcumin group and the model group (P <0. 01). Compared with the model group at the same time point, the expression of PPARy protein was significantly enhanced in the curcumin group (P <0. 05). MTT analysis showed that curcumin could inhibit the proliferation of in vitro HT 29 cells in dose and time dependent manners. The expression of PPARy protein was significantly increased in the GW9662 group and the curcumin group, showing statistical difference when compared with the normal control group (P <0. 01). Compared with the GW9662 group, the expression of PPARγ protein was significantly increased in the curcumin group (P <0. 01). CONCLUSION: Curcumin could inhibit DMH-induced rat colorectal carcinogenesis and the growth of in vitro cultured HT 29 cell line, which might be achieved by activating PPARy signal transduction pathway.
Assuntos
Neoplasias Colorretais/tratamento farmacológico , Curcumina/uso terapêutico , PPAR gama/metabolismo , Anilidas , Animais , Carcinogênese , Neoplasias Colorretais/metabolismo , Curcumina/farmacologia , Ratos , Ratos Wistar , Transdução de SinaisRESUMO
OBJECTIVE: To review experience regarding the treatment of prolactinomas by endoscopic endonasal surgery focusing on the association between presurgical dopamine agonist (DA) treatment and perioperative outcomes, surgical morbidities, endocrine outcomes, and pathological characteristics. METHODS: A single-center series of 290 cases was analyzed retrospectively and clinical data were collected. Intratumoral collagen content was assessed by Masson trichrome staining. RESULTS: Tenacious tumor consistency (27.8% vs 9.8%, P < .001) was more common in DA-pretreated patients compared with patients who underwent initial surgery. Moreover, DA-pretreated macroadenomas presented more intraoperative blood loss (200 [100-400] mL vs 175 [100-300] mL; P = .014), longer surgical duration (177 ± 95 minutes vs 154 ± 57 minutes; P = .043), and more surgical morbidities (19.4% vs 8.9%; P = .034). Additionally, DA-pretreated macroadenomas presented a higher collagen volume fraction than that of the initial surgery group (23.6 ± 2.2% vs 13.2 ± 2.1%; P = .001). Correlation analysis revealed a close correlation between collagen volume fraction and the cumulative dose of bromocriptine (BRC) in macroadenomas (r = 0.438, P < .001). Regarding endocrine outcomes, DA-pretreated microadenomas showed a lower proportion of initial remission compared with patients who underwent initial surgery (86.7% vs 100%, P = .047). CONCLUSION: This study described increased surgical difficulty and inferior endocrine outcomes associated with tumor fibrosis secondary to presurgical BRC treatment in prolactinomas. Neurosurgeons should note that presurgical BRC treatment may render subsequent surgery more challenging.
Assuntos
Agonistas de Dopamina , Neoplasias Hipofisárias , Prolactinoma , Humanos , Prolactinoma/patologia , Prolactinoma/cirurgia , Prolactinoma/tratamento farmacológico , Feminino , Masculino , Adulto , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/tratamento farmacológico , Agonistas de Dopamina/uso terapêutico , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto Jovem , Resultado do Tratamento , Bromocriptina/uso terapêutico , Idoso , Cuidados Pré-Operatórios/métodosRESUMO
BACKGROUND: Surgical treatment of complex giant pituitary adenomas (GPAs) presents significant challenges. The efficacy and safety of combining transsphenoidal and transcranial approaches for these tumors remain controversial. In this largest cohort of patients with complex GPAs, we compared the surgical outcomes between those undergoing a combined regimen and a non-combined regimen. We also examined the differences in risks of complications, costs, and logistics between the two groups, which might offer valuable information for the appropriate management of these patients. PATIENTS AND METHODS: This was a multicenter retrospective cohort study conducted at 13 neurosurgical centers. Consecutive patients who received a combined or non-combined regimen for complex GPAs were enrolled. The primary outcome was gross total resection, while secondary outcomes included complications, surgical duration, and relapse. A propensity score-based weighting method was used to account for differences between the groups. RESULTS: Out of 647 patients [298 (46.1%) women, mean age: 48.5 ± 14.0 years] with complex GPAs, 91 were in the combined group and 556 were in the noncombined group. Compared with the noncombined regimen, the combined regimen was associated with a higher probability of gross total resection [50.5% vs. 40.6%, odds ratio (OR): 2.18, 95% confidence interval (CI): 1.30-3.63, P = 0.003]. The proportion of patients with life-threatening complications was lower in the combined group than in the non-combined group (4.4% vs. 11.2%, OR: 0.25, 95% CI: 0.08-0.78, P = 0.017). No marked differences were found between the groups in terms of other surgical or endocrine-related complications. However, the combined regimen exhibited a longer average surgery duration of 1.3 h ( P < 0.001) and higher surgical costs of 22,000 CNY (~ 3,000 USD, P = 0.022) compared with the noncombined approach. CONCLUSIONS: The combined regimen offered increased rates of total resection and decreased incidence of life-threatening complications, which might be recommended as the first-line choice for these patients.
Assuntos
Adenoma , Neoplasias Hipofisárias , Humanos , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/cirurgia , Adulto , Adenoma/cirurgia , Adenoma/patologia , Resultado do Tratamento , Estudos Longitudinais , Procedimentos Neurocirúrgicos/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pontuação de PropensãoRESUMO
Activated carbon injection is widely used to control dioxins and mercury emissions. Surprisingly little attention has been paid to its modelling. This paper proposes an expansion of the classical Everaerts-Baeyens model, introducing the expression of fraction of free adsorption sites, f (s), and asserting the significant contribution of fly ash to dioxins removal. Moreover, the model monitors dioxins partitioning between vapour and particulate phase, as well as removal efficiency for each congener separately. The effects of the principal parameters affecting adsorption are analysed according to a semi-analytical, semi-empirical model. These parameters include temperature, contact time during entrained-flow, characteristics (grain-size, pore structure, specific surface area) and dosage of activated carbon, lignite cokes or mineral adsorbent, fly ash characteristics and concentration, and type of incinerator plant.
Assuntos
Incineração/métodos , Modelos Teóricos , Resíduos Sólidos , Adsorção , Carbono/química , Cinza de Carvão , Dioxinas , Gases/química , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To establish mouse lens epithelial cell lines with the genotype of Hsf4-/-. METHODS: The expended mouse lens epithelial cells, which were generated from P6 Hsf4-deficient mouse lens epithelia, were immortalized with SV40-T-antigen and named MLEC/Hsf4-/- cell. The expression of alpha A-crystallin was immunoblotted. Hsf4b cDNA was reconstituted by transiently transfection. RESULTS: The SV40-immortalized cells were in adherent growth mode with spindle morphology, pseudopodia, clear nuclear boundary membrane and cytoplasm translucent. Immunoblotting results indicated that the lens biomarker protein alpha A-crystallin was expressed in MLEC/Hsf4-/- cells. Reconstitution of Hsf4b into MLEC/Hsf4-/- cells upregulated the expression of Hsp25. CONCLUSIONS: The SV40-immortalized MLEC/Hsf4-/- cells have the lens epithelial characteristics and could be used as a tool for studying the signal transduction in vitro.