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BACKGROUND: Thoracoscopic-guided thoracic paravertebral nerve block (TG-TPVB) and thoracoscopic-guided intercostal nerve block (TG-INB) are two postoperative analgesia technology for thoracic surgery. This study aims to compared the analgesic effect of TG-TPVB and TG-INB after uniportal video-asssited thoracic surgery (UniVATS). METHODS: Fifty-eight patients were randomly allocated to the TG-TPVB group and the TG-INB group. The surgical time of nerve block, the visual analog scale (VAS) scores, the consumption of sufentanil and the number of patient-controlled intravenous analgesic (PCIA) presses within 24 h after surgery, the incidence of adverse reactions were compared between the two groups. RESULTS: The VAS scores were significantly lower during rest and coughing at 2, 6, 12, and 24 h in the TG-TPVB group than in the TG-INB group (P < 0.05). The consumption of sufentanil and the number of PCIA presses within 24 h after surgery were significantly lower in the TG-TPVB group than in the TG-INB group (P < 0.001).The surgical time of nerve block was significantly shorter in the TG-TPVB group than in the TG-INB group (P < 0.001). The incidence of bleeding at the puncture point was lower in the TG-TPVB group than that in the TG-INB group (P < 0.05). CONCLUSION: TG-TPVB demonstrated superior acute pain relieve after uniVATS, shorter surgical time and non-inferior adverse effects than TG-INB.
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Nervos Intercostais , Bloqueio Nervoso , Dor Pós-Operatória , Cirurgia Torácica Vídeoassistida , Humanos , Feminino , Masculino , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Pessoa de Meia-Idade , Cirurgia Torácica Vídeoassistida/métodos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Estudos Prospectivos , Seguimentos , Idoso , Prognóstico , Adulto , Toracoscopia/métodos , Toracoscopia/efeitos adversos , Medição da DorRESUMO
The effective treatment of acute lung injury (ALI) remains a significant challenge. Patients with ALI demonstrate an abundance of proinflammatory mediators in both bronchoalveolar lavage fluid (BALF) and circulating plasma. Bardoxolone methyl (BM) is a semi-synthetic triterpenoid derived from oleanolic acid, a natural product known for its ability to inhibit proinflammatory signaling. GSDMD is a signaling protein involved in pyroptosis, a form of programmed cell death. It has been reported that its upstream proteins play a role in the pathogenesis of ALI. However, there is currently no research examining whether the effect of BM on the occurrence and development of ALI is associated with changes in GSDMD protein. In this study, we prepared nanostructured lipid carriers loaded with BM and conjugated with anti-PECAM-1 antibody (PECAM@BM NLCs). PECAM@BM NLCs were designed to specifically bind to pulmonary vascular endothelial cells that highly express the PECAM-1 receptors. We also aimed to investigate the protective effects of PECAM@BM NLCs on ALI and elucidate the underlying molecular mechanisms. The results demonstrated that PECAM@BM NLCs accumulated in the lung tissues and significantly alleviated the inflammatory injury of ALI. This was evidenced by the changes in the lung wet/dry ratio, the total protein concentration, proinflammatory cytokines in BALF, and the histopathological progress. Additionally, we elucidated that PECAM@BM NLCs had the ability to inhibit the assembly of NLRP3 inflammasome and pro-caspase-1 complex, thereby suppressing the induction of pyroptosis. This mechanism resulted in the inhibition of N-terminal GSDMD expression and effectively prevented the progression of ALI.
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Lesão Pulmonar Aguda , Pulmão , Nanoestruturas , Ácido Oleanólico , Molécula-1 de Adesão Celular Endotelial a Plaquetas , Ácido Oleanólico/farmacologia , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/administração & dosagem , Ácido Oleanólico/química , Animais , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/patologia , Nanoestruturas/química , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Portadores de Fármacos/química , Masculino , Camundongos , Pneumonia/tratamento farmacológico , Pneumonia/patologia , Pneumonia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Camundongos Endogâmicos C57BL , Lipídeos/química , Anticorpos/farmacologia , Líquido da Lavagem Broncoalveolar/química , Humanos , Sistemas de Liberação de Medicamentos/métodos , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacosRESUMO
BACKGROUND: Circular RNAs (circRNAs), one of the major contents of exosomes, have been shown to participate in the occurrence and progression of cancers. The role and the diagnostic potential of exosome-transported circRNAs in non-small-cell lung cancer (NSCLC) remain largely unknown. METHODS: The NSCLC-associated exosomal circ_0061407 and circ_0008103 were screened by circRNA microarray. The role of circ_0061407 and circ_0008103 in NSCLC was examined in vitro and in vivo. The encapsulation of the two circRNAs into exosomes and the transport to recipient cells were observed by confocal microscopy. The effects of exosome-transported circ_0061407 and circ_0008103 on recipient cells were investigated using a co-culture device. Bioinformatics analyses were performed to predict the mechanisms by which circ_0061407 and circ_0008103 affected NSCLC. The quantitative polymerase chain reaction was used to quantify the exosome-containing circ_0061407 and circ_0008103 in the serum samples of healthy, pneumonia, benign lung tumours, and NSCLC. The diagnostic efficacy was evaluated using receiver operating characteristic curves. RESULTS: The levels of circ_0061407 and circ_0008103 within exosomes were down-regulated in the serum of patients with NSCLC. The up-regulation of circ_0061407 and circ_0008103 inhibited the proliferation, migration/invasion, cloning formation of NSCLC cells in vitro and inhibited lung tumour growth in vivo. Circ_0061407 and circ_0008103 were observed to be packaged in exosomes and transported to recipient cells, where they inhibited the proliferation, migration/invasion, and cloning formation abilities of the recipient cells. Moreover, circ_0061407 and circ_0008103 might be involved in the progression of NSCLC by interacting with microRNAs and proteins. Additionally, lower serum exosomal circ_0061407 and circ_0008103 levels were associated with advanced pathological staging and distant metastasis. CONCLUSIONS: This study identified two novel exosome-transported circRNAs (circ_0061407 and circ_0008103) associated with NSCLC. These findings may provide additional insights into the development of NSCLC and potential diagnostic biomarkers for NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Exossomos , Neoplasias Pulmonares , RNA Circular , Exossomos/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/sangue , RNA Circular/genética , RNA Circular/sangue , RNA Circular/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/sangue , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Masculino , Regulação Neoplásica da Expressão Gênica , Feminino , Camundongos Nus , Pessoa de Meia-Idade , Camundongos Endogâmicos BALB C , Curva ROC , CamundongosRESUMO
Esophageal squamous cell carcinoma (ESCC) is one of the gastrointestinal malignancies with high prevalence and poor prognosis. Previous reports suggested that circular ribose nucleic acids might exert regulatory functions in ESCC. This study aims to explore the role of circ_0000592 in ESCC progression, providing novel insights into the diagnosis and therapeutic avenues for ESCC. The GSE131969 data set was utilized to assess circ_0000592 expression in ESCC. The validation was performed in the tumorous tissues of ESCC patients (n = 80) and human-immortalized ESCC cell lines. The correlation between circ_0000592 expression and prognosis was analyzed. The impact of circ_0000592 on ESCC cell activity was evaluated through downregulating circ_0000592, as well as encompassing cell viability, migration, and invasion abilities. The downstream pathway of circ_0000592 was explored by binding site prediction from the TargetScan database, followed by in vitro and in vivo experiments. An in vivo xenograft tumor model was established to highlight the role of circ_0000592 in ESCC. Patients with ESCC exhibited higher circ_0000592 expression levels compared to noncancerous patients, which were associated with reduced survival time, higher TNM stage, and increased lymph node metastasis. The circ_0000592 downregulation suppressed cell viability, migration, and invasion abilities in vitro. Mechanistically, circ_0000592 countered the inhibitory effects on the target gene Frizzled 5 (FZD5) through interactions with miR-155-5p. The overexpression of miR-155-5p curtailed the luciferase activity of circ_0000592 in ESCC cells, inhibiting downstream molecule FZD5 protein expression and subsequently mitigating the detrimental consequences of escalated circ_0000592 expression in ESCC cells. Consistently, circ_0000592 downregulation curbed proliferation and metastasis of ESCC tumors in vivo. In summary, circ_0000592 promoted the progress of ESCC by counteracting the inhibitory impact on FZD5 through its interaction with miR-155-5p. Together, our findings highlighted circ_0000592 as a prospective therapeutic target for ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Receptores Frizzled , MicroRNAs , RNA Circular , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Linhagem Celular Tumoral , Movimento Celular , Progressão da Doença , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Receptores Frizzled/metabolismo , Receptores Frizzled/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismoRESUMO
INTRODUCTION: Ultrasound-guided thoracic paravertebral block (UTPB) is widely used for postoperative analgesia in thoracic surgery. However, it has many disadvantages. Thoracoscopy-guided thoracic paravertebral block (TTPB) is a new technique for thoracic paravertebral block (TPB). In this study, we compared the use of TTPB and UTPB for pain management after thoracoscopic radical surgery for lung cancer. METHODS: In total, 80 patients were randomly divided 1:1 into the UTPB group and the TTPB group. The surgical time of TPB, the success rate of the first puncture, block segment range, visual analog scale (VAS) scores at 2, 6, 12, 24, and 48 h post operation, and the incidence of postoperative adverse reactions were compared between the two groups. RESULTS: The surgical time of TPB was significantly shorter in the TTPB group than in the UTPB group (2.2 ± 0.3 vs. 5.7 ± 1.7 min, t = - 12.411, P < 0.001). The success rate of the first puncture and the sensory block segment were significantly higher in the TTPB group than in the UTPB group (100% vs. 76.9%, χ2 = 8.309, P < 0.001; 6.5 ± 1.2 vs. 5.1 ± 1.3 levels, t = - 5.306, P < 0.001, respectively). The VAS scores were significantly higher during rest and coughing at 48 h post operation than at 2, 6, 12, and 24 h post operation in the TTPB group. The VAS scores were significantly lower during rest and coughing at 12 and 24 h post operation in the TTPB group than in the UTPB group (rest: 2.5 ± 0.4 vs. 3.4 ± 0.6, t = 7.325, P < 0.001; 2.5 ± 0.5 vs. 3.5 ± 0.6, t = 7.885, P < 0.001; coughing: 3.4 ± 0.6 vs. 4.2 ± 0.7, t = 5.057, P < 0.001; 3.4 ± 0.6 vs. 4.2 ± 0.8, t = 4.625, P < 0.001, respectively). No significant difference was observed in terms of postoperative adverse reactions between the two groups. CONCLUSIONS: Compared with UTPB, TTPB shows advantages, such as simpler and more convenient surgery, shorter surgical time, a higher success rate of the first puncture, wider block segments, and superior analgesic effect. TTPB can effectively reduce postoperative pain due to thoracoscopic lung cancer radical surgery. TRIAL REGISTRATION: https://www.chictr.org.cn , identifier ChiCTR2300072005, prospectively registered on 31/05/2023.
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Circular RNAs are emerging players in human cancers, including esophageal squamous cell carcinoma (ESCC). Herein, we assessed the expression level of circ_0023990 and explored the molecular mechanisms of circ_0023990 in ESCC. circ_0023990, miR-6884-5p, and PAK1 expressions in ESCC tissues and cells were detected by quantitative real-time polymerase chain reaction and western blot. ESCC cells were transfected with different constructs to alter the expression of circ_0023990, miR-6884-5p, and PAK1. The effect of circ_0023990 on the proliferation, invasion, and glycolysis of ESCC cells was observed. The interaction between circ_0023990 and miR-6884-5p and between miR-6884-5p and PAK1 were explored. A mouse model of ESCC was established to study the in vivo effect of circ_0023990 knockdown on tumor formation.The expression levels of circ_0023990 was upregulated in ESCC tissues and cells. Inhibiting circ_0023990 suppressed the proliferation, invasion, and glycolysis of ESCC cells. circ_0023990 might target miR-6884-5p and consequently modulate the expression and activity of PAK1. Knockdown of circ_0023990 led to significantly reduced tumor volume and weight in mice with ESCC.These findings overall suggest an oncogenic role of circ_0023990 in ESCC. Future research is warranted to confirm the expression pattern and clinical significance of circ_0023990 in ESCC.
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Proliferação de Células , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Glicólise , MicroRNAs , Invasividade Neoplásica , RNA Circular , Quinases Ativadas por p21 , Quinases Ativadas por p21/genética , Quinases Ativadas por p21/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Camundongos , Animais , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Feminino , Masculino , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: Extracellular vesicles (EVs) participate in cancer development via cell-to-cell communication. Long non-coding RNAs (lncRNAs), one component of EVs, can play an essential role in non-small-cell lung cancer (NSCLC) through EV-mediated delivery. METHODS: The NSCLC-associated lncRNA AL139294.1 in EVs was identified via lncRNA microarray analysis. The role of AL139294.1 in NSCLC was examined in vitro and in vivo. Confocal microscopy was used to observe the encapsulation of AL139294.1 into EVs and its transport to recipient cells. A co-culture device was used to examine the effects of transported AL139294.1 on the oncogenic behaviour of recipient cells. Dual-luciferase reporter assay was performed to verify the direct interaction of miR-204-5p with AL139294.1 and bromodomain-containing protein 4 (BRD4). AL139294.1 and miR-204-5p in EVs were quantified using quantitative polymerase chain reaction. Receiver operating characteristic analyses were conducted to evaluate the diagnostic efficiency. RESULTS: The lncRNA AL139294.1 in EVs promoted NSCLC progression in vitro and in vivo. After AL139294.1 was encapsulated into EVs and transported to recipient cells, it promoted the cells' proliferation, migration, and invasion abilities by competitively binding with miR-204-5p to regulate BRD4, leading to the activation of the Wnt and NF-κB2 pathways. Additionally, the expression of serum lncRNA AL139294.1 in EVs was increased, whereas miR-204-5p in EVs was decreased in NSCLC. High levels of lncRNA AL139294.1 and low levels of miR-204-5p in EVs were associated with advanced pathological staging, lymph node metastasis, and distant metastasis, underscoring their promising utility for distinguishing between more and less severe manifestations of the disease. CONCLUSIONS: This study reveals a novel lncRNA in EVs associated with NSCLC, namely, AL139294.1, providing valuable insights into the development of NSCLC and introducing potential diagnostic biomarkers for NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Vesículas Extracelulares , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Subunidade p52 de NF-kappa B , Proteínas Nucleares , Neoplasias Pulmonares/genética , Fatores de Transcrição , Proliferação de Células , MicroRNAs/genética , Proteínas que Contêm Bromodomínio , Proteínas de Ciclo CelularRESUMO
BACKGROUND: Invasive mucinous adenocarcinoma (IMA) was a rare and specific type of lung adenocarcinoma, which was often characterized by fewer lymphatic metastases. Therefore, it was difficult to evaluate the prognosis of these tumors based on the existing tumor-node-metastasis (TNM) staging. So, this study aimed to develop Nomograms to predict outcomes of patients with pathologic N0 in resected IMA. METHODS: According to the inclusion criteria and exclusion criteria, IMA patients with pathologic N0 in The Affiliated Lihuili Hospital of Ningbo University (training cohort, n=78) and Ningbo No.2 Hospital (validation cohort, n=66) were reviewed between July 2012 and May 2017. The prognostic value of the clinicopathological features in the training cohort was analyzed and prognostic prediction models were established, and the performances of models were evaluated. Finally, the validation cohort data was put in for external validation. RESULTS: Univariate analysis showed that pneumonic type, larger tumor size, mixed mucinous/non-mucinous component, and higher overall stage were significant influence factors of 5-year progression-free survival (PFS) and overall survival (OS). Multivariate analysis further indicated that type of imaging, tumor size, mucinous component were the independent prognostic factors for poor 5-year PFS and OS. Moreover, the 5-year PFS and OS rates were 62.82% and 75.64%, respectively. In subgroups, the survival analysis also showed that the pneumonic type and mixed mucinous/non-mucinous patients had significantly poorer 5-year PFS and OS compared with solitary type and pure mucinous patients, respectively. The C-index of Nomograms with 5-year PFS and OS were 0.815 (95%CI: 0.741-0.889) and 0.767 (95%CI: 0.669-0.865). The calibration curve and decision curve analysis (DCA) of both models showed good predictive performances in both cohorts. CONCLUSIONS: The Nomograms based on clinicopathological characteristics in a certain extent, can be used as an effective prognostic tool for patients with pathologic N0 after IMA resection.
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Adenocarcinoma de Pulmão , Adenocarcinoma Mucinoso , Neoplasias Pulmonares , Humanos , Prognóstico , Neoplasias Pulmonares/patologia , Adenocarcinoma Mucinoso/cirurgia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/patologia , Estadiamento de Neoplasias , Pulmão/patologia , Estudos RetrospectivosRESUMO
Video-assisted thoracoscopic surgery (VATS) provides better option concerning pathological diagnosis and curative intention of small pulmonary nodules (SPNs) that are sometimes challenging to localize. We assess the safety and feasibility of a new localization technique for SPNs, and report experience accumulated over time. A retrospective review of the new claw-suture localization cases between February 2018 and May 2023 was performed. Nodules were localized by a novel system that has an anchor claw and a tri-colored suture, guided by computed tomography (CT). Localization and operative procedure outcomes were then assessed. A total of 590 SPNs were localized from 568 patients before operation. The median nodule size was 0.70 cm (range, 0.3-2.0 cm). The claw-suture localization was successful without dislodgment or device fracture in 574 of 590 lesions (97.3%). Failures included not meeting target distance between claw and lesion (n = 13 [2.2%]), and device displacement (n = 3 [0.5%]). Complications requiring no further medical intervention included asymptomatic pneumothorax (n = 68 [11.5%]), parenchymal hemorrhage (n = 51 [8.6%]), and hemothorax (n = 1 [0.2%]) with the exception of pleural reaction observed in 2 cases (0.3%). Additionally, the depth of pulmonary nodules was significantly associated with the occurrence of pneumothorax (P = 0.036) and parenchymal hemorrhage (P = 0.000). The median duration of the localization was 12 min (range, 7-25 min). No patient complained of remarkable pain during the entire procedure. Retrieve of device after operation was 100%. The new localization technique is a safe, feasible, and well-tolerated method to localize SPNs for VATS resection.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Pneumotórax , Nódulo Pulmonar Solitário , Humanos , Neoplasias Pulmonares/patologia , Pneumotórax/etiologia , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Estudos Retrospectivos , Hemorragia/complicações , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/cirurgiaRESUMO
BACKGROUND: Numerous studies have reported the vital roles of circular RNA (circRNA)-based competitive endogenous RNA (ceRNA) regulatory networks in cancers. Here, we established a non-small-cell lung cancer (NSCLC)-related circRNA-miRNA-mRNA axis and estimated its diagnostic value in NSCLC. METHODS: The circ_0061235-miR-3180-5p-PPM1L axis was constructed by small RNA deep sequencing, bioinformatics databases, and preliminary testing. The serum levels of the selected circ_0061235, miR-3180-5p, and PPM1L were quantified using quantitative polymerase chain reaction. Receiver operating characteristic analyses were conducted to evaluate the diagnostic power. RESULTS: The levels of circ_0061235, miR-3180-5p, and PPM1L showed close correlations according to the ceRNA regulation rule. They were significantly dysregulated in NSCLC and showed the diagnostic ability to discriminate between healthy and NSCLC, and remarkably, between benign lung tumors and NSCLC. Additionally, the down-regulated levels of hsa_circ_0061235, the up-regulated levels of miR-3180-5p, and the decreased levels of PPM1L were correlated to more aggressive features of NSCLC, such as lymph node metastasis, distant metastasis, and higher stages. Intriguingly, compared to the single circ_0061235, miR-3180-5p, PPM1L, and traditional tumor markers, the diverse combinations of circ_0061235, miR-3180-5p, and PPM1L showed much higher sensitivity and specificity to differentiate greater or lesser severity of NSCLC. GO annotation and KEGG pathway analyses revealed the underlying role of the circ_0061235-miR-3180-5p-PPM1L axis in NSCLC. CONCLUSIONS: We established a specific circRNA-miRNA-mRNA network with higher sensitivity and specificity to diagnose NSCLC, particularly more aggressive NSCLC, providing a new strategy for further developing tumor biomarkers.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , RNA Circular , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , MicroRNAs/genética , Biomarcadores Tumorais/genética , RNA Mensageiro/genética , Proliferação de CélulasRESUMO
Objective: This study aims to develop a predictive model for identifying lung cancer patients at elevated risk for bone metastases, utilizing the Unified Immunoinflammatory Index and various tumor markers. This model is expected to facilitate timely and effective therapeutic interventions, especially in the context of the growing significance of immunotherapy for lung cancer treatment. Methods: A retrospective analysis was conducted on 324 lung cancer patients treated between January 2019 and January 2021. After meeting the inclusion criteria, 241 patients were selected, with 56 exhibiting bone metastases. The cohort was divided into a training group (169 patients) and a validation group (72 patients) at a 7:3 ratio. Lasso regression was employed to identify critical variables, followed by logistic regression to construct a Nomogram model for predicting bone metastases. The model's validity was ascertained through internal and external evaluations using the Concordance Index (C-index) and Receiver Operating Characteristic (ROC) curve. Results: The study identified several factors influencing bone metastasis in lung cancer, such as the Systemic Immune-Inflammatory Index (SII), Carcinoembryonic Antigen (CEA), Neuron Specific Enolase (NSE), Cyfra21-1, and Neutrophil-to-Lymphocyte Ratio (NLR). These factors were incorporated into the Nomogram model, demonstrating high validation accuracy with C-index scores of 0.936 for internal and 0.924 for external validation. Conclusion: The research successfully developed an intuitive and accurate Nomogram prediction model utilizing clinical indicators to predict the risk of bone metastases in lung cancer patients. This tool can be instrumental in aiding clinicians in developing personalized treatment plans, thereby optimizing patient outcomes in lung cancer care.
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BACKGROUND: Neoadjuvant chemoradiation followed by esophagectomy has been established as the first-line treatment for locally advanced esophageal cancer. Postoperative enteral nutrition has been widely used to improve perioperative outcomes. However, whether to implement preoperative nutritional intervention during neoadjuvant therapy is yet to be verified by prospective studies. METHODS: POINT trial is a multicenter, open-labeled, randomized controlled trial. A total of 244 patients with surgically resectable esophageal cancer are randomly assigned to nutritional therapy group (arm A) or control group (arm B) with a 2:1 ratio. Both groups receive neoadjuvant chemotherapy with concurrent radiotherapy based on the CROSS regimen followed by minimally invasive esophagectomy. The primary endpoint is the rate of nutrition and immune-related complications after surgery. Secondary endpoints include completion rate of neoadjuvant chemoradiation and related adverse events, rate of pathological complete response, perioperative outcomes, nutritional status, overall survival, progression-free survival and quality of life. DISCUSSION: This trial aims to verify whether immunonutrition during neoadjuvant chemoradiation can reduce the rate of complications and improve perioperative outcomes. Frequent communication and monitoring are essential for a multicenter investigator-initiated trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04513418. The trial was prospectively registered on 14 August 2020, https://www. CLINICALTRIALS: gov/ct2/show/NCT04513418 .
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Neoplasias Esofágicas , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Neoplasias Esofágicas/patologia , Humanos , Estudos Multicêntricos como Assunto , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: Anlotinib is a third-line or further therapy for advanced non-small-cell lung cancer (NSCLC). However, the lack of simple biomarkers to predict the curative effect of anlotinib creates significant unmet needs in exploring the markers. This study aimed to explore the relationship between the prognostic nutritional index (PNI) and its variations and efficacy of anlotinib. METHODS: Data for patients with advanced NSCLC who received anlotinib were collected at Ningbo Medical Center Lihuili Hospital. The data included the values of pretreatment PNI (pre-PNI), posttreatment PNI (post-PNI), and ΔPNI (post-PNI minus the pre-PNI). The Kaplan-Meier method was used to generate survival curves, whereas univariate and multivariate Cox regression analyses were used to analyze survival predictors. RESULTS: A high disease control rate was associated with a high pre-PNI (p = 0.007), high post-PNI (p = 0.000), and high ΔPNI (p = 0.006). Univariable analysis revealed that pre-PNI ≤41.80, post-PNI ≤42.48, and ΔPNI ≤0.20 were significant risk factors for poor survival. According to the multivariate analysis, progression-free survival (PFS) in patients with post-PNI ≤42.48 was significantly shorter than in patients with higher values (median PFS: 1.5 months vs. 4.0 months, p = 0.010). CONCLUSIONS: Pre-PNI, ΔPNI, and post-PNI were found to be predictive factors for response in advanced NSCLC patients treated with anlotinib as a third-line or further treatment. Only post-PNI was a reliable predictor of PFS. Therefore, PNI and its variations, particularly post-PNI, are affordable and accessible predictors of NSCLC patients treated with anlotinib in clinical work.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Indóis , Neoplasias Pulmonares/tratamento farmacológico , Avaliação Nutricional , Prognóstico , Quinolinas , Estudos RetrospectivosRESUMO
Esophageal squamous cell carcinoma (ESCC) has become a major health risk to human health. Although significant clinical progress has been made in the treatment of ESCC, the prognosis of patients still needs to be improved. Therefore, it is important to screen effective molecular indicators for the prognosis of ESCC. In this study, the intersection of up-regulated genes, down-regulated genes, and Wnt signaling pathway-related genes in ESCC was taken, and 47 overlapping genes were found. PRICKLE1 was determined to be an independent prognostic factor in ESCC based on univariate and multifactorial COX risk regression models. Kaplan-Meier survival curves showed that patients in the PRICKLE1 high expression group had significantly better overall survival. In addition, we performed various experiments to examine the effects of PRICKLE1 overexpression on proliferation, migration, and apoptosis of ESCC cells. The experimental results showed that the PRICKLE1-OE group had reduced cell viability, significantly lower migration ability and significantly higher apoptosis rate compared to the NC group.Therefore, we hypothesized that high PRICKLE1 expression could be used to predict the survival rate of ESCC patients, which could be used as an independent prognostic indicator for ESCC patients and provide potential applications for ESCC clinical treatment.
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OBJECTIVE: The purpose of this study was to explore the function and gene expression regulation of the newly identified lncRNA DPP10-AS1 in lung cancer, and its potential value as a prognostic biomarker. METHODS: qRT-PCR and Western blot were conducted to detect the expression of DDP10-AS1 and DPP10 in lung cancer cell lines and tissues. The effects of DDP10-AS1 on DPP10 expression, cell growth, invasion, apoptosis, and in vivo tumor growth were investigated in lung cancer cells by Western blot, rescue experiments, colony formation, flow cytometry, and xenograft animal experiments. RESULTS: The novel antisense lncRNA DPP10-AS1 was found to be highly expressed in cancer tissues (P < 0.0001), and its upregulation predicted poor prognosis in patients with lung cancer (P = 0.0025). Notably, DPP10-AS1 promoted lung cancer cell growth, colony formation, and cell cycle progression, and repressed apoptosis in lung cancer cells by upregulating DPP10 expression. Additionally, DPP10-AS1 facilitated lung tumor growth via upregulation of DPP10 protein in a xenograft mouse model. Importantly, DPP10-AS1 positively regulated DPP10 gene expression, and both were coordinately upregulated in lung cancer tissues. Mechanically, DPP10-AS1 was found to associate with DPP10 mRNA but did not enhance DPP10 mRNA stability. Hypomethylation of DPP10-AS1 and DPP10 contributed to their coordinate upregulation in lung cancer. CONCLUSIONS: These findings indicated that the upregulation of the antisense lncRNA DPP10-AS1 promotes lung cancer malignant processes and facilitates tumorigenesis by epigenetically regulating its cognate sense gene DPP10. DPP10-AS1 may serve as a candidate prognostic biomarker and a potential therapeutic target in lung cancer.
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INTRODUCTION: Pain is still severe after single-port video-assisted thoracoscopic (SPVAT) lung wedge resection. We observed the effect of single-injection thoracic paravertebral block (TPB) via the intrathoracic approach for analgesia after SPVAT lung wedge resection. METHODS: Sixty patients undergoing SPVAT lung wedge resection were randomly divided into a control group and an observation group. All patients underwent TPB via the intrathoracic approach at the T4 level with a scalp needle before closing the chest. The patients in the observation group received 20 ml 0.375% ropivacaine at the T4 level, and the patients in the control group received 20 ml of 0.9% saline. A patient-controlled intravenous analgesic (PCIA) pump with sufentanil was attached to all patients after surgery. The sufentanil consumption and number of PCIA presses in the first 24 h after surgery were recorded. The visual analogue scale (VAS) scores (during rest and coughing) were recorded at 6 h, 12 h, 24 h, and 36 h after surgery. The incidence of adverse reactions after surgery were recorded. RESULTS: The sufentanil consumption in the observation group was significantly lower than that in the control group (34.2 ± 1.9 µg vs. 52.3 ± 2.3 µg; P < 0.001). The VAS score at 6, 12, and 24 h after surgery, the incidence of adverse reactions after surgery in the observation group were significantly lower than those in the control group (all P < 0.05). The number of PCIA presses in the observation group was significantly lower than that in the control group [0 (0-0) times vs. 3 (2-4) times, P < 0.001]. CONCLUSIONS: Single-injection TPB via the intrathoracic approach under thoracoscopic direct vision is easy to perform and can effectively alleviate postoperative pain after SPVAT lung wedge resection, with fewer adverse reactions. TRIAL REGISTRATION: ChiCTR2000034726.
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BACKGROUND: We observed the feasibility and effectiveness of multi-injection thoracic paravertebral block (TPB) via the intrathoracic approach under thoracoscopic direct vision for analgesia after thoracoscopic-laparoscopic esophagectomy (TLE). METHODS: Sixty patients undergoing TLE were randomly divided into a control group and an observation group. All patients underwent TPB via the intrathoracic approach at the three levels of T2, 5, and 8 with a scalp needle before closing the chest. The patients in the observation group received 10 ml 0.375% ropivacaine at each level, and the patients in the control group received 10 ml of 0.9% saline at each level. A patient-controlled intravenous analgesic (PCIA) pump with sufentanil was attached to all patients after surgery. The sufentanil consumption, number of PCIA presses and use of rescue analgesia in the first 24 h after surgery were recorded. The visual analogue scale (VAS) scores (rest and coughing) were recorded at 2 h, 6 h, 12 h, 24 h, and 48 h after surgery. The duration of postoperative hospital stay, active cough rate, first ambulation, and the incidence of adverse reactions after surgery was recorded. RESULTS: The sufentanil consumption in the observation group was significantly lower than that in the control group (34.7 ± 1.9 µg vs. 52.1 ± 2.1 µg; P < 0.001). The VAS score at each postoperative time point, number of PCIA presses, use of rescue analgesia, and the incidence of adverse reactions in the observation group were significantly lower than those in the control group. The postoperative active cough rate of patients in the observation group was significantly higher than those in the control group, and the times of the first ambulation after surgery and postoperative hospital stay in the observation group were significantly shorter than those in the control group (all P < 0.05). CONCLUSIONS: Multi-injection TPB via the intrathoracic approach under thoracoscopic direct vision is easy to perform and can effectively alleviate postoperative pain after TLE with fewer adverse reactions and contributing to improved postoperative recovery.
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Analgesia , Laparoscopia , Bloqueio Nervoso , Esofagectomia/efeitos adversos , Estudos de Viabilidade , Humanos , Laparoscopia/efeitos adversosRESUMO
Deformed amphibole in the plagioclase amphibolite mylonite of the Guandi Complex, Xishan, Beijing, is the research object in this study. The amphibole nanodeformation under the middle crust was analyzed using microstructural analysis and high-resolution transmission electron microscopy (TEM). Microscope observations show that the amphibolite deformations in the plagioclase amphibolite mylonite are δ and σ type porphyroclasts, and the porphyroclast tail is composed of new long-columnar crystals. Using transmission electron microscopy (TEM, and this acronyms would be defined only once), the authors observed the nanodeformation characteristics of the amphibole porphyroclast core and mantle. Dislocation tangles are dominant in the porphyroclast core, and inside the new crystal, there is little or no dislocation. Swelled new crystals surrounded by dislocation can be observed in the transition zone between the porphyroclasts and new crystals. The deformed amphibole microstructure and submicrostructure represent typical brittle-ductile transitional deformation. The deformation process can be divided into two stages: the disordered dislocation increment stage and the dislocation reduction and ordering stage. Crystalline plastic deformation occurs in the amphibole in the plagioclase amphibolite mylonite of the Xishan area, Beijing. The crystalline plastic deformation temperature in amphiboles is higher than that in plagioclase.
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Congenital heart disease (CHD) is the most commonly diagnosed congenital disorder in newborns. The incidence and mortality of CHD vary worldwide. A detailed understanding of the global, regional, and national distribution of CHD is critical for CHD prevention.We collected the incidence and mortality data of CHD from the Global Burden of Disease study 2017 database. Average annual percentage change was applied to quantify the temporal trends of CHD incidence and mortality at the global, regional, and national level, 1990-2017. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility.The incidence of CHD was relatively high in developing countries located in Africa and Asia, while low in most developed countries. Between 1990 and 2017, the CHD incidence rate remained stable at the global level, whereas increased in certain developed countries, such as Germany and France. The age-standardized mortality rate of CHD declined substantially over the last 3 decades, regardless of sex, age, and SDI region. The decline was more prominent in developed countries. We also detected a significant positive correlation between CHD incidence and CHD mortality in both 1990 and 2017, by SDI.The incidence of CHD remained stable over the last 3 decades, suggesting little improvement in CHD prevention strategies and highlighting the importance of etiological studies. The mortality of CHD decreased worldwide, albeit the greatly geographical heterogeneity. Developing countries located in Africa and Asia deserve more attention and priority in the global CHD prevention program.