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1.
Biomater Sci ; 12(20): 5266-5273, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39238274

RESUMO

Rapid and accurate detection of 7-methylguanine (m7Gua), a biomarker reflecting the degree of DNA methylation that occurs before or in the early stage of cancer, is of particular significance but remains a great challenge. Herein, a luminescent lanthanide-based covalent organic framework (Ln-COF) probe, namely DPA/Eu@ETTA-DHTA, is designed for the first time for the identification of m7Gua by assembling pyridine-2,6-dicarboxylic acid (DPA) as both an energy donor and a recognition molecule and Eu3+ ions as signal reporters into a stable COF matrix with high porosity and available binding sites. Significantly, the characteristic luminescence of Eu3+ ions can be turned on by the grafted DPA in the COF probe and effectively quenched by the addition of m7Gua via a competitive absorption process, thus achieving the sensing of m7Gua. Such a Ln-COF-based fluorescent platform presents high selectivity and a rapid response (<1 min) to m7Gua with a low detection limit (µM level) even in the presence of the main coexisting species in urine, allowing it to serve as a potentially practical probe for point-of-care monitoring of the level of m7Gua in human urine specimens. This study provides a convenient, time-saving, and economical approach for visual detection of m7Gua, and opens up new perspectives for the design of a luminescent COF-based probe for DNA methylation evaluation in diagnostics.


Assuntos
Metilação de DNA , Guanina , Elementos da Série dos Lantanídeos , Estruturas Metalorgânicas , Humanos , Elementos da Série dos Lantanídeos/química , Estruturas Metalorgânicas/química , Guanina/química , Guanina/análogos & derivados , Európio/química , Luminescência , Limite de Detecção , Corantes Fluorescentes/química
2.
Angew Chem Int Ed Engl ; 63(45): e202411956, 2024 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-39031278

RESUMO

The development of high-accuracy technologies to distinguish the quite tiny concentration change of tumor markers between negative and positive is of vital significance for early screening and diagnosis of cancers, but is still a great challenge for the conventional biosensors because of their "gradual" detection mode. Herein, a unique "leap-type" responsive lanthanide MOF-based biosensor (designated as Tb-CeMOF-X) with defect-mediated redox-/photo-activities is developed for precisely identifying acid phosphatase (ACP), an early pathological marker of prostate cancer (PCa) in serum. The engineered Tb-CeMOF-X probe achieves a bursting switch-on luminescence at the critical concentration of ACP (9 U ⋅ L-1), while keeping silent below this threshold, undergoing a qualitative signal change from "zero" to "one" between negative and positive indicators and thus significantly improving the identification precision. Significantly, such "leap-type" response performance can be further edited and amplified by rational defect engineering in the crystal structure to improve the accessibility of active centers, consequently maximizing the detection sensitivity toward ACP in the complex biological media. This study proposes the first paradigm for the development of "leap-type" biosensors with ultra-sensitive differentiation capability between negative and positive, and provides a potentially valuable tool for early and accurate screening of PCa.


Assuntos
Elementos da Série dos Lantanídeos , Estruturas Metalorgânicas , Oxirredução , Neoplasias da Próstata , Estruturas Metalorgânicas/química , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Masculino , Humanos , Elementos da Série dos Lantanídeos/química , Técnicas Biossensoriais/métodos , Fosfatase Ácida/química , Fosfatase Ácida/metabolismo , Fosfatase Ácida/sangue , Detecção Precoce de Câncer , Processos Fotoquímicos
3.
Int J Surg ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990285

RESUMO

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths. With the development of screening, patient selection and treatment strategies, patients' survival outcomes and living quality significantly improved. However, some patients still have local recurrence or residual tumors after receiving definitive therapies. Salvage surgery has been regarded as an effective option for recurrent or residual NSCLC, but its effectiveness remains undetermined. Furthermore, conversion surgery is a special type of salvage surgery for tumors converted from "initially unresectable" to "potentially resectable" status due to a favorable response to systemic treatments. Although conversion surgery is a promising curative procedure for advanced NSCLC, its concept and clinical value remain unfamiliar to clinicians. In this narrative review, we provided an overview of the safety and efficacy of salvage surgery, especially salvage surgery after sublobar resection in early-stage NSCLC. More importantly, we highlighted the concept and value of conversion surgery after systemic treatment in advanced NSCLC to gain some insights into its role in the treatment of lung cancer.

4.
Surg Infect (Larchmt) ; 25(7): 550-552, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38957959

RESUMO

Objective: The purpose of this study was to report a case of herpes simplex virus-1 (HSV-1) keratitis misdiagnosed as fungal keratitis due to its clinical presentation being similar to that of fungal keratitis, ultimately diagnosed by NGS. Patients and Methods: A 59-year-old male presented with reduced vision in the right eye, combined with a history of trauma with vegetative matter. The corneal ulcer was accompanied with feathery infiltration, satellite lesion, and endothelial plaques. In vivo confocal microscopy (IVCM) showed hyper-reflective linear, thin, and branching interlocking structures. Fungal keratitis was diagnosed. Voriconazole 100 mg orally daily, topical tobramycin and 1% voriconazole were initiated empirically right away. The condition was aggravated and penetrating keratoplasty was performed. Anterior segment optical coherence tomography (AS-OCT) demonstrated the presence of plaques with a clear boundary between plaques and endothelium, resembling the AS-OCT images observed in cases of viral keratitis. Next-generation sequencing (NGS) further detected HSV-1 deoxyribonucleic acid, and no fungal component was found. Antifungal agents were discontinued and antiviral treatments were added. Results: We successfully treated a patient with HSV-1 keratitis who was misdiagnosed due to clinical features and IVCM findings similar to fungal keratitis. The patient's infection was controlled. At 2 years after surgery, the cornea recovered well. Conclusions: HSV-1 keratitis with atypical clinical presentation can be easily misdiagnosed. This case report emphasizes the importance of NGS in diagnosing the pathogens of keratitis.


Assuntos
Erros de Diagnóstico , Herpesvirus Humano 1 , Sequenciamento de Nucleotídeos em Larga Escala , Ceratite Herpética , Humanos , Masculino , Pessoa de Meia-Idade , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 1/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Ceratite Herpética/diagnóstico , Ceratite Herpética/tratamento farmacológico , Ceratite/diagnóstico , Ceratite/microbiologia , Ceratite/virologia , Ceratite/tratamento farmacológico , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Antifúngicos/uso terapêutico , Antivirais/uso terapêutico
6.
Sheng Li Xue Bao ; 76(2): 346-352, 2024 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-38658383

RESUMO

Programmed death-ligand 1 (PD-L1) is important in maintaining central and peripheral immune tolerance in normal tissues, mediating tumor immune escape and keeping the balance between anti- and pro-inflammatory responses. Inflammation plays an important role in inflammatory lung diseases. This article reviews the research progress and potential clinical value of PD-L1 in inflammatory lung diseases, including acute lung injury, chronic obstructive pulmonary disease, asthma and idiopathic pulmonary fibrosis.


Assuntos
Asma , Antígeno B7-H1 , Doença Pulmonar Obstrutiva Crônica , Humanos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Asma/imunologia , Lesão Pulmonar Aguda/imunologia , Inflamação/imunologia , Fibrose Pulmonar Idiopática/imunologia , Fibrose Pulmonar Idiopática/metabolismo , Pneumopatias/imunologia , Pneumopatias/metabolismo , Animais
7.
Ann Surg Oncol ; 31(8): 5011-5020, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38520581

RESUMO

BACKGROUND: Noninvasively and accurately predicting subcarinal lymph node metastasis (SLNM) for patients with non-small cell lung cancer (NSCLC) remains challenging. This study was designed to develop and validate a tumor and subcarinal lymph nodes (tumor-SLNs) dual-region computed tomography (CT) radiomics model for predicting SLNM in NSCLC. METHODS: This retrospective study included NSCLC patients who underwent lung resection and SLNs dissection between January 2017 and December 2020. The radiomic features of the tumor and SLNs were extracted from preoperative CT, respectively. Ninety machine learning (ML) models were developed based on tumor region, SLNs region, and tumor-SLNs dual-region. The model performance was assessed by the area under the curve (AUC) and validated internally by fivefold cross-validation. RESULTS: In total, 202 patients were included in this study. ML models based on dual-region radiomics showed good performance for SLNM prediction, with a median AUC of 0.794 (range, 0.686-0.880), which was superior to those of models based on tumor region (median AUC, 0.746; range, 0.630-0.811) and SLNs region (median AUC, 0.700; range, 0.610-0.842). The ML model, which is developed by using the naive Bayes algorithm and dual-region features, had the highest AUC of 0.880 (range of cross-validation, 0.825-0.937) among all ML models. The optimal logistic regression model was inferior to the optimal ML model for predicting SLNM, with an AUC of 0.727. CONCLUSIONS: The CT radiomics showed the potential for accurately predicting SLNM in NSCLC patients. The ML model with dual-region radiomic features has better performance than the logistic regression or single-region models.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Metástase Linfática , Aprendizado de Máquina , Tomografia Computadorizada por Raios X , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Feminino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Idoso , Seguimentos , Prognóstico , Adulto , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Idoso de 80 Anos ou mais , Excisão de Linfonodo , Pneumonectomia , Radiômica
8.
Biochem Genet ; 62(1): 242-253, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37326897

RESUMO

Pancreatic cancer remains the common cancer with the worst prognosis because of its late diagnosis and extensive metastasis. This study aimed to investigate the effects of GABRP on pancreatic cancer metastasis and the molecular mechanism. The expression of GABRP was measured using the quantitative real-time PCR and western blot. The biological behaviors of cancer cells were assessed using the cell counting kit-8, Transwell assay, and western blot. The regulation of GABRP on the MEK/ERK pathway was detected by western blot. The results indicated that GABRP was overexpressed in pancreatic cancer tissues and cells. Knockdown of GABRP suppressed cell viability, invasion, migration, and epithelial-mesenchymal transition (EMT), whereas GABRP overexpression facilitated these biological behaviors. Inactivation of the MEK/ERK pathway reversed the effects on cellular processes induced by GABRP. Moreover, silencing of GABRP inhibited tumor growth. In conclusion, GABRP promoted the progression of pancreatic cancer by facilitating cell metastasis and tumor growth via activating the MEK/ERK pathway. The findings suggest that GABRP has the potential to be a therapeutic target for the metastatic pancreatic cancer.


Assuntos
Sistema de Sinalização das MAP Quinases , Neoplasias Pancreáticas , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Neoplasias Pancreáticas/patologia , Receptores de GABA-A/genética , Receptores de GABA-A/metabolismo , Transdução de Sinais
9.
Lipids Health Dis ; 22(1): 206, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38017484

RESUMO

BACKGROUND AND OBJECTIVE: Although the the Dietary Inflammatory Index (DII) serves to be one of the reliable indicator for hyperlipidaemia, there is still uncertainty about its relationship to prognosis in the hyperlipidaemic population. In current study, the DII levels were analyzed in relation to the mortality risk among among the hyperlipidaemic individuals with the aim of determining any prospective correlation. METHODS: 14,460 subjects with hyperlipidaemia from the 10-year (2001-2010) National Health and Nutrition Examination Survey (NHANES) were chosen for this study. The endpoint event for follow-up was all-cause mortality, and subjects were tracked for up to December 31, 2019, or death, whichever occurred first. The tertiles of the DII levels were utilized for categorizing the study population into three groups. Survival curves, Cox proportional hazards regression models, restricted cubic spline (RCS), subgroup and interaction analyses, and sensitivity analyses were employed sequentially for the purpose of evaluating the association of the DII with mortality. RESULTS: 3170 (21.92%) all-cause deaths were recorded during an average 148-month follow-up period. Kaplan-Meier survival curves indicated that the survival rate of participants divided into the low DII group was substantially improved compared to that of those in the higher DII group (log-rank P < 0.001). After controlling for confounders, higher levels of DII were observed to be meaningfully linked to an elevated risk of death, no matter whether DII was specified for the continuous (hazard ratio (HR): 1.06; 95% confidence interval (CI): 1.04-1.08) or the categorical variable (HR: 1.22; 95% CI: 1.11-1.33). The DII and mortality displayed a linear association, according to the RCS. Stratified and sensitivity analyses reinforced the proof that these findings were reliable. CONCLUSION: Among patients with hyperlipidaemia, the risk of death was positively and linearly linked with DII levels.


Assuntos
Doenças Cardiovasculares , Hiperlipidemias , Neoplasias , Humanos , Inquéritos Nutricionais , Estudos Prospectivos , Doenças Cardiovasculares/etiologia , Neoplasias/complicações , Dieta/efeitos adversos , Inflamação/etiologia , Hiperlipidemias/complicações
10.
Chem Soc Rev ; 52(22): 7707-7736, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37874584

RESUMO

Chemodynamic therapy (CDT) is a newly developed cancer-therapeutic modality that kills cancer cells by the highly toxic hydroxyl radical (˙OH) generated from the in situ triggered Fenton/Fenton-like reactions in an acidic and H2O2-overproduced tumor microenvironment (TME). By taking the advantage of the TME-activated catalytic reaction, CDT enables a highly specific and minimally-invasive cancer treatment without external energy input, whose efficiency mainly depends on the reactant concentrations of both the catalytic ions and H2O2, and the reaction conditions (including pH, temperature, and amount of glutathione). Unfortunately, it suffers from unsatisfactory therapy efficiency for clinical application because of the limited activators (i.e., mild acid pH and insufficient H2O2 content) and overexpressed reducing substance in TME. Currently, various synergistic strategies have been elaborately developed to increase the CDT efficiency by regulating the TME, enhancing the catalytic efficiency of catalysts, or combining with other therapeutic modalities. To realize these strategies, the construction of diverse nanocarriers to deliver Fenton catalysts and cooperatively therapeutic agents to tumors is the key prerequisite, which is now being studied but has not been thoroughly summarized. In particular, nanocarriers that can not only serve as carriers but are also active themselves for therapy are recently attracting increasing attention because of their less risk of toxicity and metabolic burden compared to nanocarriers without therapeutic capabilities. These therapy-active nanocarriers well meet the requirements of an ideal therapy system with maximum multifunctionality but minimal components. From this new perspective, in this review, we comprehensively summarize the very recent research progress on nanocarrier-based systems for enhanced CDT and the strategies of how to integrate various Fenton agents into the nanocarriers, with particular focus on the studies of therapy-active nanocarriers for the construction of CDT catalysts, aiming to guide the design of nanosystems with less components and more functionalities for enhanced CDT. Finally, the challenges and prospects of such a burgeoning cancer-theranostic modality are outlooked to provide inspirations for the further development and clinical translation of CDT.


Assuntos
Peróxido de Hidrogênio , Neoplasias , Humanos , Catálise , Glutationa , Radical Hidroxila , Temperatura , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral , Microambiente Tumoral
11.
Biomaterials ; 301: 122264, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37562155

RESUMO

The formulation of a drug using high-energy emulsification commonly causes drug deterioration. Exploiting the well-known Diet Coke-Mentos reaction (DCMR), a U-shaped tube reactor that can generate an eruption of bubbly flow that can serve as a low-energy emulsification platform, is proposed. The liquid in the U-tube reactor is a supersaturated solution of aqueous CO2, which mimics Diet Coke. When glass beads with rough surfaces, mimicking Mentos, are dropped into the carbonated water, an eruptive bubbly flow is spontaneously created, mediating effective emulsification at a compound water-oil interface. Experimental results demonstrate that DCMR-mediated bubbly flow may provide a versatile platform for the production of "oil-in-water" or "water-in-oil" droplets and Pickering emulsion composite particles as drug carriers. The DCMR-derived bubbly flow is generated without significant temperature elevation, so the activity of the drug to be emulsified is unaffected. In vivo results reveal the feasibility of using this low-energy emulsification platform to formulate an emulsion system that contains catalase, a temperature-sensitive oxidoreductase, to mitigate an experimentally formed paw inflammation in mice. The as-proposed emulsification platform is attractive for formulating numerous drug delivery systems on a small-scale in a customized manner to meet the needs of each individual for personalized medicine.


Assuntos
Coque , Portadores de Fármacos , Camundongos , Animais , Emulsões , Água , Dieta
12.
BMC Cancer ; 23(1): 695, 2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37488497

RESUMO

BACKGROUND: The site of lymph node metastasis (LNM) may affect the prognosis of patients with esophageal squamous cell carcinoma (ESCC). To investigate the prognoses of pararespiratory and paradigestive LNM and to propose a novel N (nN) staging system that integrates both the LNM site and count. METHODS: This study was a multicenter, large-sample, retrospective cohort study that included ESCC patients with LNM between January 2014 and December 2019 from three Chinese institutes. Patients were set into training (two institutes) and external validation (one institute) cohorts. The primary outcomes were survival differences in LNM site and the development of novel nodal staging system. The overall survival (OS) of patients with pararespiratory LNM only (Group A), paradigestive LNM only (Group B), and both sites (Group C) was evaluated by Kaplan-Meier. Cox proportional hazards models were used to identify the independent prognostic factors. An nN staging system considering both the LNM site and count was developed and evaluated by the area under the receiver operating characteristic curve (AUC). RESULTS: In total, 1313 patients were included and split into training (n = 1033) and external validation (n = 280) cohorts. There were 342 (26.0%), 568 (43.3%) and 403 (30.7%) patients in groups A, B and C, respectively. The OS of patients with pararespiratory and patients with paradigestive LNM presented significant differences in the training and validation cohorts (P < 0.050). In the training cohort, LNM site was an independent prognostic factor (hazard ratio: 1.58, 95% confidence intervals: 1.41-1.77, P < 0.001). The nN staging definition: nN1 (1-2 positive pararespiratory/paradigestive LNs), nN2 (3-6 pararespiratory LNs or 1 pararespiratory with 1paradigestive LN), nN3 (3-6 LNs with ≥ 1 paradigestive LN), nN4 (≥ 7 LNs). Subsets of patients with different nN stages showed significant differences in OS (P < 0.050). The prognostic model of the nN staging system presented higher performance in the training and validation cohorts at 3-year OS (AUC, 0.725 and 0.751, respectively) and 5-year OS (AUC, 0.740 and 0.793, respectively) than the current N staging systems. CONCLUSIONS: Compared to pararespiratory LNM, the presence of paradigestive LNM is associated with worse OS. The nN staging system revealed superior prognostic ability than current N staging systems.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Povo Asiático , Metástase Linfática , Estudos Retrospectivos , China , Estadiamento de Neoplasias , Prognóstico
13.
Front Oncol ; 13: 1082960, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37091180

RESUMO

Esophageal cancer (EC) is one of the fatal malignant neoplasms worldwide. Neoadjuvant therapy (NAT) combined with surgery has become the standard treatment for locally advanced EC. However, the treatment efficacy for patients with EC who received NAT varies from patient to patient. Currently, the evaluation of efficacy after NAT for EC lacks accurate and uniform criteria. Radiomics is a multi-parameter quantitative approach for developing medical imaging in the era of precision medicine and has provided a novel view of medical images. As a non-invasive image analysis method, radiomics is an inevitable trend in NAT efficacy prediction and prognosis classification of EC by analyzing the high-throughput imaging features of lesions extracted from medical images. In this literature review, we discuss the definition and workflow of radiomics, the advances in efficacy prediction after NAT, and the current application of radiomics for predicting efficacy after NAT.

14.
Medicine (Baltimore) ; 102(13): e33349, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37000048

RESUMO

RATIONALE: This report documents the intracardiac migration of a hook wire in a 47-year-old male patient after computed tomography (CT)-guided percutaneous hook wire localization of pulmonary ground-glass opacities. PATIENT CONCERNS: The patient underwent CT-guided hook wire localization before video-assisted thoracoscopic surgery (VATS) wedge resection for a pulmonary nodule in the right upper lung field. However, the hook wire was not found in the specimen obtained from the wedge resection. A right upper lobectomy was performed to locate the hook wire; however, it was not found. DIAGNOSIS: A transesophageal echocardiogram was performed, and the hook wire was found in the left ventricle (LV). INTERVENTIONS: The patient subsequently underwent exploratory cardiotomy to remove the foreign body. The patient was admitted to the intensive care unit for postoperative care. OUTCOMES: Postoperatively, no complications were observed, and the patient was discharged from the hospital 7 days postoperatively. He received standard lung cancer treatment afterwards. LESSONS: The present case was unique because the hook wire migrated through the bloodstream from the pulmonary vein to the left atrium, before finally reaching the LV. Based on the patient preoperative CT images, the ground glass opacities were proximal to a 2.5 mm wide vein, which drained into the pulmonary vein. The proximity of the hook wire to a blood vessel was reportedly attributed to an increased risk of hook wire migration through the bloodstream. Hematogenous hook wire migration into the heart can result in fatal complications. Early diagnosis and timely removal of the hook wire are recommended to prevent the worsening of this complication.


Assuntos
Neoplasias Pulmonares , Nódulo Pulmonar Solitário , Masculino , Humanos , Pessoa de Meia-Idade , Nódulo Pulmonar Solitário/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/etiologia , Tomografia Computadorizada por Raios X/métodos , Cirurgia Torácica Vídeoassistida/métodos , Cuidados Pós-Operatórios
15.
Rev. bras. cir. cardiovasc ; Rev. bras. cir. cardiovasc;38(1): 124-131, Jan.-Feb. 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1423097

RESUMO

ABSTRACT Introduction: Knockdown of fat mass and obesity-associated gene (FTO) can induce N6-methyladenosine (m 6A) ribonucleic acid (RNA) methylation. The objective of this study was to explore the effect of m 6A RNA methylation on atherosclerotic vulnerable plaque by FTO knockdown. Methods: A total of 50 New Zealand white rabbits were randomly divided into pure high-fat group, sham operation group, vulnerable plaque group, empty load group, and FTO knockdown group (10 rabbits/group). Results: Flow cytometry showed that helper T (Th) cells in the FTO knockdown group accounted for a significantly higher proportion of lymphocytes than in the vulnerable plaque group and empty load group (P<0.05). Th cells were screened by cell flow. The level of m 6A RNA methylation in the FTO knockdown group was significantly higher than in the vulnerable plaque group and empty load group (P<0.05). The levels of total cholesterol, triglyceride, and low-density lipoprotein C were higher at the 12th week than at the 1st week, but the high-density lipoprotein C level was lower at the 12th week than at the 1st week. At the 12th week, the interleukin-7 level was significantly lower in the adeno-associated virus-9 (AVV9)-FTO short hairpin RNA group than in the control and AVV9-green fluorescent protein groups (P<0.001). Conclusion: After successfully establishing a vascular parkinsonism rabbit model, m 6A RNA methylation can decrease Th cells and vulnerable atherosclerotic plaques.

16.
Neuroendocrinology ; 113(6): 625-640, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36720204

RESUMO

INTRODUCTION: Whether central glucagon-like peptide 1 (GLP-1)/GLP-1 receptor system mediated peripheral glucose homeostasis in patients with traumatic brain injury (TBI) is not clear. We aim to determine if plasma GLP-1 level could distinguish the non-survivors from the survivors during the first 14 days after TBI that could prognose 6 months mortality. METHODS: Metabolic, inflammatory, and hematologic profiles were examined in 73 patients with TBI in neurological intensive care unit. Factors that discriminate non-survivors from survivors were determined by two-way ANOVA. Biomarkers associated with mortality were determined by binary logistic regression and Cox proportional hazard regression. RESULTS: The non-survivors had higher infectious SOFA scores (p < 0.001), lower first 3 days' body temperature (p = 0.017), greater chance of cerebral hernia (p = 0.048), and decompressive craniectomy (p = 0.001) than the survivors. Higher 14-day plasma GLP-1 (p < 0.0001), glucose (p = 0.002), and IL-6 (p = 0.005) levels, in contrast with lower insulin level at days 4-7 (p = 0.020) were found in non-survivors than in survivors. Except the survivors who had an increased 14-day platelet number (p < 0.001), the two groups did not differ in hematological profile and intestinal barrier function. Although GLP-1 correlated closely with IL-6 in both the groups, it correlated with neither insulin nor glucose in each group. GLP-1 on days 8-10 and IL-6 on days 1-3 were positively, while insulin on days 4-7 was negatively associated with mortality. CONCLUSION: Persistent higher GLP-1 level in non-survivors over the survivors may present more severe central resistance to endogenous GLP-1 in non-survivors, which may be associated with progressive hyperglycemia with increased mortality in TBI.


Assuntos
Lesões Encefálicas Traumáticas , Hiperglicemia , Humanos , Peptídeo 1 Semelhante ao Glucagon , Interleucina-6 , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/metabolismo , Insulina , Glucose , Glicemia/metabolismo
17.
Adv Healthc Mater ; 12(2): e2201262, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36213949

RESUMO

Glucose oxidase (GOD)-mediated starvation therapy (ST) that causes intratumoral glucose depletion is a promising strategy for tumor treatment. However, the ultimate efficacy is inevitably limited by tumor hypoxia, as oxygen is a key component in the consumption of glucose by GOD. In this study, a kind of glutathione (GSH)-responsive organosilica hybrid micelles loaded with Mn3 O4 and GOD (denoted as Mn3 O4 @PDOMs-GOD) is ingeniously designed for enhanced ST and chemodynamic therapy (CDT). Specifically, the internalized Mn3 O4 @PDOMs-GOD in tumor cells consumes intracellular glucose and oxygen (O2 ) under the catalysis of GOD to generate hydrogen peroxide (H2 O2 ), which is subsequently decomposed by Mn3 O4 to liberate O2 . This cyclically regenerated O2 will form a virtuous cycle of O2 and H2 O2 compensation to enhance the ST outcome. Meanwhile, Mn3 O4 can oxidize and deplete the overexpressed GSH in the tumor microenvironment (TME) to release Mn2+ , which then catalyzes H2 O2 into highly toxic hydroxyl radicals (·OH) to accomplish chemodynamic therapy (CDT). Both in vitro and in vivo experiment results demonstrate the significant antitumor efficacy of Mn3 O4 @PDOMs-GOD by the cooperatively enhanced ST and CDT, suggesting the feasibility to develop promising therapeutic platforms with higher treatment efficacies.


Assuntos
Nanopartículas , Neoplasias , Humanos , Catálise , Glucose , Glucose Oxidase , Glutationa , Peróxido de Hidrogênio , Oxigênio , Microambiente Tumoral , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico
18.
Adv Healthc Mater ; 12(6): e2202467, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36377480

RESUMO

Lacking blood vessels is one of the main characteristics of most solid tumors due to their rapid and unrestricted growth, which thus causes the inefficient delivery efficiency of nanomedicine and tumor hypoxia. Herein, a dual "unlocking" strategy to overcome these obstacles is proposed by combining engineered hybrid nanoparticles (named ZnPc@FOM-Pt) with dexamethasone (DXM). It is verified that pretreatment of tumors with DXM can increase intratumorally micro-vessel density (delivery "unlocking") to enhance the tumor delivery efficiency of ZnPc@FOM-Pt and decrease HIF-1α expression. Correspondingly, more Pt can catalyze tumor-overexpressed H2 O2 to produce oxygen to further cause hypoxia "unlocking," ultimately achieving boosted ZnPc-based photodynamic therapy in vivo (tumor inhibition rate: 99.1%). Moreover, the immunosuppressive tumor microenvironment is efficiently reversed and the therapeutic effect of anti-PD-L1-based immunotherapy is promoted by this newly designed nanomedicine. This dual "unlocking" strategy provides an innovative paradigm on simultaneously enhancing nanomedicine delivery efficacy and hypoxia relief for tumor therapy.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Nanomedicina , Hipóxia Tumoral , Neoplasias/tratamento farmacológico , Hipóxia/tratamento farmacológico , Imunoterapia , Linhagem Celular Tumoral , Microambiente Tumoral
19.
J Robot Surg ; 17(1): 63-71, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35316487

RESUMO

Currently, robotic-assisted coronary artery bypass grafting (RACABG) is a feasible choice for myocardial revascularization. Acceptable outcomes have been reported for RACABG with single target vessels; however, the long-term benefits of multivessel RACABG with composite arterial grafts have rarely been studied. Therefore, our study investigated the long-term results of multivessel RACABG with composite arterial grafts by reviewing the clinical data of patients from Taichung Veterans General Hospital. From December 2005 to June 2015, 562 patients underwent robotic-assisted robotic minimally invasive direct coronary bypass (MIDCAB) at Taichung Veterans General Hospital. Two major composite arterial graft configurations (i.e., inverted T-graft and Y-graft) were used. Data regarding the short-term and long-term outcomes of robotic-assisted MIDCAB were obtained from the medical records. For data regarding long-term outcomes of the patients not followed up at our institution, telephone interviews were conducted in June 2019. The in-hospital mortality rate and complication rate were 2.5% and 17.6%, respectively. We completed the follow-up for 486 patients (86.4%), and postoperative coronary imaging-based evaluation performed for 157 patients. The 5-year and 10-year survival rates were 82.7% and 65.2%, respectively. The 5-year and 10-year major adverse cardiac and cerebral events-free survival rates were 86.9% and 70.9%, respectively. The 5-year patency rate of various coronary anastomoses was 85.1-100%. Our study revealed that multivessel robotic-assisted MIDCAB with composite arterial grafts provided acceptable long-term outcomes, irrespective of the composite graft configuration.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Angiografia Coronária/métodos , Ponte de Artéria Coronária , Resultado do Tratamento , Estudos Retrospectivos
20.
Surg Today ; 53(9): 1001-1012, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36068414

RESUMO

We compared posttransplant outcomes following double-lung transplantation (DLTx) and heart-lung transplantation (HLTx), based on a search of PubMed, Cochrane Library, and Embase, from inception to March 8, 2022, for studies that report outcomes of these procedures. We then performed a meta-analysis of baseline characteristics and posttransplant outcomes. Subgroup analyses were implemented according to indication, publication year, and center. This study was registered on PROSPERO (number CRD42020223493). Ten studies were included in this meta-analysis, involving 1230 DLTx patients and 1022 HLTx patients. The DLTx group was characterized by older donors (P = 0.04) and a longer allograft ischemia time (P < 0.001) than the HLTx group. The two groups had comparable 1-year, 3-year, 5-year, 10-year survival rates (all P > 0.05), with similar results identified in subgroup analyses. We found no significant differences in 1-year, 5-year, and 10-year chronic lung allograft dysfunction (CLAD)-free survival, length of intensive care unit stay and hospital stay, length of postoperative ventilation, in-hospital mortality, or surgical complications between the groups (all P > 0.05). Thus, DLTx provides similar posttransplant survival to HLTx for end-stage cardiopulmonary disease. These two procedures have a comparable risk of CLAD and other posttransplant outcomes.


Assuntos
Transplante de Coração-Pulmão , Transplante de Pulmão , Humanos , Pulmão , Doadores de Tecidos , Taxa de Sobrevida , Estudos Retrospectivos
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