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BACKGROUND: The morphology of tumor thrombus varies from person to person and it may affect surgical methods and tumor prognosis. However, studies on the morphology of tumor thrombus are limited. The purpose of our study was to evaluate the impact of tumor thrombus morphology on surgical complexity. METHODS: We retrospectively reviewed the clinical data of 229 patients with renal cell carcinoma combined with inferior vena cava (IVC) tumor thrombus who underwent surgical treatment at Peking University Third Hospital between January 2014 and December 2021. The patients were divided into floating morphology (107 patients) and filled morphology (122 patients) tumor thrombi groups. Chi-square and Mann-Whitney U tests were used for categorical and continuous variables, respectively. Postoperative complications were evaluated using the Clavien-Dindo surgical complication classification method. RESULTS: Patients with filled morphology tumor thrombus required more surgical techniques than those with floating morphology tumor thrombus, which was reflected in more open surgeries (P < 0.001), more IVC interruptions (Pâ<0.001), lesser use of the delayed occlusion of the proximal inferior vena cava (DOPI) technique (P < 0.001), and a greater need for cut-off of the short hepatic vein (P < 0.001) and liver dissociation (P = 0.001). Filled morphology significantly increased the difficulty of surgery in patients with renal cell carcinoma with tumor thrombus, reflected in longer operation time (P < 0.001), more surgical blood loss (Pâ<0.001), more intra-operative blood transfusion (P < 0.001), and longer postoperative hospital stay (P < 0.001). Filled morphology tumor thrombus also led to more postoperative complications (53% vs. 20%; P < 0.001). CONCLUSION: Compared with floating morphology thrombus, filled morphology thrombus significantly increased the difficulty of surgery in patients with renal cell carcinoma with IVC tumor thrombus.
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Carcinoma de Células Renais , Neoplasias Renais , Células Neoplásicas Circulantes , Veia Cava Inferior , Trombose Venosa , Humanos , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Veia Cava Inferior/patologia , Veia Cava Inferior/cirurgia , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , China/epidemiologia , Células Neoplásicas Circulantes/patologia , Trombose Venosa/patologia , Trombose Venosa/cirurgia , Idoso , Nefrectomia/métodos , Complicações Pós-Operatórias/epidemiologia , AdultoRESUMO
Agricultural by-products of sesame are promising bioresources in food processing. This study extracted lignin from the by-products of sesame oil production, namely, the capsules and straw of black and white sesame. Using acid, alkali, and ethanol methods, 12 distinct lignins were obtained to prepare biochar, aiming to investigate both the structural characteristics of lignin-based biochar (LBB) and its ability to remove benzo[a]pyrene (BaP) from sesame oil. The results showed that white sesame straw was the most suitable raw material for preparing biochar. In terms of the preparation method, acid-extracted lignin biochar was more effective in removing BaP than alkaline or ethanol methods. Notably, WS-1LB (white sesame straw acid-extracted lignin biochar) exhibited the highest BaP adsorption efficiency (91.44 %) and the maximum specific surface area (1065.8187 m2/g), characterized by porous structures. The pseudo 2nd and Freundlich models were found to be the best fit for the adsorption kinetics and isotherms of BaP on LBB, respectively, suggesting that a multilayer adsorption process was dominant. The high adsorption of LBB mainly resulted from pore filling. This study provides an economical and highly efficient biochar adsorbent for the removal of BaP in oil.
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Carvão Vegetal , Lignina , Óleo de Gergelim , Lignina/química , Carvão Vegetal/química , Adsorção , Óleo de Gergelim/química , Benzo(a)pireno/química , CinéticaRESUMO
In this study, three activators and two activation methods were employed to activate sesame lignin-based biochar. The biochar samples were comprehensively characterized, their abilities to adsorb benzo[a]pyrene (BaP) from sesame oil were assessed, and the mechanism was analyzed. The results showed that the biochar obtained by one-step activation was more effective in removing BaP from sesame oil than the biochar produced by two-step activation. Among them, the biochar generated by one-step activation with ZnCl2 as the activator had the largest specific surface area (1068.8776 m3/g), and the richest mesoporous structure (0.7891 m3/g); it removed 90.53 % of BaP from sesame oil. BaP was mainly adsorbed by the mesopores of biochar. Mechanistically, pore-filling, π-π conjugations, hydrogen bonding, and n-π interactions were involved. The adsorption was spontaneous and heat-absorbing. In conclusion, the preparation of sesame lignin biochar using one-step activation with ZnCl2 as the activator was found to be the best for removing BaP from sesame oil. This biochar may be an economical adsorbent for the industrial removal of BaP from sesame oil.
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Benzo(a)pireno , Carvão Vegetal , Lignina , Óleo de Gergelim , Sesamum , Carvão Vegetal/química , Lignina/química , Benzo(a)pireno/química , Adsorção , Óleo de Gergelim/química , Sesamum/química , Compostos de Zinco/química , Cloretos/químicaRESUMO
OBJECTIVE: To investigate and analyze the risk factors of massive hemorrhage in patients with renal cell carcinoma and venous tumor thrombus undergoing radical nephrectomy and removal of venous tumor thrombus. METHODS: From January 2014 to June 2020, 241 patients with renal cancer and tumor thrombus in a single center of urology at Peking University Third Hospital were retrospectively analyzed. All patients underwent radical nephrectomy and removal of venous tumor thrombus. The relevant preoperative indicators, intraoperative conditions, and postoperative data were statistically analyzed by using statistical software of SPSS 18.0. The main end point of the study was intraoperative bleeding volume greater than 2 000 mL. Logistic regression analysis was used to determine the relevant influencing factors. First, single factor Logistic regression was used for preliminary screening of influencing factors, and variables with single factor Logistic regression analysis P < 0.05 were included in multivariate Logistic regression. In all statistical analyses, P < 0.05 is considered statistically significant. RESULTS: Among the 241 patients included, there were 60 cases of massive hemorrhage, 48 males and 12 females, with a median age of 62 years. The number of non-massive hemorrhage was 181. There were 136 males and 45 females, with a median age of 59 years. Univariate analysis showed that the clinical symptoms (both systemic and local symptoms, OR 2.794, 95%CI 1.087-7.181, P=0.033), surgical approach (open surgery, OR 9.365, 95%CI 4.447-19.72, P < 0.001), Mayo grade (Mayo 3-4, OR 5.257, 95%CI 2.806-10.886, P < 0.001), American Society of Anesthesiologists (ASA) score (ASA level 3, OR 2.842, 95%CI 1.338-6.036, P=0.007), preoperative hemoglobin (OR 0.978, 95%CI 0.965-0.991, P=0.001), preoperative platelet count (OR 0.996, 95%CI 0.992-1.000, P=0.037), maximum tumor thrombus width (OR 1.061, 95%CI 1.033-1.091, P < 0.001), Complicated with bland thrombus (OR 4.493, 95%CI 2.264-8.915, P < 0.001), adrenalectomy (OR 3.101, 95%CI 1.614-5.958, P=0.001), segmental resection of the inferior vena cava (OR 2.857, 95%CI 1.395-5.852, P=0.004). There was a statistically significant difference in these aspects(P < 0.05). Multivariate Logistic regression analysis showed that there was a statistically significant difference in surgical approach (open surgery, OR 6.730, 95%CI 2.947-15.368;P < 0.001), Mayo grade (Mayo 3-4, OR 2.294, 95%CI 1.064-4.948, P=0.034), Complicated with bland thrombus (OR 3.236, 95%CI 1.492-7.020, P=0.003). CONCLUSION: Combining the results of univariate and multivariate Logistic regression analysis, the surgical approach, Mayo grade, and tumor thrombus combined with conventional thrombus were associated risk factors for massive hemorrhage during surgery for renal cell carcinoma with tumor thrombus. Patients who undergo open surgery, high Mayo grade, and tumor thrombus combined with conventional thrombus are at a relatively higher risk of massive hemorrhage.
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Carcinoma de Células Renais , Neoplasias Renais , Trombose , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma de Células Renais/patologia , Estudos Retrospectivos , Trombose/etiologia , Neoplasias Renais/complicações , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Veia Cava Inferior/cirurgia , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Trombectomia/métodos , Fatores de Risco , HemorragiaRESUMO
This study aimed to explore the magnetic resonance imaging (MRI) features of dual-phenotype hepatocellular carcinoma (DPHCC) and their diagnostic value.The data of 208 patients with primary liver cancer were retrospectively analysed between January 2016 and June 2021. Based on the pathological diagnostic criteria, 27 patients were classified into the DPHCC group, 113 patients into the noncholangiocyte-phenotype hepatocellular carcinoma (NCPHCC) group, and 68 patients with intrahepatic cholangiocarcinoma (ICC) were classified into the ICC group. Two abdominal radiologists reviewed the preoperative MRI features by a double-blind method. The MRI features and key laboratory and clinical indicators were compared between the groups. The potentially valuable MRI features and key laboratory and clinical characteristics for predicting DPHCC were identified by univariate and multivariate analyses, and the odds ratios (ORs) were recorded. In multivariate analysis, tumour without capsule (P = 0.046, OR = 9.777), dynamic persistent enhancement (P = 0.006, OR = 46.941), and targetoid appearance on diffusion-weighted imaging (DWI) (P = 0.021, OR = 30.566) were independently significant factors in the detection of DPHCC compared to NCPHCC. Serum alpha-fetoprotein (AFP) > 20 µg/L (P = 0.036, OR = 67.097) and prevalence of hepatitis B virus (HBV) infection (P = 0.020, OR = 153.633) were independent significant factors in predicting DPHCC compared to ICC. The differences in other tumour marker levels and imaging features between the groups were not significant. In MR enhanced and diffusion imaging, tumour without capsule, persistent enhancement and DWI targetoid findings, combined with AFP > 20 µg/L and HBV infection-positive laboratory results, can help to diagnose DPHCC and differentiate it from NCPHCC and ICC. These results suggest that clinical, laboratory and MRI features should be integrated to construct an AI diagnostic model for DPHCC.
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Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , alfa-Fetoproteínas , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Meios de Contraste , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética/métodos , Fenótipo , Estudos Retrospectivos , Método Duplo-CegoRESUMO
Background: To propose a quantitative model for predicting the surgical complexity of patients with renal cell carcinoma (RCC) and venous tumor thrombus (VTT). Method: The clinical data of 226 cases of RCC with VTT in Peking University Third Hospital from January 2014 to August 2020 were retrospectively analyzed. Seven indicators were selected to establish the T.H.R.O.B.V.S. system, including alkaline phosphatase, tumor thrombus height, maximum tumor diameter, obesity, bland thrombus, vascular wall invasion, and side. Each indicator was assigned with 0, (1), and 2 points, and the total scores of 0~2, 3~5, and ≥6 were set as the low-, middle-, and high-risk groups, respectively. The surgical complexity was compared and validated among groups. Results: As the risk increased, the proportion of open surgery significantly increased (P<0.001). The operation time (P<0.001), intraoperative blood loss (P<0.001), blood or plasma transfusion (P<0.001), and hospitalization (P<0.001) increased significantly. The postoperative complications (P<0.001), including notable complications (≥Clavein-Dindo II, P<0.001), were significantly different, and similar trends were shown in the validation group. Conclusion: The T.H.R.O.B.V.S. scoring system is a quantifiable and satisfactory model to predict the surgical complexity and perioperative management of RCC with VTT.
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Vacuolar protein sorting 35 (VPS35) is a major component of the retromer complex that regulates endosomal trafficking in eukaryotic cells. Recent studies have shown that VPS35 promotes tumor cell proliferation and affects the nuclear accumulation of its interacting partner. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-based mass spectrometry were used to measure the changes in nuclear protein abundance in VPS35-depleted HeLa cells. A total of 47 differentially expressed proteins were identified, including 27 downregulated and 20 upregulated proteins. Gene ontology (GO) analysis showed that the downregulated proteins included several minichromosome maintenance (MCM) proteins described as cell proliferation markers, and these proteins were present in the MCM2-7 complex, which is essential for DNA replication. Moreover, we validated that loss of VPS35 reduced the mRNA and protein expression of MCM2-7 genes. Notably, re-expression of VPS35 in VPS35 knockout HeLa cells rescued the expression of these genes. Functionally, we showed that VPS35 contributes to cell proliferation and maintenance of genomic stability of HeLa cells. Therefore, these findings reveal that VPS35 is involved in the regulation of MCM2-7 gene expression and establish a link between VPS35 and cell proliferation.
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Proteínas de Manutenção de Minicromossomo/metabolismo , Proteômica , Proteínas de Transporte Vesicular , Endossomos/metabolismo , Células HeLa , Humanos , Componente 2 do Complexo de Manutenção de Minicromossomo/metabolismo , Transporte Proteico , Proteínas de Transporte Vesicular/metabolismoRESUMO
In native bone tissue regeneration, blood vessels, providing oxygen and nutrition for tissues, can promote the regeneration of bone and accelerate the repair of a defected area. In this study, Poly(D, L-lactic-co-glycolic acid) (PLGA) inverse opal scaffolds with high pore interconnectivity were fabricated and further modified with vascular endothelial growth factor (VEGF). The rat bone marrow derived mesenchymal stem cells (rMSCs) and human umbilical vein endothelial cells (HUVECs) were co-cultured onto the scaffolds to enhance vascularization for bone tissue regeneration. Cell attachment, viability, proliferation, and morphology were detected by cell counting kit-8 (CCK-8) assay, live and dead staining and scanning electron microscopy (SEM). Hydrostatic pressure with 0-279 KPa and 1 Hz one hour per day for 7 days was applied to tissue engineered bone constructs to investigate whether the loading stimulation can promote osteogenesis and angiogenesis mutually evaluated in parallel by multiple in vitro assays and in an in vivo chicken chorioallantoic membrane (CAM) model. The results indicated that the immobilization of VEGF can improve biocompatibility of PLGA scaffolds and promote cell attachment and proliferation. The cell-scaffold constructs showed higher CD31 expression because of the angiogenic differentiation of rMSCs in hydrostatic loading culture condition in vitro. The in vivo CAM model experiment demonstrated that hydrostatic loading stimulated angiogenic differentiation of rMSCs can accelerate tubulogenesis. Furthermore, the new capillaries formed in cell-scaffold constructs were conducive to calcium deposition in vivo.
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Osteogênese , Fator A de Crescimento do Endotélio Vascular , Animais , Técnicas de Cocultura , Células Endoteliais da Veia Umbilical Humana , Humanos , Pressão Hidrostática , Ácido Láctico , Neovascularização Patológica , Porosidade , Ratos , Engenharia Tecidual/métodos , Alicerces Teciduais , Fator A de Crescimento do Endotélio Vascular/farmacologiaRESUMO
BACKGROUND: To evaluate the impact of deep invasive tumor thrombus (DITT) on the surgical complexity and prognosis of patients with renal cell carcinoma with venous tumor thrombus. METHODS: We retrospectively reviewed clinical data of 138 patients with non-metastatic renal cell carcinoma combined with venous tumor thrombus, who underwent surgical treatment in Peking University Third Hospital from January 2015 to June 2020. Patients were divided into the DITT group (84 patients) and non-invasive tumor thrombus (NITT) group (54 patients). Chi-square, t-test and Mann-Whitney U test were used for categorical and continuous variables, respectively. Kaplan-Meier plots were performed to evaluate the influence of DITT. Univariable and multivariable Cox regressions were conducted to determine independent prognostic factors and then assembled to make a nomogram to predict the survival. The performance of the nomogram was evaluated by Harrell's consistency index (C-index) and calibration plot. RESULTS: Deep invasive tumor thrombus significantly increased the difficulty of surgery for patients with renal cell carcinoma with venous tumor thrombus, which is mainly reflected in longer operation time (p < 0.001), more surgical bleeding (p â< 0.001), a higher proportion of perioperative blood transfusion (p â= 0.006), a higher proportion of open surgery (p = 0.001), a longer postoperative hospital stay (p = 0.003), and a higher proportion of postoperative complications (p = 0.001). DITT (hazard ratio [HR] = 2.781, p = 0.040) was one of the independent risk factors for worse prognosis. Multivariate analysis showed that sarcoma-like differentiation (p = 0.040), tumor thrombus invasion (p = 0.040), low hemoglobin (p = 0.003), and pathological type (p < 0.001) were independent prognostic factors. The nomogram, combining all these predictors, showed powerful prognostic ability with a C-index of 78.8% (CI: 71.2%-86.4%). The predicted risk closely matches the observed recurrence probability. CONCLUSION: Deep invasive tumor thrombus significantly increased the difficulty of surgeries for patients of renal cell carcinoma with venous tumor thrombus, and may lead to poor prognosis.
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Primary cytoreductive surgery with platinum-taxane-based chemotherapy is the standard treatment for ovarian cancer (OC) patients; however, resistance to chemotherapy is a contributing factor to OC mortality. Paclitaxel (PTX), the most widely used taxane, has become the first-line drug against OC. The molecular mechanism of PTX resistance is different from that of platinum-based agents and is still not completely elucidated. Our previous study showed that glucose-regulated protein 78 (GRP78) is involved in the resistance of OC cells to PTX. However, little is known regarding endogenous inhibitors of this gene. MicroRNAs (miRNAs) play critical roles in the regulation of gene expression; therefore, we sought to identify miRNA(s) with potential to target GRP78 under the hypothesis that miRNA(s) could serve as potential therapeutic targets. Here, we show that miR-181c, predicted to target GRP78, was downregulated in PTX-resistant OC cells and tissues. MiR-181c downregulated GRP78 expression and induced apoptosis by directly targeting its 3'-untranslated region (UTR). Overexpression of miR-181c sensitized resistant OC to PTX by inhibiting the PI3K/Akt pathway in vitro and in vivo. Taken together, our findings indicate that the delivery of miR-181c can efficiently suppress GRP78 expression and GRP78-mediated PTX resistance in OC and suggest that this strategy has therapeutic potential.
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MicroRNAs , Neoplasias Ovarianas , Regiões 3' não Traduzidas , Carcinoma Epitelial do Ovário/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Chaperona BiP do Retículo Endoplasmático/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
Post-stroke anxiety (PSA) is serious psychosomatic comorbidity among patients with stroke, but whether obesity could be positively associated with PSA is currently unknown. The purpose of this study was to investigate the potential association between obesity and subsequent anxiety risk in patients with stroke. A total of 441 patients with acute ischemic stroke (AIS) onset were consecutively recruited within 7 days, and PSA and post-stroke depression (PSD) were evaluated by using a 14-item Hamilton anxiety scale (HAMA) and 17-item Hamilton depression scale (HAMD) at the end of 1-month follow-up. The odds ratio (OR) with 95% CI was estimated for the incidental PSA by using logistic regression analysis. The incidence of PSA was 25.85% at the end of 1-month follow-up, with a significant difference between patients with and without abdominal obesity. Relative fat mass (RFM) and abdominal obesity were significantly associated with an elevated risk of PSA, and the crude ORs were 1.04 (95% CI: 1.01-1.08) and 1.93 (95% CI: 1.11-3.34), respectively. Even after adjustment for obesity-related risk factors and PSA-related clinical measurements, the association remained to be pronounced with abdominal obesity. However, RFM (OR = 1.03, 95% CI: 0.99-1.06, P = 0.053) and abdominal obesity (OR = 1.31, 95% CI: 0.80-2.15, P = 0.280) were not significantly associated with an elevated risk of PSD. Abdominal obesity was independently associated with the PSA instead of PSD, which may help predict PSA risk in clinical practice. Further prospective clinical studies with a long follow-up duration are warranted to verify this finding.
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BACKGROUND: Retroperitoneal vascular leiomyosarcoma (RVLMS) is an extremely rare disease in clinical practice, and it has poor prognosis. This article is to explore the diagnosis and treatment of RVLMS and present our experience. METHODS: Data of RVLMS patients were continuously collected in our hospital from August 2018 to February 2020: two males and two females with a median age of 56 (min-max = 33-61) years were included. Patients in whom paraganglioma could not be excluded were asked to take phenoxybenzamine before surgery. A multi-disciplinary team (MDT) meeting had been held and surgery was recommended. The operation procedures varied based on the tumor location, shape, and stage, and the core steps were "exposure of the retroperitoneum and tumor, identification of vital blood vessels, blocking the bloodstream, complete removal of the tumor and tumor thrombus, and release of blood flow". A Satinsky clamp was used to partially block the blood vessels. Follow-up was conveyed by revisits and phone calls. RESULTS: One patient underwent open surgery, and three patients underwent laparoscopic surgery, one of whom underwent conversion to open surgery. The procedures were finished successfully, with a median operative time of 314.5 (min-max = 224-467) mins. The median amount of intraoperative bleeding was 550 (min-max = 200-1500) ml, and three patients had transfusion during the operation. The mass was irregular in shape, with a median maximum size of 7.45 (min-max = 4.2-10.7) cm, and the pathological examination confirmed RVLMS, which has spindle-shape, high mitotic activity and atypia. One week after the operation, the median serum creatinine level was 85 (min-max = 70-99) µmol/L. The median follow-up time was 16 (min-max = 13-21) months, and 1 case reported asymptomatic recurrence. CONCLUSION: Uncharacteristic manifestations and imaging features contribute to the problematic diagnosis of RVLMS. Comprehensive preoperative evaluation and careful surgical planning are essential. Multicenter research is needed in the future to reach a dominant consensus.
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Laparoscopia , Leiomiossarcoma , Neoplasias Retroperitoneais , Adulto , Feminino , Humanos , Leiomiossarcoma/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Retroperitoneais/diagnóstico por imagem , Neoplasias Retroperitoneais/cirurgia , Espaço Retroperitoneal , Estudos RetrospectivosRESUMO
BACKGROUND: Anterior gradient-2 (AGR2) is a proto-oncogene involved in tumorigenesis and cancer progression. AGR2, predominantly localized in the endoplasmic reticulum (ER), is also a secreted protein detected in the extracellular compartment in multiple cancers. However, the biological functions of intracellular and extracellular AGR2 remain to be elucidated. METHODS: Based on the biochemical structure of AGR2 protein, PANC-1 pancreatic cancer cells stably expressing ER-resident or secreted AGR2 were generated by a lentivirus-mediated stable overexpression system. The capacities of cell proliferation, migration, invasion and survival were assessed in PANC-1 stable cells. Moreover, EGFR expression and activation were determined to explore the possible mechanism of AGR2 roles in pancreatic cancer tumorigenesis. RESULTS: It was discovered that secreted AGR2, but not ER-resident AGR2, promotes cell proliferation, migration and invasion of PANC-1 cells. Moreover, the data indicated that both the ER-resident and the secreted AGR2 enhance the survival capacity of PANC-1 cells after tunicamycin-induced ER stress and gemcitabine treatment. However, EGFR expression and activation were not found to be involved in AGR2-dependent oncogenic phenotypes in PANC-1 cells. CONCLUSIONS: Secreted AGR2 is predominantly involved in cell proliferation, migration and invasion in PANC-1 pancreatic cancer cells. Both secreted and ER-resident AGR2 contribute to the survival of PANC-1 cells under the challenging conditions. These findings provide insight into how different localizations of AGR2 have contributed to pancreatic cancer growth, metastasis, and drug sensitivity.
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Movimento Celular , Proliferação de Células , Desoxicitidina/análogos & derivados , Retículo Endoplasmático/patologia , Regulação Neoplásica da Expressão Gênica , Mucoproteínas/metabolismo , Proteínas Oncogênicas/metabolismo , Neoplasias Pancreáticas/patologia , Antimetabólitos Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Desoxicitidina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático , Humanos , Mucoproteínas/genética , Invasividade Neoplásica , Proteínas Oncogênicas/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proto-Oncogene Mas , Células Tumorais Cultivadas , GencitabinaRESUMO
Vagus nerve stimulation (VNS) restores autonomic balance, suppresses inflammation action and minimizes cardiomyocyte injury. However, little knowledge is known about the VNS' role in cardiomyocyte phenotype, sarcomere organization, and energy metabolism of infarcted hearts. VNS in vivo and acetylcholine (ACh) in vitro optimized the levels of α/ß-MHC and α-Actinin positive sarcomere organization in cardiomyocytes while reducing F-actin assembly of cardiomyocytes. Consistently, ACh improved glucose uptake while decreasing lipid deposition in myocytes, correlating both with the increase of Glut4 and CPT1α and the decrease of PDK4 in infarcted hearts in vivo and myocytes in vitro, attributing to improvement in both glycolysis by VEGF-A and lipid uptake by VEGF-B in response to Ach. This led to increased ATP levels accompanied by the repaired mitochondrial function and the decreased oxygen consumption. Functionally, VNS improved the left ventricular performance. In contrast, ACh-m/nAChR inhibitor or knockdown of VEGF-A/B by shRNA powerfully abrogated these effects mediated by VNS. On mechanism, ACh decreased the levels of nuclear translocation of FoxO3A in myocytes due to phosphorylation of FoxO3A by activating AKT. FoxO3A overexpression or knockdown could reverse the specific effects of ACh on the expression of VEGF-A/B, α/ß-MHC, Glut4, and CPT1α, sarcomere organization, glucose uptake and ATP production. Taken together, VNS optimized cardiomyocytes sarcomere organization and energy metabolism to improve heart function of the infarcted heart during the process of delaying and/or blocking the switch from compensated hypertrophy to decompensated heart failure, which were associated with activation of both P13K/AKT-FoxO3A-VEGF-A/B signaling cascade.
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Proteína Forkhead Box O3/metabolismo , Insuficiência Cardíaca/metabolismo , Miócitos Cardíacos/metabolismo , Sarcômeros/metabolismo , Estimulação do Nervo Vago/métodos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator B de Crescimento do Endotélio Vascular/metabolismo , Animais , Diferenciação Celular/fisiologia , Metabolismo Energético , Insuficiência Cardíaca/patologia , Masculino , Miócitos Cardíacos/patologia , Fenótipo , Ratos , Ratos Sprague-Dawley , Sarcômeros/patologia , Transdução de SinaisRESUMO
BACKGROUND: Radical nephrectomy and thrombectomy is the standard surgical procedure for the treatment of renal cell carcinoma (RCC) with tumor thrombus (TT). But the estimation of intra-operative blood loss is only based on the surgeon's experience. Therefore, our study aimed to develop Peking University Third Hospital score (PKUTH score) for the prediction of intra-operative blood loss volume in radical nephrectomy and thrombectomy. METHODS: The clinical data of 153 cases of renal mass with renal vein (RV) or inferior vena cava tumor thrombus admitted to Department of Urology, Peking University Third Hospital from January 2015 to May 2018 were retrospectively analyzed. The total amount of blood loss during operation is equal to the amount of blood sucked out by the aspirator plus the amount of blood in the blood-soaked gauze. Univariate linear analysis was used to analyze risk factors for intra-operative blood loss, then significant factors were included in subsequent multivariable linear regression analysis. RESULTS: The final multivariable model included the following three factors: open operative approach (Pâ<â0.001), Neves classification IV (Pâ<â0.001), inferior vena cava resection (Pâ=â0.001). The PKUTH score (0-3) was calculated according to the number of aforementioned risk factors. A significant increase of blood loss was noticed along with higher risk score. The estimated median blood loss from PKUTH score 0 to 3 was 280âmL (interquartile range [IQR] 100-600âmL), 1250âmL (IQR 575-2700âmL), 2000âmL (IQR 1250-2900âmL), and 5000âmL (IQR 4250-8000âmL), respectively. Meanwhile, the higher PKUTH score was, the more chance of post-operative complications (Pâ=â0.004) occurred. A tendency but not significant overall survival difference was found between PKUTH risk score 0 vs. 1 to 3 (Pâ=â0.098). CONCLUSION: We present a structured and quantitative scoring system, PKUTH score, to predict intra-operative blood loss volume in radical nephrectomy and thrombectomy.
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Carcinoma de Células Renais , Neoplasias Renais , Perda Sanguínea Cirúrgica , Carcinoma de Células Renais/cirurgia , Hospitais , Humanos , Neoplasias Renais/cirurgia , Nefrectomia , Estudos Retrospectivos , Trombectomia , Universidades , Veia Cava Inferior/cirurgiaRESUMO
Lung cancer is the leading cause of cancer death worldwide. Early detection of lung cancer is helpful to provide the best possible clinical treatment for patients. Due to the limited number of radiologist and the huge number of chest x-ray radiographs (CXR) available for observation, a computer-aided detection scheme should be developed to assist radiologists in decision-making. While deep learning showed state-of-the-art performance in several computer vision applications, it has not been used for lung nodule detection on CXR. In this paper, a deep learning-based lung nodule detection method was proposed. We employed patch-based multi-resolution convolutional networks to extract the features and employed four different fusion methods for classification. The proposed method shows much better performance and is much more robust than those previously reported researches. For publicly available Japanese Society of Radiological Technology (JSRT) database, more than 99% of lung nodules can be detected when the false positives per image (FPs/image) was 0.2. The FAUC and R-CPM of the proposed method were 0.982 and 0.987, respectively. The proposed approach has the potential of applications in clinical practice.
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Aprendizado Profundo , Neoplasias Pulmonares/diagnóstico , Pulmão/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologiaRESUMO
Background: The growth rate of centenarians was unusually rapid in recent decades, ushering in an era of longevity. This study aims to explore the difference between centenarians and non-centenarians using quantitative research, and to scientifically guide residents to develop the correct lifestyle and health care ways. Methods: From October 2013 to August 2017. A cross-sectional survey was conducted on 271 centenarians and 570 non-centenarians by using a questionnaire to assess longevity and health issues which was developed for the needs of the study, who came from 29 counties and districts in 11 cities of Zhejiang province, China. Two hundred and fifty-five valid questionnaires were returned, with an effective response rate of 94.1%. Meanwhile, data of 526 non-centenarians from Zhejiang province was collected as a control group, with an effective response rate of 92.3%. Results: The prevalence rates of tumor, stomach and duodenal ulcer, diabetes, bronchial asthma, and chronic obstructive pulmonary disease, tuberculosis among centenarians were all lower than those among non-centenarians. The oral health of centenarians is better than that of non-centenarians. The consumption of coarse cereals, pasta, other staple foods and fruits among centenarians was higher than that of non-centenarians. The percentage of centenarians who smoke or engage in recreational activities every day was lower than that of non-centenarians. Conclusions: We should give full play to the role of preventive medicine and health management to safeguard the health of residents. Pay attention to oral health, and develop the good habit of loving teeth. The diet should be rich and varied, and increase the intake of grains and fruits. Give up smoking, limit alcohol, spirit-preserving with calming, follow the law of scientific regimen.
RESUMO
BACKGROUND: Radical nephrectomy with thrombectomy is one of the most difficult and complicated urological operations. But the roles of renal tumor volume and thrombus level in surgical complexity and prognostic outcome are not clear. This study aimed to evaluate the surgical complexity and prognostic outcome between the volume of renal cell carcinoma (RCC) and the level of venous tumor thrombus. METHODS: The clinical data of 67 RCC cases with renal vein or inferior vena cava (IVC) tumor thrombus from January 2015 to May 2018 were retrospectively analyzed. Among these 67 cases, 21 (31.3%) were small tumors with high-level thrombus (tumor ≤7âcm in diameter and thrombus Neves Level II-IV), while 46 (68.7%) were large tumors with low-level thrombus group (tumor >7âcm in diameter and thrombus Level 0-I). Clinical features, operation details, and pathology data were collected. Univariable and multivariable logistic regression analyses were applied to evaluate the risk factors for small tumor with high-level thrombus. RESULTS: Patients with small tumors and high-level thrombus were more likely to have longer operative time (421.9â±â135.1âmin vs. 282.2â±â101.9âmin, tâ=â4.685, Pâ<â0.001), more surgical bleeding volume (1200 [325, 2900] mL vs. 500 [180, 1000] mL, Uâ=â270.000, Pâ=â0.004), more surgical blood transfusion volume (800 [0, 1400] mL vs. 0 [0, 800] mL, Uâ=â287.500, Pâ=â0.004), more plasma transfusion volume (0 [0, 800] mL vs. 0 [0, 0] mL, Uâ=â319.000, Pâ=â0.004), higher percentage of open operative approach (76.2% vs. 32.6%, χâ=â11.015, Pâ=â0.001), higher percentage of IVC resection (33.3% vs. 0%, χâ=â17.122, Pâ<â0.001), and higher percentage of post-operative complications (52.4% vs. 19.6%, χâ=â7.415, Pâ=â0.010) than patients with large tumors and low-level thrombus. In multivariate analysis, decreased hemoglobin (Hb) (odds ratio [OR]: 0.956, 95% confidence interval [CI]: 0.926-0.986, Pâ=â0.005) and non-sarcomatoid differentiation (OR: 0.050, 95% CI: 0.004-0.664, Pâ=â0.023) were more likely to form small tumors with high-level tumor thrombus rather than large tumor with small tumor thrombus. The estimated mean cancer-specific survival times of small tumor with high-level thrombus and large tumor with low-level thrombus were 31.6â±â3.8 months and 32.5â±â2.9 months, without statistical significance (Pâ=â0.955). After univariate and multivariate Cox proportional hazard survival regression analyses, only distant metastasis (hazard ratio [HR]: 3.839, Pâ=â0.002), sarcomatoid differentiation (HR: 7.923, Pâ<â0.001), alkaline phosphatase (HR: 2.661, Pâ=â0.025), and severe post-operative complications (HR: 10.326, Pâ=â0.001) were independent predictors of prognosis. CONCLUSIONS: The level of the tumor thrombus was more important than the diameter of the primary kidney tumor in affecting the complexity of surgery. In the same T3 stage, neither the renal tumor diameter nor the tumor thrombus level was an independent risk factor for prognosis.
Assuntos
Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Trombose/patologia , Trombose/cirurgia , Idoso , Feminino , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Nefrectomia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Veia Cava Inferior/patologia , Veia Cava Inferior/cirurgiaRESUMO
The release of inflammatory cytokines, that plays a dominant role in local pancreatic inflammation and systemic complications in severe acute pancreatitis (SAP). High-mobility group box 1 (HMGB1) is implicated in the mechanism of organ dysfunction and bacterial translocation in SAP. This current study aims to investigate possible role of HMGB1 in the intestinal mucosal barrier dysfunction of SAP, and the effect of anti-HMGB1 antibody treatment in intestinal mucosal injury in SAP. Our data revealed that the HMGB1 expression was significantly increased in AP mice induced by caerulein and LPS, and the inhibition of HMGB1 played a protective role in intestinal mucosal barrier dysfunction, reduced the serum level of other proinflammatory cytokines include IL-1ß, IL-6, TNF-α. Next we investigated the downstream receptors involving in HMGB1 signaling. We found that the expressions of toll-like receptor (TLR) 4 and TLR9 were elevated in ileum of AP mice, the administration of HMGB1 neutralizing antibody significantly reduced the TLR4 and TLR9 expression. It was concluded that HMGB1 contributed the mechanism to the intestinal mucosal barrier dysfunction during AP. Blockade of HMGB1 by administration of HMGB1 neutralizing antibody may be a beneficial therapeutic strategy in improving intestinal mucosal barrier dysfunction in SAP.
Assuntos
Proteína HMGB1/metabolismo , Mucosa Intestinal/metabolismo , Pancreatite Necrosante Aguda/metabolismo , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Ceruletídeo/toxicidade , Proteína HMGB1/genética , Proteína HMGB1/imunologia , Interleucina-1beta/sangue , Interleucina-6/sangue , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Pancreatite Necrosante Aguda/tratamento farmacológico , Pancreatite Necrosante Aguda/etiologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismo , Fator de Necrose Tumoral alfa/sangueRESUMO
ß-Cyclodextrin modified camptothecin (CPT-CD) was synthesized through esterification reaction and "click chemistry" to greatly improve the solubility of CPT in aqueous solution, and then, a supramolecular nanoparticle was constructed by strong noncovalent interaction between ß-cyclodextrin and adamantane and amphiphilic interaction by simply mixing CPT-CD and adamantane modified hyaluronic acid (HA-ADA) together. The obtained nanoparticle had a hydrophilic HA shell, which could target and recognize HA receptors overexpressed on the surface of cancer cells, and a hydrophobic CPT core, which could protect CPT from hydrolyzation. The results of cytotoxicity experiments showed that the nanoparticle we have designed in this work exhibited similar anticancer activities to, but with much lower side effects than, the commercial chemotherapeutic drug CPT in vitro. We believe that this work might provide a strategy for improving the treatment performance of CPT in laboratory and clinical settings.