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BACKGROUND/AIMS: Colorectal cancer (CRC) is the third most common type of cancer worldwide. Sprouty proteins are modulators of mitogeninduced signal transduction processes and therefore can influence the process of cancerogenesis. The encoded protein of Sprouty homolog 4 (SPRY4) is associated with various human cancers. However, its biological role and clinical significance in CRC development and progression are unknown. METHODS: The aim of this study was to evaluate the expression and biological role of SPRY4 in colorectal cancer. qRT-PCR was performed to investigate the expression of SPRY4 in tumor tissues and corresponding non tumor colorectal tissues from 70 patients. The effect of SPRY4 on proliferation was evaluated by MTT and colony formation assays. CRC cells transfected with SPRY4 were injected into nude mice to study the effect of SPRY4 on tumorigenesis in vivo. RESULTS: The lower expression of SPRY4 was remarkably correlated with deep tumor invasion and advanced TNM stage. Multivariate analyses revealed that SPRY4 expression served as an independent predictor for overall survival. Using 5-aza treatment, we also observed that SPRY4 expression can be affected by DNA methylation. Further experiments revealed that overexpressed SPRY4 significantly inhibited CRC cell proliferation both in vitro and in vivo. CONCLUSION: Our study demonstrated that SPRY4 is involved in the development and progression of colorectal cancer by regulating cell proliferation and shows that SPRY4 may be a potential diagnostic and prognostic target in patients with colorectal cancer.
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Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas do Tecido Nervoso/genética , Western Blotting , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Metilação de DNA/genética , Regulação para Baixo/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Proteínas do Tecido Nervoso/metabolismo , Fosforilação , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
The essence of endogenous turbidity in Chinese medicine (CM) is different from cream, fat, phlegm, retention, damp, toxicity, and stasis. Along with the development of modern scientific technologies and biology, researches on the essence of endogenous turbidity should keep pace with the time. Its material bases should be defined and new connotation endowed at the microscopic level. The essence of turbidity lies in abnormal functions of zang-fu organs. Sugar, fat, protein, and other nutrient substances cannot be properly decomposed, but into semi-finished products or intermediate metabolites. They are inactive and cannot participate in normal material syntheses and decomposition. They cannot be transformed to energy metabolism, but also cannot be synthesized as executive functioning of active proteins. If they cannot be degraded by autophagy-lysosome or ubiquitin-prosome into glucose, fatty acids, amino acids, and other basic nutrients to be used again, they will accumulate inside the human body and become endogenous turbidity. Therefore, endogenous turbidity is different from final metabolites such as urea, carbon dioxide, etc., which can transform vital qi. How to improve the function of zang-fu organs, enhance its degradation by autophagy-lysosome or ubiquitin-prosome is of great significance in normal operating of zang-fu organs and preventing the emergence and progress of related diseases.
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Medicina Tradicional Chinesa , Autofagia , Humanos , Complexo de Endopeptidases do ProteassomaRESUMO
Objective: This study aimed to estimate the effects of the volume of preperitoneal balloon (PPB) on arterial and venous hemorrhage in a swine pelvic fracture model. Methods: Twenty-four swine were randomized into 0-mL, 500-mL, 800-mL, and 1000-mL intra-hematoma PPB groups. They were subjected to open-book pelvic fracture and reproducible injuries in the external iliac artery and vein. The pelvic binder and IH-PPBs with different volumes of fluid were applied to control the active hemorrhage after arterial and venous injuries. The survival time and rate during 60-min observation and digital subtraction angiography (DSA) images were the primary endpoints in this study. Secondary endpoints included survival rate within 70 min, peritoneal pressure, hemodynamics, blood loss, infusion fluid, blood pH, and lactate concentration. Results: Our results indicated that the 800-mL and 1000-mL groups had a higher survival rate (0%, 50%, 100% and 100% for 0, 500, 800, and 1000-mL groups respectively; p < 0.0001) and longer survival time (13.83 ± 2.64, 24.50 ± 6.29, 55.00 ± 6.33, and 60.00 ± 0.00 min for 0, 500, 800, and 1,000 groups respectively; p < 0.0005) than the 0-mL or 500-mL groups during the 60 min observation. Contrastingly, survival rate and time were comparable between 800-mL and 1000-mL groups during the 60-min observation. The IH-PPB volume was associated with an increase in the pressure of the balloon and the preperitoneal pressure but had no effect on the bladder pressure. Lastly, the 1000-mL group had a higher mean arterial pressure and systemic vascular resistance than the 800-mL group. Conclusion: IH-PPB volume-dependently controls vascular bleeding after pelvic fracture in the swine model. IH-PPB with a volume of 800 mL and 1000 mL efficiently managed pelvic fracture-associated arterial and venous hemorrhage and enhanced survival time and rate in the swine model without evidences of visceral injury.
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Purpose: This study aims to compare the conventional lung protective ventilation strategy (LPVS) with driving pressure-guided ventilation in obese patients undergoing laparoscopic sleeve gastrectomy (LSG). Methods: Forty-five patients undergoing elective LSG under general anesthesia were randomly assigned to the conventional LPVS group (group L) or the driving pressure-guided ventilation group (group D) using random numbers generated by Excel. The primary outcome was the driving pressure of both groups 90 min after pneumoperitoneum. Results: After 30 min of pneumoperitoneum, 90 min of pneumoperitoneum, 10 min of closing the pneumoperitoneum, and restoring the supine position, the driving pressure of group L and group D were 20.0 ± 2.9 cm H2O vs 16.6 ± 3.0 cm H2O (P < 0.001), 20.7 ± 3.2 cm H2O vs 17.3 ± 2.8 cm H2O (P < 0.001), and 16.3 ± 3.1 cm H2O vs 13.3 ± 2.5 cm H2O (P = 0.001), respectively; the respiratory compliance of groups L and D were 23.4 ± 3.7 mL/cm H2O vs 27.6 ± 5.1 mL/cm H2O (P = 0.003), 22.7 ± 3.8 mL/cm H2O vs 26.4 ± 3.5 mL/cm H2O (P = 0.005), and 29.6 ± 6.8 mL/cm H2O vs 34.7 ± 5.3 mL/cm H2O (P = 0.007), respectively. The intraoperative PEEP in groups L and group D was 5 (5-5) cm H2O vs 10 (9-11) cm H2O (P < 0.001). Conclusion: An individualized peep-based driving pressure-guided ventilation strategy can reduce intraoperative driving pressure and increase respiratory compliance in obese patients undergoing LSG.
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ABSTRACT: Objective: This study evaluated the feasibility of a combination of pelvic binder and rectal balloon compression in managing fatal venous hemorrhage in a canine model of pelvic fracture. Methods: Rectums from humans (rectal cancer patients), swine, and canines were retrieved to determine their elasticity by measuring their stress and strain. Canines were selected as the animal model in this study because their rectum demonstrated more reversible strain than swine rectum. Doppler ultrasound was used to assess the effect of rectal balloon volume on the blood flow of pelvic iliac blood vessels in three canines. A rectal balloon of 250 mL was chosen to control pelvic venous bleeding as it could provide a peak effect in reducing the blood flow of bilateral internal iliac veins. Then, the open-book pelvic fracture with fatal bleeding of both internal iliac veins animal model was built. The animals were divided into four groups after the modeled surgery to undergo no treatment, pelvic binder, rectal balloon compression, or a combination of pelvic binder and rectal balloon compression. The treatment efficacy was evaluated based on their survival time, survival rate, blood loss, bleeding rate, infusion rate, blood pH, lactate concentration, the stability of hemodynamics, blood loss, and fluid infusion volume. Results: Our results showed that after the reproducible injuries in both internal iliac veins, the combination of pelvic binder and rectal balloon compression was associated with the best survival rate and survival time compared with the other treatment groups. In addition, the combination of pelvic binder and rectal balloon compression exhibited more stable hemodynamics than the pelvic binder or rectal balloon compression treatment alone. Conclusions: This study demonstrated the potential feasibility of using pelvic binder combined with rectal balloon compression to manage the fatal venous bleeding in pelvic fractures.
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Fraturas Ósseas , Reto , Humanos , Animais , Cães , Suínos , Hemorragia/complicações , Pelve , Veia Ilíaca/lesões , Veia Ilíaca/cirurgiaRESUMO
Tumor suppressor genes are frequently deleted or mutated in lung cancer. The RNA-binding motif protein 10 (RBM10) gene has the ability to suppress tumor activity, but the role of RBM10 during the development of lung cancer has yet to be elucidated. The current study investigated the expression levels of RBM10 in non-tumor and tumor tissues obtained from patients with adenocarcinoma using reverse transcription-polymerase chain reaction and western blot analysis, and identified a reduction in RBM10 expression in lung tumor tissue. To investigate the in vitro and in vivo function of RBM10, A549 human non-small cell lung cancer cells were transfected with the pcDNA-RBM10 vector. Flow cytometry was used to analyze the levels of apoptosis in the transfected cells. Western blot analysis was used to evaluate the expression of B-cell lymphoma 2 (Bcl-2), cleaved caspase-3, caspase-9 and poly (ADP-ribose) polymerase (PARP) proteins in A549 cells and tissues from the A549 xenograft Bagg Albino coat (BALB/c) nude mice model. RBM10 mRNA levels were significantly decreased in adenocarcinoma cells, but not in the non-tumor tissues. The A549 cells and tumor tissues exhibited significant growth inhibition following transfection with the pcDNA-RBM10 vector, which was determined using a cell proliferation assay. Flow cytometry analysis of cells stained with Annexin V/propidium iodide indicated that the overexpression of RBM10 induced apoptosis in A549 cells. The present study demonstrated that the expression levels of Bcl-2 protein were decreased and the expression levels of cleaved caspase-3, caspase-9 and PARP proteins were significantly increased in the A549 cells and cells from ex vivo tumor tissues that were injected with RBM10 vector-containing Salmonella enterica subspecies enterica serovar typhimurium. Notably, the current study identified that the accumulated and stable overexpression of RBM10 in the xenograft BALB/c nude mice model significantly inhibited the tumor growth rate. These results may provide novel insights into the use of RBM10 for lung cancer diagnosis and therapy.