RESUMO
Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by progressive cognitive dysfunction and an impaired ability to carry out daily life functions. Mitochondrial dysfunction and ß-amyloid (Aß) deposition are the most common causes of AD. Antioxidants have been shown to delay brain aging and AD development; however, it remains unknown whether the antioxidant peptide SS31 can protect mitochondrial and synaptic function and delay the progression of behavioral deficits in early-stage AD in vivo. Therefore, in this study we compared mitochondrial and synaptic changes, as well as the protective effects of SS31, in APP/PS1 transgenic mice and C57BL/6J control mice. The APP/PS1 transgenic mice exhibited elevated expression of Aß40/Aß42 and mitochondrial fission protein DLP1 and reduced expression of synaptophysin (SYN) and postsynaptic density protein 95 (PSD95) reductions, as well as increased levels of neuronal apoptosis and ROS in the hippocampus, and long-term treatment with SS31 reversed these effects. Furthermore, the cognitive impairments observed in APP/PS1 transgenic mice were reversed by SS31 treatment. Our findings show that SS31 lowers ROS and Aß levels, protecting mitochondrial homeostasis and synaptic integrity, and ultimately improving behavioral deficits in early-stage AD. This suggests that SS31 is a potential pharmacological agent for treating or slowing the progression of AD.
Assuntos
Doença de Alzheimer , Placa Amiloide , Camundongos , Animais , Placa Amiloide/tratamento farmacológico , Placa Amiloide/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos C57BL , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Camundongos Transgênicos , Mitocôndrias/metabolismo , Antioxidantes/farmacologia , Modelos Animais de Doenças , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Presenilina-1/metabolismoRESUMO
OBJECTIVES: To evaluate the efficacy and safety of marking ground glass nodules (GGNs) with pulmonary nodules localization needle (PNLN) prior to video-assisted thoracoscopic surgery (VATS). MATERIALS AND METHODS: From June 2020 to February 2021, all patients with GGNs who received CT-guided localization using PNLN before VATS were enrolled. Clinical and imaging data were retrospectively analyzed. RESULTS: A total of 352 consecutive patients with 395 GGNs were included in the study. The mean diameter of GGNs was 0.95 ± 0.48 cm, and the shortest distance from nodules to the pleura was 1.73 ± 0.96 cm. All 395 GGNs were marked using PNLNs. The time required for marking was 7.8 ± 2.2 min. The marking success rate was 99.0% (391/395). The marking failure of four nodules was all due to the unsatisfactory position of PNLNs. No marker dislocation occurred. Marking-related complications included pneumothorax in 63 cases (17.9%), hemorrhage in 34 cases (9.7%), and hemoptysis in 6 cases (1.7%). All the complications were minor and did not need special treatment. Localization and VATS were performed on the same day in 95 cases and on different days in 257 cases. All GGNs were successfully removed by VATS. No patient converted to thoracotomy. Histopathological examination revealed 74 (18.7%) benign nodules and 321 (81.3%) malignant nodules. CONCLUSIONS: It is safe and reliable to perform preoperative localization of GGNs using PNLNs, which can effectively guide VATS to remove GGNs. KEY POINTS: ⢠Preoperative localization of GGNs could effectively guide VATS to remove GGNs. ⢠PNLN was based on the marking principle of hook-wire, through the improvement of its material, specially designed to mark pulmonary nodules. ⢠The application of PNLN to mark GGNs had high success rate, good patient tolerance, and no dislocation. Meanwhile, VATS could be performed 2 to 3 days after marking GGNs with PNLN.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Estudos Retrospectivos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/cirurgia , Cirurgia Torácica Vídeoassistida/métodosRESUMO
Breast cancer has the highest incidence and mortality in the female population. Forkhead box M1 (FOXM1) known as a transcription factor is upregulated and associated with poor prognosis in a variety of cancers. However, the molecular mechanisms of FOXM1 on breast cancer progression are poorly understood. In this study, we found that FOXM1 was up-regulated in breast cancer. FOXM1 promoted cell proliferation, clonal formation, and migration capacity in triple negative breast cancer by increasing transcriptional activity of YAP1. FOXM1 also maintained cell stemness via the Hippo pathway. The YAP1-TEAD binding inhibitor Verteporfin reduced the transcription level of OCT4 and NANOG but the Hippo pathway activator XMU-MP-1 could increase the transcription level of OCT4 and NANOG. In summary, our findings indicated that FOXM1 promoted breast cancer progression through the Hippo pathway, and it was suggested a new strategy to treat breast cancer.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias da Mama/metabolismo , Movimento Celular/fisiologia , Proteína Forkhead Box M1/metabolismo , Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/química , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Proliferação de Células/fisiologia , Proteína Forkhead Box M1/genética , Técnicas de Silenciamento de Genes , Humanos , Proteína Homeobox Nanog/metabolismo , Fator 3 de Transcrição de Octâmero/metabolismo , Fosforilação/genética , Fatores de Transcrição/química , Regulação para Cima , Proteínas de Sinalização YAPRESUMO
OBJECTIVES: To develop a prognostic nomogram based on the albumin-bilirubin (ALBI) grade for prediction of the long-term survival of patients with intermediate-stage hepatocellular carcinoma (HCC) after transarterial chemoembolization combined with microwave ablation (TACE-MWA). METHODS: We retrospectively studied 546 consecutive patients with intermediate-stage HCC according to the Barcelona Clinic Liver Cancer guidelines who underwent TACE-MWA between January 2000 and December 2016. Overall survival (OS) and progression-free survival (PFS) were analyzed. The predictive value of the ALBI grade was investigated. The prognostic nomogram was constructed using the independent predictors assessed by the multivariate Cox proportional hazards model. RESULTS: After a median follow-up of 35.0 months (range, 4.0-221.0 months), 380 patients had died. The median OS was 35.0 months (95% confidence interval (CI), 30.84-39.16 months), and the median PFS was 6.5 months (95% CI, 6.13-6.87 months). The ALBI grade was validated as an independent predictor of OS (p < 0.001). Multivariate analyses showed that Eastern Cooperative Oncology Group performance status score more than 0, presence of liver cirrhosis, a-fetoprotein level above 400 ng/mL, tumor size greater than 5 cm, tumor number more than 3, advanced ALBI grade, and treatment sessions of TACE or MWA fewer than 3 were independently associated with overall mortality. The prognostic nomogram incorporating these eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770 (95% CI, 0.746-0.795). CONCLUSIONS: The prognostic nomogram based on the ALBI grade resulted in reliable efficacy for prediction of individualized OS in patients with intermediate-stage HCC after TACE-MWA. KEY POINTS: ⢠TACE-MWA was associated with a median overall survival of 35.0 months for patients with intermediate-stage HCC. ⢠A prognostic nomogram was built to predict individualized survival of patients with intermediate-stage HCC after TACE-MWA. ⢠The prognostic nomogram incorporating eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770.
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Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Micro-Ondas/uso terapêutico , Estadiamento de Neoplasias/métodos , Nomogramas , Terapia por Radiofrequência/métodos , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
Lysine demethylase 5B (KDM5B) is up-regulated in many cancers, including breast cancer. However, the underlying metabolic mechanisms of KDM5B on breast cancer progression are poorly understood. Here, we showed that KDM5B expression positively correlates with metastasis in breast cancer. Cell functional analyses were demonstrated that KDM5B knockdown and KDM5B inhibitor AS-8351 inhibited breast cancer cell proliferation and migration. Furthermore, we reported that KDM5B knockdown and AS-8351 reversed epithelial-mesenchymal transition (EMT) and decreased the protein levels of fatty acid synthase (FASN) and ATP citrate lyase (ACLY) in MCF-7 and MDA-MB-231â¯cells. Interestingly, we found that activation of AMP-activated protein kinase (AMPK) signaling pathway is involved in KDM5B-mediated EMT and lipid metabolism reprogramming in breast cancer cells. As a result, silencing of KDM5B-induced activation of AMPK signaling pathway inhibited breast cancer cell proliferation and migration. Taken together, our findings indicated that KDM5B was a novel regulator of lipid metabolism reprogramming, and it was suggested a new strategy to treat breast cancer.
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Neoplasias da Mama/metabolismo , Movimento Celular/fisiologia , Histona Desmetilases com o Domínio Jumonji/metabolismo , Metabolismo dos Lipídeos/fisiologia , Proteínas Nucleares/metabolismo , Proteínas Repressoras/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/fisiologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/fisiologia , Feminino , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacosRESUMO
BACKGROUND: This study aims to analyze the effect of the body mass index (BMI) on E2, P and LH values in females who received intrauterine insemination (IUI) treatment on human chorionic gonadotropin (HCG) day. METHODS: A total of 2319 cycles of IUI-assisted pregnancy treatment were selected in our hospital. Based on the BMI, female infertility patients are divided into three groups: normal weight group, overweight and obese group. RESULTS: For patients with natural cycles and ≤ 35 years old, there were 440, 178 and 197 cases in the three groups, respectively. For patients with natural cycles and > 35 years old, there were 90, 83 and 81 cycles in the three groups, respectively. For patients with induced ovulation cycle and ≤ 35 years old, there were 425, 203 and 516 cases in the three groups, respectively. For patients with induced ovulation cycle and > 35 years old, there were 26, 26 and 54 cases in the three groups, respectively. CONCLUSION: When a patient is ≤35 years old, the BMI affects the E2, LH and P values on the day of artificial insemination. However, the BMI is negatively correlated with E2, LH and P in IUI on HCG day. After controlling for age and assisted pregnancy, the correlation analysis revealed that the BMI is negatively correlated with hormone E2 and LH. The higher the BMI was, the lower the levels of hormones E2, LH and P became. However, in the present study, the BMI did not significantly improve the clinical pregnancy rate of patients who received IUI.
Assuntos
Índice de Massa Corporal , Gonadotropina Coriônica/sangue , Inseminação Artificial , Indução da Ovulação/métodos , Taxa de Gravidez , Adulto , Estradiol/sangue , Feminino , Humanos , Hormônio Luteinizante , GravidezRESUMO
Abnormal metabolism of tumour cells is closely related to the occurrence and development of breast cancer, during which the expression of NF-E2-related factor 2 (Nrf2) is of great significance. Metastatic breast cancer is one of the most common causes of cancer death worldwide; however, the molecular mechanism underlying breast cancer metastasis remains unknown. In this study, we found that the overexpression of Nrf2 promoted proliferation and migration of breast cancers cells. Inhibition of Nrf2 and overexpression of Kelch-like ECH-associated protein 1 (Keap1) reduced the expression of glucose-6-phosphate dehydrogenase (G6PD) and transketolase of pentose phosphate pathway, and overexpression of Nrf2 and knockdown of Keap1 had opposite effects. Our results further showed that the overexpression of Nrf2 promoted the expression of G6PD and Hypoxia-inducing factor 1α (HIF-1α) in MCF-7 and MDA-MB-231 cells. Overexpression of Nrf2 up-regulated the expression of Notch1 via G6PD/HIF-1α pathway. Notch signalling pathway affected the proliferation of breast cancer by affecting its downstream gene HES-1, and regulated the migration of breast cancer cells by affecting the expression of EMT pathway. The results suggest that Nrf2 is a potential molecular target for the treatment of breast cancer and targeting Notch1 signalling pathway may provide a promising strategy for the treatment of Nrf2-driven breast cancer metastasis.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Movimento Celular , Glucosefosfato Desidrogenase/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Receptor Notch1/metabolismo , Regulação para Cima , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Modelos Biológicos , Via de Pentose Fosfato , Transdução de SinaisRESUMO
Colorectal cancer (CRC) is the third-leading cause of cancer mortality worldwide. HACE1 function as a tumor-suppressor gene and is downregulated in several kinds of cancers. However, the distribution and clinical significance of HACE1 in CRC is still not clarified. In this study, we found that the HACE1 expression is greatly downregulated in CRC tissues and cell lines. Moreover, the HACE1 expression was significantly associated with inhibition of CRC cell proliferation, metastasis, and invasion. HACE1 inhibited epithelial-mesenchymal transition in CRC cells. Furthermore, we found that HACE1 altered the protein expression of the Hippo pathway by downregulation of YAP1. HACE1 suppresses the invasive ability of CRC cells by negatively regulating the YAP1 pathway. Our data indicates that HACE1 directly targets YAP1 and induces downregulation of YAP1, thereby increasing the activity of the Hippo pathway. In summary, these findings demonstrated that HACE1-YAP1 axis had an important part in the CRC development and progression.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Movimento Celular/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Fatores de Transcrição/genética , Ubiquitina-Proteína Ligases/deficiência , Regulação para Cima/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Transdução de Sinais , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteínas de Sinalização YAPRESUMO
Purpose: To compare the predictive value of albumin-bilirubin (ALBI) grade, platelet-ALBI (PALBI) grade and Child-Turcotte-Pugh (CTP) class in patients with large hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) combined with microwave ablation (TACE-MWA). Methods: A total of 349 consecutive HCC patients (89.1% male; mean [± SD] age 53.4 ± 12.27 years) from three medical centers, who underwent TACE-MWA for up to 3 HCCs with maximum diameters of 5.1-8.0 cm between January 2000 and June 2018, were investigated. Overall survival (OS) and progression-free survival (PFS) were analyzed. The prognostic performances of ALBI grade, PALBI grade and CTP class were compared. Results: TACE procedures were performed using lobaplatin (20-50 mg), epirubicin (30-60 mg), lipiodol (5-25 mL) and gelatin sponge particles (350-560 µm). The end point of the TACE procedure was stasis of blood flow in the feeder artery. The median follow-up duration was 28.0 months, the median OS was 28.0 months (95% confidence interval [CI] 23.55-32.45 months), and the median PFS was 4.8 months (95% CI 4.26-5.34 months). Patients with a ablation margin size of 11-15 mm experienced better PFS than those with a margin size of 6-10 or 0-5 mm (median, 6.5 versus [vs] 4.0 vs 2.3 months; p < .001). PALBI grade demonstrated significantly greater area under the curve values than ALBI grade or CTP class in predicting 1-, 3- and 5-year OS. Conclusions: PALBI grade provided better predictive value than ALBI grade or CTP class in patients with large HCCs after TACE-MWA.
Assuntos
Técnicas de Ablação , Bilirrubina/sangue , Plaquetas , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Micro-Ondas/uso terapêutico , Albumina Sérica/análise , Índice de Gravidade de Doença , Adulto , Idoso , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico por imagem , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Numerous well-known processes of complex systems such as spreading and cascading are mainly affected by a small number of critical nodes. Identifying influential nodes that lead to broad spreading in complex networks is of great theoretical and practical importance. Since the identification of vital nodes is closely related to propagation dynamics, a novel method DynamicRank that employs the probability model to measure the ranking scores of nodes is suggested. The influence of a node can be denoted by the sum of probability scores of its i order neighboring nodes. This simple yet effective method provides a new idea to understand the identification of vital nodes in propagation dynamics. Experimental studies on both Susceptible-Infected-Recovered and Susceptible-Infected-Susceptible models in real networks demonstrate that it outperforms existing methods such as Coreness, H-index, LocalRank, Betweenness, and Spreading Probability in terms of the Kendall τ coefficient. The linear time complexity enables it to be applied to real large-scale networks with tens of thousands of nodes and edges in a short time.
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BACKGROUND/AIMS: To evaluate the curative effect and clinical application of hepatic arterial infusion (HAI) chemotherapy combined with endogenetic field tumor hyperthermia (EFTH) in patients with hilar cholangiocarcinoma. METHODOLOGY: Nine patients with unresectable hilar cholangiocarcinoma were enrolled. They were first treated with HAI using gemcitabine, and then carboplatin was continuously infused intra-arterially whereas EFTH was applied to the hilar region for 60 min. After hyperthermia, 5-fluorouracil was administered intra-arterially for three days. The same dose of gemcitabine was administered intravenously on Day 8. The side effects, tumor markers, tumor response and overall survival (OS) were observed and assessed. RESULTS: Nine patients underwent 27 cycles of the combination therapy. Of the nine patients, five patients achieved complete remission and they are still alive, and four died. Of the four patients who died, two achieved partial remission, one had stable disease, and one had progressive disease. The tumor markers decreased at varied degrees among the seven patients. The overall response rate was 77.78% (7/9), and the disease control rate was 88.89% (8/9). The treatment had no severe side effects and complications, including grade 3/4 hematological toxicities. CONCLUSIONS: HAI chemotherapy combined with EFTH is safe, minimally invasive, and well tolerated.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/terapia , Artéria Hepática , Hipotermia Induzida/métodos , Idoso , Biomarcadores Tumorais/análise , Carboplatina/uso terapêutico , Terapia Combinada , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Diagnóstico por Imagem , Feminino , Fluoruracila/uso terapêutico , Humanos , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
PURPOSE: To assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) of gemcitabine and oxaliplatin (GEMOX) plus systemic gemcitabine chemotherapy (GEM-SYS) in combination with lenvatinib and programmed cell death protein-1 (PD-1) inhibitor for patients with large unresectable intrahepatic cholangiocarcinoma (uICC). METHODS: From November 2019 to December 2022, 21 large uICC patients who underwent GEMOX-HAIC (Day 1) and GEM-SYS (Day 8) (3w/cycle) combined with lenvatinib and PD-1 inhibitor were retrospectively enrolled. Local tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were analyzed. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. AEs were evaluated by the common terminology criteria for adverse events (CTCAE) version 5.0. RESULTS: After a median follow-up duration of 16.0 months (range 5-43.5 months), 17 patients had died. The median OS was 19.5 months (range 9-43.5 months), and the median PFS was 6.0 months (range 2.5-38.5 months). The 1-, 2-, and 3-year OS rates were 71.4 %, 42.9 %, and 19.0 %, respectively. The 1-, 2-, and 3-year PFS rates were 33.3 %, 19.0 %, and 9.5 %, respectively. Complete response, partial response, stable disease, and progressive disease were observed in 0 (0 %), 11 (52.3 %), 5 (23.8 %), and 5 (23.8 %) patients, respectively. The disease control rate and objective response rate were 76.1 % and 52.3 %, respectively. None of the enrolled patients experienced grade 5 AEs. CONCLUSIONS: GEMOX-HAIC plus GEM-SYS in combination with lenvatinib and PD-1 inhibitor was effective and well tolerated for patients with large uICC.
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BACKGROUND AND AIM: To evaluate the clinical benefits of transarterial chemoembolization (TACE) monotherapy or TACE combined with percutaneous microwave coagulation therapy (PMCT) and the long-term survival rate of patients with large primary hepatocellular carcinoma (HCC) treated with these techniques. METHODS: This is a retrospective study involving 136 patients with unresectable large HCC (189 tumor nodules, ≥ 5.0 cm in diameter) admitted to Sun Yat-Sen University Memorial Hospital (Guangzhou, China) between January 2004 and December 2011. The median follow-up time was 41 months (range, 6-96 months). Of these patients, 80 patients received TACE monotherapy and 56 patients received TACE combined with PMCT. The median interval between treatments and overall survival (OS) were hierarchically analyzed using log-rank tests. RESULTS: All patients successfully underwent TACE alone or TACE with PMCT with no serious complications. The median survival time was 13 months (range, 3-84 months) for the TACE group and 25 months (range, 7-96 months) for the TACE-PMCT group. The 1-year, 3-year, and 5-year OS rates were 62.5%, 17.5%, and 5.0% in the TACE group, respectively. In contrast, in the TACE-PMCT group, the 1-year, 3-year, and 5-year OS rates were 87.5%, 50.0%, and 10.0%, respectively. This difference was statistically significant between the groups (P < 0.001). CONCLUSIONS: TACE combined with PMCT had advantages in prolonging OS with satisfying time to progression and improving liver function in patients with large unresectable HCC. The results suggest that further prospective studies are required to confirm the findings of this study.
Assuntos
Técnicas de Ablação , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Técnicas de Ablação/métodos , Adulto , Idoso , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/métodos , Terapia Combinada , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Radiografia Intervencionista , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Carga TumoralRESUMO
OBJECTIVE: To investigate the incidence of air embolism (AE) related to CT-guided localization of pulmonary ground-glass nodules (GGNs) prior to video-assisted thoracoscopic surgery (VATS). METHODS: The data of all patients who received CT-guided localization of GGNs before VATS from May 2020 to October 2021 were retrospectively analyzed. RESULTS: A total of 1395 consecutive patients with 1553 GGNs were enrolled. AEs occurred in seven patients (0.5%). In four of the seven patients with AE, the embolism was detected before the patients left the CT table and emergency treatments were carried out. Among them, one patient had chest tightness and unilateral limb dyskinesia, one patient had convulsions and transient loss of consciousness, and two patients had no definite clinical symptoms. After a short-term high-flow oxygen inhalation, the clinical symptoms of two patients with symptomatic AE disappeared and two patients with asymptomatic AE did not show any symptoms. In the remaining three patients with AE, the embolism were detected retrospectively when evaluating the images in the PACS for this study. Fortunately, these three patients never developed clinical symptoms related to AE. All seven patients with AE underwent VATS on the day of localization and all GGNs were successfully removed under the guidance of markers. CONCLUSION: The incidence of AE related to CT-guided localization of GGNs was 0.5%, which was significantly higher than expected. Post-localization whole thoracic CT should be performed and observed carefully so as to avoid missed AE and delayed treatment. ADVANCES IN KNOWLEDGE: The incidence of AE related to CT-guided localization of GGNs was 0.5%. In order to timely detect AE, whole thoracic CT scan rather than local CT in the lesion area should be performed after localization. A small amount of AE may be missed if the post- localization CT images are not carefully observed.
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Embolia Aérea , Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Humanos , Neoplasias Pulmonares/patologia , Embolia Aérea/diagnóstico por imagem , Embolia Aérea/etiologia , Estudos Retrospectivos , Nódulo Pulmonar Solitário/cirurgia , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Tomografia Computadorizada por Raios X/métodosRESUMO
TREK-1 is a member of the two-pore domain potassium channel family that is known as a leak channel and plays a key role in many physiological and pathological processes. The conformational transition of the selectivity filter is considered as an effective strategy for potassium channels to control the course of potassium efflux. It is well known that TREK-1 is regulated by a large volume of extracellular and intracellular signals. However, until now, little was known about the selectivity filter gating mechanism of the channel. In this research, it was found that Ba(2+) blocked the TREK-1 channel in a concentration- and time-dependent manner. A mutagenesis analysis showed that overlapped binding of Ba(2+) at the assumed K(+) binding site 4 (S4) within the selectivity filter was responsible for the inhibitory effects on TREK-1. Then, Ba(2+) was used as a probe to explore the conformational transition in the selectivity filter of the channel. It was confirmed that collapsed conformations were induced by extracellular K(+)-free and acidification at the selectivity filters, leading to nonconductive to permeable ions. Further detailed characterization demonstrated that the two conformations presented different properties. Additionally, the N-terminal truncated isoform (ΔN41), a product derived from alternative translation initiation, was identified as a constitutively nonconductive variant. Together, these results illustrate the important role of selectivity filter gating in the regulation of TREK-1 by the extracellular K(+) and proton.
Assuntos
Bário/farmacologia , Ativação do Canal Iônico/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio de Domínios Poros em Tandem/antagonistas & inibidores , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Animais , Sítios de Ligação/genética , Cátions Bivalentes/farmacologia , Cátions Monovalentes/metabolismo , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Ativação do Canal Iônico/fisiologia , Transporte de Íons/fisiologia , Mutagênese , Potássio/metabolismo , Canais de Potássio de Domínios Poros em Tandem/genética , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Estrutura Terciária de Proteína , Xenopus laevisRESUMO
AIM: To elucidate the role of vascular endothelial growth factor-165b (VEGF-165b) in blood-retinal barrier (BRB) injury in the rat acute glaucoma model. METHODS: In this study, the rat acute high intraocular pressure (HIOP) model was established before and after intravitreous injection of anti-VEGF-165b antibody. The expression of VEGF-165b and zonula occludens-1 (ZO-1) in rat retina was detected by double immunofluorescence staining and Western blotting, and the breakdown of BRB was detected by Evans blue (EB) dye. RESULTS: The intact retina of rats expressed VEGF-165b and ZO-1 protein, which were mainly located in the retinal ganglion cell layer and the inner nuclear layer and were both co-expressed with vascular endothelial cell markers CD31. After acute HIOP, the expression of VEGF-165b was up-regulated; the expression of ZO-1 was down-regulated at 12h and then recovered at 3d; EB leakage increased, peaking at 12h. After intravitreous injection of anti-VEGF-165b antibody, the expression of VEGF-165b protein was no significantly changed; and the down-regulation of the expression of ZO-1 was more obvious; EB leakage became more serious, peaking at 3d. EB analysis also showed that EB leakage in the peripheral retina was greater than that in the central retina. CONCLUSION: The endogenous VEGF-165b protein may protect the BRB from acute HIOP by regulating the expression of ZO-1. The differential destruction of BRB after acute HIOP may be related to the selective loss of retinal ganglion cells.
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OBJECTIVES: To evaluate the effect of the position of microcoil proximal end on the incidence of microcoil dislocation during CT-guided microcoil localization of pulmonary nodules (PNs). METHODS: This retrospective study included all patients with PNs who received CT-guided microcoil localization before video-assisted thoracoscopic urgery (VATS) resection from June 2016 to December 2019 in our institution. The microcoil distal end was less than 1 cm away from the nodule, and the microcoil proximal end was in the pleural cavity (the pleural cavity group) or chest wall (the chest wall group). The length of microcoil outside the pleura was measured and divided into less than 0.5 cm (group A), 0.5 to 2 cm (group B) and more than 2 cm (group C). Microcoil dislocation was defined as complete retraction into the lung (type I) or complete withdrawal from the lung (type II). The rate of microcoil dislocation between different groups was compared. RESULTS: A total of 519 consecutive patients with 571 PNs were included in this study. According to the position of microcoils proximal end on post-marking CT, there were 95 microcoils in the pleural cavity group and 476 in the chest wall group. The number of microcoils in group A, B, and C were 67, 448 and 56, respectively. VATS showed dislocation of 42 microcoils, of which 30 were type II and 12 were type I. There was no statistical difference in the rate of microcoil dislocation between the pleural cavity group and the chest wall group (6.3% vs 7.6%, x2 = 0.18, p = 0.433). The difference in the rate of microcoil dislocation among group A, B, and C was statistically significant (11.9%, 5.8%, and 14.3% for group A, B, and C, respectively, x2 = 7.60, p = 0.008). In group A, 75% (6/8) of dislocations were type I, while all eight dislocations were type II in group C. CONCLUSIONS: During CT-guided microcoil localization of PNs, placing the microcoil proximal end in the pleura cavity or chest wall had no significant effect on the incidence of microcoil dislocation. The length of microcoil outside the pleura should be 0.5 to 2 cm to reduce the rate of microcoil dislocation. ADVANCES IN KNOWLEDGE:: CT-guided microcoil localization can effectively guide VATS to resect invisible and impalpable PNs. Microcoil dislocation is the main cause of localization failure. The length of microcoil outside the pleura is significantly correlated with the rate and type of microcoil dislocation. Placing the microcoil proximal end in the pleura cavity or chest wall has no significant effect on the rate of microcoil dislocation.
Assuntos
Marcadores Fiduciais , Neoplasias Pulmonares/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Radiografia Intervencionista/métodos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Idoso , Feminino , Marcadores Fiduciais/efeitos adversos , Marcadores Fiduciais/estatística & dados numéricos , Migração de Corpo Estranho/diagnóstico por imagem , Humanos , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Masculino , Nódulos Pulmonares Múltiplos/cirurgia , Cavidade Pleural/diagnóstico por imagem , Estudos Retrospectivos , Nódulo Pulmonar Solitário/cirurgia , Cirurgia Torácica Vídeoassistida , Parede Torácica/diagnóstico por imagemRESUMO
OBJECTIVES: To compare the efficacy and safety of pre-operative localization of ground glass nodule (GGN) using embolization microcoils and the locating needles designed for pulmonary nodules. METHODS: From June 2019 to December 2020, 429 patients who received CT-guided localization of single GGN before video-assisted thoracoscopic surgery (VATS) were enrolled. The diameter and depth of GGNs were 0.84 ± 0.39 cm and 1.66 ± 1.37 cm. Among 429 cases, the first 221 GGNs were marked with microcoils (the microcoil group), and the remaining 208 GGNs were marked with the locating needles designed for pulmonary nodules (the locating needle group). SPSS 17.0 statistical software was used to compare the marking success rate, marking time, marking-related complications between two groups. p values < 0.05 were considered statistically significant. RESULTS: The marking time in the microcoil group was longer than that in the locating needle group (11.1 ± 3.9 vs 8.2 ± 2.0 min, t = -7.87, p = 0.000). The marking success rate in the microcoil group was lower than that in the locating needle group (91.4% vs 98.6%, χ2 = 11.27, p = 0.001). In the microcoil group, marking failures included 16 cases of microcoil dislocation and 3 cases of unsatisfactory microcoil position, while all 3 cases of marking failure in the locating needle group were due to unsatisfactory anchor position. No significant differences in the incidence of total complications (23.1% vs 22.1%), pneumothorax (18.1% vs 19.2%), hemorrhage (9.5% vs 9.1%), and hemoptysis (1.8% vs 1.4%) were observed between the two groups. All the complications were minor and did not need special treatment. Except for one case in the microcoil group, which was converted to thoracotomy, the remaining 428 GGNs were successfully resected by VATS. CONCLUSIONS: It is safe and effective to perform pre-operative localization of GGN using either embolization microcoil or the locating needle designed for pulmonary nodules. The locating needle is superior to microcoil for marking GGN in terms of procedure time and the success rate. The complication rate of both methods is similar. ADVANCES IN KNOWLEDGE: The locating needle designed for pulmonary nodules has recently been used to mark pulmonary nodule. Its structure can effectively avoid dislocation after localization, and the marking process is simple and quick. Compared with localization using microcoil, it takes less time and has higher success rate to mark GGNs using the locating needle. The complication rate of both methods is similar.
Assuntos
Embolização Terapêutica/instrumentação , Agulhas , Radiografia Intervencionista , Nódulo Pulmonar Solitário/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Cuidados Pré-Operatórios , Nódulo Pulmonar Solitário/patologia , Nódulo Pulmonar Solitário/cirurgia , Cirurgia Torácica VídeoassistidaRESUMO
OBJECTIVE: To evaluate the feasibility, safety, and effectiveness of CT-guided microcoil localization of solitary pulmonary nodules (SPNs) for guiding video-assisted thoracoscopic surgery (VATS). MATERIALS AND METHODS: Between June 2016 and October 2019, 454 consecutive patients with 501 SPNs who received CT-guided microcoil localization before VATS in our institution were enrolled. The diameter of the nodules was 0.93 ± 0.49 cm, and the shortest distance from the nodules to the pleura was 1.41 ± 0.95 cm. The distal end of the microcoil was placed less than 1 cm away from the nodule, and the proximal end was placed outside the visceral pleura. VATS was performed under the guidance of implanted microcoils without the aid of intraoperative fluoroscopy. RESULTS: All 501 nodules were marked with microcoils. The time required for microcoil localization was 12.8 ± 5.2 minutes. Microcoil localization-related complications occurred in 179 cases (39.4%). None of the complications required treatment. A total of 463 nodules were successfully resected under the guidance of implanted microcoils. VATS revealed 38 patients with dislocated microcoils, of which 28 underwent wedge resection (21 cases under the guidance of the bleeding points of pleural puncture, 7 cases through palpation), 5 underwent direct lobectomy, and the remaining 5 underwent a conversion to thoracotomy. In 4 cases, a portion of the microcoil remained in the lung parenchyma. CONCLUSION: CT-guided microcoil localization of SPNs is safe and reliable. Marking the nodule and pleura simultaneously with microcoils can effectively guide the resection of SPNs using VATS without the aid of intraoperative fluoroscopy.
Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Fluoroscopia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Cuidados Pré-Operatórios , Radiografia Intervencionista , Estudos Retrospectivos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/cirurgia , Cirurgia Torácica Vídeoassistida , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: The present study aims to evaluate the effect of monosodium glutamate on testicular spermatogenesis in mice from the perspective of the hypothalamic-pituitary-testicular axis and whether this destructive effect is alleviated with time. METHODS: Neonatal mice were randomly divided into a monosodium glutamate (MSG) group and a control group, just below the interscapular region after birth with 10 µL MSG to deliver 4 mg/g (body mass), or with equivalent volumes of 0.9% saline. Samples which involved blood, brains and testicles of mice were collected and measured at puberty at 60 days and adulthood at 90 days. RESULTS: The results show that the fluorescence intensity of GnRH nerve fibers, the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) hormones in the reproductive system, the number of spermatocytes and spermatozoa in testicular sections, the body length, body weight, testicular weight, and testicular index in the 60-day-old mice in monosodium glutamate group (MSG60 group) and the MSG90 group were lower than those in the 60-day-old mice in normal control group (NC60 group) (p < 0.05), but the number of apoptotic cells in the testicular section was higher than in the NC60 group (p < 0.05). When the 90-day-old mice in monosodium glutamate group (MSG90 group) was compared with the MSG60 group, except for body weight and testicular weight increase (p < 0.05), there is no significant difference in the other parameters mentioned above (p > 0.05). CONCLUSION: Monosodium glutamate can cause reproductive toxicity to male mice by damaging GnRH neurons, and this reproductive toxicity cannot be relieved spontaneously over time. These findings are supported by observed histological changes.