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OBJECTIVE: The outcomes of the best medical treatment (BMT) and intervention treatment (INT) in a single-center experience were reported in type B intramural hematoma (IMH). METHODS: From February 2015 to February 2021, a total of 195 consecutive patients with type B IMH were enrolled in the study. The primary end point was mortality, and the secondary end points included clinical and imaging outcomes. The clinical outcomes were aortic-related death, retrograde type A aortic dissection, stent graft-induced new entry tear, endoleak, and reintervention. The imaging outcome was evaluated through the latest follow-up computed tomography angiography, which included aortic rupture, aortic dissection, aortic aneurysm, rapid growth of aortic diameter, newly developed or enlarged penetrating aortic ulcer or ulcer-like projection (ULP) and increased aortic wall thickness. Kaplan-Meier curves were used to assess the association between different treatments. RESULTS: Among the enrolled patients, 115 received BMT, and 80 received INT. There was no significant difference in early (1.7% vs 2.5%; P = 1.00) and midterm all-cause death (8.3% vs 5.2%; P = .42) between the BMT and INT groups. However, patients who underwent INT were at risk of procedure-related complications such as stent graft-induced new entry tear and endoleaks. The INT group was associated with a profound decrease in the risk of ULP, including newly developed ULP (4.3% vs 26.9%; P < .05), ULP enlargement (6.4% vs 31.3%; P < .05), and a lower proportion of high-risk ULP (10.9% vs 45.6%; P < .05). Although there was no significant difference in the incidence of IMH regression between the two groups, the maximum diameter of the descending aorta in patients receiving INT was larger compared with those treated with BMT. CONCLUSIONS: Based on our limited experience, patients with type B IMH treated with BMT or INT shared similar midterm clinical outcome. Patients who underwent INT may have a decreased risk of ULPs, but a higher risk of procedure-related events and patients on BMT should be closely monitored for ULP progression.
Assuntos
Implante de Prótese Vascular , Procedimentos Endovasculares , Hematoma , Humanos , Masculino , Feminino , Hematoma/diagnóstico por imagem , Hematoma/etiologia , Hematoma/terapia , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Resultado do Tratamento , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Procedimentos Endovasculares/instrumentação , Fatores de Risco , Fatores de Tempo , Stents , Angiografia por Tomografia Computadorizada , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/mortalidade , Doenças da Aorta/terapia , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/mortalidade , Dissecção Aórtica/cirurgia , Dissecção Aórtica/terapia , Medição de Risco , Complicações Pós-Operatórias/etiologia , Prótese Vascular , Hematoma Intramural AórticoRESUMO
BACKGROUND: Secondary aortic intervention (SAI) following thoracic endovascular aortic repair (TEVAR) is not uncommon. However, a satisfactory management system has not been established for these patients. We aimed to report our single-center experience with SAI after prior TEVAR for type B aortic dissection (TBAD). METHODS: From January 2010 to May 2017, 860 eligible patients with TBAD underwent TEVAR. One hundred seven (12.4%) patients required SAI, either endovascularly (n=76) or surgically (n=31). The main indications for SAI were entry flow (n=58 [54.2%]), aneurysm expansion of the proximal or remote aorta (n=26 [24.3%]), retrograde type A aortic dissection (n=11 [10.3%]), distal stent-graft-induced new entry tear (n=6 [5.6%]), and stent migration (n=4 [3.7%]). The Kaplan-Meier curves were generated to determine the degree of freedom from SAI and the prognosis. Cox proportional hazards were used to screen for risk factors for SAI and poor prognosis. RESULTS: The overall 30-day mortality rate after SAI was 4.7% (n=5): endovascular (n=2 [2.6%]) vs open surgery (n=3 [9.7%]; p=0.145). The cumulative survival rates with or without SAI were 86.3%±3.6% vs 95.7%±0.8% at 3 years and 82.0%±4.2% vs 92.2%±1.1% at 5 years, respectively (log-rank p<0.001). Although no significant difference in survival was observed, the incidence of SAI was significantly greater in patients who underwent TEVAR during the chronic phase (acute [11.6%] vs subacute [9.6%] vs chronic [27.8]; p<0.001). Multivariate regression analysis revealed that prior TEVAR in the chronic phase (hazard ratio [HR]=1.73, 95% confidence interval [CI]=1.03-2.90; p=0.039), maximum aortic diameter (HR=1.05, 95% CI=1.04-1.07; p<0.001), and arch involvement (HR=1.48, 95% CI=1.01-2.18; p=0.048) were predictors of the incidence of SAI. In addition, the maximum aortic diameter was demonstrated to be the only risk factor for prognosis after adjusting for confounding factors. CONCLUSIONS: Thoracic endovascular aortic repair for chronic TBAD patients should be reconsidered. Open surgery is preferable for those with proximal progression, whereas endovascular treatment is more suitable for distal lesions. Close surveillance and timely reintervention after TEVAR, whether via endovascular techniques or open surgery, are necessary to prevent devastating complications. CLINICAL IMPACT: The management of patients with type B aortic dissection (TBAD) after thoracic endovascular aortic repair (TEVAR) is challenging. We summarized our single-center experience regarding secondary aortic intervention after TEVAR for TBAD. We found that TEVAR for chronic TBAD patients should be carefully evaulated, and open surgery is recommended for those with proximal progession, while endovascular treatment is more preferable for distal lesions.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Piper longum L., a medicinal and food homologous herb, has a traditional history of use in treating gastrointestinal and neurological disorders. Piperine (PIP) the main alkaloid of P. longum, exists neuroprotective effects on various animal models of Parkinson's disease (PD). Nevertheless, the underlying mechanism, particularly the role of PIP in promoting gut-brain autophagy for α-Synuclein (α-Syn) degradation in PD, remains incompletely understood. AIM OF THE STUDY: To explore the role of PIP in regulating the gut-brain autophagy signaling pathway to reduce α-Syn levels in both the colon and substantia nigra (SN) of PD model rats. MATERIALS AND METHODS: Behavioral experiments were conducted to assess the impact of PIP on 6-hydroxydopamine (6-OHDA)-induced PD rats. The intestinal microbiome composition and intestinal metabolites were analyzed by metagenomics and GC-MS/MS. The auto-phagosomes were visualized by transmission electron microscopy. Immunohistochemistry, immunofluorescence, and western blotting were performed to assess the levels of tyrosine hydroxylase (TH), α-Syn, LC3II/LC3I, p62, and the PI3K/AKT/mTOR pathway in both the SN and colon of the rats. The pathway-related inhibitor and agonist were used to verify the autophagy mechanism in the SH-SY5Y cells overexpressing A53T mutant α-Syn (A53T-α-Syn). RESULTS: PIP improved autonomic movement and gastrointestinal dysfunctions, reduced α-Syn aggregation and attenuated the loss of dopaminergic neurons in 6-OHDA-induced PD rats. After oral administration of PIP, the radio of LC3II/LC3I increased and the expression of p62 was degraded, as well as the phosphorylation levels of PI3K, AKT and mTOR decreased in the SN and colon of rats. The effect of PIP on reducing A53T-α-Syn through the activation of the PI3K/AKT/mTOR-mediated autophagy pathway was further confirmed in A53T-α-Syn transgenic SH-SY5Y cells. This effect could be inhibited by the autophagy inhibitor bafilomycin A1 and the PI3K agonist 740 Y-P. CONCLUSIONS: Our findings suggested that PIP could protect neurons by activating autophagy to degrade α-Syn in the SN and colon, which were related to the suppression of PIP on the activation of PI3K/AKT/mTOR signaling pathway.
Assuntos
Alcaloides , Benzodioxóis , Neuroblastoma , Doença de Parkinson , Piperidinas , Alcamidas Poli-Insaturadas , Ratos , Humanos , Animais , Doença de Parkinson/tratamento farmacológico , alfa-Sinucleína/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Oxidopamina , Espectrometria de Massas em Tandem , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Encéfalo/metabolismo , AutofagiaRESUMO
To re-evaluate the prognostic value of absolute lymphocyte count (ALC) in pediatric immune thrombocytopenia (ITP) from the perspective of age. A total of 242 ITP pediatric patients, including 141 newly diagnosed ITP (nITP), 89 chronic ITP (cITP), and 12 persistent ITP, were retrospectively reviewed for this study. These patients were divided into 3 groups according to age (group 1, ≤24 m; group 2, 24-72 m; and group 3, >72 m). The ALC detected at admission was significantly different between nITP and cITP patients without considering their age difference (5.22 vs. 3.55×10 9 /L, P <0.001). However, no significant difference was discovered after age stratification (≤24 m: 6.52 vs. 5.34×10 9 /L, P =0.161; 24-72 m: 3.78 vs. 3.63×10 9 /L, P =0.748; > 72 m: 2.53 vs. 2.40×10 9 /L, P =0.748). ROC analysis showed that the prognostic value of ALC in ITP children was limited (area under curve (AUC): ≤24 m, 24-72 m, and >72 m were 0.591, 0.570, and 0.542, respectively). Analysis of covariance showed there was no significant difference in ALC between nITP and cITP when considering age as a covariate ( P =0.131). Instead, the ROC showing that platelet to lymphocyte ratio (PLR) has prognostic value in pediatric ITP independent of age stratification (≤24 m: AUC, 0.688; 24-72 m: AUC, 0.741; >72 m: AUC, 0.680). In conclusion, there was no significant difference of ALC between nITP and cITP patients when stratified by different age groups, and PLR may be an optional prognostic indicator for ITP.
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Púrpura Trombocitopênica Idiopática , Criança , Humanos , Púrpura Trombocitopênica Idiopática/diagnóstico , Prognóstico , Estudos Retrospectivos , Contagem de LinfócitosRESUMO
OBJECTIVES: The aim of this work was to investigate the impact of machine-learning-derived baseline lean psoas muscle area (LPMA) for patients undergoing thoracic endovascular aortic repair. METHODS: A retrospective study was undertaken of acute and subacute complicated type B aortic dissection patients who underwent endovascular treatment from 2010 to 2017. LPMA (a marker of frailty) was calculated by multiplying psoas muscle area and density measured at L3 level from the computed tomography. The optimal cut-off value of LPMA was determined by the Cox hazard model with restricted cubic spline. RESULTS: A total of 428 patients who met the inclusion criteria were included in this study. Patients were classified into low LPMA group (n = 218) and high LPMA group (n = 210) using the cut-off value of 395 cm2 Hounsfield unit. An automatic muscle segmentation algorithm was developed based on U-Net architecture. There was high correlation between machine-learning method and manual measurement for psoas muscle area (r = 0.91, P < 0.001) and density (r = 0.90, P < 0.001). Multivariable regression analyses revealed that baseline low LPMA (<395 cm2 Hounsfield unit) was an independent positive predictor for 30-day (odds ratio 5.62, 95% confidence interval 1.20-26.23, P = 0.028) and follow-up (hazard ratio 5.62, 95% confidence interval 2.68-11.79, P < 0.001) mortality. Propensity score matching and subgroup analysis based on age (<65 vs ≥65 years) confirmed the independent association between baseline LPMA and follow-up mortality. CONCLUSIONS: Baseline LPMA could profoundly affect the prognosis of patients undergoing thoracic endovascular aortic repair. It was feasible to integrate the automatic muscle measurements into clinical routine.
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Dissecção Aórtica , Procedimentos Endovasculares , Sarcopenia , Humanos , Idoso , Músculos Psoas/diagnóstico por imagem , Estudos Retrospectivos , Sarcopenia/diagnóstico por imagem , Sarcopenia/etiologia , Resultado do Tratamento , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Prognóstico , Procedimentos Endovasculares/efeitos adversos , Aprendizado de Máquina , Fatores de RiscoRESUMO
Chemotherapy is the first-line treatment for human retinoblastoma (RB), but the occurrence of drug resistance greatly limited its efficacy in practice. RING-finger protein 6 (RNF6) is an E3 ubiquitin ligase that is aberrantly upregulated in a range of cancers and plays important roles in cancer progression. However, the role of RNF6 in RB is largely unknown. In this study, we investigated the role of RNF6 in RB drug resistance. Two carboplatin-resistant RB cells, Y-79/CR and SO-Rb50/CR, were generated based on Y-79 and SO-Rb50 cells. RT-PCR and western blot analyses showed that RNF6 expression on both mRNA and protein levels was significantly increased in Y-79/CR and SO-Rb50/CR cells comparing to their parental cells. Knockdown of RNF6 using siRNA in Y-79/CR and SO-Rb50/CR cells resulted in cells sensitive to carboplatin on a RNF6 siRNA dose dependent manner. Similarly, RNF6 overexpression in parental Y-79 and SO-Rb50 cells could help cells gain resistance to carboplatin on a RNF6 expression dependent manner. Signaling pathway analyses revealed that JAK2/STAT3 pathway was involved in the RNF6-induced carboplatin resistance in RB cells. We further revealed that RNF6 expression in both Y-79 and SO-Rb50 cells could render cells resistant to multiple anti-cancer drugs including carboplatin, vincristine and etoposide, an implication of RNF6 as a biomarker for RB drug resistance. Taken together, our study has revealed that RNF6 is upregulated in drug-resistant RB cells and RNF6 promotes drug resistance through JAK2/STAT3 signaling pathway. The importance of RNF6 in RB cells drug resistance may represent this protein as a potential biomarker and treatment target for drug resistance in RB.
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Neoplasias da Retina , Retinoblastoma , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Resistência a Medicamentos , Humanos , Janus Quinase 2 , Neoplasias da Retina/tratamento farmacológico , Neoplasias da Retina/genética , Retinoblastoma/tratamento farmacológico , Retinoblastoma/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de SinaisRESUMO
We assessed the acute and chronic effects of copper (Cu2+) on the antioxidant system in golden trout (Oncorhynchus mykiss aguabonita). The median lethal concentration after 96 h was determined as 0.24 mg L-1. We then used 0.06 (L) and 0.12 mg L-1 (H) Cu2+ to assess the responses of the antioxidant system to long-term exposure. The activities of superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, reduced glutathione, and oxidized glutathione were measured in gill and liver tissue after 24 and 72 h and 7, 14, 21, and 28 days of exposure, as well as after 16 days of recovery in Cu2+-free water. Cu2+ accumulated to a greater extent in the liver than in the gill (0.61-0.75 mg kg-1 vs. 24.0-69.9 mg kg-1 in L group and 0.98-1.47 mg kg-1 vs. 33.3-66.03 mg kg-1 in H group). In the gill, we observed increases in the activities of superoxide dismutase, catalase, and glutathione peroxidase, as well as in the concentrations of reduced glutathione and oxidized glutathione. In the liver of L group, we observed increases in glutathione reductase activity and in the levels of reduced glutathione and oxidized glutathione. In L group, the activity of superoxide dismutase and reduced glutathione content increased after 24 h and then decreased over time, while catalase and glutathione reductase activity and oxidized glutathione levels increased. Data from the recovery period indicated that higher concentrations of Cu2+ may induce irreversible oxidative damage to the gill of golden trout.
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Cobre/toxicidade , Brânquias/efeitos dos fármacos , Fígado/efeitos dos fármacos , Oncorhynchus mykiss/metabolismo , Animais , Catalase/metabolismo , Cobre/metabolismo , Brânquias/enzimologia , Brânquias/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Dose Letal Mediana , Fígado/enzimologia , Fígado/metabolismo , Oxirredução/efeitos dos fármacos , Distribuição Aleatória , Superóxido Dismutase/metabolismoRESUMO
Here we develop a new method for the sensitive detection of DNA and cellular telomerase using an enzyme-triggered terminal extension strategy that the produced strand can light up multiple beacons on the surface of gold nanoparticles.
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DNA de Neoplasias/análise , Telomerase/análise , Linhagem Celular Tumoral , Ouro/química , Humanos , Nanopartículas Metálicas/química , Espectrometria de Fluorescência , Propriedades de Superfície , Telomerase/metabolismoRESUMO
Intestinal barrier damage after scald and burns, other trauma or major operations result in severe intestinal infections that cause serious consequences. Therefore, it is important to develop methods to protect intestinal barrier after severe burns. This study used rats that had full-thickness burn of approximately 30% of the total body surface area to investigate the effect and mechanism of glucose-insulin-potassium (GIK) and provide experimental evidence for application of GIK in protecting the intestine after burns or other trauma and major surgeries. The results show that the degree of intestinal damage and plasma diamine oxidase (DAO) levels in GIK (the concentrations of glucose, insulin, sodium chloride and potassium chloride were 100 g l(-1), 70 U l(-1), 9 g l(-1) and 5 g l(-1), respectively) and insulin (30 IU l(-1)) treatment groups were significantly lower than that in control group; the status of anti-inflammatory and pro-inflammatory cytokines and the ratio between them in GIK and insulin groups also significantly improved compared to those in control group; intestinal tumour necrosis factor-alpha (TNFα), nuclear factor-kappaB (NF-κB) and interleukin-10 (IL-10) messenger RNA (mRNA) expression and IL10/TNFα in GIK and insulin groups 2 days after the injury were also improved significantly compared to those in control group. All the indices including body weight detected in GIK group were improved to those in insulin group. Taken together, these results show that GIK and insulin show protective effect on intestine after severe burn, which may relate to controlling hyperglycaemia and regulating intestinal expression of NFκB and pro-inflammatory and anti-inflammatory cytokine genes by GIK and insulin; the protective effect of GIK on intestinal tissue after severe burn is superior to that of using insulin alone, which may attribute to improving the nutritional status by glucose supplement and the relatively higher dose of insulin in the GIK group.