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BACKGROUND AND AIM: Esophageal squamous cell carcinoma (ESCC) is the most significant subtype of esophageal cancer featured with high occurrence. Long noncoding RNAs (lncRNAs) have been proved to modulate the biological properties of cancer cells, including cell proliferation, invasion, migration, and apoptosis. LncRNA protein tyrosine phosphatase receptor type G-antisense RNA 1 (PTPRG-AS1) has been reported to play as an oncogene in diverse cancers. However, the detailed function PTPRG-AS1 may exert in ESCC is unclear. METHODS: PTPRG-AS1 expression in ESCC cells was investigated via quantitative reverse transcription real-time polymerase chain reaction (RT-qPCR). The effects of PTPRG-AS1 on ESCC cell proliferation, migration, glycolysis, and stemness were verified through functional assays. Mechanism assays including RIP assay, RNA pull down assay, and luciferase reporter assays were performed to verify the molecular mechanism of PTPRG-AS1. RESULTS: PTPRG-AS1 silencing hindered the proliferation, migration, glycolysis and stemness of ESCC cells. PTPRG-AS1 regulated pyruvate dehydrogenase kinase 1 (PDK1) expression via sponging miR-599. The PTPRG-AS1/miR-599/PDK1 axis was further verified to aggravate the progression of ESCC cells. CONCLUSION: PTPRG-AS1 sponged miR-599 to up-regulate PDK1 expression, thereby promoting the proliferation and migration as well as glycolysis and stemness properties of ESCC cells.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Monoéster Fosfórico Hidrolases , RNA Longo não Codificante , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Glicólise/genética , Humanos , MicroRNAs/metabolismo , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de SinaisRESUMO
The calcium-sensing receptor (CaSR) is involved in the pathophysiology of many cardiovascular diseases, including myocardial infarction (MI) and hypertension. The role of Calhex231, a specific inhibitor of CaSR, in myocardial fibrosis following MI is still unclear. Using Wistar rats, we investigated whether Calhex231 ameliorates myocardial fibrosis through the autophagy-NLRP3 inflammasome pathway in macrophages post myocardial infarction (MI). The rats were randomly divided into sham, MI and MI + Calhex231 groups. Compared with the sham rats, the MI rats consistently developed severe cardiac function, myocardial fibrosis and infiltration of inflammatory cells including macrophages. Moreover, inflammatory pathway including activation of NLRP3 inflammasome, IL-1ß and autophagy was significantly up-regulated in myocardial tissue, infiltrated cardiac macrophages and peritoneal macrophages of the MI rats. These impacts were reversed by Calhex231. In vitro, studies revealed that calindol and rapamycin exacerbated MI-induced autophagy and NLRP3 inflammasome activation in peritoneal macrophages. Calhex231 and 3-Methyladenine (a specific inhibitor of autophagy) attenuated both autophagy and NLRP3 inflammasome activation; however, the caspase-1 inhibitor Z-YVAD-FMK did not. Our study indicated that Calhex231 improved cardiac function and ameliorated myocardial fibrosis post MI, likely via the inhibition of autophagy-mediated NLRP3 inflammasome activation; this provides a new therapeutic target for ventricular remodelling-related cardiovascular diseases.
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Benzamidas/farmacologia , Cardiomiopatias/etiologia , Cardiomiopatias/metabolismo , Cicloexilaminas/farmacologia , Inflamassomos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Infarto do Miocárdio/complicações , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Autofagia/efeitos dos fármacos , Biomarcadores , Cardiomiopatias/patologia , Modelos Animais de Doenças , Fibrose , Imunofluorescência , Imuno-Histoquímica , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Masculino , Ratos , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND The aim of this study was to investigate the surgical method, postoperative complications, and gastrointestinal motility of thoraco-laparoscopic esophagectomy in the treatment of esophageal cancer. MATERIAL AND METHODS Using random sampling method, we selected 132 esophageal cancer patients who were treated in our hospital from January 2012 to December 2014; these patients were regarded as the study group and underwent thoraco-laparoscopy 3-field surgery treatment. Another 108 esophageal cancer patients admitted to our hospital over the same period were regarded as the control group and underwent traditional open McKeown esophagectomy. RESULTS The amount of blood loss and postoperative drainage of pleural fluid in the study group were significantly lower (P<0.05) and the time to removal of the chest tube and hospital stay were significantly shorter (P<0.05). The incidence of anastomotic fistula, vocal cord paralysis, chylothorax, and arrhythmia were significantly lower in the study group than in the control group (P<0.05). However, no significant differences in the incidence of pneumonia, atelectasis, or acute respiratory distress were detected (P>0.05). For postoperative gastrointestinal motility, first flatus time, first defecation time, and bowel tone recovery time after the operation, as well as the total amount of gastric juice draining, were reduced in the thoraco-laparoscopic esophagectomy group (P<0.05). The postoperative MTL and NO levels were higher but VIP level was lower in the thoraco-laparoscopic group (P<0.05). CONCLUSIONS Thoraco-laparoscopic esophagectomy was technically feasible and safe; it was associated with lower incidence of certain postoperative complications and had less effect on postoperative gastrointestinal motility. Skilled technique and cooperation could further shorten the operation time and might lead to better patient outcomes.
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Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Toracoscopia/métodos , Adulto , Idoso , Perda Sanguínea Cirúrgica , Neoplasias Esofágicas/fisiopatologia , Feminino , Motilidade Gastrointestinal/fisiologia , Humanos , Laparoscopia/métodos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Período Pós-OperatórioRESUMO
Accelerated progression of residual non-small cell lung cancer (NSCLC) after incomplete radiofrequency ablation (RFA) has frequently been reported. In this study, NSCLC cells A549, CCL-185, and H358 were treated using a water bath at 47°C for 5, 10, 15, 20, and 25 min gradually to establish the sublines A549-H, CCL-185-H, and H358-H, respectively. A549-H, CCL-185-H, and H358-H cells showed a significant increase in proliferation rate when compared with their corresponding parental cellsin vitro The expression of hypoxia-inducible factor-1α (HIF-1α) was obviously upregulated in both A549-H and CCL-185-H cells. Silencing of HIF-1α abolished the insufficient RFA-induced proliferation in A549-H and CCL-185-H cells. Furthermore, insufficient RFA treatment markedly elevated the phosphorylation of ERK1/2 and Akt, but not of p38 MAPK or JNK, in A549-H and CCL-185-H cells. The inhibitor of Akt, LY294002, but not the inhibitor of ERK1/2, PD98059, suppressed the upregulation of HIF-1α and the proliferation of A549-H and CCL-185-H cellsin vitro Thein vivoresults confirmed that insufficient RFA could trigger the tumor growth, upregulate the HIF-1α expression, and activate Akt in A549 xenograft tumors. Our data suggest that insufficient RFA can promote thein vitroandin vivogrowth of NSCLC via upregulating HIF-1α through the PI3K/Akt signals.
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Carcinoma Pulmonar de Células não Pequenas/radioterapia , Proliferação de Células , Neoplasias Pulmonares/radioterapia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Animais , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Xenoenxertos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
The aim of the study was to elucidate the impact of different moisture phases during gas injection on coalbed methane displacement. The coal samples were treated with two methods: water vapor adsorption and liquid water stirring. The differences in the coal samples treated with various moisture phases during gas injection for coalbed methane displacement were investigated by using the isothermal adsorption curves of CH4, N2, and H2O in coal and N2 displacement of CH4 in coal. The results indicate that variations in the gas adsorption capacity of coal are treated with different moisture phases. The gas adsorption capacities and displacement capacities of the coal samples treated with the water vapor adsorption methods are better than those treated with the stirring methods. In the isothermal adsorption experiment, for the coal samples treated with different moisture phases, at a moisture content of 2.75%, the saturated adsorption capacities of CH4/N2 are 0.204/0.189 (cm3/g), and at a moisture content of 5.63%, the saturated adsorption capacities of CH4/N2 are 0.151/0.139 (cm3/g). In addition, in the displacement experiment, for the coal samples treated with different moisture phases, at a moisture content of 2.75%, the difference in the total gas adsorption capacities is 0.62 cm3/g and the difference in the CH4 adsorption capacities is 0.473 cm3/g, and at a moisture content of 5.63%, the difference in the total gas adsorption capacities is 0.3 cm3/g and the difference in CH4 adsorption capacities is 0.22 cm3/g. For the coal samples treated with various moisture phases, the differences in the CH4/N2 adsorption and displacement capacities are greater at a moisture content of 2.75% than at 5.63%. Notably, the moisture phase has only a marginal influence on the CH4 desorption capacity and desorption rate. The study is important to understand the interactions between coal and moisture.
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As the most frequently diagnosed cancer, lung cancer (LC) is the most common cause of cancerrelated death worldwide. In total, ~85% of malignant lung tumors belong to nonsmall cell LC, of which ~50% are lung adenocarcinoma (LUAD). Integrin subunit ß4 (ITGB4) is upregulated in lung glandular cancer and elevated ITGB4 levels predict an adverse clinical outcome. However, the biological function of ITGB4 in promoting LUAD progression remains unclear. In the present study, the upregulation of ITGB4 in LUAD tissue samples was demonstrated. To understand the biological role of ITGB4, ITGB4 expression was knocked down in A549 and PC9 cells through transfection with specific small interfering RNAs. The results demonstrated that the downregulation of ITGB4 attenuated A549 and PC9 cell proliferation, promoted cell apoptosis and inhibited colony formation, cell migration and cell invasion. To understand the mechanism of ITGB4, high throughput sequencing was performed using ITGB4knocked down A549 cells, followed by bioinformatics analysis. It was found that the genes upregulated by ITGB4 were significantly enriched in metabolism and related pathways, and the genes downregulated by ITGB4 were enriched in cell cycle and related pathways. In conclusion, the findings of the present study highlighted the oncogenic function of ITGB4 in LUAD and uncovered potential mechanisms fundamental to the progression of the disease.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proliferação de Células/genética , Movimento Celular/genética , Células A549 , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Integrina beta4/genética , Integrina beta4/metabolismoRESUMO
This study aimed to evaluate the safety and efficacy of camrelizumab combined with chemotherapy during preoperative neoadjuvant therapy in patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC) of clinical Stages II and III. The patients received camrelizumab plus chemotherapy regimen on Day 1 for up to three to four cycles (3 weeks per cycle). The probabilities of overall survival (OS) were 55.6% at 12 months and 35.6% at 18 months (45 patients). The disease-free survival (DFS) rates were 70.0% at 12 months and 63.3% at 18 months (30 patients). The median OS and DFS were not reached. The proportion of patients at postneoadjuvant pathological tumor stages ypT0, ypT2, and ypT3 were 10 (33.3%), 14 (46.7%), and 6 (20.0%), respectively, and those at stages ypN0 and ypN1 were 19 (63.3%) and 11 (36.7%), respectively. Additionally, the pathological complete response rate was 33.3% (95% confidence interval [CI]: 0.154-0.512), and the major pathologic response rate was 46.7% (95% CI: 0.277-0.656). Grade ≥3 adverse events (AEs) were reported in five patients (11.1%), with vomiting being the most common AE (three patients; 3.3%). Other common AEs of any grade included decreased lymphocyte count (48.9%), reactive capillary endothelial proliferation (46.7%), decreased white blood cell count (40.0%), anemia (31.1%), and vomiting (31.1%). The combination of camrelizumab and neoadjuvant chemotherapy in patients with locally advanced resectable ESCC demonstrated promising efficacy and acceptable safety.
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Anticorpos Monoclonais Humanizados , Carcinoma , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/cirurgia , Terapia Neoadjuvante , Estudos Retrospectivos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Vômito , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
AIM: Some studies have reported that body composition profiles affect clinical outcomes of multidisciplinary treatments in several types of cancers; however, a paucity of data exists on the association in neoadjuvant immunotherapy. In the present study, we aimed to investigate the effect of body composition on the clinical outcomes of patients with esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunotherapy plus chemotherapy (nICT). METHODS: Clinicopathological data and computed tomography (CT) images of 85 patients with locally advanced ESCC who underwent esophagectomy after nICT were collected. At diagnosis and before surgery, the CT scan of the third lumbar vertebra was chosen to evaluate the skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), the subcutaneous and the visceral adiposity index. The relationships between body composition and tumor response after nICT and postoperative complications were analyzed. RESULTS: The clinical stage (Odds Ratio (OR) 0.345, 95% confidence interval (CI) 0.141-0.844, p = 0.020) and change in SMI (∆SMI, OR 1.394, 95% CI 1.061-1.832, p = 0.017) were associated with tumor remission after nICT. Moreover, the multivariate logistic analysis revealed that ∆SMI (OR 0.598, 95% CI 0.433-0.828, p = 0.002) was associated with the incidence of postoperative complications. Patients with ∆SMI <-1 had a higher rate of postoperative complications (56% vs 15%, p < 0.001). CONCLUSIONS: For ESCC, ∆SMI is associated with the pathological response after nICT and postoperative complications. Further analysis is needed to clarify whether nutritional intervention during neoadjuvant therapy increases SMI and thus improves clinical outcomes.
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Composição Corporal , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Terapia Neoadjuvante , Humanos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Masculino , Feminino , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Esofagectomia , Imunoterapia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
Our previous study revealed that 1-nitropyrene (1-NP) exposure evoked pulmonary fibrosis in mice. However, the exact mechanism remained elusive. We found that 1-NP induced telomere damage and cellular senescence in mice lungs, and two alveolar epithelial cells lines. 1-NP downregulated telomere repeat binding factor 2 (TRF2), and upregulated FBXW7. Mechanistically, 1-NP-caused TRF2 ubiquitination and proteasomal degradation depended on E3 ubiquitin ligase activity of FBXW7. Moreover, 1-NP upregulated FBXW7 m6A modification via an ALKBH5-YTHDF1-dependent manner. Further analysis suggested 1-NP promoted ALKBH5 SUMOylation and subsequent proteasomal degradation. Additionally, 1-NP evoked mitochondrial reactive oxygen species (mtROS) overproduction. Mito-TEMPO, a mitochondrial-targeted antioxidant, mitigated 1-NP-caused mtROS overproduction, ALKBH5 SUMOylation, FBXW7 m6A modification, TRF2 degradation, cellular senescence, and pulmonary fibrosis. Taken together, mtROS-initiated ALKBH5 SUMOylation and subsequent FBXW7 m6A modification is indispensable for TRF2 degradation and cellular senescence in alveolar epithelial cells during 1-NP-induced pulmonary fibrosis. Our study provides target intervention measures towards 1-NP-evoked pulmonary fibrosis.
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Adenina/análogos & derivados , Fibrose Pulmonar , Pirenos , Sumoilação , Animais , Camundongos , Proteína 7 com Repetições F-Box-WD/genética , Proteína 7 com Repetições F-Box-WD/metabolismo , Células Epiteliais Alveolares/metabolismo , Fibrose Pulmonar/induzido quimicamenteRESUMO
[This corrects the article DOI: 10.3389/fgene.2024.1381690.].
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The ALOG (Arabidopsis LSH1 and Oryza G1) family proteins, namely, DUF640 domain-containing proteins, have been reported to function as transcription factors in various plants. However, the understanding of the response and function of ALOG family genes during reproductive development and under abiotic stress is still largely limited. In this study, we comprehensively analyzed the structural characteristics of ALOG family proteins and their expression profiles during inflorescence development and under abiotic stress in rice. The results showed that OsG1/OsG1L1/2/3/4/5/6/7/8/9 all had four conserved helical structures and an inserted Zinc-Ribbon (ZnR), the other four proteins OsG1L10/11/12/13 lacked complete Helix-1 and Helix-2. In the ALOG gene promoters, there were abundant cis-acting elements, including ABA, MeJA, and drought-responsive elements. Most ALOG genes show a decrease in expression levels within 24 h under ABA and drought treatments, while OsG1L2 expression levels show an upregulated trend under ABA and drought treatments. The expression analysis at different stages of inflorescence development indicated that OsG1L1/2/3/8/11 were mainly expressed in the P1 stage; in the P4 stage, OsG1/OsG1L4/5/9/12 had a higher expression level. These results lay a good foundation for further studying the expression of rice ALOG family genes under abiotic stresses, and provide important experimental support for their functional research.
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After the coal seam is injected with water, the moisture content in the coal body increases, which affects the output capacity of coalbed methane (CBM). In order to improve the effect of CBM mining, the classical anthracite molecular model has been selected. To analyze the influence of different placement orders of water and methane on the characteristics of coal-adsorbing methane from the micro point of view, a molecular simulation method is used for comprehensive consideration in the study. The results show that H2O does not change the mechanism of CH4 adsorption by anthracite, but it inhibits the adsorption of methane by anthracite. When water enters the system afterward, there arises an equilibrium pressure point where water plays the most significant role in inhibiting methane adsorption by anthracite coals, which increases with increasing moisture content. When water enters the system first, no equilibrium pressure point occurs. The excess adsorption of methane by anthracite when water enters second is higher. The reason is that H2O can replace CH4 at the higher energy adsorption sites of the anthracite structure, while CH4 can only be adsorbed at the lower energy sites, and some of CH4 is not adsorbed. For the coal samples with a low-moisture content system, the equivalent heat of adsorption of CH4 increases first rapidly and then slowly with the increase of pressure. However, it decreases with pressure in the high-moisture content system. The variation of the equivalent heat of adsorption further explains the variation of the magnitude of methane adsorption under different conditions.
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Exposure to air pollution has been proven to be associated with impaired fetal lung development. However, due to the lack of reliable human source models, it is still challenging to deeply understand the human fetal lung development under PM2.5 exposure. Here, we utilized human embryonic stem cell (hESC) line H9 to generate lung bud tip progenitor organoids (LPOs), a process that mimics early stages of fetal lung development including definitive endoderm (DE) formation, anterior foregut endoderm (AFE) differentiation and lung progenitor cell specification, to evaluate potential pulmonary developmental toxicity of PM2.5. We demonstrated that PM2.5 exposure the entire LPOs induction from hESCs significantly affected cellular proliferation of LPOs, and altered the expression of lung progenitor cell markers NKX2.1, SOX2 and SOX9, which are canonically defined subsequently proximal-distal airways specification. To explore the dynamic influences of PM2.5 exposure at different stages of LPOs specification, we also found that PM2.5 exposure significantly affected the expression of several transcriptional factors that are important for the differentiation of DE and AFE. Mechanistically, we suggested PM2.5-induced developmental toxicity to LPOs was partially linked with the Wnt/ß-catenin signaling pathway. Therefore, our findings further emphasize the substantial health risks in the development of respiratory system associated with prenatal exposure to PM2.5.
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Pulmão , Organoides , Feminino , Humanos , Gravidez , Diferenciação Celular , Pulmão/metabolismo , Linhagem Celular , Material Particulado/toxicidade , Material Particulado/metabolismoRESUMO
INTRODUCTION: Parietal pleurectomy with bullectomy has been established as an effective method for preventing the recurrence of primary spontaneous pneumothorax (PSP). Our center introduced enhanced technical measures in uniportal thoracoscopic parietal pleurectomy with bullectomy for patients with PSP, aiming to document our initial experience and assess the procedure's effectiveness in preventing the recurrence of PSP. METHODS: We analyzed the clinical data of 86 patients with PSP who underwent the improved uniportal thoracoscopic parietal pleurectomy with bullectomy between July 2019 and August 2022. During the procedure, the parietal pleura above the second intercostal space was stripped but not removed. Instead, it was retained in the thoracic cavity using a piece of pedunculated pleura. Subsequently, the stumps of the lung were covered by the preserved parietal pleura. RESULTS: The results of the study showed that the mean operative time was 59.87 ± 16.93 min, and the postoperative drainage duration averaged 3.94 ± 2.17 days. The mean intraoperative blood loss was 24.33 ± 48.91 ml, and the mean postoperative drainage volume was 289.00 ± 170.03 ml. Prolonged air leakage for more than 5 days was observed in five patients (5.81%), but no other postoperative complications were recorded. During the follow-up, one patient (1.16%) experienced a recurrence of pneumothorax. CONCLUSIONS: The perioperative results of bullectomy with the improved pleurectomy technique are deemed satisfactory. The various technical steps attempted at our center are found to be feasible and safe, and they may contribute to reducing the rates of recurrence in PSP.
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Pneumotórax , Procedimentos Cirúrgicos Torácicos , Humanos , Pneumotórax/cirurgia , Estudos Retrospectivos , Pleura/cirurgia , Complicações Pós-Operatórias , Recidiva , Cirurgia Torácica Vídeoassistida/métodos , Resultado do TratamentoRESUMO
Long-flame coal is a bituminous coal with the lowest metamorphic degree, accounting for 16.1% of China's coal reserves. With increases in mining depths and intensities, mine gas disasters related to the mining of long-flame coal are becoming increasingly serious. Therefore, the exploration of the effect of moisture on the adsorption of methane in coal can provide support for popularizing the application of hydraulic measures in long-flame coal mining areas. In this paper, a molecular structure model of long-flame coal was established by molecular dynamics and the Monte Carlo method. The adsorption characteristics of methane in long-flame coal structures under different pressures were simulated, and the effects of different amounts of water on the methane adsorption and adsorption heat were explored. The results show that, under the same adsorption equilibrium pressure, the methane adsorption rate decreases with increasing water content, and with increasing adsorption equilibrium pressure, the adsorption capacity of methane increases gradually; this increasing trend is in agreement with the Langmuir equation. The water adsorption of coal is greater than the methane adsorption of coal. With the increase in the number of water molecules, when coal-based molecules adsorb methane and then adsorb water molecules, the adsorption heat of methane is reduced, and the desorption of methane molecules is promoted.
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In this study, we examined the effects of castration and testosterone replacement on ß-adrenoceptor and G protein expression in rats subjected to doxorubicin-induced heart failure. Five groups were included in this report: control, sham-castration with heart failure, castration with heart failure, castration+testosterone replacement with heart failure and castration+testosterone replacement and flutamide with heart failure. At 4 weeks post-treatment, echocardiography, hemodynamics and histopathology were assessed. Castration led to a further deterioration in myocardial performance, apoptosis and fibrosis, while testosterone replacement ameliorated these effects. Data obtained from Western blots revealed that testosterone upregulated the expression of ß(2)-adrenoceptor, Gs, Gi(2) and bcl2 levels, downregulated the expression of ß(3)-adrenoceptor, Gi(3) and GRK2 levels, and did not modify the expression of ß(1)-adrenoceptor levels in the hearts of castrated rats subjected to doxorubicin-induced heart failure. Analyses of serum 17ß-estradiol concentrations test confirmed that these effects of testosterone were exerted through the androgen pathway. Thus our findings suggest that testosterone may have beneficial effects for male heart failure patients with androgen deficiency and this protection involves modulation of the cardiac ß-adrenergic system.
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Insuficiência Cardíaca/metabolismo , Receptores Adrenérgicos beta/metabolismo , Testosterona/farmacologia , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Doxorrubicina/farmacologia , Ecocardiografia , Estrogênios/sangue , Flutamida/farmacologia , Quinase 2 de Receptor Acoplado a Proteína G/genética , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Coração/efeitos dos fármacos , Insuficiência Cardíaca/induzido quimicamente , Hemodinâmica , Masculino , Miocárdio/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Testosterona/sangue , Testosterona/fisiologiaRESUMO
BACKGROUND: Esophagectomy is the standard treatment for early-stage esophageal cancer but is associated with high morbidity and mortality. Thus, endoscopic resection is increasingly used as an alternative option. However, the literature is inconsistent regarding the efficacy of these treatments. This meta-analysis aimed to compare the efficacy and safety of these two treatments. METHODS: A systematic electronic search of PubMed, EMBASE, and the Cochrane Library was performed for studies comparing endoscopic resection and surgery for early-stage esophageal cancer. The overall survival, tumor recurrence, major adverse events, procedure-related mortality, and R0 resection rates were investigated. Forest plots were constructed based on the random-effects model. RESULTS: We found 15 studies involving 2,467 and 2,264 patients who underwent endoscopic resection and surgery, respectively. The meta-analysis showed that patients undergoing endoscopic resection had significantly fewer major adverse events (relative risk, 0.46; 95% confidence interval, 0.33-0.64) and a lower procedure-related mortality rate (relative risk, 0.27; 95% confidence interval, 0.10-0.73) than those undergoing surgery. The number of postprocedural stricture events did not significantly differ between the two treatments (relative risk, 0.89; 95% confidence interval, 0.53-1.49). Endoscopic resection was associated with higher recurrence rates (relative risk, 1.69; 95% confidence interval, 0.99-2.89) and lower R0 resection rates (relative risk, 0.92; 95% confidence interval, 0.86-0.98) than surgery. There may be some advantage conferred by esophagectomy in the long-term survival outcomes (hazard ratio, 1.21; 95% confidence interval, 1.02-1.43). DISCUSSION: Endoscopic resection is a minimally invasive and safe treatment for early-stage esophageal cancer. However, esophagectomy may be associated with better long-term survival.
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BACKGROUND: Ferroptosis is a newly generated regulatory cell death promoted by the accumulated lipid-based reactive oxygen species (ROS). Solute carrier family 7 member 11 (SLC7A11), the cystine/glutamate antiporter, is known as a ferroptosis executor that exhibits a positive correlation with carcinoma progression because of antioxidant function. Nonetheless, it is yet unclear on the understanding of ferroptosis regulation in lung cancer. METHODS: Database, qRT-PCR, Western-blot (WB), and immunohistochemistry were utilized to determine SLC7A11 expression and function, as well as gene iron related to necrosis in clinical tissue specimens and cells; a ferroptosis inducer, inhibitors, and SLC7A11 lentivirus were used to confirm SLC7A11's biological activity in cell viability, oxidative stress, lipid peroxidation, and iron ion enrichment in non-small cell lung cancer (NSCLC) in different cells; lentivirus was used to infect lung adenocarcinoma cell lines to acquire miR-27a-3p overexpression and knockdown cell lines, and to detect SLC7A11 level through qRT-PCR and WB. The influence of upregulated/downregulated miR-27a-3p on ferroptosis and other related biological characteristics of lung adenocarcinoma cell lines was detected. RESULTS: Upregulated SLC7A11 was shown in NSCLC patients and cells, and increased SLC7A11 had a relation to the poorly prognostic status of NSCLC patients. Besides, a novel miRNA, miR-27a-3p, was an essential modulator of ferroptosis via directly targeting SLC7A11 in NSCLC cells. Overexpressing miR-27a-3p led to SLC7A11 suppression via directly binding to its 3'-UTR, followed by the reduction of erastin-caused ferroptosis. In contrast, inhibited miR-27a-3p resulted in an increase in NSCLC cells' sensitivity to erastin. Of importance, the accumulated lipid ROS and cell death of iron peptide mediated by anti-miR-27a-3p can be eliminated by impeding the glutamylation process. Our literature collectively uncovered that miR-27a-3p modulated ferroptosis by targeting SLC7A11 in NSCLC cells, illustrating the important role of miRNA in ferroptosis. CONCLUSION: MiR-27a-3p modulates ferroptosis via targeting SLC7A11 in NSCLC cells, implying the significant role of miR-27a-3p/SLC7A11 in ferroptosis.
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BACKGROUND: The lower neck and upper mediastinum are the major regions for postoperative radiotherapy (PORT) in thoracic esophageal squamous cell carcinoma (TESCC). However, there is no uniform standard regarding the delineation of nodal clinical target volume (CTVnd). This study aimed to map the recurrent lymph nodes in the cervical and upper mediastinal regions and explore a reasonable CTVnd for PORT in TESCC. METHODS: We retrospectively reviewed patients in our hospital with first cervical and/or upper mediastinal lymph node recurrence (LNR) after upfront esophagectomy. All of these recurrent lymph nodes were plotted on template computed tomography (CT) images with reference to surrounding structures. The recurrence frequency at different stations was investigated and the anatomic distribution of recurrent lymph nodes was analyzed. RESULTS: A total of 119 patients with 215 recurrent lymph nodes were identified. There were 47 (39.5%) patients with cervical LNR and 102 (85.7%) patients with upper mediastinal LNR. The high-risk regions were station 101L/R, station 104L/R, station 106recL/R, station 105 and station 106pre for upper TESCC and station 104L/R, station 106recL/R, station 105, station 106pre and station 106tbL for middle and lower TESCCs. LNR in the external group of station 104L/R was not common, and LNR was not found in the narrow spaces where the trachea was in close contact with the innominate artery, aortic arch and mediastinal pleura. LNR below the level of the cephalic margin of the superior vena cava was also not common for upper TESCC. CONCLUSIONS: The CTVnd of PORT in the cervical and upper mediastinal regions should cover station 101L/R, station 104L/R, station 106recL/R, station 105 and station 106pre for upper TESCC and station 104L/R, station 106recL/R, station 105, station 106pre and station 106tbL for middle and lower TESCCs. Based on our results, we proposed a useful atlas for guiding the delineation of CTVnd in TESCC.
RESUMO
OBJECTIVES: The purse string-stapled anastomotic technique is a method for minimally invasive oesophagectomy with intrathoracic anastomosis, in which a purse string is hand sewn without the necessity of specialized devices, such as OrVil and Endo-Stitch. Since this technique was first reported by our surgical team in 2012, several measures in the operation have been refined. Furthermore, there are very few literature reports on the major complications of minimally invasive oesophagectomy with this technique. This article studies the major complications of minimally invasive Ivor Lewis oesophagectomy with this technique and explores methods for prevention and treatment. METHODS: Clinical data of 215 patients with oesophageal cancer who underwent thoracoscopic laparoscopic oesophagectomy with intrathoracic anastomosis from October 2011 to December 2015 were analysed. No patients received preoperative radiotherapy and chemotherapy. During the operation, the purse string was simply hand sewn before it was tightened and tied, and anastomosis was performed using a circular stapler. RESULTS: Six (2.79%) patients developed anastomotic leakage, and all of them were treated conservatively. Three (1.40%) patients experienced postoperative haemorrhage; of them, 2 were cured with conservative treatment. The remaining patient was cured by endoscopic management using titanium clips. Thirty-nine (18.14%) patients experienced postoperative pulmonary complications. One (1.47%) patient died due to pulmonary infection with respiratory failure although he had received mechanical ventilator support after tracheotomy. Five (2.33%) patients developed chyle leakage and 5 (2.33%) patients developed recurrent laryngeal nerve injuries. CONCLUSIONS: The incidence of major complications is acceptable for thoracoscopic laparoscopic oesophagectomy with intrathoracic anastomosis using this purse string-stapled anastomotic technique, which is feasible and safe to perform. Some measures designed in the operation will be conducive to reduce the incidence of major complications.