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1.
Ecotoxicol Environ Saf ; 273: 116142, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38394757

RESUMO

BACKGROUND: The relationship between brominated flame retardants (BFRs) exposure and the human liver was still not well understood. METHODS: A total of 3108 participants (age > 12) from the National Health and Nutrition Examination Survey (NHANES) database spanning from 2005 to 2016 were included as the study population, with nine BFRs exhibiting a detection rate of over 70% serving as the exposure factor. The singular effects and combined effects of BFRs exposure on liver injury, non-alcoholic fatty liver disease (NAFLD), and advanced hepatic fibrosis (AHF) were evaluated separately. Finally, COX regression was employed to explore the hazard ratios associated with individual BFRs. RESULTS: In our analysis of individual exposures, we found significant positive association of PBB153 with alanine aminotransferase (ALT), PBB153 with aspartate aminotransferase (AST), PBDE47, PBDE85, PBDE99, PBDE100, and PBDE154 with alkaline phosphatase (ALP), PBDE28 and PBB153 with gamma-glutamyl transaminase (GGT), PBB153 with the risk of NAFLD and AHF; and significant negative association of PBB153 with ALP, PBDE28, PBDE47, PBDE99, PBDE100, PBDE85, PBDE209, and PBDE154 with albumin (ALB), PBB153 with AST/ALT. The nonlinear analysis results from Restricted Cubic Spline (RCS) further validated these associations (all P<0.05). In the mixed analysis combining Weighted Quantile Sum (WQS) regression and Quantile G-computation (QGC) analysis, BFRs were positively associated with ALT (ß>0, P<0.001), GGT (ß>0, P<0.001), and the risk of NAFLD (OR>1, P=0.007). Conversely, BFRs exhibited significant negative correlations with ALP (ß<0, P<0.001), ALB (ß<0, P<0.001), and AST/ALT (ß<0, P<0.001). Furthermore, the COX regression analysis revealed that PBB153 had the highest hazard ratio among the BFRs. CONCLUSIONS: BFR exposure may increase the risk of liver injury and NAFLD, with no significant association with AHF risk. The impact of BFR exposure on liver health should not be overlooked, especially in individuals residing in impoverished areas.


Assuntos
Retardadores de Chama , Hepatopatia Gordurosa não Alcoólica , Bifenil Polibromatos , Humanos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Retardadores de Chama/toxicidade , Retardadores de Chama/análise , Inquéritos Nutricionais , Fígado , Fosfatase Alcalina , Alanina Transaminase , Cirrose Hepática
2.
Mediators Inflamm ; 2023: 9335166, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36879557

RESUMO

Ischemic stroke is a kind of central nervous disease characterized by high morbidity, high mortality, and high disability. Inflammation and autophagy play important roles in cerebral ischemia/reperfusion (CI/R) injury. The present study characterizes the effects of TLR4 activation on inflammation and autophagy in CI/R injury. An in vivo CI/R rat injury model and an in vitro hypoxia/reoxygenation (H/R) SH-SY5Y cell model were established. Brain infarction size, neurological function, cell apoptosis, inflammatory mediators' levels, and gene expression were measured. Infarction, neurological dysfunction, and neural cell apoptosis were induced in CI/R rats or in H/R-induced cells. The expression levels of NLRP3, TLR4, LC3, TNF-α, interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-18 (IL-18) clearly increased in I/R rats or in H/R-induced cells, while TLR4 knockdown significantly suppressed NLRP3, TLR4, LC3, TNF-α, and interleukin-1/6/18 (IL-1/6/18) in H/R-induced cells, as well as cell apoptosis. These data indicate that TLR4 upregulation induced CI/R injury via stimulating NLRP3 inflammasome and autophagy. Therefore, TLR4, is a potential therapeutic target to improve management of ischemic stroke.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Neuroblastoma , Traumatismo por Reperfusão , Humanos , Animais , Ratos , Fator de Necrose Tumoral alfa , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Receptor 4 Toll-Like , Autofagia , Inflamação , Interleucina-1 , Interleucina-6
3.
Biomed Eng Online ; 21(1): 49, 2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35870978

RESUMO

Ocular diseases are closely related to the physiological changes in the eye sphere and its contents. Using biomechanical methods to explore the relationship between the structure and function of ocular tissue is beneficial to reveal the pathological processes. Studying the pathogenesis of various ocular diseases will be helpful for the diagnosis and treatment of ocular diseases. We provide a critical review of recent biomechanical analysis of ocular diseases including glaucoma, high myopia, and diabetes. And try to summarize the research about the biomechanical changes in ocular tissues (e.g., optic nerve head, sclera, cornea, etc.) associated with those diseases. The methods of ocular biomechanics research in vitro in recent years are also reviewed, including the measurement of biomechanics by ophthalmic equipment, finite element modeling, and biomechanical analysis methods. And the preparation and application of microfluidic eye chips that emerged in recent years were summarized. It provides new inspiration and opportunity for the pathogenesis of eye diseases and personalized and precise treatment.


Assuntos
Glaucoma , Disco Óptico , Fenômenos Biomecânicos , Córnea/fisiologia , Análise de Elementos Finitos , Humanos , Pressão Intraocular , Esclera
4.
BMC Cardiovasc Disord ; 21(1): 604, 2021 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-34922443

RESUMO

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) and del Nido (DN) cardioplegia are intracellular-type and extracellular-type solution respectively, both can provide a long period of myocardial protection with single-dose infusion, but studies comparing the two are rare for adult cardiac surgery. This study aims to evaluate whether DN is suitable for cardioplegia in complex and high-risk valve surgery with long-term cardiac ischemia when compared with HTK. METHODS: The perioperative records of adult patients infused with DN/HTK as a cardioplegic solution who underwent complex valve surgery with an expected myocardial ischaemic duration longer than 90 min between Oct 2018 and Oct 2019 were analysed retrospectively. RESULTS: Of the 160 patients who received DN/HTK and underwent complex valve surgery, we propensity matched 73 pairs. Both groups achieved satisfactory cardiac arrest effects, and no significant difference was found in their cTnI and CK-MB levels within 12 to 72 h postoperatively. The DN group had a higher rate of return to spontaneous rhythm (0.88 v 0.52, P < 0.001), a lower frequency of postoperative severe arrythmias (12% v 26%, P = 0.036), a higher postoperative stroke volume (65 v 59 ml, P = 0.011) and a higher cardiac output (6.0 v 4.9 L/min, P = 0.007) as evaluated by echocardiography, fewer transfusions and shorter ICU stays (both P < 0.05). The two groups had similar inotrope usage and similar incidences of low cardiac output, morbidities and mortality. Subgroup analysis showed that when the aortic clamping time was greater than 120 min, the advantages of DN were weakened. CONCLUSIONS: DN can be safely applied to complex valve surgery, and it has a similar myocardial protection effect as HTK. Further prospective studies are required to verify these retrospective findings. Trial registration retrospectively registered.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Eletrólitos/administração & dosagem , Parada Cardíaca Induzida , Doenças das Valvas Cardíacas/cirurgia , Valvas Cardíacas/cirurgia , Lidocaína/administração & dosagem , Sulfato de Magnésio/administração & dosagem , Manitol/administração & dosagem , Cloreto de Potássio/administração & dosagem , Bicarbonato de Sódio/administração & dosagem , Soluções/administração & dosagem , Adolescente , Adulto , Idoso , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Eletrólitos/efeitos adversos , Feminino , Glucose/administração & dosagem , Glucose/efeitos adversos , Parada Cardíaca Induzida/efeitos adversos , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/fisiopatologia , Valvas Cardíacas/diagnóstico por imagem , Valvas Cardíacas/fisiopatologia , Humanos , Lidocaína/efeitos adversos , Sulfato de Magnésio/efeitos adversos , Masculino , Manitol/efeitos adversos , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Cloreto de Potássio/efeitos adversos , Procaína/administração & dosagem , Procaína/efeitos adversos , Recuperação de Função Fisiológica , Estudos Retrospectivos , Bicarbonato de Sódio/efeitos adversos , Soluções/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
5.
Cell Physiol Biochem ; 46(5): 2103-2113, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29723859

RESUMO

BACKGROUND/AIMS: Ischemic stroke is still one of the leading debilitating diseases with high morbidity and mortality. NADPH oxidase (NOX)-derived reactive oxygen species (ROS) play an important role in cerebral ischemia/reperfusion (I/R) injury. However, the mechanism underlying the regulation of ROS generation is still not fully elucidated. This study aims to explore the role of transforming growth beta (TGF-ß) signals in ROS generation. METHODS: Sprague-Dawley rats were subjected to I/R injury, and PC-12 cells were challenged by hypoxia/reoxygenation (H/R) and/or treated with activin receptor-like kinase (ALK5) inhibitor Sb505124 or siRNA against ALK5. Brain damage was evaluated using neurological scoring, triphenyl tetrazolium chloride staining, hematoxylin and eosin staining, infarct volume measurement, TUNEL staining, and caspase-3 activity measurement. Expression of TGF-ß and oxidative stress-related genes was analyzed by real-time polymerase chain reaction and Western blot; NOX activity and ROS level were measured using spectrophotometry and fluorescence microscopy, respectively. RESULTS: I/R contributed to severe brain damage (impaired neurological function, brain infarction, tissue edema, apoptosis), TGF-ß signaling activation (upregulation of ALK5, phosphorylation of SMAD2/3) and oxidative stress (upregulation of NOX2/4, rapid release of ROS [oxidative burst]). However, Sb505124 significantly reversed these alterations and protected rats against I/R injury. As in the animal results, H/R also contributed to TGF-ß signaling activation and oxidative stress. Likewise, the inhibition of ALK5 or ALK5 knockdown significantly reversed these alterations in PC-12 cells. Other than ALK5 knockdown, ALK5 inhibition had no effect on the expression of ALK5 in PC-12 cells. CONCLUSIONS: Our studies demonstrated that TGF-ß signaling activation is involved in the regulation of NOX2/NOX4 expression and exacerbates cerebral I/R injury.


Assuntos
Isquemia Encefálica/genética , NADPH Oxidase 2/genética , NADPH Oxidase 4/genética , Estresse Oxidativo , Traumatismo por Reperfusão/genética , Regulação para Cima , Animais , Benzodioxóis/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Imidazóis/uso terapêutico , Masculino , NADPH Oxidase 2/metabolismo , NADPH Oxidase 4/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Piridinas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo
6.
Pancreatology ; 18(8): 935-944, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30316690

RESUMO

The transient receptor potential TRPM8 ion channel is required for cellular proliferation in pancreatic epithelia and adenocarcinoma. To elucidate the mechanism that mediates the function of TRPM8, we examined its role in the proliferation and invasion of pancreatic cancer (PC) cells. TRPM8 expression increased in both the PC tissues and cell lines; a high TRPM8 expression was correlated with poorer prognosis in patients with PC. In PC cell lines, PACN-1 and BxPC-3, Ca2+ influxes could be evoked by TRPM8; the sensitivity of PC cells to gemcitabine was increased, while the proliferation and invasion of PC cells were suppressed after RNA interference-mediated silencing of TRPM8. The mechanism of TRPM8 in gemcitabine-based chemotherapy was then investigated. The expression and activity of multidrug resistance-associated proteins, P-gp, MRP-2, LRP, was significantly reduced in response to TRPM8 silence. Moreover, TRPM8 knockdown significantly increased hENT1 protein levels and the ratio of Bax/Bcl-2 while decreased the protein levels of RRM1. Thus, TRPM8 is required for PC cell proliferation and invasion and was closely related to the gemcitabine sensitivity of PC. The modulation of TRPM8 expression may help improve treatment response of PC by combining with traditional chemotherapy.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Inativação Gênica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Canais de Cátion TRPM/genética , Adulto , Idoso , Cálcio/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Terapia Combinada , Desoxicitidina/uso terapêutico , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 2 Associada à Farmacorresistência Múltipla , Invasividade Neoplásica , Neoplasias Pancreáticas/patologia , Prognóstico , RNA Interferente Pequeno/uso terapêutico , Canais de Cátion TRPM/antagonistas & inibidores , Gencitabina
7.
Ren Fail ; 40(1): 611-617, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30396300

RESUMO

OBJECTIVE: The association between poor intraoperative glycemic control and postoperative acute kidney injury (AKI) in adult cardiac surgery has been observed, but data in the pediatrics remain unknown. We performed a hypothesis that intraoperative hyperglycemia and/or wider glycemic fluctuation were associated with the incidence of postoperative AKI in pediatric cardiac surgery. METHODS: A retrospective study was performed in pediatrics who underwent cardiac surgery from 2013 to 2016. Perioperative glycemic data up to 48 hours after surgery were collected and analyzed. Patients with AKI were matched 1:1 with patients without AKI by a propensity score. Variables of demographic data, preoperative renal function and glycemic level, perioperative cardiac condition were matched. RESULTS: The incidence of AKI was 11.5% (118/1026), with 53.4% (63/118), 30.5% (36/118), and 16.1% (19/118) categorized as AKIN stages I, II, and III, respectively. Children who experienced AKI were younger and cyanotic, underwent more complex surgeries, had higher peak intraoperative glucose levels, wider intraoperative glycemic fluctuation, greater inotropic scores and more transfusions, and poor outcomes (all p < .05). After matching, the AKI group had significantly wider intraoperative glycemic fluctuation (p < .05). Logistic regression showed intraoperative glycemic fluctuation was one of the risk factors for AKI (p = .033) and degree of AKI severity stage increased when the glycemic fluctuation increased (p < .01). CONCLUSIONS: Wider intraoperative glycemic fluctuation, but not hyperglycemia, was associated with an increased incidence of postoperative AKI after pediatric cardiac surgery.


Assuntos
Injúria Renal Aguda/epidemiologia , Glicemia/análise , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Injúria Renal Aguda/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Modelos Logísticos , Masculino , Monitorização Intraoperatória , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença
8.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 43(9): 1007-1013, 2018 Sep 28.
Artigo em Zh | MEDLINE | ID: mdl-30333293

RESUMO

OBJECTIVE: To investigate the incidence of postoperative abnormal liver function test (aLFT) for the children with heart surgery, and to analyze the clinical characteristics and risk factors.
 Methods: A total of 143 children younger than 18 years old who underwent heart surgery in 2017 were enrolled in this study. The liver function were examined one day preoperation and consecutive 5 days after operation. The clinical data of perioperative period were recorded and the risk factors for aLFT were analyzed.
 Results: There were 43/143 (30%) cases had aLFT, including 5/143 (3.5%) acute liver injury (ALI). In the 6 liver function tests, total bilirubin, and glutamic-oxalacetic aminotransferase and glutamic-pyruvic aminotransferase increased to the peak at the first day and the second day after operation, respectively, and albumin declined to the lowest level at the fourth day after operation. aLFT happened most common at the first day after operation(22/43, 51.2%). The patients in the aLFT(+) group had smaller body size, more proportion of the risk adjustment for congenital heart sugery-1 (RACHS-1) score ≥ 3 and cyanosis, longer cardiopulmonary bypass (CPB) time, higher postoperative cardiac troponin (cTnI) value, higher inotropic score (IS), more transfusion, and longer mechanical ventilation time than those in the aLFT(-) group. The aLFT(+) group had longer ICU and hospital time, higher morbidity and mortality than those in the aLFT(-) group (P<0.05). Logistic regression showed that RACHS-1≥3, cyanosis, CPB time, cTnI, IS, transfusion, and mechanical ventilation time were the risk factors for aLFT. Multiple factor analysis showed the mechanical ventilation time was an independent risk factor for aLFT (P<0.05).
 Conclusion: aLFT is common in children after congenital heart operation, which could deteriorate to poor outcome. The mechanical ventilation time is an independent risk factor for aLFT.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas , Fígado , Complicações Pós-Operatórias , Adolescente , Criança , Pré-Escolar , Cardiopatias Congênitas/cirurgia , Humanos , Fígado/lesões , Fígado/patologia , Modelos Logísticos , Respiração Artificial , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
9.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(6): 475-480, 2018 Jun.
Artigo em Zh | MEDLINE | ID: mdl-29972122

RESUMO

OBJECTIVE: To study whether hypoalbuminemia after pediatric cardiopulmonary bypass (CPB) for cardiac surgery is a risk factor for postoperative acute kidney injury (AKI). METHODS: A retrospective analysis was performed on the clinical data of 1 110 children who underwent CPB surgery between 2012 and 2016. According to the minimum serum albumin within 48 hours postoperatively, these patients were divided into hypoalbuminemia group (≤35 g/L) and normal albumin group (>35 g/L). The two groups were compared in terms of perioperative data and the incidence of AKI. Furthermore, the incidence of AKI was compared again after propensity score matching for the unbalanced factors during the perioperative period. The perioperative risk factors for postoperative AKI were analyzed by logistic regression. RESULTS: The overall incidence rate of postoperative AKI was 13.78% (153/1 110), and the mortality rate was 2.52% (28/1 110). The mortality rate of children with AKI was 13.1% (20/153). The patients with hypoalbuminemia after surgery (≤35 g/L) accounted for 44.50% (494/1 110). Before and after propensity score matching, the hypoalbuminemia group had a significantly higher incidence of AKI than the normal albumin group (P<0.05). The children with AKI had a significantly lower serum albumin level after surgery than those without AKI (P<0.05). The multivariate logistic regression analysis showed albumin ≤35 g/L was one of the independent risk factors for postoperative AKI. CONCLUSIONS: Albumin ≤35 g/L within 48 hours postoperatively is an independent risk factor for postoperative AKI in children after CPB surgery.


Assuntos
Injúria Renal Aguda/etiologia , Ponte Cardiopulmonar/efeitos adversos , Cardiopatias/cirurgia , Hipoalbuminemia/etiologia , Complicações Pós-Operatórias/etiologia , Injúria Renal Aguda/epidemiologia , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Hipoalbuminemia/epidemiologia , Lactente , Recém-Nascido , Masculino , Período Perioperatório , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(11): 1196-1201, 2017 Nov.
Artigo em Zh | MEDLINE | ID: mdl-29132469

RESUMO

OBJECTIVE: To analyze the perioperative clinical data of children with congenital heart disease complicated by acute kidney injury (AKI) after cardiopulmonary bypass (CPB) surgery, and to explore potential factors influencing the prognosis. METHODS: A retrospective analysis was performed among 118 children with congenital heart disease who developed AKI within 48 hours after CPB surgery. RESULTS: In the 118 patients, 18 died after 48 hours of surgery. Compared with the survivors, the dead children had significantly higher incidence of cyanotic disease and Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) scores before surgery; during surgery, the dead children had significantly longer CPB time and aortic cross-clamping time, a significantly higher proportion of patients receiving crystalloid solution for myocardial protection, and a significantly higher mean blood glucose level. Within 48 hours after surgery, the dead children had significantly higher positive inotropic drug scores, significantly higher creatinine values, a significantly higher incidence of stage 3 AKI, a significantly higher proportion of patients receiving renal replacement the, and significantly higher usage of blood products (P<0.05). The mortality rate of the patients increased with increased intraoperative blood glucose levels (P<0.05). Patients with intraoperative blood glucose levels >8.3 mmol/L had a significantly lower postoperative cumulative survival rate and a significantly shorter mean survival time than those with blood glucose levels ≤ 8.3 mmol/L (P<0.05). CONCLUSIONS: Intraoperative blood glucose levels are associated with the prognosis in children with congenital heart disease complicated by AKI after CPB surgery. Maintaining good intraoperative blood glucose control can improve the prognosis of the children.


Assuntos
Injúria Renal Aguda/etiologia , Cardiopatias Congênitas/cirurgia , Complicações Pós-Operatórias/etiologia , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Ponte Cardiopulmonar , Pré-Escolar , Feminino , Cardiopatias Congênitas/mortalidade , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos
11.
J Card Surg ; 30(4): 338-45, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25652312

RESUMO

BACKGROUND: Magnesium is often used to supplement cardioplegic solutions during cardiopulmonary bypass due to its cardioprotective effect during ischemia and reperfusion. The aim of this meta-analysis was to evaluate the effects of magnesium-supplemented cardioplegia versus an inactive (placebo) control cardioplegia on reducing cardiac injury after cardiac arrest surgery, as found by randomized, controlled trials. METHODS: The Medline, Cochrane Library, and Chinese literature databases (CJFD, CBM, CSJD, Wanfang) were comprehensively searched for reports of randomized, controlled trials (RCTs) evaluating magnesium-supplemented cardioplegic solutions. The clinical parameters and outcomes of interest were the incidence of postoperative low cardiac output, auto-rebeating rate, ICU stay length, new onset postoperative atrial fibrillation, peak value of CK-MB (and/or cTnI), incidence of myocardial infarction, and in-hospital mortality. RESULTS: Ten trials, with a total of 1214 patients, were included. The frequency of low cardiac output, inotropic utilization, and myocardial infarction, as well as auto-rebeating rate, length of ICU stay and in-hospital mortality, were similar between the two groups. There was a marginal reduction in the incidence of new-onset postoperative atrial fibrillation in the magnesium-supplemented cardioplegia group. CONCLUSIONS: The advantage of magnesium-supplemented cardioplegia, compared with cardioplegia without magnesium, remains unconvincing based on the current evidence. The decision to add magnesium to the cardioplegic solution to a patient undergoing cardiac arrest surgery should be carefully considered.


Assuntos
Cardiotônicos , Bases de Dados Bibliográficas , Magnésio/administração & dosagem , Magnésio/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/prevenção & controle , Baixo Débito Cardíaco/epidemiologia , Baixo Débito Cardíaco/prevenção & controle , Soluções Cardioplégicas , Ponte Cardiopulmonar , Mortalidade Hospitalar , Humanos , Incidência , Tempo de Internação , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle
12.
BMC Genom Data ; 24(1): 59, 2023 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-37814219

RESUMO

BACKGROUND: Previous research has already indicated an elevated risk of breast cancer (BC) among survivors of malignant lymphoma, but the underlying reasons remain unknown. Our objective is to elucidate the causal relationship between malignant lymphoma and BC through Mendelian randomization (MR). Genome-wide association studies (GWAS) data from 181,125 Hodgkin lymphoma (HL) patients and 181,289 non-Hodgkin lymphoma (NHL) patients from the FinnGen Consortium were utilized as exposure. We selected single nucleotide polymorphisms (SNPs) strongly associated with the exposure as instrumental variables to investigate their relationship with BC in a cohort of 107,722 participants. Subsequently, we obtained data from the UK Biobank containing gender-stratified information on HL, NHL, and BC. We validated the findings from our analysis and explored the impact of gender. The Inverse-Variance Weighted (IVW) method served as the primary reference for the two-sample MR, accompanied by tests for heterogeneity and pleiotropy. RESULTS: The analysis results from the FinnGen consortium indicate that there is no causal relationship between HL and NHL with BC. HL (OR = 1.01, 95% CI = 0.98-1.04, p = 0.29), NHL (OR = 1.01, 95% CI = 0.96-1.05, p = 0.64). When utilizing GWAS data from the UK Biobank that includes different gender cohorts, the lack of association between HL, NHL, and BC remains consistent. HL (OR = 1.08, 95% CI = 0.74-1.56, p = 0.69), HL-Female (OR = 0.84, 95% CI = 0.59-1.19, p = 0.33), NHL (OR = 0.89, 95% CI = 0.66-1.19, p = 0.44), and NHL-Female (OR = 0.81, 95% CI = 0.58-1.11, p = 0.18). CONCLUSIONS: The two-sample MR analysis indicates that there is no significant causal relationship between malignant lymphoma (HL and NHL) and BC. The association between malignant lymphoma and breast cancer requires further in-depth research and exploration.


Assuntos
Neoplasias da Mama , Doença de Hodgkin , Linfoma não Hodgkin , Linfoma , Humanos , Feminino , Análise da Randomização Mendeliana , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Correlação de Dados , Estudo de Associação Genômica Ampla , Linfoma/epidemiologia , Linfoma/genética , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/genética
13.
Front Endocrinol (Lausanne) ; 14: 1256132, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38116315

RESUMO

Background: Breast cancer (BC) poses a serious threat to human health. Disulfidptosis is a recently discovered form of cell death associated with cancer prognosis and progression. However, the relationship between BC and disulfidptosis remains unclear. Methods: We integrated single-cell sequencing and transcriptome sequencing in BC to assess the abundance and mutation status of disulfidptosis-associated genes (DAGs). Subsequently, we clustered the samples based on DAGs and constructed a prognostic model associated with disulfidptosis. Additionally, we performed pathway enrichment, immune response, and drug sensitivity analyses on the model. Finally, we validated the prognostic genes through Immunohistochemistry (IHC). Results: The single-cell analysis identified 21 cell clusters and 8 cell types. By evaluating the abundance of DAGs in different cell types, we found specific expression of the disulfidoptosis core gene SLC7A11 in mesenchymal stem cells (MSCs). Through unsupervised clustering of DAGs, we identified two clusters. Utilizing differentially expressed genes from these clusters, we selected 7 genes (AFF4, SLC7A11, IGKC, IL6ST, LIMD2, MAT2B, and SCAND1) through Cox and Lasso regression to construct a prognostic model. External validation demonstrated good prognostic prediction of our model. BC patients were stratified into two groups based on riskscore, with the high-risk group corresponding to a worse prognosis. Immune response analysis revealed higher TMB and lower TIDE scores in the high-risk group, while the low-risk group exhibited higher CTLA4/PD-1 expression. This suggests that both groups may respond to immunotherapy, necessitating further research to elucidate potential mechanisms. Drug sensitivity analysis indicated that dasatinib, docetaxel, lapatinib, methotrexate, paclitaxel, and sunitinib may have better efficacy in the low-risk group. Finally, Immunohistochemistry (IHC) validated the expression of prognostic genes, demonstrating higher levels in tumor tissue compared to normal tissue. Conclusion: Our study has developed an effective disulfidptosis-related prognostic prediction tool for BC and provides personalized guidance for the clinical management and immunotherapy selection of BC patients.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Medicina de Precisão , Taxa de Sobrevida , Imunoterapia , Docetaxel , Fatores de Elongação da Transcrição
14.
Oxid Med Cell Longev ; 2022: 1296816, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35855866

RESUMO

Ischemic stroke is a common disease that led to high mortality and high disability. NADPH oxidase 2- (NOX2-) mediated oxidative stress and long noncoding RNA have important roles in cerebral ischemia/reperfusion (CI/R) injury, whereas whether there is interplay between them remains to be clarified. This study was performed to observe the role of lncRNA PINK1-antisense RNA (PINK1-AS) in NOX2 expression regulation. An in vivo rat model (MCAO) and an in vitro cell model (H/R: hypoxia/reoxygenation) were utilized for CI/R oxidative stress injury investigation. The expression levels of lncRNA PINK1-AS, activating transcription factor 2 (ATF2), NOX2, and caspase-3 and the production level of ROS and cell apoptosis were significantly increased in CI/R injury model rats or in H/R-induced SH-SY5Y cells, but miR-203 was significantly downregulated. There was positive correlation between PINK1-AS expression level and ROS production level. PINK1-AS and ATF2 were found to be putative targets of miR-203. Knockdown of lncRNA PINK1-AS or ATF2 or the overexpression of miR-203 significantly reduced oxidative stress injury via inhibition of NOX2. Overexpression of lncRNA PINK1 significantly led to oxidative stress injury in SH-SY5Y cells through downregulating miR-203 and upregulating ATF2 and NOX2. lncRNA PINK1-AS and ATF2 were the targets of miR-203, and the lncRNA PINK1-AS/miR-203/ATF2/NOX2 axis plays pivotal roles in CI/R injury. Therefore, lncRNA PINK1-AS is a possible target for CR/I injury therapy by sponging miR-203.


Assuntos
Fator 2 Ativador da Transcrição , Isquemia Encefálica , MicroRNAs , RNA Longo não Codificante , Traumatismo por Reperfusão , Fator 2 Ativador da Transcrição/genética , Fator 2 Ativador da Transcrição/metabolismo , Animais , Apoptose/fisiologia , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Infarto Cerebral/genética , Infarto Cerebral/metabolismo , Infarto Cerebral/patologia , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neuroblastoma/genética , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Estresse Oxidativo/genética , Proteínas Quinases/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo
15.
Front Oncol ; 12: 1066698, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36591447

RESUMO

Gastrointestinal (GI) cancer is a global health problem with wide lesions and numerous cases. The increased morbidity and mortality of GI cancer is a socio-economic challenge for decades to come. Melatonin, a nature indolamine, exerts a crucial role in molecular interactions involved in multiple functional and physiological processes. Increasing evidence indicates that melatonin can modulate GI tract, decrease the occurrence of GI cancer, and enhance the sensitivity to chemoradiotherapy. However, little is known about the exact role of melatonin in anti-carcinogenesis. In this review, we discuss the action of the beneficial effects of melatonin in GI carcinogenesis. Furthermore, we compile the understanding of the role of melatonin in GI cancer, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), colorectal cancer (CRC), and pancreatic cancer (PC). In addition, the potential therapeutic application and clinical evaluation of melatonin in GI cancer are also discussed.

16.
Interact Cardiovasc Thorac Surg ; 31(6): 820-826, 2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-33130854

RESUMO

OBJECTIVES: An autologous platelet-rich plasma pheresis (aPP) strategy can harvest partial whole blood that is separated into erythrocytes, plasma and platelets, and can reduce blood loss and transfusion during cardiovascular surgery using cardiopulmonary bypass (CPB). However, the blood and organ conservation effects of this technique have not been confirmed in the context of complex aortic surgery. METHODS: Perioperative records of 147 adult patients who underwent complex aortic surgery were analysed retrospectively. RESULTS: All patients received regular blood conservation treatment, and 57 patients received aPP. Whether or not the participants were propensity matched, decreased platelet and cryoprecipitate transfusions were found in the aPP group (both P < 0.001), but there were non-significant differences in erythrocyte transfusion, Sequential Organ Failure Assessment scores and other outcomes when compared with the same parameters in the non-aPP group. The aPP group had a higher arterial oxygen partial pressure to inhaled oxygen concentration ratio on postoperative days 1, 2 and 7 than the non-aPP group (P < 0.001, P < 0.001 and P = 0.048, respectively). CONCLUSIONS: The utilization of aPP was associated with a reduction in allogeneic platelet and cryoprecipitate transfusions as well as minor lung-protective effects during complex aortic surgery using CPB.


Assuntos
Doenças da Aorta/cirurgia , Plaquetas , Transfusão de Sangue Autóloga/métodos , Transfusão de Sangue/métodos , Plasmaferese/métodos , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
17.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 34(7): 630-3, 2009 Jul.
Artigo em Zh | MEDLINE | ID: mdl-19648675

RESUMO

OBJECTIVE: To determine the possible mechanism for chronic pancreatitis causing pancreatic duct stones. METHODS: A total of 172 patients with chronic pancreatitis (n=67), pancreatic duct stones (n=62), and pancreatic injury (n=43), admitted to from August 2000 to October 2008, preoperatively diagnosed by endoscopic retrograde cholangiopancreatograpby(ERCP) or computed tomography(CT), and intraoperatively confirmed by exploration and biopsy, were divided into 3 groups. Pancreatic fluid was drawn to test the concentrations of pancreatic stone protein (PSP), lactoferrin (LF) and Ca2+. RESULTS: The chronic pancreatitis (the CP group) presented hard consistency, shrinkage and nodular fibrosis of the pancreas; besides the above symptoms, the pancreatic duct stones (the PS group) presented dilatation of the pancreatic ductal system with various stones; pancreatic injury (the PI group) presented broken pancreas of different grades with fluid or blood. Compared with that of the PI group, PSP concentration of both the PS group and the CP group was elevated (P<0.05), and was more apparent in the CP group. Concentrations of LF and Ca2+ were also elevated (P<0.05), which were more obvious in the PS group. CONCLUSION: Decreased concentrations of PSP and increased concentrations of LF and Ca2+ may play very important roles in chronic pancreatitis causing pancreatic duct stones.


Assuntos
Cálculos/etiologia , Litostatina/metabolismo , Ductos Pancreáticos , Suco Pancreático/metabolismo , Pancreatite Crônica/complicações , Adulto , Idoso , Cálcio/metabolismo , Cálculos/metabolismo , Feminino , Humanos , Lactoferrina/metabolismo , Masculino , Pessoa de Meia-Idade , Pancreatopatias/metabolismo
18.
Int J Clin Exp Pathol ; 12(8): 3089-3095, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31934150

RESUMO

INTRODUCTION: Enteric duplication cysts are rare congenital anomalies. They are lined by gastrointestinal mucosa, connected to the digestive tract, and share smooth muscle layers and a common blood supply. In rare cases, duplication cysts are isolated from the digestive tract and have a unique blood supply. No patient with isolated duplication cysts that are located in the retroperitoneum and associated with an accessory pancreatic lobe at the onset have been reported to date. MATERIALS AND METHODS: A 10-year-old Asian boy complained of left upper abdominal pain for more than 3 months. Contrast-enhanced computed tomography showed that the main pancreatic duct in the tail of the pancreas was dilated. A soft tissue density shadow was observed around the tail of the pancreas. The lesion was connected to the main pancreatic duct and the blood was supplied from a branch of the splenic artery. Surgical exploration and pathologic specimens resulted in the diagnosis of an isolated retroperitoneal enteric duplication cyst associated with an accessory pancreatic lobe. The patient received treatments of rehydration, antibiotics, and protease inhibitors. Due to the poor conservative treatment effect in internal medicine, a surgical resection of abnormal tissue was performed. RESULTS: The boy did not have abdominal pain again in the first year after leaving the hospital. DISCUSSION: For repeated abdominal pain in young people, especially in children, an enteric duplication cyst needs to be ruled out. This case was difficult to diagnose and imaging examination was not able to determine whether it is located in the anterior peritoneum or the retroperitoneum. For such cases, surgical exploration is necessary, and surgical resection can achieve more satisfactory results.

19.
Oncol Lett ; 18(5): 5215-5224, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31612032

RESUMO

Interleukin (IL)-8 and extracellular signal-regulated kinase (ERK) 2 play key roles in tumor progression, but the relationship between IL-8 and/or ERK2 expression in hepatocellular carcinoma (HCC) tissues and postoperative recurrence or survival is unclear. The expression levels of IL-8 and ERK2 in both HCC tissues and non-tumor liver tissues were analyzed using the Oncomine™ database and immunohistochemistry assay. Reverse transcription-quantitative PCR was then used to evaluate the expression levels of IL-8 and ERK2 in the tumor tissues of 67 patients with HCC undergoing radical hepatectomy. Pearson's correlation, Kaplan-Meier, Cox univariate and multivariate survival analyses were utilized to determine the correlation between IL-8 and ERK2 expression in HCC tissues, and their potential prognostic significance. As indicated by the data from the Oncomine™ database, and the patient samples, IL-8 and ERK2 were expressed at significantly higher levels in HCC tissues than in non-tumor liver tissues (P<0.05). The rates of high IL-8 and ERK2 expression in HCC tissues were 43.28 (29/67) and 34.33% (23/67), respectively, and the IL-8 and ERK2 expression levels were positively correlated (r=0.764; P<0.001). Both ERK2 expression and IL-8/ERK2 co-expression were significantly associated with tumor size and differentiation (P<0.05). Additionally, high expression levels of IL-8, ERK2 and IL-8/ERK2 co-expression were all significantly associated with poor overall survival (OS; P<0.05) and disease-free survival (DFS; P<0.05). Multivariate Cox regression analysis also showed that high expression levels of IL-8, ERK2, and IL-8 and ERK2 were independent prognostic factors for OS and DFS (P<0.05). The results of the present study indicate a significant increase in the risk of recurrence and mortality in HCC patients with high expression levels of IL-8 and/or ERK2, compared with patients with low expression. Therefore, IL-8 and ERK2 may be predictors of postoperative prognosis in patients with HCC.

20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 33(7): 642-4, 2008 Jul.
Artigo em Zh | MEDLINE | ID: mdl-18667781

RESUMO

OBJECTIVE: To determine the route and ways of debridement and drainage of infected necrosis for severe acute pancreatitis (SAP) combined with pancreatic infection. METHODS: Clinical data of 28 patients with SAP accompanied with secondary pancreatic infection, who underwent lumbo-retroperitoneal debridement, drainage and lavage after the operation were retrospectively investigated. RESULTS: Four patients underwent one operation, 21 underwent 2 operations, and 3 underwent 3 operations. All patients recovered or improved and were discharged by postoperative lavage. Four patients had complications, including 1 gastrointestinal bleeding,1 intestinal fistula and 2 pancreatic fistula. CONCLUSION: Debridement and drainage of infected necrosis for SAP combined with pancreatic infection via lumbo-retroperitoneal route is direct, safe and effective.


Assuntos
Desbridamento , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Pancreatite Necrosante Aguda/cirurgia , Espaço Retroperitoneal/cirurgia , Adulto , Idoso , Drenagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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