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1.
Cytokine ; 179: 156598, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38583255

RESUMO

BACKGROUND: Allograft rejection remains a major obstacle to long-term graft survival. Although previous studies have demonstrated that IL-37 exhibited significant immunomodulatory effects in various diseases, research on its role in solid organ transplantation has not been fully elucidated. In this study, the therapeutic effect of recombinant human IL-37 (rhIL-37) was evaluated in a mouse cardiac allotransplantation model. METHODS: The C57BL/6 recipients mouse receiving BALB/c donor hearts were treated with rhIL-37. Graft pathological and immunohistology changes, immune cell populations, and cytokine profiles were analyzed on postoperative day (POD) 7. The proliferative capacities of Th1, Th17, and Treg subpopulations were assessed in vitro. Furthermore, the role of the p-mTOR pathway in rhIL-37-induced CD4+ cell inhibition was also elucidated. RESULTS: Compared to untreated groups, treatment of rhIL-37 achieved long-term cardiac allograft survival and effectively alleviated allograft rejection indicated by markedly reduced infiltration of CD4+ and CD11c+ cells and ameliorated graft pathological changes. rhIL-37 displayed significantly less splenic populations of Th1 and Th17 cells, as well as matured dendritic cells. The percentages of Tregs in splenocytes were significantly increased in the therapy group. Furthermore, rhIL-37 markedly decreased the levels of TNF-α and IFN-γ, but increased the level of IL-10 in the recipients. In addition, rhIL-37 inhibited the expression of p-mTOR in CD4+ cells of splenocytes. In vitro, similar to the in vivo experiments, rhIL-37 caused a decrease in the proportion of Th1 and Th17, as well as an increase in the proportion of Treg and a reduction in p-mTOR expression in CD4+ cells. CONCLUSIONS: We demonstrated that rhIL-37 effectively suppress acute rejection and induce long-term allograft acceptance. The results highlight that IL-37 could be novel and promising candidate for prevention of allograft rejection.


Assuntos
Aloenxertos , Rejeição de Enxerto , Transplante de Coração , Interleucina-1 , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Proteínas Recombinantes , Animais , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Camundongos , Proteínas Recombinantes/farmacologia , Interleucina-1/metabolismo , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Células Th1/imunologia , Células Th1/efeitos dos fármacos , Células Th17/imunologia , Células Th17/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Masculino , Serina-Treonina Quinases TOR/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
2.
Front Cardiovasc Med ; 10: 1160142, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37547252

RESUMO

Objective: This article aims to investigate the incidence rate of retrograde type A aortic dissection (RTAD) and the risk factors of RTAD in relation to thoracic endovascular aortic repair (TEVAR). Methods: Patients with thoracic aortic disease who underwent TEVAR at Henan Provincial People's Hospital from January 2004 to December 2019 were enrolled in the present research. The risk factors associated with RTAD following TEVAR using univariate and multiple logistic regression analyses. Results: During the study period, A total of 1,688 TEVAR patients were included in this study, and of these, 1,592 cases were included in the type B aortic dissection (TBAD) group, and 96 cases were included in the non-TBAD group. There were 1,230 cases of aortic dissection and 362 cases of aortic intramural hematoma and/or penetrating ulcer in the TBAD group. The non-TBAD group included 68 cases of thoracic aortic aneurysm, 21 cases of thoracic aortic pseudoaneurysm, and seven cases of congenital aortic coarctation. The overall incidence rate of RTAD was 1.1% (18/1,688) in patients, all of which occurred in the TBAD group. The cohort comprised 18 RTAD patients with an average age of 56.78, consisting of 13 males and 5 females. Among them, 13 individuals exhibited hypertension. Ten instances happened within the TEVAR perioperative period, including two cases during the surgery, six cases occurred within three months, two cases occurred after one year, and the longest interval was 72 months following TEVAR. TEVAR was successfully implemented in 17 patients, while the operation technique was temporarily altered in one case. The new entry position for RTAD was identified as the proximal region of the stent graft (SG) in 13 patients, while in five cases, the entry site was more than 2 cm away from the proximal region of the SG. 17 cases were at the greater curvature of the aorta, and one case was at the lesser curvature. Multivariate logistic regression analysis revealed that the SG oversizing ratio is a relevant risk factor for RTAD. However, ascending aortic diameter, aortic arch type, SG type, and anchored region were not directly related to the occurrence of RTAD. Conclusion: RTAD is a rare yet catastrophic complication. It could occur both during the procedure, early and late postoperative periods. Maintaining an appropriate SG oversizing ratio is crucial to minimize the risk of RTAD.

3.
Front Immunol ; 13: 931783, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935954

RESUMO

Background: IL-37 is a recently identified cytokine with potent immunosuppressive functions. The research fronts of IL-37 are worth investigating, and there is no bibliometric analysis in this field. The purpose of this study is to construct the intellectual base and predict research hotspots of IL-37 research both quantitatively and qualitatively according to bibliometric analysis. Methods: The articles were downloaded from the Web of Science Core Collection (WoSCC) database from the inception of the database to 1 April 2022. CiteSpace 5.8.R3 (64-bit, Drexel University, Philadelphia, PA, USA) and Online Analysis Platform of Literature Metrology (https://bibliometric.com/) were used to perform bibliometric and knowledge-map analyses. Results: A total of 534 papers were included in 200 academic journals by 2,783 authors in 279 institutions from 50 countries/regions. The journal Cytokine published the most papers on IL-37, while Nature Immunology was the most co-cited journal. The publications belonged mainly to two categories of Immunology and Cell Biology. USA and China were the most productive countries. Meanwhile, the University of Colorado Denver in USA produced the highest number of publications followed by Radboud University Nijmegen in the Netherlands and Monash University in Australia. Charles A. Dinarello published the most papers, while Marcel F. Nold had the most co-citations. Top 10 co-citations on reviews, mechanisms, and diseases were regarded as the knowledge base. The keyword co-occurrence and co-citations of references revealed that the mechanisms and immune-related disorders were the main aspects of IL-37 research. Notably, the involvement of IL-37 in various disorders and the additional immunomodulatory mechanisms were two emerging hotspots in IL-37 research. Conclusions: The research on IL-37 was thoroughly reviewed using bibliometrics and knowledge-map analyses. The present study is a benefit for academics to master the dynamic evolution of IL-37 and point out the direction for future research.


Assuntos
Bibliometria , Internet , Citocinas , Previsões , Humanos , Países Baixos
4.
Biomed Res Int ; 2022: 2680110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35782053

RESUMO

Background: Immunotherapy has been considered as a promising cancer treatment for hepatocellular carcinoma (HCC). However, due to the particular immune environment of the liver, identifying patients who could benefit from immunotherapy is critical in clinical practice. Methods: The pyroptosis gene expression database of 54 candidates from The Cancer Genome Atlas (TCGA) were collected to discover the critical prognostic-related pyroptosis genes. A novel pyroptosis gene model was established to calculate the risk score. Kaplan-Meier analysis and receiver operating characteristic curve (ROC) were used to verify its predictive ability. The International Cancer Genome Consortium (ICGC) data was collected as external validation data to verify the model's accuracy. We employed multiple bioinformatics tools and algorithms to evaluate the tumor immune microenvironment (TIME) and the response to immunotherapy. Results: Our study found that most pyroptosis genes were expressed differently in normal and tumor tissues and that their expression was associated with the prognosis. Then, a precise four-pyroptosis gene model was generated. The one-year area under the curves (AUCs) among the training, internal, and external validation patients were 0.901, 0.727, and 0.671, respectively. An analysis of survival data revealed that individuals had a worse prognosis than patients with low risk. The analysis of TIME revealed that the low-risk group had more antitumor cells, fewer immunosuppressive cells, stronger immune function, less immune checkpoint gene expression, and better immunotherapy response than the high-risk group. Immunophenoscore (IPS) analysis also demonstrated that the low-risk score was related to superior immune checkpoint inhibitors therapy. Conclusion: A nomogram based on the four-pyroptosis gene signature was a novel tool to predict the effectiveness of immunotherapy for HCC. Therefore, individualized treatment targeting the pyroptosis genes may influence TIME and play an essential role in improving the prognosis in HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Humanos , Fatores Imunológicos , Imunoterapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Nomogramas , Piroptose/genética , Microambiente Tumoral/genética
5.
Front Immunol ; 13: 859972, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35663940

RESUMO

Background: Mesenchymal stem cells (MSCs) have important research value and broad application prospects in liver diseases. This study aims to comprehensively review the cooperation and influence of countries, institutions, authors, and journals in the field of MSCs in liver diseases from the perspective of bibliometrics, evaluate the clustering evolution of knowledge structure, and discover hot trends and emerging topics. Methods: The articles and reviews related to MSCs in liver diseases were retrieved from the Web of Science Core Collection using Topic Search. A bibliometric study was performed using CiteSpace and VOSviewer. Results: A total of 3404 articles and reviews were included over the period 2001-2021. The number of articles regarding MSCs in liver diseases showed an increasing trend. These publications mainly come from 3251 institutions in 113 countries led by China and the USA. Li L published the most papers among the publications, while Pittenger MF had the most co-citations. Analysis of the most productive journals shows that most are specialized in medical research, experimental medicine and cell biology, and cell & tissue engineering. The macroscopical sketch and micro-representation of the whole knowledge field are realized through co-citation analysis. Liver scaffold, MSC therapy, extracellular vesicle, and others are current and developing areas of the study. The keywords "machine perfusion", "liver transplantation", and "microRNAs" also may be the focus of new trends and future research. Conclusions: In this study, bibliometrics and visual methods were used to review the research of MSCs in liver diseases comprehensively. This paper will help scholars better understand the dynamic evolution of the application of MSCs in liver diseases and point out the direction for future research.


Assuntos
Pesquisa Biomédica , Hepatopatias , Células-Tronco Mesenquimais , Bibliometria , Humanos , Hepatopatias/terapia , Publicações
6.
Int J Gen Med ; 15: 3525-3540, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386863

RESUMO

Background: The prognostic value of m6A-related genes in hepatocellular carcinoma (HCC) and its correlation with the immune microenvironment still requires further investigation. Methods: Consensus clustering by m6A related genes was used to classify 374 patients with HCC from The Cancer Genome Atlas (TCGA) database. Then we performed the least absolute shrinkage and selection operator (LASSO) to construct the m6A related genes model. The International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) datasets were used to verify and evaluate the model. ESTIMATE, CIBERSORTx, the expression levels of immune checkpoint genes, and TIDE were used to investigate the tumor microenvironment (TME) and the response to immunotherapy. Gene set enrichment analyses (GSEA), tumor-associated macrophages (TAMs), and gene-drug sensitivity were also analyzed. Results: By expression value and regression coefficient of five m6A related genes, we constructed the risk score of each patient. The patients with a higher risk score had a considerably poorer prognosis in the primary and validated cohort. For further discussing TME and the response to immunotherapy, we divided the entire set into two groups based on the risk score. Our findings implied that the tumor-infiltrating lymphocytes (TILs) were proportional to the risk scores, which seemed to contradict that patients with higher scores had a poor prognosis. Further, we found that the high-risk group had higher expression of PD-L1, CTLA-4, and PDCD1, indicating immune dysfunction, which may be a fundamental reason for poor prognosis. This was further reinforced by the fact that the low-risk group responded better than the high-risk group to monotherapy and combination therapy. Conclusion: The m6A related risk score is a new independent prognostic factor that correlates with immunotherapy response. It can provide a new therapeutic strategy for improving individual immunotherapy in HCC.

7.
Ther Clin Risk Manag ; 17: 889-901, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34475758

RESUMO

OBJECTIVE: This study aimed to discover the ceRNAs network in the pathophysiological development of human colorectal cancer (CRC) and to screen biomarkers for target therapy and prognosis by using integrated bioinformatics analysis. METHODS: Data on gene expressions of mRNAs, miRNAs, and circRNAs and clinical information were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases, respectively. Differentially expressed mRNAs (DEmRNAs) were identified by using the DESeq2 package of R software. Functional enrichment analysis was conducted using the ClusterProfiler package of R software. The protein-protein interaction (PPI) network was shown by the STRING website. Survival analysis of hub genes was performed using the survival package in R software. Interactions among hub genes, differentially expressed miRNAs (DEmiRNAs), and differentially expressed circRNAs (DEcircRNAs) were used to construct the ceRNAs network. RESULTS: A total of 412 DEmRNAs including 82 upregulated and 330 downregulated genes were screened out between 473 CRC and 41 normal samples. Two hundred and sixty DEcircRNAs including 253 upregulated and 7 downregulated genes were altered between 23 CRC and 23 normal samples. One hundred and ninety DEmiRNAs including 82 upregulated and 108 downregulated genes were obtained between 450 CRC and 8 normal samples. A ceRNAs and PPI network were successfully constructed, and TIMP1 associated with prognosis was employed. CONCLUSION: The present study identified a novel circRNAs-miRNAs-mRNA ceRNAs network, which implied that TIMP1 and related miRNAs, circRNAs were potential biomarkers underlying the development of CRC, providing new insights for survival predictions and therapeutic targets.

9.
Int Immunopharmacol ; 100: 108080, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34454287

RESUMO

Organ transplantation is an effective treatment strategy for patients with irreversible organ failure or congenital organ dysfunction. Oxymatrine (OMT) is a quinolizidine alkaloid with protective and anti-inflammatory effects on tissues and organs. The objective of this study was to investigate whether OMT could exert protective effects in cardiac allografts by regulating immune cells. In vitro cell proliferation and co-culture experiments were used to measure the effects of OMT on splenocyte proliferation and differentiation. In the in vivo study, C57BL/6 mice transplanted with BALB/c cardiac grafts were randomly divided into untreated, low-dose OMT treated, middle-dose OMT treated, high-dose OMT treated, and rapamycin-treated groups. Haematoxylin and eosin and immunohistochemical staining were used to assess pathological changes in the grafts, and fluorescence-activated cell sorting analysis was performed to measure the percentages of immune cells. The results showed that, in the in vitro study, OMT inhibited splenocyte proliferation, decreased the percentage of mature dendritic cells (DCs), and increased the percentage of regulatory T cells (Tregs) and regulatory B cells (Bregs). In the in vivo study, OMT exerted allograft protective effects by prolonging survival time, alleviating pathological damages to the cardiac allograft, decreasing intragraft CD3+ cell and increasing intragraft Foxp3+ cell infiltration, decreasing the percentages of mature DCs, increasing the percentages of Tregs and Bregs, and inhibiting the function of DCs. In conclusion, our study demonstrates that OMT exerted a protective effect on cardiac allografts by regulating immunotolerant cells. More in-depth studies of OMT may provide additional insight into the use of immunosuppressive drugs as a post-transplantation treatment strategy.


Assuntos
Alcaloides/farmacologia , Aloenxertos/efeitos dos fármacos , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/efeitos adversos , Quinolizinas/farmacologia , Alcaloides/uso terapêutico , Aloenxertos/imunologia , Aloenxertos/patologia , Animais , Linfócitos B Reguladores/efeitos dos fármacos , Linfócitos B Reguladores/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Modelos Animais de Doenças , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Humanos , Tolerância Imunológica/efeitos dos fármacos , Masculino , Camundongos , Quinolizinas/uso terapêutico , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia
10.
Front Immunol ; 12: 672849, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995416

RESUMO

Background: Chronic rejection characterized by chronic allograft vasculopathy (CAV) remains a major obstacle to long-term graft survival. Due to multiple complicated mechanisms involved, a novel therapy for CAV remains exploration. Although mesenchymal stromal cells (MSCs) have been ubiquitously applied to various refractory immune-related diseases, rare research makes a thorough inquiry in CAV. Meanwhile, melatonin (MT), a wide spectrum of immunomodulator, plays a non-negligible role in transplantation immunity. Here, we have investigated the synergistic effects of MT in combination with MSCs in attenuation of CAV. Methods: C57BL/6 (B6) mouse recipients receiving BALB/c mouse donor aorta transplantation have been treated with MT and/or adipose-derived MSCs. Graft pathological changes, intragraft immunocyte infiltration, splenic immune cell populations, circulating donor-specific antibodies levels, cytokine profiles were detected on post-operative day 40. The proliferation capacity of CD4+ and CD8+ T cells, populations of Th1, Th17, and Tregs were also assessed in vitro. Results: Grafts in untreated recipients developed a typical pathological feature of CAV characterized by intimal thickening 40 days after transplantation. Compared to untreated and monotherapy groups, MT in combination with MSCs effectively ameliorated pathological changes of aorta grafts indicated by markedly decreased levels of intimal hyperplasia and the infiltration of CD4+ cells, CD8+ cells, and macrophages, but elevated infiltration of Foxp3+ cells. MT either alone or in combination with MSCs effectively inhibited the proliferation of T cells, decreased populations of Th1 and Th17 cells, but increased the proportion of Tregs in vitro. MT synergized with MSCs displayed much fewer splenic populations of CD4+ and CD8+ T cells, Th1 cells, Th17 cells, CD4+ central memory T cells (Tcm), as well as effector memory T cells (Tem) in aorta transplant recipients. In addition, the percentage of splenic Tregs was substantially increased in the combination therapy group. Furthermore, MT combined with MSCs markedly reduced serum levels of circulating allospecific IgG and IgM, as well as decreased the levels of pro-inflammatory IFN-γ, TNF-α, IL-1ß, IL-6, IL-17A, and MCP-1, but increased the level of IL-10 in the recipients. Conclusions: These data suggest that MT has synergy with MSCs to markedly attenuate CAV and provide a novel therapeutic strategy to improve the long-term allograft acceptance in transplant recipients.


Assuntos
Aorta/transplante , Rejeição de Enxerto/imunologia , Melatonina/farmacologia , Transplante de Células-Tronco Mesenquimais/métodos , Linfócitos T/imunologia , Aloenxertos , Animais , Rejeição de Enxerto/patologia , Transplante de Coração/métodos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
11.
J Med Virol ; 93(5): 2938-2946, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33470428

RESUMO

Evidence in the literature suggests that air pollution exposure affects outcomes of patients with COVID-19. However, the extent of this effect requires further investigation. This study was designed to investigate the relationship between long-term exposure to air pollution and the case fatality rate (CFR) of patients with COVID-19. The data on air quality index (AQI), PM2.5, PM10, SO2 , NO2 , and O3 from 14 major cities in China in the past 5 years (2015-2020) were collected, and the CRF of COVID-19 patients in these cities was calculated. First, we investigated the correlation between CFR and long-term air quality indicators. Second, we examined the air pollutants affecting CFR and evaluated their predictive values. We found a positive correlation between the CFR and AQI (1, 3, and 5 years), PM2.5 (1, 3, and 5 years), and PM10 (1, 3, and 5 years). Further analysis indicated the more significant correlation for both AQI (3 and 5 years) and PM2.5 (1, 3, and 5 years) with CFR, and moderate predictive values for air pollution indicators such as AQI (1, 3, and 5 years) and PM2.5 (1, 3, and 5 years) for CFR. Our results indicate that long-term exposure to severe air pollution is associated with higher CFR of COVID-19 patients. Air pollutants such as PM2.5 may assist with the prediction of CFR for COVID-19 patients.


Assuntos
Poluição do Ar/efeitos adversos , COVID-19/mortalidade , Exposição por Inalação/efeitos adversos , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , China/epidemiologia , Cidades/estatística & dados numéricos , Humanos , Exposição por Inalação/análise , Mortalidade , Valor Preditivo dos Testes , SARS-CoV-2
12.
BMC Urol ; 21(1): 1, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407372

RESUMO

BACKGROUND: Osteochondroma is the most common benign bone neoplasm and is sometimes referred to as osteocartilaginous exostosis. The symptoms caused by osteochondroma are rare, especially the urogenital complications. Therefore, this tumour is sometimes misdiagnosed. CASE PRESENTATION: This report described a 70-year-old woman with hematuria who was initially misdiagnosed with a bladder tumour in the outpatient department by a urologist. However, during cystoscopy, we found that the mass did not resemble a bladder tumor. Multidisciplinary approach with careful analysis of the imaging data suggested the diagnosis of osteochondroma. Open surgical excision of the mass was done and histology confirmed the diagnosis of benign osteochondroma. After 6 months of follow-up, the patient was still asymptomatic. CONCLUSIONS: This case illustrates that hematuria is caused by not only urogenital disease but also osteochondroma. We present this case to draw the attention of clinicians to osteochondroma of the pubic symphysis.


Assuntos
Neoplasias Ósseas/complicações , Hematúria/etiologia , Osteocondroma/complicações , Sínfise Pubiana , Idoso , Feminino , Humanos
13.
J Comp Eff Res ; 9(3): 201-218, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31975614

RESUMO

Aim: To evaluate and compare the short-term outcomes of robotic surgery and laparoscopic approach in distal pancreatectomy (DP). Materials & methods: EMBASE, PubMed, the Cochrane Library, CNKI and Wan Fang database were retrieved from the inception of electronic databases to June 2019. All analyses were performed using Stata/SE 15.1 version (StataCorp). Results: Twenty-two papers were included, four of which were prospective studies and the rest were retrospective studies. There was significant difference in spleen preservation rate (odds ratio: 2.020; 95% CI: 1.085-3.758; p = 0.027), operation time (mean difference [MD]: 27.372; 95% CI: 8.236-47.210; p = 0.000), the length of hospital stay (MD: -0.911; 95% CI: -1.287 to -0.535; p = 0.000), conversion rate (rate difference: -0.090; 95% CI: -1.287 to -0.535; p = 0.000), operation cost (MD: 2816.564; 95% CI: 1782.028-3851.064; p = 0.000). However, no significant difference was detected in estimated blood loss, total complication, severe complication, lymph nodules harvest, blood transfusion rate, total pancreatic fistula, severe pancreatic fistula, R0 resection rate and mortality. Conclusion: Both robotic and laparoscopic DP are safe and feasible. Although robotic DP increases the operation cost, the spleen-preserving rate is much higher. Robotic surgery may be an alternative approach to DP.


Assuntos
Laparoscopia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Transfusão de Sangue , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Pancreatectomia/efeitos adversos , Fístula Pancreática/complicações , Fístula Pancreática/cirurgia , Neoplasias Pancreáticas , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Baço/cirurgia , Resultado do Tratamento
14.
Oxid Med Cell Longev ; 2019: 9192413, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31049140

RESUMO

Oxidative stress induced by long-term glucocorticoid (GC) use weakens the repair capacity of bone tissue. Nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase (NOX) is a superoxide-generating enzyme that plays an important role in regulating bone metabolism. To clarify the role of nonphagocytic NOX isoforms in osteoblast reactive oxygen species (ROS) generation and apoptosis, dexamethasone was used to establish a high-dose GC environment in vitro. A dose-dependent increase in intracellular ROS generation was demonstrated, which was accompanied by increased osteoblastic MC3T3-E1 cell apoptosis. Addition of the ROS inhibitor NAC (N-acetyl-L-cysteine) or NOX inhibitor DPI (diphenyleneiodonium) reversed this effect, indicating that NOX-derived ROS can induce osteoblast apoptosis under high-dose dexamethasone stimulation. NOX1, NOX2, and NOX4 are NOX homologs recently identified in bone tissue. To clarify the NOX isoforms that play a role in osteoblast ROS generation, Nox1, Nox2, and Nox4 mRNA expression and NOX2 and NOX4 protein expression were analyzed. Nox1 and Nox4 mRNA expression was elevated in a dose-dependent manner after culture in 100 nM, 250 nM, 500 nM, or 1000 nM dexamethasone, and the increased expression of NOX1 mRNA was more significant compared with NOX4 mRNA. Small interfering RNAs (siRNAs) were used to confirm the role of NOX1 and NOX4 in ROS generation. To clarify the signaling pathway in ROS-induced osteoblast apoptosis, mitogen-activated protein kinase (MAPK) signaling molecules were analyzed. Phosphorylated ASK1 and p38 levels were significantly higher in the 1000 nM dexamethasone group, which NAC or DPI markedly attenuated. However, the total mRNA and protein levels of ASK1 and p38 between the dexamethasone group and control were not significantly different. This is related to ROS regulating the posttranslational modification of ASK1 and p38 in MC3T3-E1 cell apoptosis. Altogether, NOX1- and NOX4-derived ROS plays a pivotal role in high-dose dexamethasone-induced preosteoblast apoptosis by increasing phosphorylated ASK1 and p38 and may be an important mechanism in steroid-induced avascular necrosis of the femoral head (SANFH).


Assuntos
Apoptose/efeitos dos fármacos , Dexametasona/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Osteoblastos/enzimologia , Animais , Linhagem Celular , Dexametasona/efeitos adversos , Isoenzimas/metabolismo , MAP Quinase Quinase Quinase 5/metabolismo , Camundongos , NADP/metabolismo , Osteoblastos/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
J Comp Eff Res ; 7(12): 1181-1193, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30484699

RESUMO

AIM: A meta-analysis concentrated on the effect of intramedullary and extramedullary systems on total knee arthroplasty. METHOD: Potential academic articles were identified from Cochrane Library, Medline, PubMed, Embase, ScienceDirect, CNKI, WanFang, VIP and other databases. The STATA version was used to analyze the pooled data. RESULTS: There are obvious significant differences in drainage volume and transfusion rate. There was no significant difference in lower limb coronal alignment, coronal and sagittal alignment of the femoral component, operation time, postoperative knee score and complications. CONCLUSION: Our meta-analysis shows that the alignment of the extramedullary distal femur osteotomy is as accurate as intramedullary systems. Furthermore, extramedullary distal femur osteotomy without invading the femoral medullary cavity could reduce postoperative bleeding and the transfusion rate. Furthermore, research is required to test the robustness of our findings when more data is available and by undertaking both Bayesian and frequentist methods. When more data are available, the heterogeneity can be further explored through sensitivity analysis, and the available data can be combined to verify the hypothesis.


Assuntos
Artroplastia do Joelho/instrumentação , Artroplastia do Joelho/métodos , Teorema de Bayes , Pesquisa Comparativa da Efetividade/métodos , Humanos
16.
Drug Des Devel Ther ; 12: 2277-2284, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30087552

RESUMO

PURPOSE: We performed a meta-analysis to systematically assess the effect of adjunctive administration of dexamethasone with antibiotic therapy in the clinical course of septic arthritis (SA) in children. METHOD: Potential academic articles were identified from the Cochrane Library, Medline, PubMed, Embase, ScienceDirect, and other databases. The time range we retrieved from was from the inception of electronic databases to January 2018. The reference lists of identified studies were manually checked to identify other potentially eligible trials. The STATA version 11.0 (Stata Corporation, College Station, TX, USA) was used to analyze the pooled data. RESULTS: Three randomized controlled trials, and one retrospective cohort study were included in the meta-analysis. There were significant differences in the days of hospitalization (mean difference [MD] = -4.226, 95% CI: -4.785 to -3.667, P=0.001), the days of intravenous antibiotics treatment (MD = -3.593, 95% CI: -4.825 to -2.361, P=0.001), the days of oral antibiotics treatment (MD = -1.658, 95% CI: -2.539 to -0.777, P=0.001), and the days to normalization of C-reactive protein (MD = -3.075, 95% CI: -3.362 to -2.788, P=0.001). CONCLUSION: The present meta-analysis base points strongly toward a beneficial effect for corticosteroids in SA. Corticosteroids as adjunctive therapy with antibiotics in the treatment of children with SA could shorten the number of days of hospitalization, the days of intravenous antibiotics treatment, the days of oral antibiotics treatment, and the days to normalization of C-reactive protein. We recommend corticosteroids as adjunctive therapy with antibiotics in the treatment of children with SA.


Assuntos
Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Artrite Infecciosa/tratamento farmacológico , Administração Oral , Corticosteroides/administração & dosagem , Antibacterianos/administração & dosagem , Criança , Estudos de Coortes , Terapia Combinada , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos
17.
J Orthop Surg Res ; 13(1): 186, 2018 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-30049276

RESUMO

BACKGROUND: To investigate the incidence and related risk factors of delirium in elderly patients with hip fracture. METHODS: This is a retrospective study, performed in a medical center from October 2014 to February 2017, which enrolled all subjects aged over 65 years who were admitted for hip surgeries (hip arthroplasty, proximal femoral nail fixation). Univariate and multivariate logistic analysis was used to determine the incidence and risk factors of delirium. Delirium was assessed according to the Confusion Assessment Method (CAM). RESULTS: Overall, 19.29% of total 306 patients (mean age 81.9 ± 5.4 years) were identified as delirium. The delirium was significantly associated (p < 0.05) with the factors of age, hospitalization, diabetes, preoperative hematocrit (HCT), perioperative protein consumption, transfusion volume, preoperative leukocyte level, albumin level, American Society of Anesthesiologists (NYHA) classification, American Society of Anesthesiologists (ASA) classification, blood loss, coronary heart disease, and cerebral infarction. Multivariate analysis of the variables confirmed that age (> 75 years old), diabetes, and ASA classification (> 2 level) are the independent risk factors of postoperative delirium (POD). In addition, patients in delirium had prolonged hospitalization and high perioperative albumin infusion. CONCLUSION: The elderly patients over the age of 75 years with the history of diabetes or ASA classification > 2 level were at higher risk of POD. Delirium is an important postoperative complication, which had prolonged hospitalization and high perioperative albumin infusion. LEVEL OF EVIDENCE: III.


Assuntos
Delírio , Fraturas do Quadril , Complicações Pós-Operatórias , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Quadril/complicações , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de Risco
18.
Medicine (Baltimore) ; 96(34): e7736, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28834878

RESUMO

Open reduction and internal fixation with Kirschner (K) wires has been reported as an efficient and convenient technique for pediatric lateral condyle distal humeral fractures. However, no single study has been large enough to definitively determine whether the K-wires should be buried or unburied. Therefore, we performed a meta-analysis pooling the results from several clinical trials to compare the outcome of using buried versus unburied K-wires. Potential academic articles were identified from the Cochrane Library, Medline (1966-2017.3), PubMed (1966-2017.3), Embase (1980-2017.3), ScienceDirect (1985-2017.3), and other databases. Gray studies were identified from the references of included literature reports. RevMan 5.1 was used to analyze the pooling of data. Nonrandomized controlled trials were included in this meta-analysis. There was a significant difference in the duration of wires in situ (MD = -13.28, 95% confidence interval: -16.42 to -10.14, P < .00001). No significant differences were found regarding infection, superficial infection, total complications, delayed union, or reoperation. Unburied K-wire fixation for treatment of lateral condyle distal humeral fractures in children does not increase the total infection rate, superficial infection, reoperation rate, or complications. However, unburied K-wire fixation is of benefit for early extraction and impartial cost savings.


Assuntos
Fios Ortopédicos , Fixação Interna de Fraturas/métodos , Fraturas do Úmero/cirurgia , Redução Aberta/métodos , Criança , Humanos , Complicações Pós-Operatórias/epidemiologia
19.
Lipids Health Dis ; 12: 180, 2013 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-24314261

RESUMO

BACKGROUND: Both L-4F, one apolipoprotein A-1 mimetic peptide, and statins can reduce progression of atherosclerosis by different mechanisms. The combination of the two drugs can cause lesion regression by rendering HDL anti-inflammatory. We postulated that combination of L-4F and simvastatin may stimulate cholesterol efflux and related proteins expressions to alleviate atherosclerosis. METHODS: Thirty male wild-type (W-T) C57 BL/6 mice and apo E(-/-) mice were divided into five groups: W-T group, atherosclerosis (AS) group, simvastatin group, L-4F group and the combination of simvastatin and L-4F group. After 16 weeks, serum lipids, atherosclerotic lesion areas, cholesterol efflux and the expressions of related proteins including ABCA1, SR-BI, ABCG1, LXRα and PPARγ were evaluated. RESULTS: The aortic atherosclerotic lesion areas were reduced more significantly by combination of both drugs than single agent, and cholesterol efflux was promoted more in combination group than simvastatin and L-4F group. Besides, the combination group promoted expressions of cholesterol efflux related proteins. CONCLUSIONS: The combination of L-4F and simvastatin reduced atherosclerotic lesions, which stimulates cholesterol efflux by promoting the expressions of related proteins. In addition, these results help us further understand that the regression of the atherosclerosis would be assessed by reduction in LDL-C with increase of cholesterol efflux.


Assuntos
Aterosclerose/tratamento farmacológico , Colesterol/metabolismo , Expressão Gênica/efeitos dos fármacos , Hipolipemiantes/farmacologia , Peptídeos/farmacologia , Placa Aterosclerótica/tratamento farmacológico , Sinvastatina/farmacologia , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Apolipoproteína A-I/química , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Transporte Biológico/efeitos dos fármacos , LDL-Colesterol/sangue , Quimioterapia Combinada , Lipoproteínas/genética , Lipoproteínas/metabolismo , Receptores X do Fígado , Masculino , Camundongos , Camundongos Knockout , Mimetismo Molecular , Receptores Nucleares Órfãos/genética , Receptores Nucleares Órfãos/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Placa Aterosclerótica/genética , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Receptores Depuradores Classe B/genética , Receptores Depuradores Classe B/metabolismo
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