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1.
J Card Fail ; 28(4): 604-613, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35105522

RESUMO

BACKGROUND: This is first-in-man investigation of an implantable Heartech left ventricular partitioning device (LVPD) therapy for chronic heart failure (HF) after a myocardial infarction. METHODS AND RESULTS: Initially, 16 patients were chosen from 3 cardiac centers within China. All patients were treated with percutaneous ventricular restoration involving the Heartech LVPD implantation. Major adverse cardiovascular and cerebrovascular events were documented. Functional status, echocardiograph evaluation, European five-dimensional health scale, 6-minute walk test before the procedure and at postoperative follow-ups were recorded. We demonstrated successful implantation and device function with a success rate of 93.75%. One patient suffered a fatal myocardial infarction within the 12 ± 1 month follow-up. However, other patients did not report any major adverse cardiovascular and cerebrovascular events at their 12 ± 1 month follow-ups. After the operation, the average left ventricular end-systolic volume index decreased dramatically (66.00 mL/m2, interquartile range [IQR] 63.00-89.00 mL/m2 vs 48.00 mL/m2, IQR 32.25-68.25 mL/m2, P = .001), along with the left ventricular end-diastolic volume index (105.00 mL/m2, IQR 90.00-130.00 mL/m2 vs 76.50 mL/m2, IQR 57.75-120.25 mL/m2, P = .002). The left ventricular ejection fraction (35.00%, IQR 27.00-38.00% vs 42.50%, IQR 34.75-50.25%, P = .003), 6-minute walk test (383.13 ± 108.70 m vs 491.17 ± 118.44 m, P = .01), and European five-dimensional health scale (65.93 ± 11.25 vs 82.50 ± 5.44, P < .001), in turn, improved significantly. CONCLUSIONS: In our study, the Heartech LVPD was demonstrated as both safe and effective in reducing LV volume, enhancing LV function after implantation. These results remain constant at least till the 12 month follow-up. (Trial Registration: NCT02938637.).


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/cirurgia , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda , Remodelação Ventricular
2.
Biochem Biophys Res Commun ; 588: 15-22, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34942529

RESUMO

Insulin resistance (IR) attributed by the deficiency of lipophagy, is an abnormal state of downregulation of insulin-mediated glucose uptake and use into the liver. Chromosome 9 open reading frame 72 (C9orf72) variously modulates autophagy. We investigated the role and the downstream pathway of C9orf72 in hepatic IR. We found that C9orf72 knockdown alleviated hepatic IR by lipophagy promotion in T2DM mice and in IR-challenged hepatocytes in vitro. C9orf72 interacted with and activated cell division cycle 42 (Cdc42) protein in IR-challenged hepatocytes, Which in turn, inhibits lipophagy by promoting neural Wiskott-Aldrich syndrome protein (N-WASP) expression and activation. C9orf72 inhibited lipophagy by activating the Cdc42/N-WASP axis to facilitate hepatic IR; therefore, the knockdown of C9orf72 may be potentially therapeutic for the treatment of IR.


Assuntos
Autofagia , Proteína C9orf72/metabolismo , Técnicas de Silenciamento de Genes , Resistência à Insulina , Fígado/metabolismo , Fígado/patologia , Animais , Diabetes Mellitus Tipo 2/patologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Ligação Proteica , Proteína Neuronal da Síndrome de Wiskott-Aldrich/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo
3.
Cardiol J ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34811717

RESUMO

BACKGROUND: Investigating the prognostic value of the Murray law-based quantitative flow ratio (µQFR) on the clinical outcome after treatment of in-stent restenosis (ISR) with a drug-coated balloon (DCB). METHODS: Patients participating in a previous randomized clinical trial for DCB-ISR were post-hoc analyzed. The primary endpoint was vessel-oriented composite endpoint (VOCE), defined as cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization. µQFRs at baseline and after DCB angioplasty was calculated, and its prognostic value as a predictor of VOCE was explored in Cox regression. RESULTS: A total of 169 lesions in 169 patients were analyzed. At one-year follow-up, 20 VOCEs occurred in 20 patients. Receiver-operating characteristic curve analysis identified a post-procedural µQFR of ≤ 0.89 as the best cut-off to predict VOCE (area under curve [AUC]: 0.74; 95% confidence interval [CI]: 0.67-0.80; p < 0.001), superior to post-procedural in-stent percent diameter stenosis (DS), which reported an AUC of 0.61 (95% CI: 0.53-0.68; p = 0.18). Post-procedural µQFR was significantly lower in patients with VOCE compared with those without (0.88 [interquartile range: 0.79-0.94] vs. 0.96 [interquartile range: 0.91-0.98], respectively; p < 0.001). After correction for potential confounders, post-procedural µQFR ≤ 0.89 was associated with a 6-fold higher risk of VOCE than lesions with µQFR > 0.89 (hazard ratio: 5.94; 95% CI: 2.33-15.09; p < 0.001). CONCLUSIONS: Post-procedural µQFR may become a promising predictor of clinical outcome after treatment of DES-ISR lesions by DCB angioplasty.

4.
Am J Transl Res ; 13(10): 11329-11340, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34786061

RESUMO

Myocardial infarction (MI) is one of the leading causes of morbidity and mortality worldwide. The immune response plays a central role in post-MI cardiac repair. A growing body of evidence suggests that oncostatin M (OSM), a pleiomorphic cytokine of the interleukin (IL)-6 family, participates in the cardiac healing and remodeling process. However, previous studies have shown inconsistent results, and the exact mechanisms underlying this process have not yet been fully elucidated. We verified whether OSM is involved in the healing process and cardiac remodeling after MI and sought to explore its potential mechanisms. Our data implied OSM's role in facilitating the post-MI healing process in mice, manifested by improved cardiac functional performance and a reduction in fibrotic changes. Furthermore, our flow cytometry analysis revealed that OSM influences the dynamics of cardiac monocytes and macrophages. In mice with a blunted C-X-C motif receptor (CCR)2 signaling pathway, OSM reserved its protective roles and polarized cardiac macrophages toward a reparative phenotype. Moreover, OSM reduced the number of matrix metalloproteinase (MMP)-9+ immune cells and increased the number of tissue inhibitor of metalloproteinase (TIMP)-1+ immune cells in the infarct area, mitigating the maladaptive remodeling following MI. These findings demonstrate that OSM favorably modulates cardiac remodeling, partially by accelerating the shift in the cardiac macrophage phenotype from M1 to M2 and by correcting the MMP-9 and TIMP-1 balance.

5.
Sci Rep ; 11(1): 7330, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795781

RESUMO

Although the drug-eluting stent (DES) has become the standard for percutaneous coronary intervention (PCI)-based revascularization, concerns remain regarding the use of DES, mainly due to its permanent rigid constraint to vessels. A drug-eluting bioresorbable stent (BRS) was thus developed as an alternative to DES, which can be absorbed entirely after its therapeutic period. Magnesium (Mg)-based BRSs have attracted a great deal of attention due to their suitable mechanical properties, innovative chemical features, and well-proven biocompatibility. However, the primary disadvantage of Mg-based BRSs is the rapid degradation rate, resulting in the early loss of structural support long before the recovery of vascular function. Recently, a new type of patented Mg-Nd-Zn-Zr alloy (JDBM) was developed at Shanghai Jiao Tong University to reduce the degradation rate compared to commercial Mg alloys. In the present investigation, a poly(D,L-lactic acid)-coated and rapamycin eluting (PDLLA/RAPA) JDBM BRS was prepared, and its biosafety and efficacy for coronary artery stenosis were evaluated via in vitro and in vivo experiments. The degree of smooth muscle cell adhesion to the PDLLA/RAPA coated alloy and the rapamycin pharmacokinetics of JDBM BRS were first assessed in vitro. JDBM BRS and commercial DES FIREHAWK were then implanted in the coronary arteries of a porcine model. Neointimal hyperplasia was evaluated at 30, 90, and 180 days, and re-endothelialization was evaluated at 30 days. Furthermore, Micro-CT and optical coherence tomography (OCT) analyses were performed 180 days after stent implantation to evaluate the technical feasibility, biocompatibility, and degradation characteristics of JDBM BRS in vivo. The results show the ability of a PDLLA/RAPA coated JDBM to inhibit smooth muscle cell adhesion and moderate the drug release rate of JDBM BRS in vitro. In vivo, low local and systemic risks of JDBM BRS were demonstrated in the porcine model, with preserved mechanical integrity after 6 months of implantation. We also showed that this novel BRS was associated with a similar efficacy profile compared with standard DES and high anti-restenosis performance. These findings may confer long term advantages for using this BRS over a traditional DES.


Assuntos
Vasos Coronários/efeitos dos fármacos , Vasos Coronários/patologia , Stents Farmacológicos , Magnésio/química , Ligas , Animais , Aorta Torácica/patologia , Adesão Celular , Contenção de Riscos Biológicos , Angiografia Coronária/métodos , Reestenose Coronária , Microscopia Eletrônica de Varredura , Miócitos de Músculo Liso/citologia , Neodímio/química , Segurança do Paciente , Intervenção Coronária Percutânea , Poliésteres/química , Ratos , Sirolimo/farmacologia , Estresse Mecânico , Suínos , Tomografia de Coerência Óptica , Microtomografia por Raio-X , Zinco/química , Zircônio/química
6.
Ren Fail ; 43(1): 307-312, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33538236

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is associated with an increased risk of the progression of coronary artery disease (CAD). However, there are few data on the relationship between CAD severity and the duration of CKD. This study assessed the predictive value of the duration of kidney dysfunction in CKD patients with CAD severity. METHODS: In 145 patients (63.4% male, n = 92; mean age, 68.8 ± 12.8 years) with CKD, severity of CAD was assessed by coronary angiography and quantified by SYNTAX scores, and duration of kidney dysfunction was either assessed by checking historical biochemical parameters of individuals or was based on enquiries. RESULTS: Patients with high SYNTAX scores (≥ 22) had a greater prevalence of cardiovascular risk factors including age, gender, history of heart failure and smoking. In CKD patients, SYNTAX scores were positively correlated to duration of CKD and serum uric acid (UA), and negatively correlated to high-density lipoprotein-cholesterol (HDL-C) and ApoA1 levels. Univariate binary logistic regression and multivariate logistic analyses showed that SYNTAX scores correlated significantly with CKD duration, UA, and HDL-C. Receiver-operating characteristic analysis was used to explore a time point when coronary angiography application was economical and effective and yielded a Youden index of 6.5 years. CONCLUSIONS: Together, our results demonstrated that the duration of kidney dysfunction was an independent correlate of the severity of CAD in patients with CKD. Our findings suggest that coronary angiography should be considered for CKD patients with renal insufficiency having lasted for more than 6.5 years.


Assuntos
Angiografia Coronária/estatística & dados numéricos , Doença da Artéria Coronariana/diagnóstico , Insuficiência Renal Crônica/complicações , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/patologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Progressão da Doença , Feminino , Taxa de Filtração Glomerular/fisiologia , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo
7.
BMC Nephrol ; 22(1): 66, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33622294

RESUMO

BACKGROUND: Sulfation of tyrosine, yielding O-sulfotyrosine, is a common but fixed post-translational modification in eukaryotes. Patients with increased circulating O-sulfotyrosine levels experience a faster decline in renal function with progression to end-stage renal disease (ESRD). In the present study, we measured serum O-sulfotyrosine levels in individuals with chronic kidney disease (CKD) and acute kidney injury (AKI) to explore its ability to differentiate AKI from CKD. METHODS: A total of 135 patients (20 with AKI and 115 with CKD) were recruited prospectively for liquid chromatography-mass spectrometry assessment of circulating O-sulfotyrosine. We also studied C57BL/6 mice with CKD after 5/6 nephrectomy (Nx). Blood samples were drawn from the tail vein on Day 1, 3, 5, 7, 14, 30, 60, and 90 after CKD. Serum separation and characterization of creatinine, blood urea nitrogen (BUN), and O-sulfotyrosine was performed. Thus, the time-concentration curves of the O-sulfotyrosine level demonstrate the variation of kidney dysfunction. RESULTS: The serum levels of O-sulfotyrosine were markedly increased in patients with CKD compared with AKI. Median O-sulfotyrosine levels in CKD patients versus AKI, respectively, were as follows:243.61 ng/mL(interquartile range [IQR] = 171.90-553.86) versus 126.55 ng/mL (IQR = 48.19-185.03, P = 0.004). In patients with CKD, O-sulfotyrosine levels were positively correlated with creatinine, BUN, and Cystatin C (r = 0.63, P < 0.001; r = 0.49, P < 0.001; r = 0.61, P < 0.001, respectively) by the multivariate linear regression analysis (ß = 0.71, P < 0.001; ß = 0.40, P = 0.002; ß = 0.73, P < 0.001, respectively). However, this association was not statistically significant in patients with AKI (r = - 0.17, P = 0.472; r = 0.11, P = 0.655; r = 0.09, P = 0.716, respectively). The receiver operating characteristic (ROC) analysis illustrated that the area under the curve was 0.80 (95% confidence interval [CI] 0.71-0.89; P < 0.001) and the optimal cut-off value of serum O-sulfotyrosine suggesting AKI was < 147.40 ng/mL with a sensitivity and specificity of 80.90 and 70.00% respectively. In animal experiments, serum levels of O-sulfotyrosine in mice were elevated on Day 7 after 5/6 nephrectomy (14.89 ± 1.05 vs. 8.88 ± 2.62 ng/mL, P < 0.001) until Day 90 (32.65 ± 5.59 vs. 8.88 ± 2.62 ng/mL, P < 0.001). CONCLUSION: Serum O-sulfotyrosine levels were observed correlated with degrading renal function and in CKD patients substantially higher than those in AKI patients. Thus serum O-sulfotyrosine facilitated the differential diagnosis of AKI from CKD.


Assuntos
Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Tirosina/análogos & derivados , Idoso , Animais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Tirosina/sangue
8.
Exp Clin Endocrinol Diabetes ; 129(8): 601-610, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32932529

RESUMO

BACKGROUND AND AIMS: Liver expressed antimicrobial peptide 2 (LEAP2) is recently identified as a regulator in energy metabolism. This study aims to 1) investigate the role of leap2 in hepatic steatosis in C57BL/6 mice; 2) evaluate the association between circulating LEAP2 levels and liver fat contents in a hospital based case-control study. METHODS: The rodent experiment: western blotting and qPCR were performed to evaluate leap2 levels, lipid metabolism pathways and insulin signaling. shRNA was used to knockdown leap2. The clinical study: commercial ELISA kits were used to measure circulating LEAP2 levels (validated by western blotting). Liver fat content was estimated using MRI-derived proton density fat fraction and FibroScan-derived controlled attenuation parameter. RESULTS: The rodent experiment found the hepatic expression and secreted levels of leap2 were increased in mice with diet-induced steatosis. Leap2 knockdown ameliorated steatosis via lipolytic/lipogenic pathway and improved insulin sensitivity via IRS/AKT signaling. The clinical study reported increased circulating levels of LEAP2 in the subjects with steatosis. Moreover, LEAP2 correlated positively with age, body mass index, waist-to-hip ratio, liver fat content, fasting insulin and HOMA-IR, whereas inversely with acyl-ghrelin. Furthermore, the circulating levels of LEAP2 are dependent on liver fat content, acyl-ghrelin and fasting glucose. Lastly, circulating LEAP2 is an independent predictor of NAFLD. CONCLUSIONS: The study suggests LEAP2 is associated with hepatic steatosis, which may involve lipolytic/lipogenic pathway and insulin signaling.


Assuntos
Peptídeos Catiônicos Antimicrobianos/sangue , Fígado Gorduroso/metabolismo , Adulto , Animais , Proteínas Sanguíneas , Modelos Animais de Doenças , Fígado Gorduroso/sangue , Fígado Gorduroso/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade
9.
Esophagus ; 18(1): 144-151, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32519226

RESUMO

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder. Proton pump inhibitors (PPIs) are first-line drugs for GERD. For those who fail to respond to PPIs, adding prokinetics to PPIs is recommended and several trials have been conducted to evaluate the efficacy of prokinetic-PPI combination therapy. METHODS: A systematic literature search was performed using PubMed and the Cochrane Library databases before February 2019 for randomized controlled trials (RCTs), which compared the efficacy of prokinetics plus PPI treatment with that of PPI monotherapy. Relevant studies were examined and data were extracted independently by two investigators. The risk ratios (RRs) with 95% CIs were used to evaluate the responder rate, and standard mean differences (SMDs) or mean differences (MDs) with 95% CIs were used for symptom score changes. Statistical heterogeneity was evaluated by the I2 statistic. Either a fixed-effect or a random-effect model was established for calculating the pooled data. RESULTS: A total of 14 studies, comprising 1,437 patients were ultimately included in the meta-analysis. The pooled analysis showed that compared to PPI monotherapy, addition of prokinetics to PPI did not elevate the rate of endoscopic responders (RR = 0.996, 95% CI 0.929 - 1.068, p = 0.917), but improved symptom response (RR = 1.185, 95% CI 1.042 - 1.348, p = 0.010). Additionally, the combined therapy achieved a greater symptom relief than monotherapy both in FSSG and GERD-Q subgroups (MD = - 2.978, 95% CI - 3.319 to - 2.638, p < 0.001; MD = - 0.723, 95% CI - 0.968 to - 0.478, p < 0.001). CONCLUSIONS: Adding prokinetics to PPIs achieves symptomatic improvement compared to PPI monotherapy, thus can enhance life quality of GERD patients. However, the combined treatment seems to have no significant effect on mucosal healing.


Assuntos
Refluxo Gastroesofágico , Inibidores da Bomba de Prótons , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Inibidores da Bomba de Prótons/uso terapêutico , Resultado do Tratamento
10.
Coron Artery Dis ; 32(6): 526-533, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33229940

RESUMO

BACKGROUND: Treatment of coronary in-stent restenosis (ISR) remains challenging in contemporary clinical applications. Drug-coated balloon (DCB) angioplasty offers an effective treatment for ISR. Shenqi is a novel iopromide-based paclitaxel-coated balloon and its clinical safety, effectiveness and angiographic efficacy in patients with ISR have not been investigated. METHODS: A total of 216 subjects with the first occurrence of ISR at 11 investigational sites in China were randomly allocated in a 1:1 fashion to treatment with DCB SeQuent Please or Shenqi. Clinical follow-up was planned at 1, 6, 9 and 12 months, and angiographic follow-up was planned at 9 months. The study was powered for the primary endpoint of 9-month in-segment late loss. RESULTS: At 9-month follow-up, the in-segment late loss was 0.29 ± 0.43 mm with Shenqi versus 0.30 ± 0.46 mm with SeQuent Please, and the one-sided 97.5% upper confidence limit of the difference was 0.14 mm, achieving noninferiority of Shenqi compared with SeQuent Please (P = 0.002). In total, 12 patients developed target lesion failure (TLF) in the Shenqi group compared with 16 patients in the SeQuent Please group (10.91% versus 15.09%; P = 0.42) within 1 year. TLF was mainly driven by target lesion revascularization (9.09%) followed by target vessel-related myocardial infarction (1.82%) and cardiovascular death (0.91%) in the Shenqi group. CONCLUSIONS: Shenqi DCB was noninferior to SeQuent Please DCB for the primary endpoint of 9-month in-segment late loss. Shenqi DCB may become an attractive alternative treatment for patients with coronary ISR, withholding the need for additional stent implantation.


Assuntos
Angioplastia Coronária com Balão , Reestenose Coronária/tratamento farmacológico , Stents Farmacológicos , Medicamentos de Ervas Chinesas/uso terapêutico , Iohexol/análogos & derivados , Paclitaxel/uso terapêutico , China , Materiais Revestidos Biocompatíveis , Angiografia Coronária , Feminino , Humanos , Iohexol/uso terapêutico , Masculino , Pessoa de Meia-Idade
11.
Front Cardiovasc Med ; 7: 596107, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195485

RESUMO

Background: Mitsugumin 53 (MG53), a muscle-specific protein belonging to the TRIM family, has been demonstrated to protect the heart against oxidative injury. Although previous studies indicated that ischemic hearts released MG53 into circulation in mice, its effects in humans remains unknown. We aimed to evaluate the prognostic value of MG53 in patients with ST-segment elevation myocardial infarction (STEMI). Methods: Serum levels of MG53 were measured in 300 patients with STEMI, all patients were followed for 3 years. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular (CV) death, heart failure causing-rehospitalization, recurrent myocardial infarction (MI), and stroke. Results: Patients with a higher concentration of serum MG53 tended to be older, with a history of diabetes. MG53 levels were also highly associated with indicators reflecting heart function, such as left ventricular ejection fraction (LVEF), N terminal pro B type natriuretic peptide (NT-pro-BNP), and cardiac troponin I (cTnI) at baseline. Kaplan-Meier survival curves demonstrated that patients with MG53 levels above the cutoff value (132.17 pg/ml) were more likely to have MACEs. Moreover, it was found to be a significant predictor of CV death (HR: 6.12; 95% CI: 2.10-17.86; p = 0.001). Furthermore, the C-statistic and Integrated Discrimination Improvement (IDI) values for MACEs were improved with MG53 as an independent risk factor or when combined with cTnI. Conclusions: MG53 is a valuable prognostic marker of MACE in patients with AMI, independent of established conventional risk factors, highlighting the significance of MG53 in risk stratification post-MI.

12.
World J Surg Oncol ; 18(1): 193, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32746835

RESUMO

BACKGROUND: The impact of primary tumor resection (PTR) on the prognosis of unresectable metastatic colorectal cancer (mCRC) patients remains debatable. We aimed to develop several prognostic nomograms which could be useful in predicting whether patients might benefit from PTR or not. METHODS: Patients diagnosed as mCRC without resected metastasis were identified from the Surveillance Epidemiology and End Results database and randomly assigned into two groups: a training cohort (6369 patients) and a validation cohort (2774 patients). Univariate and multivariable Cox analyses were performed to identify the independent predictors and construct nomograms that could independently predict the overall survival (OS) of unresectable mCRC patients in PTR and non-PTR groups, respectively. The performance of these nomograms was assessed by the concordance index (C-index), calibration curves, and decision curve analysis (DCA). RESULTS: Based on the result of univariate and multivariable Cox analyses, two nomograms were respectively constructed to predict the 1-year OS rates of unresectable mCRC patients when receiving PTR and not. The first one included age, gender, tumor grade, proximal colon, N stage, CEA, chemotherapy, radiotherapy, histology type, brain metastasis, liver metastasis, lung metastasis, and bone metastasis. The second nomogram included age, race, tumor grade, primary site, CEA, chemotherapy, brain metastasis, and bone metastasis. These nomograms showed favorable sensitivity with the C-index range of 0.700-0.725. The calibration curves and DCAs also exhibited adequate fit and ideal net benefits in prognosis prediction and clinical application. CONCLUSIONS: These practical prognosis nomograms could assist clinicians in making appropriate treatment decisions to effectively manage the disease.


Assuntos
Neoplasias do Colo , Nomogramas , Humanos , Estadiamento de Neoplasias , Prognóstico , Programa de SEER
14.
Cancer Biomark ; 28(3): 391-396, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32474463

RESUMO

BACKGROUND: Recent evidence support that netrin-1 involves in colorectal carcinogenesis. OBJECTIVE: This study was to evaluate the performance of serum netrin-1 for detection of colorectal cancer (CRC) in both clinical/screening sets. METHODS: A total of 115 consecutive patients with CRC and matched healthy controls were included in Clinical Set. Fifty subjects with CRC, 50 subjects with advanced adenoma (AA), and 150 matched control participants free of neoplasia were included in Screening Set. RESULTS: In Clinical set, subjects with CRC presented higher levels of serum netrin-1 (513.9 ± 22.6 pg/mL) than controls (347.8 ± 20.3 pg/mL, p< 0.0001). Similar in Screening set, serum netrin-1 was higher in CRC (644.5 ± 37.0 pg/mL, both p< 0.0001), compared with controls (407.7 ± 14.8 pg/mL) and AA (416.5 ± 18.5 pg/mL). However, there was no difference between controls and AA (p= 0.752). Compared with the low netrin-1 group, the high group presented increased risk of CRC (Clinical set: OR = 4.300, p< 0.001; Screening set: OR = 7.731, p< 0.001). ROC curve of netrin-1 was developed to detect CRC (Clinical set: AUC 0.703; Screening set: AUC 0.759). CONCLUSIONS: It suggests netrin-1 as a potential biomarker for CRC detection.


Assuntos
Adenoma/diagnóstico , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Netrina-1/sangue , Adenoma/sangue , Adulto , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Estudos de Viabilidade , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos
15.
Adv Ther ; 37(4): 1579-1590, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32146703

RESUMO

BACKGROUND: Diabetes mellitus (DM) plays an important role in restenosis and late in-stent thrombosis (ST). The current study using optical coherence tomography (OCT) aims to compare target lesion neointima in patients with or without diabetes after zotarolimus-eluting stent (ZES) treatment. METHODS: OCT images of 90,212 struts and quantitative coronary angiography (QCA) in 62 patients (32 with DM and 30 without DM) with 69 de novo coronary lesions (34 DM and 35 non-DM) both after ZES implantation and 12 ± 1 month angiographic follow-up were recorded. Patient characteristics, lesion characteristics, clinical outcomes, and OCT findings including neointimal thickness, coverage, malapposition, and intimal morphology were analyzed. RESULTS: Baseline patient characteristics and lesion characteristics data were similar between the two groups. Higher neointimal thickness (0.14 ± 0.09 mm vs. 0.09 ± 0.04 mm, p = 0.021), more neovascularization (3.03 ± 6.24 vs. 0.52 ± 1.87, p = 0.017) and higher incidence of layered signal pattern (12.19 ± 19.91% vs. 4.28 ± 9.02%, p = 0.049) were observed in diabetic lesions comparing with non-diabetic lesions. No differences were found in malapposition, uncovered percentage, and thrombus between the two groups (all p > 0.05). Occurrence of clinical adverse events was also similar during the follow-up period (p > 0.05). CONCLUSION: Although more neointimal proliferation and more neovascularization were found in diabetic coronary lesions when compared with non-diabetic lesions, treatment with ZES showed similar stent malapposition rate at 1-year follow-up. The data indicated that ZES treatment could possibly be effective in treating diabetic coronary lesions. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01747356.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Stents Farmacológicos , Sirolimo/análogos & derivados , Idoso , Estudos de Casos e Controles , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/diagnóstico por imagem , Angiopatias Diabéticas/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Sirolimo/uso terapêutico , Tomografia de Coerência Óptica , Resultado do Tratamento
16.
Front Physiol ; 11: 617845, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33391037

RESUMO

Background: Mitsugumin 53 or Tripartite motif 72 (MG53/TRIM72), a myokine/cardiokine belonging to the tripartite motif family, can protect the heart from ischemic injury and regulate lipid metabolism in rodents. However, its biological function in humans remains unclear. This study sought to investigate the relationship between circulating MG53 levels and coronary artery disease (CAD). Methods: The concentration of MG53 was measured by enzyme-linked immunosorbent assay (ELISA) in serum samples from 639 patients who underwent angiography, including 205 controls, 222 patients with stable CAD, and 212 patients with acute myocardial infarction (AMI). Logistic and linear regression analyses were used to analyze the relationship between MG53 and CAD. Results: MG53 levels were increased in patients with stable CAD and were highest in patients with AMI. Additionally, patients with comorbidities, such as chronic kidney disease (CKD) and diabetes also had a higher concentration of MG53. We found that MG53 is a significant diagnostic marker of CAD and AMI, as analyzed by logistic regression models. Multivariate linear regression models revealed that serum MG53 was significantly corelated positively with SYNTAX scores. Global Registry of Acute Coronary Events (GRACE) scores also correlated with serum MG53 levels, indicating that MG53 levels were associated with the severity of CAD and AMI after adjusting for multiple risk factors and clinical biomarkers. Conclusion: MG53 is a valuable diagnostic marker whose serum levels correlate with the presence and severity of stable CAD and AMI, and may represent a novel biomarker for diagnosing CAD and indicating the severity of CAD.

17.
Mol Med Rep ; 20(6): 5183-5189, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31661145

RESUMO

Dexmedetomidine (DEX), a highly specific and selective α2 adrenergic receptor agonist, has been demonstrated to possess potential cardioprotective effects. However, the mechanisms underlying this process remain to be fully illuminated. In the present study, a myocardial infarction (MI) animal model was generated by permanently ligating the left anterior descending coronary artery in mice. Cardiac function and collagen content were evaluated by transthoracic echocardiography and picrosirius red staining, respectively. Apoptosis was determined by the relative expression levels of Bax and Bcl­2 and the myocardial caspase­3 activity. Additionally, nicotinamide adenine dinucleotide phosphate oxidase (NOX)­derived oxidative stress was evaluated by the relative expression of Nox2 and Nox4, along with the myocardial contents of malondialdehyde (MDA) and superoxide dismutase (SOD) activity. It was demonstrated that intraperitoneal DEX treatment (20 µg/kg/day) improved the systolic function of the left ventricle, and decreased the fibrotic changes in post­myocardial infarction mice, which was paralleled by a decrease in the levels of apoptosis. Subsequent experiments indicated that the restoration of redox signaling was achieved by DEX administration, and the over­activation of NOXs, including Nox2 and Nox4, was markedly inhibited. In conclusion, this present study suggested that DEX was cardioprotective and limited the excess production of NOX­derived ROS in ischemic heart disease, implying that DEX is a promising novel drug, especially for patients who have suffered MI.


Assuntos
Cardiotônicos/farmacologia , Dexmedetomidina/farmacologia , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/tratamento farmacológico , Função Ventricular/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Biomarcadores , Biópsia , Modelos Animais de Doenças , Fibrose , Masculino , Camundongos , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/metabolismo
18.
Clin Chim Acta ; 499: 134-141, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31526774

RESUMO

BACKGROUND: Ectodysplasin A (EDA), a new hepatokine, may be involved in energy metabolism. This study aims to 1) investigate the role of EDA in hepatic steatosis in C57BL/6 mice and HepG2 cells; 2) evaluate serum EDA in nonalcoholic fatty liver disease (NAFLD) in human. METHODS: This study comprises an experimental study in vitro and in vivo and a hospital based case-control study. Western blotting, qPCR and ELISA were used to measure EDA levels. siRNA and shRNA were performed to knockdown EDA. An Adipokine Magnetic Bead Panel was performed to measure serum adipokines. RESULTS: Increased levels of hepatic and secreted EDA were detected in steatosis, in vivo and in vitro. Steatosis was ameliorated by EDA knockdown in vitro, while intrahepatic triglycerides content and liver enzymes were improved in vivo. Furthermore, knockdown of EDA upregulated lipolytic genes and suppressed lipogenic genes. Serum EDA in subjects with NAFLD was higher. Moreover, it reveals associations between circulating EDA and higher odds of NAFLD, while circulating EDA presented a practicable performance to identify NAFLD. Lastly, serum EDA level was dependent on BMI, TNF-α, T2DM and obesity. CONCLUSIONS: EDA aggravates steatosis by striking balance between lipid deposition and elimination. It was a potential biomarker of NAFLD.


Assuntos
Biomarcadores Tumorais/sangue , Ectodisplasinas/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Animais , Ectodisplasinas/deficiência , Ectodisplasinas/genética , Feminino , Células Hep G2 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Análise Multivariada , Hepatopatia Gordurosa não Alcoólica/patologia , RNA Mensageiro/sangue , RNA Mensageiro/genética , Células Tumorais Cultivadas
19.
Sci Rep ; 9(1): 10816, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31346234

RESUMO

Recent evidence has indicated that the lymphatic vessel endothelial hyaluronan receptor (LYVE-1) is implicated in chronic inflammation and the lymphatic immune response. The soluble form of LYVE-1 (sLYVE-1) is produced by ectodomain shedding of LYVE-1 under pathological conditions including cancer and chronic inflammation. In this study, 1014 consecutive patients who underwent coronary angiography from May 2015 to September 2015 were included to investigate whether serum sLYVE-1 is associated with coronary artery disease (CAD) and its concomitant diseases includes chronic kidney disease (CKD). Results showed that there was no significant difference in sLYVE-1 levels between patients with CAD and without. However, a significantly higher level of sLYVE-1 was seen in patients with renal dysfunction compared to those with a normal eGFR. Results were validated in a separate cohort of 259 patients who were divided into four groups based on their kidney function assessed by estimated glomerular filtration rate (eGFR). Simple bivariate correlation analysis revealed that Lg[sLYVE-1] was negatively correlated with eGFR (r = -0.358, p < 0.001) and cystatin C (r = 0.303, p < 0.001). Multivariable logistic regression analysis revealed that the increase in Lg[sLYVE-1] was an independent determinant of renal dysfunction (odds ratio = 1.633, p = 0.007). Therefore, renal function should be considered when serum sLYVE-1 is used as a biomarker for the detection of pathological conditions such as chronic inflammation and cancer. Further study is required to elucidate the exact role of sLYVE-1 in renal function.


Assuntos
Doença das Coronárias/sangue , Nefropatias/sangue , Proteínas de Transporte Vesicular/sangue , Idoso , Biomarcadores/sangue , Angiografia Coronária , Doença das Coronárias/fisiopatologia , Cistatina C/sangue , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Biomed Res Int ; 2019: 8967306, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223623

RESUMO

Background: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habits in the absence of any detectable organic illnesses. Interest in the effect of dietary opponents to the IBS pathogenesis has been increased in recent years. This study aims to review previous studies to determine the relationship between IBS prevalence in community and dietary energy and macronutrients intakes according to the national nutrition surveys. Methods: A literature search was conducted in PubMed and EMBASE to September, 2018, to identify population-based studies that reported the prevalence of IBS. Daily energy intake, daily carbohydrates, and protein and fat percent contribution to energy intake (%) were obtained from study population-based national nutrition survey. The correlations of prevalence of IBS and dietary intakes were obtained by Spearman coefficient or Pearson coefficient. Results: Global prevalence of IBS was 11.7%. There was no correlation between overall prevalence of IBS of individual countries and national energy intake (P = 0.785), protein proportion (P = 0.063), carbohydrates proportion (P = 0.505), or fat proportion (P = 0.384) according to the years when the studies were conducted. No correlations were detected between dietary intake and male or female IBS prevalence. Interestingly, protein proportion was positively correlated with the prevalence of IBS in Rome III criteria (r = 0.569). Conclusion: Our findings demonstrate that dietary energy and macronutrients intake do not play a direct role in prevalence of IBS. However, IBS diagnostic criteria seem to have a bias on the correlation between prevalence of IBS and dietary intake. Further studies are needed to confirm the correlation between prevalence of IBS and specific dietary intake.


Assuntos
Ingestão de Energia , Síndrome do Intestino Irritável , Nutrientes , Feminino , Humanos , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/fisiopatologia , Masculino , Prevalência
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