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Although recent studies increasingly suggest the potential anti-cancer effect of quercetin, the exact underlying mechanism remains poorly demonstrated in oral squamous cell carcinoma (oSCC). Therefore, our research explored the impacts of quercetin on the ferroptosis and mTOR/S6KP70 axis in oSCC cell lines. After treating oSCC cells with quercetin or indicated compounds and transfection with SLC7A11- or S6KP70-overexpressing plasmid, cell viability was detected by CCK-8 assay. The level of ferroptosis in oSCC cells was assessed by measuring ROS and GSH levels. The activation of mTOR/S6KP70 axis was assessed by Western blotting. Quercetin promoted ferroptosis in an mTOR/S6KP70-dependent manner to inhibit tumor growth in oSCC cells. Mechanistically, we revealed that quercetin induced lipid peroxidation and reduced GSH levels by repressing SLC7A11 expression in oSCC cells. Specifically, the effects of quercetin on ferroptosis and mTOR and S6KP70 phosphorylation were partially blocked by both mTOR agonist and S6KP70 overexpression. Moreover, mTOR inhibitor promoted ferroptosis in quercetin-treated oSCC cells. Our findings showed that ferroptosis may be a new anti-tumor mechanism of quercetin. Additionally, we identified that quercetin can target mTOR/S6KP70 cascade to inhibit the growth of oSCC cells.
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Sistema y+ de Transporte de Aminoácidos , Ferroptose , Neoplasias Bucais , Quercetina , Serina-Treonina Quinases TOR , Animais , Humanos , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Camundongos Nus , Neoplasias Bucais/patologia , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , Quercetina/farmacologia , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transdução de Sinais/efeitos dos fármacos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
OBJECTIVE: Long noncoding RNAs (lncRNAs) play an increasingly important role in various autoimmune diseases. We aimed to characterize the expression profiles of lncRNAs in peripheral blood mononuclear cells (PBMCs) from RA patients and to assess the potential of these lncRNAs as RA biomarkers. METHODS: Whole-transcriptome sequencing was used to establish a lncRNA expression profile. A total of 155 RA patients, 145 healthy controls, 59 systemic lupus erythematosus (SLE) patients and 59 primary Sjögren's syndrome (pSS) patients were recruited for this study. Four candidate lncRNAs (linc00152, lnc-ADM-1, ITSN1-2, and lnc-FTH1-7) were validated via qRT-PCR in independent samples, and their expression, association with RA clinical features and value as RA biomarkers were evaluated. RESULTS: Linc00152 and lnc-ADM-1 exhibited upregulated expression (p = 0.001, p = 0.014, respectively), while ITSN1-2 and lnc-FTH1-7 exhibited downregulated expression (both p < 0.001, respectively) in RA patients compared to controls. Lnc-ADM-1 and lnc-FTH1-7 expression correlated positively with the C4 level (p = 0.016 and p = 0.012, respectively). ITSN1-2 levels were negatively associated with CRP levels (p = 0.024). Linc00152, lnc-ADM-1, ITSN1-2, and lnc-FTH1-7 showed potential as RA biomarkers, with the four-lncRNA panel distinguishing RA patients from controls, SLE patients, or pSS patients (AUC = 0.886, 0.746, and 0.749, respectively). CONCLUSION: The altered expression of linc00152, lnc-ADM-1, ITSN1-2 and lnc-FTH1-7 in RA patients suggested that these genes may serve as potential biomarkers for RA and could be involved in its pathogenesis.
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Artrite Reumatoide , Biomarcadores , Leucócitos Mononucleares , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/sangue , Artrite Reumatoide/genética , Artrite Reumatoide/sangue , Leucócitos Mononucleares/metabolismo , Masculino , Feminino , Biomarcadores/sangue , Pessoa de Meia-Idade , Adulto , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Síndrome de Sjogren/genética , Síndrome de Sjogren/sangue , Perfilação da Expressão Gênica , IdosoRESUMO
OBJECTIVE: This study aims to investigate the prevalence of dyslipidemia and assess the joint association of physical activity (PA) and diet quality on dyslipidemia risk in urban areas of Xinjiang. METHODS: Conducted from July 2019 to September 2021 in Xinjiang, China, this cross-sectional study involved 11,855 participants (mean age 47.1 ± 9.4 years, 53.1% male). Standard methods were used to measure plasma cholesterol levels, and validated questionnaires were employed to evaluate dietary habits and PA. The definition of dyslipidemia is based on 2023 Chinese guidelines for lipid management. PA was divided into guideline-recommended moderate-to-vigorous physical activity (MVPA) and non-MVPA, following World Health Organization guidelines. The Food Frequency Questionnaire was used to obtain the intake frequency of each dietary term. Each item was scored based on consumption frequency and divided into three groups (good, intermediate, and poor) based on total dietary score. Multivariate logistic regression analysis was performed to identify dyslipidemia risk factors, as well as the joint association of PA and diet quality. RESULTS: Dyslipidemia prevalence among urban adults in Xinjiang was 39.3%, with notable sex disparities (52.6% in males vs. 24.3% in females, P < 0.001). Among participants with dyslipidemia, the awareness, treatment and control rates were 6.9%, 3.1%, and 1.9%, respectively. A significant multiplicative interaction between PA and diet quality is associated with dyslipidemia (P for interaction < 0.05). Less PA and poor diet quality were associated with an increased odds of dyslipidemia. Even individuals with poor (OR = 1.464, 95% CI: 1.106-1.939) or intermediate (OR = 1.229, 95% CI: 1.003-1.505) diet quality but adhering to recommended MVPA had lower odds of dyslipidemia compared to those with good diet quality but inadequate MVPA (OR = 1.510, 95% CI: 1.252-1.821). CONCLUSIONS: Dyslipidemia prevalence was 39.3% in urban adults in Xinjiang, with limited awareness, treatment, and control. Following guideline-recommended MVPA and maintaining good diet quality were protective against dyslipidemia. Low levels of PA associated with a higher prevalence of dyslipidemia, even in individuals with good diet quality.
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Dieta , Dislipidemias , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Exercício Físico , Fatores de Risco , Dislipidemias/epidemiologia , China/epidemiologiaRESUMO
Background: Quantitative flow ratio (QFR) is an angiography-based fractional flow reserve measurement without pressure wire or induction of hyperemia. A recent innovation that uses combined geometrical data and hemodynamic boundary conditions to measure QFR from a single angiographic view has shown the potential to measure QFR of the renal artery-renal QFR (rQFR). Objective: The aim of this pilot study was to assess the feasibility of rQFR measurement and the contribution of rQFR in selecting patients with atherosclerotic renal artery stenosis (ARAS) undergoing revascularization. Methods: This retrospective trial enrolled patients who had ARAS (50-90%) and hypertension. The enrolled patients were treated by optimal antihypertensive medication or revascularization, respectively, and the therapeutic strategies were based on rFFR measurement and/or clinical feature. Results: A total of 55 patients underwent rQFR measurement. Among the enrolled patients, 18 underwent optimal antihypertensive medication and 37 underwent revascularization, 19 patients in whom rQFR and rFFR were both assessed. During the 180-day follow-up, 25 patients saw an improvement in their blood pressure among the 37 patients that underwent revascularization. ROC analysis revealed that rQFR had a high diagnostic accuracy for predicting blood pressure improvement (AUCrQFR = 0.932, 95% CI 0.798-0.998). The ideal cut-off value of rQFR for predicting blood pressure improvement after revascularization is ≤0.72 (sensitivity: 72.00%, specificity: 100%). The paired t test and Bland-Altman analyses demonstrated good agreement between rQFR and rFFR (t = 1.887, 95% CI -0.021 to 0.001, 95% limits of agreement: -0.035 to 0.055, p = 0.075). The Spearman correlation test reveals that there was a significant positive correlation between rQFR and rFFR (r = 0.952, 95% CI 0.874 to 0.982, p < 0.001). Conclusion: The rQFR has the potential to enhance the ability of angiography to detect functionally significant renal artery stenosis during angiography and to produce results that are comparable to invasive hemodynamic assessment.
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Aterosclerose , Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Obstrução da Artéria Renal , Humanos , Anti-Hipertensivos/uso terapêutico , Aterosclerose/diagnóstico por imagem , Angiografia Coronária/métodos , Vasos Coronários , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Projetos Piloto , Valor Preditivo dos Testes , Artéria Renal , Obstrução da Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/terapia , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
PURPOSE: In the randomized, single-center, PKUFH phase 3 trial, dose-intensified (72 Gy) radiation therapy was compared with conventional (66 Gy) radiation therapy. In a previous study, we found no significant difference in biochemical progression-free survival (bPFS) between the 2 cohorts at 4 years. In the current analysis, we provide 7-year outcomes. METHODS AND MATERIALS: Patients with stage pT3-4, positive surgical margins, or a prostate-specific antigen increase ≥0.2 ng/mL after radical prostatectomy were randomly assigned 1:1 to receive either 72 Gy in 36 fractions or 66 Gy in 33 fractions. All the patients underwent image guided intensity modulated radiation therapy. The primary endpoint was bPFS. Secondary endpoints were distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS) as estimated using the Kaplan-Meier method. RESULTS: Between September 2011 and November 2016, 144 patients were enrolled with 73 and 71 in the 72- and 66-Gy cohorts, respectively. At a median follow-up of 89.5 months (range, 73-97 months), there was no difference in 7-year bPFS between the 72- and 66-Gy cohorts (70.3% vs 61.2%; hazard ratio [HR], 0.73; 95% CI, 0.41-1.29; P = .274). However, in patients with a higher Gleason score (8-10), the 72-Gy cohort had statistically significant improvement in 7-year bPFS compared with the 66-Gy cohort (66.5% vs 30.2%; HR, 0.37; 95% CI, 0.17-0.82; P = .012). In addition, in patients with multiple positive surgical margins, the 72-Gy cohort had statistically significant improvement in 7-year bPFS compared with single positive surgical margin (82.5% vs 57.5%; HR, 0.36; 95% CI, 0.13-0.99; P = .037). The 7-year DMFS (88.4% vs 84.9%; HR, 0.93; 95% CI, 0.39-2.23; P = .867), CSS (94.1% vs 95.5%; HR, 1.19; 95% CI, 0.42-3.39; P = .745), and OS (92.8% vs 94.1%; HR, 1.29; 95% CI, 0.51-3.24; P = .594) had no statistical differences between the 72- and 66-Gy cohorts. CONCLUSIONS: The current 7-year bPFS results confirmed our previous findings that dose escalation (72 Gy) demonstrated no improvement in 7-year bPFS, DMFS, CSS, or OS compared with the 66-Gy regimen. However, patients with a higher Gleason score (8-10) or multiple positive surgical margins might benefit from the 72-Gy regimen, but this requires further prospective research.
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Neoplasias da Próstata , Radioterapia de Intensidade Modulada , Masculino , Humanos , Margens de Excisão , Seguimentos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/tratamento farmacológico , Radioterapia de Intensidade Modulada/métodos , Intervalo Livre de Progressão , Antígeno Prostático Específico , Intervalo Livre de DoençaRESUMO
Background: The endoscopic nasojejunal (NJ) placement plays a pivotal role in the nutritional support of critically ill patients. However, the conventional endoscopy-guided tube insertion method presents issues of excessive procedural duration. We have enhanced the traditional endoscopy-guided catheter placement method, enabling a faster and more convenient catheter insertion. Methods: We improved the traditional endoscopically guided technique by incorporating an extra silk thread knot at the 25 cm mark on the jejunal segment of the NJ tube to assist endoscopists in accurate tube placement. We conducted the improved NJ tube placement on critically ill patients in need of enteral nutrition (EN). Laboratory data were retrospectively collected before and after the 7-day period of NJ tube placement and EN treatment to evaluate the effectiveness and safety of the improved method. Results: A total of 88 critically ill patients, with an average age of 59.6±15.5 years, and a male ratio of 86.4%, who underwent the improved NJ tube placement method were enrolled into analysis finally, achieving a 100% success rate of NJ tube insertion. The average time for tube insertion was 5.9±2.2 min, with a mean insertion depth of 108.8±12.5 cm. The EN tolerance score was 0.79±0.98. Following 7 days of EN therapy, the patients showed significant improvement in serum albumin levels compared to baseline (36.42 vs. 33.66 g/L, P<0.001). Conclusions: The improved endoscopically guided NJ tube placement technique is a rapid and safe procedure with excellent patient tolerance. It significantly improves the nutritional status of critically ill patients and facilitates the administration of EN, which requires further validation through randomized controlled trials.
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OBJECTIVE: To examine the efficacy and safety of telitacicept in the treatment of patients with SLE in everyday clinical practice. METHODS: Seventy-two patients with active SLE who received telitacicept for more than 24 weeks at multiple centres in China between 2019 and 2022 were retrospectively identified. Twenty-one of these patients received 52 continuous weeks of treatment with telitacicept. Treatment outcomes were analysed separately according to whether patients had renal or haematological abnormalities. Trajectory analysis was performed to identify patients with a limited response. Factors contributing to a limited response were explored by multivariable logistic regression analysis. RESULTS: After treatment with telitacicept for 4, 12, 24 and 52 weeks, 22.22%, 54.17%, 72.22% and 80.95% of patients, respectively, achieved an SLE Responder Index 4; 8.33%, 26.39%, 34.72% and 47.62% achieved a Lupus Low Disease Activity State; and 0%, 4.17%, 8.33% and 23.81% achieved remission. Significant decreases in serum IgA, IgG and IgM levels were observed at 4 weeks and showed a downward trend at 12, 24 and 52 weeks. The median 24-hour urinary protein declined from 1323.5 mg to 224.0 mg in patients with lupus nephritis after treatment with telitacicept for 52 weeks. Furthermore, a large proportion of patients (10 of 13) with haematological abnormalities recovered after 52 weeks of treatment with telitacicept. No severe adverse events were reported during the observation period. Age appeared to have a negative impact on treatment efficacy. CONCLUSIONS: Telitacicept demonstrated favourable efficacy and safety in patients with active SLE and improved the renal and haematological manifestations of the disease.
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Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Estudos Retrospectivos , Nefrite Lúpica/tratamento farmacológico , Resultado do TratamentoRESUMO
Purpose: We investigated the hypothesis that MHR (monocyte-to-high density lipoprotein cholesterol ratio) is related to the severity of coronary artery in ACS (acute coronary syndrome). Methods: In this case-control study, we recruited 15,853 participants undergoing the first time percutaneous coronary intervention (PCI) including 4093 normal controls, 10,518 chronic coronary artery disease (CAD), and 1242 ACS cases. Examination of demographic clinical data and biochemical profiles, as well as MHR values, were performed before PCI. The relationship between MHR and severity of coronary artery lesion in ACS was analyzed. We also used a flow cytometric assay to distinguish CD14+/CD16- classical monocyte subsets in peripheral blood mononucleated cells from CAD patients. Results: MHR was higher in patients with ACS compared with MHR in normal control and chronic CAD (normal control vs chronic CAD vs ACS: 0.46 ± 0.27 × 109/mmol vs 0.53 ± 0.29 × 109/mmol vs 0.73 ± 0.47 × 109/mmol, P < 0.001). MHR showed a significantly progressive increase as the angiographic severity of coronary lesions increased (single vessel lesion vs multi-vessel lesions in ACS: 0.54 ± 0.31 × 109/mmol vs 0.58 ± 0.35 × 109/mmol, P < 0.001), and classical monocyte subset to HDL-C ratio (CMHR) was increased in with CAD patients compared with control [4.69 (IQR, 1.06, 2.97) × 103/mmol vs 1.92 (IQR, 0.92, 3.04) × 103/mmol, P = 0.02]. Using a multivariate analysis, after adjusting for age, gender, body mass index (BMI), diabetes, and dyslipidemia, MHR was positively associated with multi-vessel lesions in ACS [OR (odds ratio): 1.28 (95% CI: 1.03-1.59, P = 0.029)]. Conclusion: MHR level could be a potential predictor of coronary artery lesion severity in ACS.
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Objective: The human Disabled-2 (Dab2) protein is an endocytic adaptor protein, which plays an essential role in endocytosis of transmembrane cargo, including low-density lipoprotein cholesterol (LDL-C). As a candidate gene for dyslipidemia, Dab2 is also involved in the development of type 2 diabetes mellitus(T2DM). The aim of this study was to investigate the effects of genetic variants of the Dab2 gene on the related risk of T2DM in the Uygur and Han populations of Xinjiang, China. Methods: A total of 2,157 age- and sex-matched individuals (528 T2DM patients and 1,629 controls) were included in this case-control study. Four high frequency SNPs (rs1050903, rs2255280, rs2855512 and rs11959928) of the Dab2 gene were genotyped using an improved multiplex ligation detection reaction (iMLDR) genotyping assay, and the forecast value of the SNP for T2DM was assessed by statistical analysis of clinical data profiles and gene frequencies. Results: We found that in the Uygur population studied, for both rs2255280 and rs2855512, there were significant differences in the distribution of genotypes (AA/CA/CC), and the recessive model (CC vs. CA + AA) between T2DM patients and the controls (P < 0.05). After adjusting for confounders, the recessive model (CC vs. CA + AA) of both rs2255280 and rs2855512 remained significantly associated with T2DM in this population (rs2255280: OR = 5.303, 95% CI [1.236 to -22.755], P = 0.025; rs2855512: OR = 4.892, 95% CI [1.136 to -21.013], P = 0.033). The genotypes (AA/CA/CC) and recessive models (CC vs. CA + AA) of rs2855512 and rs2255280 were also associated with the plasma glucose and HbA1c levels (all P < 0.05) in this population. There were no significant differences in genotypes, all genetic models, or allele frequencies between the T2DM and control group in the Han population group (all P > 0.05). Conclusions: The present study suggests that the variation of the Dab2 gene loci rs2255280 and rs2855512 is related to the incidence of T2DM in the Uygur population, but not in the Han population. In this study, these variations in Dab2 were an independent predictor for T2DM in the Uygur population of Xinjiang, China.
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Proteínas Adaptadoras de Transdução de Sinal , Proteínas Reguladoras de Apoptose , Diabetes Mellitus Tipo 2 , Humanos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , População do Leste Asiático , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genéticaRESUMO
Postmenopausal osteoporosis is one of the most common metabolic diseases in old women, and supplementing estrogen through bioactive substances is one of the important ways to improve menopausal syndrome. Some studies have confirmed that soybean isoflavone has estrogenic activity, and the main active component of soybean isoflavones is isoflavone aglycones. However, few studies have investigated the improvement effect of high-purity soy isoflavone aglycones on postmenopausal osteoporosis. Thus, the effect of different doses of high-purity soybeans isoflavone aglycone on the ovariectomized female osteoporosis rat model was evaluated by oral gavage. The rats were divided into seven experimental groups including SHAM, OVX, EE, SIHP, AFDP-L, AFDP-M, and AFDP-H, which was administered for 60 days from 30 days after ovariectomy. We collected blood from the abdominal aorta of rats on the 30th, 60th, and 90th days respectively, analyzed its serum biochemistry, and took out the femur for micro-CT imaging and bone microstructure parameter analysis. Results showed that the intervention effect of AFDP-H group on osteoporosis rats at 60 and 90 days was similar to that of EE group, and superior to the OVX group, SIHP group, AFDP-L group, AFDP-M group. The AFDP-H group inhibited the decrease in serum bone markers, bone density, trabeculae quantity, trabeculae thickness, and bone volume fraction, and increased the trabecular separation caused by ovariectomy, thereby significantly improving bone microstructure. It also prevented continuous weight gain and increased cholesterol levels in female rats. This study provided theoretical to application of soybean isoflavone aglycone in the intervention of osteoporosis. and confirmed that could replace chemical synthetic estrogen drugs.
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OBJECTIVE: To investigate the possible association between AT1R gene polymorphisms and major adverse cardiovascular and cerebrovascular events (MACCEs) in hypertension patients combined with or without coronary artery disease (CAD) in Xinjiang. METHODS: 374 CAD patients and 341 non-CAD individuals were enrolled as study participants and all of them have a hypertension diagnosis. AT1R gene polymorphisms were genotyped by SNPscan™ typing assays. During the follow-up in the clinic or by telephone interview, MACCEs were recorded. Kaplan-Meier curves and Cox survival analyses were used to explore the association between AT1R gene polymorphisms and the occurrence of MACCEs. RESULTS: AT1R gene rs389566 was associated with MACCEs. The TT genotype of the AT1R gene rs389566 had a significantly higher probability of MACCEs than the AA + AT genotype (75.2% vs. 24.8%, P = 0.033). Older age (OR = 1.028, 95% CI: 1.009-1.0047, P = 0.003) and TT genotype of rs389566 (OR = 1.770, 95% CI: 1.148-2.729, P = 0.01) were risk factors of MACCEs. AT1R gene rs389566 TT genotype may be a predisposing factor for the occurrence of MACCEs in hypertensive patients. CONCLUSION: We should also pay more attention to the prevent of MACCEs in hypertension patients combined with CAD. Especially those elderly hypertensive patients carrying AT1R rs389566 TT genotype requires avoidance of unhealthy lifestyle, better management of blood pressure control and reduce the occurrence of MACCEs.
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Doença da Artéria Coronariana , Hipertensão , Receptor Tipo 1 de Angiotensina , Idoso , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/genética , Genótipo , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/genética , Polimorfismo Genético , Receptor Tipo 1 de Angiotensina/genética , Fatores de RiscoRESUMO
Objective: Unplanned admission to the intensive care unit (ICU) is the major in-hospital adverse event for patients with dilated cardiomyopathy (DCM). We aimed to establish a nomogram of individualized risk prediction for unplanned ICU admission in DCM patients. Methods: A total of 2,214 patients diagnosed with DCM from the First Affiliated Hospital of Xinjiang Medical University from January 01, 2010, to December 31, 2020, were retrospectively analyzed. Patients were randomly divided into training and validation groups at a 7:3 ratio. The least absolute shrinkage and selection operator and multivariable logistic regression analysis were used for nomogram model development. The area under the receiver operating characteristic curve, calibration curves, and decision curve analysis (DCA) were used to evaluate the model. The primary outcome was defined as unplanned ICU admission. Results: A total of 209 (9.44%) patients experienced unplanned ICU admission. The variables in our final nomogram included emergency admission, previous stroke, New York Heart Association Class, heart rate, neutrophil count, and levels of N-terminal pro b-type natriuretic peptide. In the training group, the nomogram showed good calibration (Hosmer-Lemeshow χ 2 = 14.40, P = 0.07) and good discrimination, with an optimal-corrected C-index of 0.76 (95% confidence interval: 0.72-0.80). DCA confirmed the clinical net benefit of the nomogram model, and the nomogram maintained excellent performances in the validation group. Conclusion: This is the first risk prediction model for predicting unplanned ICU admission in patients with DCM by simply collecting clinical information. This model may assist physicians in identifying individuals at a high risk of unplanned ICU admission for DCM inpatients.
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Our previous study has shown that ATP action on P2X7R could be the second signal to induce the onset of gouty arthritis. However, the functional changes of P2X7R single nucleotide polymorphisms (SNPs) on the effects of ATP-P2X7R-IL-1ß signaling pathway and uric acid remained unknown. We aimed to investigate the association between the functional change of P2X7R containing the Ala348 to Thr polymorphisms (rs1718119) and the pathogenesis of gout. First, 270 gout patients and 70 hyperuricemic patients (without gout attack history in recent 5 years) were recruited for genotyping. In addition, the changes of ATP-induced pore formation were assessed in HEK-293T cells overexpressing different mutants in P2RX7, and the effects on P2X7R-NLRP3-IL-1ß pathway activation were explored in P2RX7 overexpression THP-1 cells. The risk allele for gout was A at rs1718119, and the AA and AG genotypes exhibited a higher risk of gout. Furthermore, Ala348 to Thr mutants increased P2X7-dependent ethidium+ bromide uptake, upregulated IL-1ß and NLRP3 levels as compared to the wild-type. We suggest that genetic polymorphisms of P2X7R containing the Ala348 to Thr are associated with the increased risk of gout, showing an enhanced gain-of-function effect on the development of this disease.
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Gota , Hiperuricemia , Receptores Purinérgicos P2X7 , Humanos , Trifosfato de Adenosina/metabolismo , Gota/genética , Hiperuricemia/genética , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Polimorfismo de Nucleotídeo Único , Receptores Purinérgicos P2X7/genéticaRESUMO
OBJECTIVE: The aim of this work was to evaluate the predictive value of FAR combined with CACS for MACCEs. BACKGROUND: The fibrinogen-albumin-ratio (FAR), a novel biomarker of inflammation, is associated with the severity of coronary artery disease (CAD). Coronary calcification score (CACS) is associated with the severity of coronary stenosis and is closely related to the prognosis of CAD patients. What is the prognostic value of FAR in patients with chest pain, which has not been reported. This study aims to evaluate the relationship between CACS and FAR and their impact on prognosis in patients with suspected CAD. METHODS: We used information from 12,904 individuals who had coronary computed tomography angiography (CTA) for chest pain and tracked down any significant adverse cardiac and cerebrovascular events (MACCEs). The following formula was used to calculate FAR: fibrinogen (g/L)/albumin (g/L). Patients were separated into groups with greater levels of FAR (FAR-H) and lower levels of FAR (FAR-L) in accordance with the ideal cut-off value of FAR for MACCEs prediction. In addition, patients were divided into three groups based on their CACS scores (CACS ≤ 100, 100 < CACS ≤ 400, and CACS > 400). RESULTS: 4946 patients [62(55-71) years, 64.4% male] were ultimately enrolled in the present study. During follow-up, a total of 234 cases (4.7%) of MACCEs were documented. Linear regression analysis results showed that CACS (R2 = 0.004, Standard ß = 0.066, P < 0.001) was positively associated with FAR in patients with chest pain.Compared to ones with FAR-L, FAR-H had an increased risk for MACCEs (adjusted HR 1.371(1.053-1.786) P = 0.019). Multivariate Cox regression showed that age (adjusted HR 1.015 95% CI 1.001-1.028;p = 0.03), FAR (adjusted HR 1.355 95% CI 1.042-1.763;p = 0.023),FBG (adjusted HR 1.043 95% CI 1.006-1.083;p = 0.024) and CACS (adjusted HR 1.470 95% CI 1.250-1.727;p < 0.001) were the independent risk factors for MACCEs. The FAR and CACS significantly improved MACCEs risk stratification, contributing to substantial net reclassification improvement ( NRI 0.122, 95% CI 0.054-0.198, P < 0.001) and integrated discrimination improvement(IDI 0.011, 95% CI 0.006-0.017, P < 0.001). CONCLUSION: FAR was an independent risk factor for MACCEs. The results showed that CACS was positively associated with FAR in patients with suspected CAD. A higher level of FAR and heavier coronary calcification burden was associated with worse outcomes among patients with suspected CAD. FAR and CACS improved the risk identification of patients with suspected CAD, leading to a significant reclassification of MACCEs.
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Doença da Artéria Coronariana , Calcificação Vascular , Feminino , Humanos , Masculino , Dor no Peito , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/complicações , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Calcificação Vascular/diagnóstico por imagem , Pessoa de Meia-Idade , IdosoRESUMO
OBJECTIVE: To clarify the effects of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) on the clinical outcomes of patients with coronary heart disease (CHD) complicated with reduced ejection fraction heart failure (HFrEF) through meta-analysis. METHODS: Three major literature databases - PubMed, Web of Science, and Cochrane - were searched by search terms and the literature retrieval time was publications dating from January 2007 to December 2021. To search for observational studies and randomized controlled trials (RCT) comparing the efficacy of PCI and CABG in patients with CHD and HFrEF, the abstract or full text of the literature was read and the final included literature was determined, according to inclusion and exclusion criteria. The quality of the included literature was evaluated using the Ottawa scale and data extraction was further completed. Data analysis was made using RevMan5.4 and R4.1 software; relevant forest plots and funnel plots were made, according to the extracted data. Egger's test was used to evaluate whether the data had publication bias. Outcomes were the major adverse cardiovascular events (MACE). RESULTS: A total of 10 studies were included and 11,032 subjects were included, made up of 5,521 cases of PCI and 5,511 cases of CABG. The results showed no significant difference between the two groups in cardiac mortality (CM) (RR=1.13, 95% CI 0.98-1.30, P = 0.10) and in overall all-cause mortality (ACM) (RR=1.12, 95% CI 0.92-1.37, P = 0.25). In the subgroup analysis of ACM, in the subgroups with left ventricular ejection fraction (LVEF) less than 35% and exceeding 35% and less than 50% (RR=1.12, 95% CI 0.92-1.37, P = 0.25) between the two groups, there was no statistical difference. However, among other MACE, compared with the PCI group, the CABG group had a lower risk of MACE (RR=1.58, 95%CI 1.49-1.70, P < 0.00001), myocardial infarction (MI) (RR=1.99, 95% CI 1.02-3.88, P = 0.04), heart failure (HF) (RR=1.29, 95% CI 1.17-1.43, P < 0.00001) and revascularization (RR=2.74, 95% CI 1.93-3.90, P < 0.00001). Finally in the CABG group, the risk of stroke or transient ischemic attack (TIA) was higher (RR=0.71, 95% CI 0.58-0.86, P = 0.0006) than the PCI group. CONCLUSIONS: The mortality rates of PCI and CABG were similar in patients with CHD complicated with HFrEF. Compared with PCI, CABG had a lower incidence of MACE, MI, HF, and revascularization, and a higher incidence of stroke or TIA.
Assuntos
Doença das Coronárias , Insuficiência Cardíaca , Ataque Isquêmico Transitório , Infarto do Miocárdio , Intervenção Coronária Percutânea , Acidente Vascular Cerebral , Humanos , Ponte de Artéria Coronária , Volume Sistólico , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: To investigate the clinical features of preexcitation-induced dilated cardiomyopathy in infants and evaluate safety and efficacy of radiofrequency ablation (RFCA) in these patients. METHODS: This study included 10 infants (4 males and 6 females) with mean age of 6.78±3.14 months, mean weight of 8.11±1.71 kg, and mean left ventricular ejection fraction (LVEF) was 32.6±10.34%. Tachycardiomyopathy has been excluded and all patients were refractory to the drugs. All of these 10 patients underwent RFCA. RESULTS: All the accessory pathways in these patients were located on right free wall and the acute success rate was 100%. No complication associated with the procedure occurred. In one case preexcitation recurred and was ablated successfully during the second attempt. There were 3 patients with mild cardiac dysfunction (LVEF, 40≤LVEF<50%), 3 with moderate (30≤LVEF<40%), and 4 with severe cardiac dysfunction (LVEF<30%, the ages were 3, 6, 7, and 10 months, respectively). The time for LVEF normalization was 1 week, 1 to 3 months, and ≥3 months, respectively. In 3 of the 4 severe cardiac dysfunction patients, the LVEF normalized at 3, 6, and 12 months after ablation, the LVEF of the remaining case did not recover at 3 months and is still being followed. CONCLUSIONS: Ventricular preexcitation could lead to severe cardiac dysfunction during infancy. RFCA may be a safe and effective treatment option in right free wall accessory pathways, even in infants with cardiac dysfunction. Cases of more severe cardiac dysfunction might require a longer time for LVEF recovery after RFCA.
Assuntos
Cardiomiopatia Dilatada , Ablação por Cateter , Cardiopatias , Síndromes de Pré-Excitação , Masculino , Feminino , Humanos , Lactente , Volume Sistólico , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/cirurgia , Função Ventricular Esquerda , Ablação por Cateter/efeitos adversos , Síndromes de Pré-Excitação/diagnóstico , Síndromes de Pré-Excitação/cirurgia , Resultado do TratamentoRESUMO
Objective: Coronary artery disease (CAD) is a the most common type of heart disease, and is associated with the highest mortality rate. The role of the ß3-adrenergic receptor gene (ADRB3) in energy homeostasis and lipolysis suggests that it may be associated with obesity, insulin resistance, diabetes, and hypertension. Herein, we sought to examine the relationship between CAD and variants of the ADRB3 gene in individuals with Han and Uygur ethnicities in China. Methods: All 1022 participants were genotyped for two ADRB3 single nucleotide polymorphisms (SNPs; rs1892818 and rs9693898) using real-time polymerase chain reaction (TaqMan). Uygur (259 CAD patients, 161 control group) and Han (308 CAD patients, 294 control group) were included in two case-control studies. We subsequently developed a predictive model using ADRB3 genetic variation and clinical variables to predict risk of CAD. Results: The rs1892818 CT genotype (8.5% vs 3.9%, p = 0.019) and T allele (4.3% vs 1.9%, p = 0.021) were more frequently detected in the control subjects compared to CAD patients of the Han population but not in the Uygur population. The rs9693898 was not associated with CAD in either ethnic population. Logistic regression analysis further demonstrated that carriers of the rs1892818 CT genotype had a lower risk of CAD than did those with the CC genotype (CT vs CC, p = 0.044, odds ratio [OR] = 0.441, 95% confidence interval [CI]: 0.199-0.976). Using this data, we constructed a predictive nomogram model for CAD with an area under the curve (95% CI) of 0.722 (0.682, 0.761). Conclusions: Our results suggest that rs1892818 is associated with CAD in the Han population and that the CT genotype of rs1892818 may serve as a protective factor for CAD in Han individuals. The proposed nomograms can be used for the prediction of CAD in this population.
Assuntos
Doença da Artéria Coronariana , Receptores Adrenérgicos beta 3 , Humanos , Estudos de Casos e Controles , China , Doença da Artéria Coronariana/genética , População do Leste Asiático/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Nomogramas , Polimorfismo de Nucleotídeo Único , Receptores Adrenérgicos beta 3/genética , Fatores de RiscoRESUMO
Quantitative systems pharmacology holds the promises of integrating results from laboratory animals or in vitro human systems into the design of human pharmacokinetic/pharmacodynamic (PK/PD) models allowing for precision and personalized medicine. However, reliable and general in vitro-to-in vivo extrapolation and interspecies scaling methods are still lacking. Here, we developed a translational strategy for the anticancer drug oxaliplatin. Using ex vivo PK data in the whole blood of the mouse, rat, and human, a model representing the amount of platinum (Pt) in the plasma and in the red blood cells was designed and could faithfully fit each dataset independently. A "purely physiologically-based (PB)" scaling approach solely based on preclinical data failed to reproduce human observations, which were then included in the calibration. Investigating approaches in which one parameter was set as species-specific, whereas the others were computed by PB scaling laws, we concluded that allowing the Pt binding rate to plasma proteins to be species-specific permitted to closely fit all data, and guaranteed parameter identifiability. Such a strategy presenting the drawback of including all clinical datasets, we further identified a minimal subset of human data ensuring accurate model calibration. Next, a "whole body" model of oxaliplatin human PK was inferred from the ex vivo study. Its three remaining parameters were estimated, using one third of the available patient data. Remarkably, the model achieved a good fit to the training dataset and successfully reproduced the unseen observations. Such validation endorsed the legitimacy of our scaling methodology calling for its testing with other drugs.
Assuntos
Antineoplásicos , Humanos , Ratos , Camundongos , Animais , Oxaliplatina , Antineoplásicos/farmacocinética , Modelos Biológicos , FarmacocinéticaRESUMO
OBJECTIVE: To investigate the correlation between ventricular pre-excitation-related dyssynchrony, on cardiac dysfunction, and recovery. METHODS AND RESULTS: This study included 76 children (39 boys and 37 girls) with a median age of 5.25 (2.67-10.75) years. The patients with pre-excitation-related cardiac dysfunction (cardiac dysfunction group, n = 34) had a longer standard deviation of the time-to-peak systolic strain of the left ventricle and larger difference between the maximum and minimum times-to-peak systolic strain than those with a normal cardiac function (normal function group, n = 42) (51.77 ± 24.70 ms versus 33.29 ± 9.48 ms, p < 0.05; 185.82 ± 92.51 ms versus 111.93 ± 34.27 ms, p < 0.05, respectively). The cardiac dysfunction group had a maximum time-to-peak systolic strain at the basal segments of the anterior and posterior septa and the normal function group at the basal segments of anterolateral and posterolateral walls. The prevalence of ventricular septal dyssynchrony in the cardiac dysfunction group was significantly higher than that in the normal function group (94.1% (32/34) versus 7.7% (3/42), p < 0.05). The patients with ventricular septal dyssynchrony (n = 35) had a significantly higher prevalence of intra-left ventricular systolic dyssynchrony than those with ventricular septal synchrony (n = 41) (57.1% (20/35) versus 14.6% (6/41), p < 0.05). During follow-up after pathway ablation, the patients who recovered from intra-left ventricular dyssynchrony (n = 29) had a shorter left ventricular ejection fraction recovery time than those who did not (n = 5) (χ2 = 5.94, p < 0.05). Among the patients who recovered, 93.1% (27/29) had a normalised standard deviation of the time-to-peak systolic strain and difference between the maximum and minimum times-to-peak systolic strain within 1 month after ablation. CONCLUSION: Ventricular pre-excitation may cause ventricular septal dyssynchrony; thus, attention must be paid to intra-left ventricular dyssynchrony and cardiac dysfunction. Whether intra-left ventricular systolic dyssynchrony can resolve within 1 month may be a new early predictor of patient prognosis.