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1.
Artigo em Inglês | MEDLINE | ID: mdl-39041258

RESUMO

PURPOSE: This study aims to understand the role of cirrhosis in promoting hepatocellular carcinoma (HCC) progression by analyzing the differential expression of long noncoding RNAs (lncRNAs) between cirrhotic hepatocellular carcinoma (CHCC) and noncirrhotic hepatocellular carcinoma (NCHCC). METHODS: A transcriptional profile array was used to identify differentially expressed lncRNAs. Subsequently, a specific lncRNA was selected to evaluate the clinical significance, potential functions, regulatory targets, and pathways through both in vitro and in vivo experiments. RESULTS: The study identified a lncRNA, which we termed DERCNC, an acronym for Differentially Expressed RNA between Cirrhotic and Non-Cirrhotic HCC. DERCNC was significantly more highly expressed in CHCC than in NCHCC. Clinically, elevated levels of DERCNC expression were positively correlated with both the cirrhotic state and tumor stage and inversely correlated with tumor differentiation. Furthermore, high expression of DERCNC was associated with a poor prognosis for patients. Conditioned medium from the hepatic stellate cell (LX2) was found to enhance DERCNC expression, SOX9 expression, and tumor proliferation. Overexpression of DERCNC similarly promoted tumor proliferation and increased SOX9 levels. Conversely, DERCNC silencing resulted in the opposite effects. Moreover, the pro-proliferative function of DERCNC was reversible through the modulation of SOX9 expression. Further mechanistic studies revealed that DERCNC upregulated SOX9 by increasing the enrichment of H3K27ac modifications near the SOX9 promoter. CONCLUSION: In conclusion, DERCNC expression in CHCC has significant clinical implications and can aggravate tumor proliferation by targeting SOX9. This represents a novel mechanism by which cirrhosis promotes tumor progression.

3.
Med Oncol ; 40(12): 339, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37875691

RESUMO

To investigate the role of neuropilin1 (Nrp1) in glucose metabolism and proliferation of hepatocellular carcinoma (HCC) cells and to analyze its mechanism of action. The CRISPR gene knockout technique was used to knock out the Nrp1 gene in two HCC cell lines. The effect of Nrp1 on the proliferation of HCC cells was assessed in the CCK8 assay and plate cloning assay. The expression levels of glucose consumption, lactate production, and essential proteins of the glycolytic pathway were detected to explore the effect of Nrp1 on glucose metabolism in HCC cells. Using CoCl2 to revert the expression of hypoxia inducible factor-1α (HIF-1α), the role of HIF-1α in the pro-HCC cell metabolism of Nrp1 were demonstrated. The protein synthesis inhibitor CHX and proteasome inhibitor MG-132 was used to analyze the molecular mechanism of action of Nrp1 on HIF-1α. The Kaplan-Meier method was used to calculate survival rates and plot survival curves. Based on the CCK8 assay and plate cloning assay, we found that Nrp1 knockout significantly inhibited the proliferation of HCC cells. Nrp1 inhibitor suppressed lactate production and glucose consumption in HCC cells. Knockout of Nrp1 decreased the expression of glycolytic pathway-related proteins and HIF-1α protein. Furthermore, by joint use of CoCl2 and NRP1 knockout, we confirmed that reverting HIF-1α expression could reverse the effect of Nrp1 knockout on HCC cell metabolism in vitro. Mechanistically, Nrp1 showed a close correlation with the stability of HIF-1α protein in protein stability assay. Finally, we revealed that high expression of Nrp1 in HCC tissues was associated with poor overall survival and disease-free survival of the patients. Nrp1 accelerates glycolysis and promotes proliferation of HCC by regulating HIF-1α protein stability and through the VEGF/Nrp1/HIF-1α positive feedback loop.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Retroalimentação , Neuropilina-1/genética , Neuropilina-1/metabolismo , Proliferação de Células , Glucose , Cobalto/farmacologia , Cobalto/metabolismo , Lactatos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
4.
Int J Radiat Biol ; 99(12): 1879-1889, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37523652

RESUMO

PURPOSE: The application of high-intensity focused ultrasound (HIFU) in hepatocellular carcinoma (HCC) was promising. However, whether the effect of HIFU is comparable with that of transarterial chemoembolization (TACE) has not been determined. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Web of Science, WanFang Data, CqVip, CNKI, and CBM databases were searched for randomized controlled trials (RCTs), cohort studies, and case-control studies. The methodological quality of each study was evaluated. When there is no statistical heterogeneity, the fixed effect model would be used to merge data. Otherwise, the random effect model would be utilized. Sensitivity analyses were conducted by excluding one study each time. Subgroup analyses were conducted based on age, sex, tumor number, relative number of the patients with Child-Pugh C grade in each group, the percentage of patients with Child-Pugh C grade in the whole study, and tumor load. Publication bias was evaluated by Egger's test and Begg's test. RESULTS: Six cohort studies including 188 patients from HIFU group and 224 patients from TACE group were obtained for further analysis. The meta-analysis suggested HIFU and TACE showed no differences in postoperative 1-year overall survival (OS) rate, tumor response (including complete response, partial response, stable disease, and progressive disease), and postoperative complications. Moreover, compared with TACE, HIFU showed higher postoperative 6-month and 2-year OS rates. Subgroup analyses, meta regression analysis and sensitivity analyses indicated the findings above were reliable. Additionally, no potential publication bias was detected. CONCLUSION: For HCC, when compared with TACE, HIFU might show comparable safety but better effect. Considering the limitations of current studies, more well-designed studies are needed to validate our conclusion.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Resultado do Tratamento , Quimioembolização Terapêutica/efeitos adversos , Estudos de Coortes
5.
Front Oncol ; 12: 797349, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35419281

RESUMO

Background: The study was conducted to explore whether high-intensity focused ultrasound (HIFU) can improve the effect of transcatheter arterial chemoembolization (TACE) in intermediate and advanced hepatocellular carcinoma (HCC). Methods: PubMed, Embase, Cochrane Library, Web of Science, Wanfang Data, CQVIP, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical (CBM) databases were searched for randomized controlled trials (RCTs) comparing the effect of TACE in combination with HIFU group (group A) to TACE alone group (group B) in treating intermediate and advanced HCC. The primary outcomes were overall survival (OS) rate and tumor response rate. The odds ratio (OR) and 95% confidence interval (CI) for each study were calculated and then pooled with fixed effects model or random effects model. Sensitivity analyses and subgroup analyses were conducted. A publication bias was also evaluated. Results: After literature selection, eleven RCTs involving 803 patients were included in this meta-analysis. This meta-analysis revealed that group A was associated with an increased 6-month OS rate (OR = 0.20), 12-month OS rate (OR = 0.23), 24-month OS rate (OR = 0.32), and overall response rate (WHO criterion, OR = 0.22; RECIST criterion, OR = 0.30). Furthermore, subgroup analyses showed no bias in the result. Given the limited number of studies that reported major complications, no additional meta-analysis of complication was conducted. Despite no special treatment, any complication following HIFU treatment was found to subside within 3-7 days. Conclusion: TACE in combination with HIFU is associated with increased OS and tumor response in intermediate and advanced HCC. Current evidence supports the use of HIFU after TACE treatment in intermediate and advanced HCC.

6.
BMJ Open ; 12(4): e049789, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35414539

RESUMO

OBJECTIVES: The study was designed to clarify the difference between extrahepatic cholangiocarcinoma (ECC) and intrahepatic cholangiocarcinoma (ICC) in postoperative cancer-specific death. DESIGN: Patients diagnosed with ECC and ICC after surgery, who are identified from the Surveillance, Epidemiology and End Results programme, are eligible for this retrospective cohort study. SETTING: Survival between groups was compared using the traditional Kaplan-Meier method and the cumulative incidence function (CIF) method. Propensity score-matched (PSM) analysis was conducted to balance the differences in vital variables between groups. The HR and 95% CI for ECC relative to ICC were used to quantify the risk of death. Subgroup analysis was further used to evaluate the stability of the differences between groups. RESULTS: The study included 876 patients with ECC and 1194 patients with ICC. Before PSM, with the Kaplan-Meier method, postoperative overall survival and cancer-specific death for ECC were worse than those for ICC. However, with the CIF method, no difference in postoperative cancer-specific death was found. After PSM, all differences in the considered traits were balanced, and 173 pairs of patients were retained. Survival analysis found that there was no difference in postoperative all-cause death (Kaplan-Meier method, p=0.186) or cancer-specific death (Kaplan-Meier and CIF methods, p=0.500 and p=0.913, respectively), which was consistent with subgroup analysis. CONCLUSIONS: ECC and ICC showed no difference in postoperative cancer-specific death, both in the natural state and in multiple variable-matched conditions. TRIAL REGISTRATION NUMBER: researchregistry4175.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias dos Ductos Biliares/epidemiologia , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/cirurgia , Humanos , Prognóstico , Estudos Retrospectivos , Fatores de Risco
7.
Free Radic Biol Med ; 168: 81-94, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-33781891

RESUMO

Metabolic reprogramming is a hallmark of cancer, including hepatocellular carcinoma (HCC). However, its role in HCC remains to be elucidated. Herein, we identified GTP cyclohydrolase 1 (GCH1), the first rate-limiting enzyme in tetrahydrobiopterin (BH4) de novo biosynthesis, as a novel metabolic regulator of HCC. GCH1 was frequently down-regulated in HCC tissues and cell lines by promoter methylation. Low GCH1 expression was associated with larger tumor size, increased tumor number, and worse prognosis in two independent cohorts of HCC patients. Functionally, GCH1 silencing promoted HCC growth in vitro and in vivo, while GCH1 overexpression exerted an opposite effect. The metabolite BH4 inhibited HCC growth in vitro and in vivo. GCH1 silencing exerted its growth-promoting effect through directly inhibiting BH4 de novo biosynthesis. Mechanistically, GCH1 silencing activated ASK1/p38 signaling; pharmacological or genetic inhibition of ASK1 or p38 abolished GCH1 silencing-induced growth-promoting effect. Further mechanistic studies found that GCH1 silencing-induced BH4 reduction resulted in an increase of intracellular superoxide anion levels in a dose-dependent manner, which mediated the activation of ASK1/p38 signaling. Collectively, our study reveals that epigenetic silencing of GCH1 promotes HCC growth by activating superoxide anion-mediated ASK1/p38 signaling via inhibiting BH4 de novo biosynthesis, suggesting that targeting GCH1/BH4 pathway may be a promising therapeutic strategy to combat HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biopterinas/análogos & derivados , Biopterinas/metabolismo , Carcinoma Hepatocelular/genética , Epigênese Genética , GTP Cicloidrolase/metabolismo , Humanos , Neoplasias Hepáticas/genética , Superóxidos
8.
Carcinogenesis ; 42(5): 724-732, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-33480980

RESUMO

Low-carbohydrate diets have become a popular approach for weight loss in recent years. However, whether low-carbohydrate diets are associated with the risk of pancreatic cancer remains to be elucidated. Hence, we examined the association of low-carbohydrate diets with the risk of pancreatic cancer in a US population. A population-based cohort of 95 962 individuals was identified. A low-carbohydrate-diet score was calculated to quantify adherence to this dietary pattern, with higher scores indicating greater adherence. Cox regression was used to calculate risk estimate for the association of the low-carbohydrate-diet score with the risk of pancreatic cancer. Subgroup analysis was used to identify the potential effect modifiers. After an average follow-up of 8.87 years (875856.9 person-years), we documented a total of 351 pancreatic cancer cases. In the fully adjusted model, the highest versus the lowest quartiles of the overall low-carbohydrate-diet score were found to be associated with a reduced risk of pancreatic cancer (hazard ratioquartile 4 versus 1: 0.61; 95% confidence interval: 0.45, 0.82; Ptrend < 0.001). Subgroup analysis found that the inverse association of low-carbohydrate diets with the risk of pancreatic cancer was more pronounced in individuals aged ≥65 years than in those aged <65 years (Pinteraction = 0.015). Similar results were obtained for animal and vegetable low-carbohydrate-diet scores. In conclusion, low-carbohydrate diets, regardless of the type of protein and fat, are associated with a lower risk of pancreatic cancer in the US population, suggesting that adherence to low-carbohydrate diets may be beneficial for pancreatic cancer prevention. Future studies should validate our findings in other populations.


Assuntos
Dieta com Restrição de Carboidratos/efeitos adversos , Carboidratos da Dieta/metabolismo , Neoplasias Pancreáticas/metabolismo , Idoso , Estudos de Coortes , Gorduras na Dieta/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/patologia , Fatores de Risco , Redução de Peso/fisiologia
9.
Transl Cancer Res ; 10(5): 2080-2090, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-35116529

RESUMO

BACKGROUND: The effectiveness and safety of focused ultrasound ablation surgery (FUAS) for primary hepatocellular carcinoma (HCC) treatment has not been fully evaluated. This study analyzed the effectiveness and safety of FUAS compared to radiofrequency ablation (RFA). METHODS: Studies published before November 1, 2020, in the following databases were analyzed: PubMed, Embase, Cochrane Library, Web of Science, Wanfang Data, CqVip, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical (CBM) database. All publications were reviewed independently by two authors. Both randomized controlled trials (RCTs) and cohort studies examining the effectiveness and safety of FUAS and RFA were considered. RCTs and cohort studies' methodological quality were evaluated using the Cochrane collaboration tool and the Newcastle-Ottawa Scale, respectively. RESULTS: A total of 6,597 records were identified, from which 3 cohort studies were selected for quantitative synthesis. All studies had relatively high methodological quality. The meta-analysis indicated that FUAS and RFA had comparable 3-month overall survival (OS) rates [risk ratio (RR): 0.99, 95% confidence interval (CI): 0.86 to 1.14], 6-month OS rates (RR: 1.03, 95% CI: 0.82 to 1.29), and 1-year OS rates (RR: 0.96, 95% CI: 0.84 to 1.11). Also, individual studies reported that the tumor response (reflected by tumor response and tumor ablation rate) and posttreatment complications were comparable between patients treated with FUAS and patients treated with RFA. Due to the limited number of studies reporting tumor response and posttreatment complications, further meta-analyses could not be conducted. DISCUSSION: FUAS and RFA were comparable in terms of effectiveness and safety in the treatment of primary HCC. However, current evidence is limited, and more prospective RCTs are warranted to confirm these findings.

10.
Transl Cancer Res ; 10(6): 2738-2746, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35116584

RESUMO

BACKGROUND: This study was designed to explore the prognostic and diagnostic value of Sex-Determining Region Y-Box 9 (SOX9) in cirrhotic hepatocellular carcinoma HCC (CHCC) and noncirrhotic hepatocellular carcinoma (NCHCC). METHODS: SOX9 tissue expression was detected using data from The Cancer Genome Atlas (TCGA) database and our cohort. The Kaplan-Meier method was used to analyze differences in survival between high/low SOX9 expression groups. Univariate analysis and multivariate analysis were used to identify independent risk factors associated with overall survival (OS). Receiver operating characteristic (ROC) curve and area under the curve (AUC) were utilized for evaluation of the diagnostic efficacy of SOX9. RESULTS: SOX9 was found to exhibit differential expression between HCC and adjacent normal tissues but not between CHCC and NCHCC, which was confirmed by RNA sequencing, quantitative real-time polymerase chain reaction and immunohistochemical staining. Kaplan-Meier survival analysis and multivariate analysis revealed that high SOX9 expression was closely related to the OS in NCHCC but not that in CHCC. In CHCC and NCHCC, SOX9 expression was positively associated with serum α-fetoprotein levels. The AUC of SOX9 in differentiating HCC and adjacent normal tissues in CHCC and NCHCC was 0.77 and 0.78, respectively, and no significant difference was found between them. CONCLUSIONS: High SOX9 expression may aid prognostic evaluation in NCHCC but not in CHCC. SOX9 expression was not different between CHCC and NCHCC, but it has reliable and comparable diagnostic value in both CHCC and NCHCC.

11.
Carcinogenesis ; 41(11): 1576-1582, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-32188964

RESUMO

The difference of the patients bearing hepatocellular carcinoma (HCC) with and without cirrhosis at clinical level has not been completely determined. This study compared their differences in clinicopathological traits and prognostic factors for relapse-free survival (RFS) and overall survival (OS). Animal model was established to validate the result of clinical observation. As a result, 82 patients bearing HCC with no cirrhosis (HCC-NC) and 146 patients bearing HCC with cirrhosis (HCC-C) were included. HCC-NC exhibited shorter prothrombin time and higher plasma albumin than HCC-C. In HCC-NC, satellite nodule was an independent risk factor for OS, and high γ-glutamyl transpeptidase was an independent risk factor for RFS. In HCC-C, female sex was an independent risk factor for OS. Stratified analysis showed the OS and RFS of HCC-NC were better than HCC-C in conditions like without cancer embolus (in the portal vein or bile duct), without lymphadenopathy in hepatic portal, without satellite nodule and with small or high-differentiated tumor. Animal model analysis showed HCC-NC had a higher liver/body weight ratio, less tumor count and smaller max tumor volume than HCC-C. In conclusion, clinicopathological traits and risk factors influencing postoperative OS and RFS differed between patients with HCC-C and HCC-NC.


Assuntos
Carcinoma Hepatocelular/patologia , Cirrose Hepática/complicações , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/patologia , Animais , Apoptose , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/metabolismo , Proliferação de Células , Feminino , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Taxa de Sobrevida , Carga Tumoral , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
12.
BMC Surg ; 19(1): 128, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488117

RESUMO

BACKGROUND: The aim of the study was to develop a scoring system for the prediction of postoperative complications of open hepatectomy. METHOD: All consecutive patients receiving open hepatectomy from 2015 to 2017 were included in the study. Univariate and multivariate analyses were used to confirm the risk factors for postoperative complications. Afterwards, a novel scoring system was developed to predict the postoperative complications. RESULTS: The study included a total of 207 patients. For the test dataset, multivariate analysis indicated that diabetes, scale of surgery, serum potassium, and blood loss versus body weight were independent risk factors of the postoperative complications. The area under the curve (AUC) of the novel scoring system we proposed for prediction of postoperative complications of hepatectomy was 0.803, which is comparable with the AUCs of previous scoring systems. Furthermore, in the validation dataset, the corresponding AUC of the new scoring system was 0.717. CONCLUSION: This novel and simplified scoring system can effectively predict the postoperative complications of open hepatectomy and could help identify patients who are at high risk of postoperative complications.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco
13.
J Cell Mol Med ; 23(11): 7673-7684, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31468674

RESUMO

Stromal cell-derived factor-1 (SDF-1) is a well-characterized cytokine that protects heart from ischaemic injury. However, the beneficial effects of native SDF-1, in terms of promoting myocardial repair, are limited by its low concentration in the ischaemic myocardium. Annexin V (AnxA5) can precisely detect dead cells in vivo. As massive cardiomyocytes die after MI, we hypothesize that AnxA5 can be used as an anchor to carry SDF-1 to the ischaemic myocardium. In this study, we constructed a fusion protein consisting of SDF-1 and AnxA5 domains. The receptor competition assay revealed that SDF-1-AnxA5 had high binding affinity to SDF-1 receptor CXCR4. The treatment of SDF-1-AnxA5 could significantly promote phosphorylation of AKT and ERK and induce chemotactic response, angiogenesis and cell survival in vitro. The binding membrane assay and immunofluorescence revealed that AnxA5 domain had the ability to specifically recognize and bind to cells injured by hypoxia. Furthermore, SDF-1-AnxA5 administered via peripheral vein could accumulate at the infarcted myocardium in vivo. The treatment with SDF-1-AnxA5 attenuated cell apoptosis, enhanced angiogenesis, reduced infarcted size and improved cardiac function after mouse myocardial infarction. Our results suggest that the bifunctional SDF-1-AnxA5 can specifically bind to dead cells. The systemic administration of bifunctional SDF-1-AnxA5 effectively provides cardioprotection after myocardial infarction.


Assuntos
Anexina A5/metabolismo , Quimiocina CXCL12/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/fisiopatologia , Proteínas Recombinantes de Fusão/uso terapêutico , Administração Intravenosa , Animais , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quimiotaxia/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/patologia , Isquemia Miocárdica/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Neovascularização Fisiológica/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Receptores de Quimiocinas/metabolismo , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/farmacologia , Transdução de Sinais/efeitos dos fármacos
14.
Biomaterials ; 192: 15-25, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30415102

RESUMO

Medical coatings cooperated with biomacromolecules can regulate biological events and tissue responses, thus increasing medical implant longevity and providing improved and/or new therapeutic functions. In particular, medical coatings, which can load the correct species and doses of biomacromolecules according to individual diagnoses, will significantly optimize treatment effects and satisfy the rising clinical need of "precision medicine". Herein, we report on a dynamic microporous coating with an ultrafast self-healing property to fulfill the "load-and-play" concept for "precision medicine". A structure-switchable coating based on poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) triblock copolymer network is constructed. The coating can be switched to microporous morphology via a water swelling and freeze-drying process. Then, through a mild thermo-trigger as low as 40 °C, this spongy coating can undergo self-healing to switch back to a pore-free structure within minutes to even 5 s. Based on this dynamic coating, we suggest a simple and versatile method to encapsulate biomacromolecules for surface-mediated delivery. The ultrafast self-healing of the microporous structure enables uniform incorporation of biomacromolecules with an easily achieved high loading of albumin of 16.3 µg/cm2 within 1 min. More importantly, controllable encapsulation can be realized by simple control of the concentration of the loading solution. We further demonstrate that the encapsulated biomacromolecules retained their bioactivity. This work may benefit clinicians with flexibility to provide personalized medical coatings for individual patients during treatment.


Assuntos
Preparações de Ação Retardada/química , Poliésteres/química , Polietilenoglicóis/química , Animais , Stents Farmacológicos , Células Endoteliais da Veia Umbilical Humana , Humanos , Porosidade , Coelhos , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/farmacocinética , Temperatura , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/farmacocinética
15.
Cell Physiol Biochem ; 48(4): 1443-1456, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30064138

RESUMO

BACKGROUND/AIMS: Few studies have been designed to directly investigate the exact mechanisms underlying the different phenotypes between cirrhotic and non-cirrhotic hepatocellular carcinoma (HCC). This study aimed to illuminate the incidence and developmental mechanisms for both types of HCC through differentially expressed microRNAs (miRNAs) using bioinformatic analysis. METHODS: The miRNA-seq data and clinical data of patients (from The Cancer Genome Atlas (TCGA) database) were utilized to determine differentially expressed miRNAs between cirrhotic and non-cirrhotic HCC. Afterwards, the function of the selected miRNAs was predicted with online tools. Furthermore, the miRNA expression and clinical significance were validated by external datasets and our experiment. RESULTS: The present study included 135 non-cirrhotic and 80 cirrhotic patients to find differentially expressed miRNAs. Among them, four miRNAs (mir-1296, mir-23c, mir-149, and mir-95) were finally selected for further validation and analysis. Correlation analysis found that two miRNAs are greatly associated with the non-cirrhotic HCC patients' clinical traits, such as the T, M, and N tumor stages. However, only mir-23c was associated with the cirrhotic HCC patients' tumor T and N stages. Furthermore, survival analysis revealed that increased mir-149 in non-cirrhotic HCC, patients' age and the existence of vessels in the tumor in cirrhotic HCC were independent risk factors for the patients' postoperative overall survival. Functional and interaction analyses also supported the notion that these miRNAs function through some pathways that influence the behavior of the HCC. These results are strongly supported by analysis of extra datasets and our experiment. CONCLUSIONS: The cirrhotic and non-cirrhotic HCC types involve differentially expressed miRNAs, which are correlated with distinctive pathological traits. To some extent, non-cirrhotic HCC seems more dependent on miRNA network regulation, but additional studies are needed to confirm this conclusion.


Assuntos
Carcinoma Hepatocelular/patologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/mortalidade , Biologia Computacional , Intervalo Livre de Doença , Feminino , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/mortalidade , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Taxa de Sobrevida , alfa-Fetoproteínas/análise
16.
Int J Surg ; 56: 83-93, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29906644

RESUMO

BACKGROUND: Step-up therapy is the recommended therapy for infected necrotizing pancreatitis (INP). However, the most appropriate secondary therapy for use after initial drainage has not been fully determined. This meta-analysis was designed to evaluate the efficacy and safety of retroperitoneal versus open intraperitoneal necrosectomy as part of a step-up strategy for INP. MATERIALS AND METHODS: Eight online databases were searched for randomized controlled trials (RCTs) and cohorts comparing retroperitoneal and open intraperitoneal step-up approaches for treating INP. The data was pooled with a random-effects model. RESULTS: A total of 21 controlled studies (one RCT and twenty cohorts) and 2177 patients were included in this study. Our meta-analysis showed that the retroperitoneal group had a lower postoperative complication rate [risk ratio (RR) = 0.575, 95% confidence interval (CI) = 0.459 to 0.719, P < 0.001], lower postoperative mortality (RR = 0.525, 95% CI = 0.430 to 0.642, P < 0.001), higher technical success rate (RR = 1.313, 95% CI = 1.017 to 1.694, P = 0.037), similar surgical reintervention rate (RR = 0.930, 95% CI = 0.783 to 1.106, P = 0.411), shorter operative time [standardized mean difference (SMD) = -2.402, 95% CI = -3.642 to -1.161, P < 0.001], and shorter hospital stay (SMD = -2.034, 95% CI = -3.041 to -1.026, P < 0.001) than the open group. These results were supported by a subgroup analysis. CONCLUSION: For treating INP, the retroperitoneal approach is safer and more effective than the open intraperitoneal approach.


Assuntos
Pâncreas/cirurgia , Pancreatite Necrosante Aguda/cirurgia , Peritônio/cirurgia , Espaço Retroperitoneal/cirurgia , Adulto , Drenagem/métodos , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
17.
Surg Laparosc Endosc Percutan Tech ; 28(2): 67-72, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29528948

RESUMO

OBJECTIVE: This study aimed to compare the recurrence rates of nonparasitic hepatic cysts that were treated with laparoscopy or open fenestration. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Web of Science, Wan-fang data, CNKI, CqVip, and CBM were searched for randomized controlled trials, cohort, and case-control studies that reported on the treatment of nonparasitic hepatic cysts with laparoscopy or with open fenestration. Studies that were published from the establishment of the databases to October 1, 2016 were retrieved. STATA software (version 13) was utilized for statistical analysis. RESULTS: A total of 31 studies were included. Meta-analysis showed that the recurrence rates of hepatic cysts between the laparoscopy-deroofing and open-deroofing groups had no difference (odds ratio, 0.72; 95% confidence interval, 0.50-1.02; P=0.061). This result was in agreement with the result of subgroup analysis for solitary and multiple hepatic cyst. CONCLUSIONS: These findings underscore the distinct role of laparoscopy deroofing in the treatment of hepatic cysts because of the certainty of its long-term curative effect.


Assuntos
Cistos , Hepatectomia/métodos , Laparoscopia/métodos , Laparotomia/métodos , Hepatopatias , Fígado/cirurgia , Cistos/diagnóstico , Cistos/epidemiologia , Cistos/cirurgia , Humanos , Fígado/diagnóstico por imagem , Hepatopatias/diagnóstico , Hepatopatias/epidemiologia , Hepatopatias/cirurgia , Recidiva , Resultado do Tratamento
18.
Surg Endosc ; 31(4): 1524-1537, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27553801

RESUMO

OBJECTIVE: To compare the effectiveness and safety of single-port versus multi-port laparoscopic surgery for treating liver diseases. METHODS: Several databases were systematically searched for randomized controlled trials, cohort studies, and case-control studies on the use of single-port versus multi-port laparoscopic surgery to treat liver diseases from their inception until March 24, 2016. The primary outcomes were the operative time, volume of intraoperative blood loss, rate of postoperative complications, median length of postoperative stay, recovery time of gastrointestinal function, volume of postoperative drainage, and postoperative drainage time. The study-specific effect sizes and their 95 % confidence interval were all combined to calculate the pooled value by using a random-effects model. RESULTS: A total of nine studies were included, which involved 277 patients. The total and subgroup data were combined by meta-analysis. This meta-analysis showed that single-port and multi-port laparoscopic liver surgery for treating liver diseases did not differ in terms of operative time (P = 0.48), rate of postoperative complications (P = 0.56), median length of postoperative stay (P = 0.80), and recovery time of gastrointestinal function (P = 0.54). For liver diseases, the single-port group exhibited a lower volume of intraoperative blood loss than that presented by the multi-port group (P = 0.0006). In the hepatic resection subgroup, a lower volume of intraoperative blood loss was noted in the single-port group (P < 0.0001). By contrast, in the hepatic cyst subgroup, the single-port group showed a higher volume of intraoperative blood loss (P = 0.02) but a shorter median length of postoperative stay (P = 0.02). The findings of the potential subgroup analysis in these outcomes were consistent with the total data. CONCLUSION: Compared with multi-port laparoscopic surgery, the single-port method showed comparable effectiveness and safety for the treatment of liver diseases in terms of current evidence.


Assuntos
Hepatectomia/métodos , Laparoscopia/métodos , Hepatopatias/cirurgia , Complicações Pós-Operatórias/cirurgia , Perda Sanguínea Cirúrgica , Humanos , Tempo de Internação , Duração da Cirurgia , Resultado do Tratamento
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