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1.
Nat Commun ; 15(1): 8036, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39271701

RESUMO

Molecular imaging holds the potential for noninvasive and accurate grading of liver fibrosis. It is limited by the lack of biomarkers that strongly correlate with liver fibrosis grade. Here, we discover the grading potential of fibroblast activation protein alpha (FAPα) for liver fibrosis through transcriptional analysis and biological assays on clinical liver samples. The protein and mRNA expression of FAPα are linearly correlated with fibrosis grade (R2 = 0.89 and 0.91, respectively). A FAPα-responsive MRI molecular nanoprobe is prepared for quantitatively grading liver fibrosis. The nanoprobe is composed of superparamagnetic amorphous iron nanoparticles (AFeNPs) and paramagnetic gadoteric acid (Gd-DOTA) connected by FAPα-responsive peptide chains (ASGPAGPA). As liver fibrosis worsens, the increased FAPα cut off more ASGPAGPA, restoring a higher T1-MRI signal of Gd-DOTA. Otherwise, the signal remains quenched due to the distance-dependent magnetic resonance tuning (MRET) effect between AFeNPs and Gd-DOTA. The nanoprobe identifies F1, F2, F3, and F4 fibrosis, with area under the curve of 99.8%, 66.7%, 70.4%, and 96.3% in patients' samples, respectively. This strategy exhibits potential in utilizing molecular imaging for the early detection and grading of liver fibrosis in the clinic.


Assuntos
Endopeptidases , Cirrose Hepática , Imageamento por Ressonância Magnética , Proteínas de Membrana , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Endopeptidases/metabolismo , Proteínas de Membrana/metabolismo , Gelatinases/metabolismo , Compostos Organometálicos/química , Masculino , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/metabolismo , Feminino , Compostos Heterocíclicos/química , Pessoa de Meia-Idade , Animais , Meios de Contraste/química
2.
Artigo em Inglês | MEDLINE | ID: mdl-39231880

RESUMO

INTRODUCTION: Accurate diagnosis of liver fibrosis is crucial for preventing cirrhosis and liver tumors. Liver fibrosis is driven by activated hepatic stellate cells (HSCs) with elevated CD44 expression. We developed hyaluronic acid (HA)-coated gadolinium-based nanoprobes to specifically target CD44 for diagnosing liver fibrosis using T1-weighted magnetic resonance imaging (MRI). MATERIALS AND METHODS: NaGdF4 nanoparticles (NPs) were synthesized via thermal decomposition and modified with polyethylene glycol (PEG) to obtain non-targeting NaGdF4@PEG NPs. These were subsequently coated with HA to target HSCs, resulting in liver fibrosis-targeting NaGdF4@PEG@HA nanoprobes. Characterization includedd transmission electron microscopy and X-ray diffraction. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8). Internalization of NaGdF4@PEG@HA nanoprobes by mouse HSCs JS1 cells via ligand-receptor interaction was observed using flow cytometry and confocal laser scanning microscopy (CLSM). Liver fibrosis was induced in C57BL/6 mice using a methionine-choline deficient (MCD) diet. MRI performance and nanoprobe distribution in fibrotic and normal livers were analyzed using a GE Discovery 3.0T MR 750 scanner. RESULTS: NaGdF4@PEG@HA nanoprobes exhibited homogeneous morphology, low toxicity, and a high T1 relaxation rate (7.645 mM⁻¹s⁻¹). CLSM and flow cytometry demonstrated effective phagocytosis of NaGdF4@PEG@HA nanoprobes by JS1 cells compared to NaGdF4@PEG. MRI scans revealed higher T1 signals in fibrotic livers compared to normal livers after injection of NaGdF4@PEG@HA. NaGdF4@PEG@HA demonstrated higher targeting ability in fibrotic mice. CONCLUSIONS: NaGdF4@PEG@HA nanoprobes effectively target HSCs with high T1 relaxation rate, facilitating efficient MRI diagnosis of liver fibrosis.

3.
Respirology ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39197870

RESUMO

BACKGROUND AND OBJECTIVE: Radiofrequency ablation (RFA) is an emerging treatment of lung cancer, yet it is accompanied by certain safety concerns and operational limitations. This first multi-centre, large-scale clinical trial aimed to investigate the technical performance, efficacy and safety of an innovative transbronchial RFA system for lung tumours. METHODS: The study enrolled patients with malignant lung tumours who underwent transbronchial RFA using an automatic saline microperfusion system between January 2021 and December 2021 across 16 medical centres. The primary endpoint was the complete ablation rate. The performance and safety of the technique, along with the 1-year survival rates, were evaluated. RESULTS: This study included 126 patients (age range: 23-85 years) with 130 lung tumours (mean size: 18.77 × 14.15 mm) who had undergone 153 transbronchial RFA sessions, with a technique success rate of 99.35% and an average ablation zone size of 32.47 mm. At the 12-month follow-up, the complete ablation rate and intrapulmonary progression-free survival rates were 90.48% and 88.89%, respectively. The results of patients with ground-glass nodules (GGNs) were superior to those of the patients with solid nodules (12-month complete ablation rates: solid vs. pure GGN vs. mixed GGN: 82.14% vs. 100% vs. 96.08%, p = 0.007). No device defects were reported. Complications such as pneumothorax, haemoptysis, pleural effusion, pulmonary infection and pleural pain were observed in 3.97%, 6.35%, 8.73%, 11.11% and 10.32% of patients, respectively. Two subjects died during the follow-up period. CONCLUSION: Transbronchial RFA utilizing an automatic saline microperfusion system is a viable, safe and efficacious approach for the treatment for lung tumours, particularly for patients with GGNs.

4.
Heliyon ; 10(15): e35227, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39165966

RESUMO

Based on the China National Knowledge Infrastructure (CNKI) and Web of Science (WOS) databases, this article analyzes the deductive context, cooperation network, and research hotspots of land development rights (LDR) research in the Chinese and international literature by using CiteSpace software, and it also explores the implications of this research for the theory and practice of national territory spatial planning (NTSP) in China. The results show that (1) the literature on LDR in Chinese and international journal articles initially appeared in 1995 and 1973, respectively, researches in China experienced three stages: embryonic fluctuating development, rapid growth and stable development, and wave development, while international researches experienced two stages: embryonic fluctuating and a gradually increasing development. (2) Among these scholars and research institutions, there is no obvious difference between Chinese and international scholars, while the Renmin University of China and the State University System of Florida are the research institutions with the largest number of Chinese and international journal articles, respectively. (3) In terms of publishing journals, international journals mainly focus on land policy, cities, and resource fields, while Chinese journals mainly focus on the agricultural economy, civil and commercial law, economic systems, and macroeconomic management fields. (4) The direction and scale of thematic research vary greatly, with Chinese research mainly conducted from the perspectives of rights attribution and benefits distribution, while international research mainly focuses on the operation of the right-to-development system and its impact on the environment. In the future, studies focus on China's need to strengthen the research and institutional practice of LDR at the legal level, value level, and extension level following national conditions, formulate a land value-added benefit distribution system with efficiency and fairness, and strengthen the practice of LDR in China's NTSP based on the differences between urban and rural development.

6.
Int J Antimicrob Agents ; 64(2): 107235, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38851462

RESUMO

BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.


Assuntos
Antibacterianos , Infecções Comunitárias Adquiridas , Levofloxacino , Quinolonas , Humanos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Levofloxacino/uso terapêutico , Levofloxacino/efeitos adversos , Levofloxacino/administração & dosagem , Método Duplo-Cego , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Adulto , Idoso , Resultado do Tratamento , Quinolonas/uso terapêutico , Quinolonas/administração & dosagem , Quinolonas/efeitos adversos , Administração Intravenosa , Infusões Intravenosas , Adulto Jovem , Pneumonia/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Idoso de 80 Anos ou mais
7.
Thorax ; 78(12): 1197-1205, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37734951

RESUMO

BACKGROUND: Traditional electromagnetic navigation bronchoscopy (ENB) is a real-time image-guided system and used with thick bronchoscopes for the diagnosis of peripheral pulmonary nodules (PPNs). A novel ENB that could be used with thin bronchoscopes was developed. This study aimed to evaluate the diagnostic yield and the experience of using this ENB system in a real clinical scenario. METHODS: This multicentre study enrolled consecutive patients with PPNs adopting ENB from March 2019 to August 2021. ENB was performed with different bronchoscopes, ancillary techniques and sampling instruments according to the characteristics of the nodule and the judgement of the operator. The primary endpoint was the diagnostic yield. The secondary endpoints included the diagnostic yield of subgroups, procedural details and complication rate. RESULTS: In total, 479 patients with 479 nodules were enrolled in this study. The median lesion size was 20.9 (IQR, 15.9-25.9) mm. The overall diagnostic yield was 74.9% (359/479). A thin bronchoscope was used in 96.2% (461/479) nodules. ENB in combination with radial endobronchial ultrasound (rEBUS), a guide sheath (GS) and a thin bronchoscope was the most widely used guided method, producing a diagnostic yield of 74.1% (254/343). The median total procedural time was 1325.0 (IQR, 1014.0-1676.0) s. No severe complications occurred. CONCLUSION: This novel ENB system can be used in combination with different bronchoscopes, ancillary techniques and sampling instruments with a high diagnostic yield and safety profile for the diagnosis of PPNs, of which the combination of thin bronchoscope, rEBUS and GS was the most common method in clinical practice. TRIAL REGISTRATION NUMBER: NCT03716284.


Assuntos
Neoplasias Pulmonares , Nódulo Pulmonar Solitário , Humanos , Broncoscopia/efeitos adversos , Broncoscopia/métodos , Nódulo Pulmonar Solitário/diagnóstico , Nódulo Pulmonar Solitário/patologia , Estudos Prospectivos , Fenômenos Eletromagnéticos , Neoplasias Pulmonares/patologia
8.
Nanoscale Adv ; 5(15): 3994-4001, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37496625

RESUMO

Endometriosis is a tumor-like disease with high recurrence. In this case, the accurate imaging-based diagnosis of endometriosis can help clinicians eradicate it by improving their surgical plan. However, although contrast agents can improve the visibility of the tissue of interest in vivo via magnetic resonance imaging (MRI), the lack of biomarkers in endometriosis hinders the development of agents for its targeted imaging and diagnosis. Herein, aiming at the enriched vascular endothelial growth factor (VEGF) in endometriosis, we developed a targeting MRI contrast agent modified with bevacizumab, i.e., NaGdF4@PEG@bevacizumab-Cy5.5 nanoparticles (NPBCNs), to detect endometriosis. NPBCNs showed negligible cytotoxicity and high affinity towards VEGF in endometrial cells in vitro. Furthermore, NPBCNs generated a strong signal enhancement in vivo in endometriosis lesions in rats in T1-weighted images via MRI at 3 days post-injection, as confirmed by the histopathological staining results and fluorescence imaging on the same day. Our approach can enable NPBCNs to target endometriosis effectively, thus avoiding missed diagnoses.

9.
Lung Cancer ; 180: 107194, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37163774

RESUMO

BACKGROUND: Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) which revealed the systematic and central nervous system (CNS) antitumor activities for EGFR T790M-mutated advanced NSCLC in previous clinical studies and is further analyzed here. METHODS: Eligible patients from the previous phase I and phase IIb studies of rezivertinib were included for pooled analysis. Post-progressive patients who received a prescribed dosage (≥180 mg) of rezivertinib orally once daily were included in full analysis set (FAS), while those with stable, asymptomatic CNS lesions, including measurable and non-measurable ones at baseline were included in CNS full analysis set (cFAS). Patients with measurable CNS lesions were included in CNS evaluable for response set (cEFR). BICR-assessed CNS objective response rate (CNS-ORR), CNS disease control rate (CNS-DCR), CNS duration of response (CNS-DoR), CNS progression-free survival (CNS-PFS), and CNS depth of response (CNS-DepOR) were evaluated. RESULTS: 355 patients were included in FAS, among whom 150 and 45 patients were included in cFAS and cEFR. This pooled analysis showed the CNS-ORR was 32.0% (48/150; 95% CI: 24.6-40.1%) and the CNS-DCR was 42.0% (63/150; 95% CI: 34.0-50.3%) in cFAS, while that in cEFR were 68.9% (31/45; 95% CI: 53.4-81.8%) and 100% (45/45; 95% CI: 92.1-100.0%). In cEFR, the median CNS-DepOR and the mean of CNS-DepOR were -52.0% (range: -100.0 to 16.1%) and -46.8% (95% CI: -55.5 to -38.1%). In cFAS, the median CNS-DoR and CNS-PFS were 13.8 (95% CI: 9.6-not calculable [NC]) and 16.5 (95% CI: 13.7-NC) months. CONCLUSIONS: Rezivertinib demonstrated encouraging clinical CNS efficacy among advanced NSCLC patients with EGFR T790M mutation and CNS metastases.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Compostos de Anilina/uso terapêutico , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Sistema Nervoso Central/patologia , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia
10.
Clin Respir J ; 17(5): 343-356, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37094822

RESUMO

Acquired digestive-respiratory tract fistulas occur with abnormal communication between the respiratory tract and digestive tract caused by a variety of benign or malignant diseases, leading to the alimentary canal contents in the respiratory tract. Although various departments have been actively exploring advanced fistula closure techniques, including surgical methods and multimodal therapy, some of which have gotten good clinical effects, there are few large-scale evidence-based medical data to guide clinical diagnosis and treatment. The guidelines update the etiology, classification, pathogenesis, diagnosis, and management of acquired digestive-respiratory tract fistulas. It has been proved that the implantation of the respiratory and digestive stent is the most important and best treatment for acquired digestive-respiratory tract fistulas. The guidelines conduct an in-depth review of the current evidence and introduce in detail the selection of stents, implantation methods, postoperative management and efficacy evaluation.


Assuntos
Fístula do Sistema Digestório , População do Leste Asiático , Fístula do Sistema Respiratório , Humanos , Consenso , Sistema Respiratório , Fístula do Sistema Respiratório/diagnóstico , Fístula do Sistema Respiratório/etiologia , Fístula do Sistema Respiratório/terapia , Stents/efeitos adversos , Resultado do Tratamento , Fístula do Sistema Digestório/diagnóstico , Fístula do Sistema Digestório/etiologia , Fístula do Sistema Digestório/terapia
11.
J Comput Assist Tomogr ; 46(6): 961-967, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36399536

RESUMO

OBJECTIVE: Inferior intercavernous sinus (iICS) is a venous channel below the pituitary gland. Inferior intercavernous sinus injury is predisposed to cause venous bleeding during dura incision in transsphenoidal surgery for pituitary adenomas. Therefore, this study aimed to perform a radiological assessment of iICS before transsphenoidal surgery for pituitary microadenoma. METHODS: A retrospective evaluation was performed on 156 patients who underwent magnetic resonance imaging examinations in our hospital before endoscopic transsphenoidal surgery for pituitary microadenoma. Both sagittal reformatted and coronal contrast-enhanced (CE) sampling perfection with application optimized contrast using different flip angle evolutions (SPACE) images were interpreted for the presence, shape, and size of the iICS. RESULTS: In CE SPACE, the iICS was identified in 72 patients (46.15%) with pituitary microadenoma. The iICS was appeared as a filiform-shaped hyperintense structure below the pituitary gland on coronal CE SPACE planes and a crescent-shaped hyperintense structure on sagittal CE SPACE planes. The mean ± SD width, depth, and height of iICS were 11.15 ± 3.47 mm, 5.29 ± 1.24 mm, and 1.41 ± 0.19 mm, respectively. CONCLUSIONS: Contrast-enhanced SPACE may serve as a promising technique in evaluating iICS and individualized preoperative planning before transsphenoidal surgery for pituitary microadenoma.


Assuntos
Adenoma , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/patologia , Estudos Retrospectivos , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Adenoma/patologia , Imageamento por Ressonância Magnética/métodos
12.
J Thorac Oncol ; 17(11): 1306-1317, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36049654

RESUMO

INTRODUCTION: Rezivertinib (BPI-7711) is a novel third-generation EGFR tyrosine kinase inhibitor (TKI) targeting both EGFR-sensitizing mutations and EGFR T790M mutation. This study aimed to evaluate the efficacy and safety of rezivertinib in patients with locally advanced or metastatic/recurrent EGFR T790M-mutated NSCLC. METHODS: Patients with locally advanced or metastatic/recurrent NSCLC with confirmed EGFR T790M mutation who progressed after first-/second-generation EGFR TKI therapy or primary EGFR T790M mutation were enrolled. Patients received rezivertinib at 180 mg orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate (ORR) assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included disease control rate (DCR), duration of response, progression-free survival (PFS), overall survival, and safety. This study is registered with Clinical Trials.gov (NCT03812809). RESULTS: A total of 226 patients were enrolled from July 5, 2019, to January 22, 2020. By the data cutoff date on January 24, 2022, the median duration of follow-up was 23.3 months (95% confidence interval [CI]: 22.8-24.0). The ORR by blinded independent central review was 64.6% (95% CI: 58.0%-70.8%), and DCR was 89.8% (95% CI: 85.1%-93.4%). The median duration of response was 12.5 months (95% CI: 10.0-13.9), and median PFS was 12.2 months (95% CI: 9.6-13.9). The median overall survival was 23.9 months (95% CI: 20.0-not calculated [NC]). Among 91 (40.3%) patients with central nervous system (CNS) metastases, the median CNS PFS was 16.6 months (95% CI: 11.1-NC). In 29 patients with more than or equal to one brain target lesion at baseline, the CNS ORR and CNS DCR were 69.0% (95% CI: 49.2%-84.7%) and 100% (95% CI: 88.1%-100%), respectively. Time to progression of CNS was 16.5 months (95% CI: 9.7-NC). Of 226 patients, 188 (83.2%) had at least one treatment-related adverse event, whereas grade more than or equal to 3 occurred in 45 (19.9%) patients. No interstitial lung disease was reported. CONCLUSIONS: Rezivertinib was found to have promising efficacy and favorable safety profile for patients with locally advanced or metastatic/recurrent NSCLC with EGFR T790M mutation.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
13.
Artigo em Inglês | MEDLINE | ID: mdl-35805616

RESUMO

The improvement of green economic efficiency (GEE) should be realized under reasonable urban land development intensity (ULDI). Improving GEE can also help alleviate the negative externalities of excessive or unreasonable ULDI. Clarifying the interactive response mechanism between GEE and ULDI is a key link in regional sustainable development. Therefore, this paper uses the super-efficiency slack-based model (SBM) method, panel entropy method, and panel vector auto regression model to comprehensively analyze the interactive response relationship between GEE and ULDI in 283 prefecture-level cities in China from 2003 to 2019. This paper finds that: (1) during the research period, both the GEE and ULDI showed a relatively obvious upward trend, which is manifested in the fact that ULDI increased year by year while GEE overall increased in volatility. The growth and evolution trend of ULDI and GEE has the characteristics of interaction and coordination; (2) there is a two-way interactive Granger causality between ULDI and GEE, showing a positive interactive response effect; and (3) both ULDI and GEE have positive inertial growth and self-enhancement mechanisms. In the long run, GEE has a greater impact on the change of ULDI.


Assuntos
Conservação de Recursos Energéticos , Desenvolvimento Econômico , China , Cidades , Eficiência , Desenvolvimento Sustentável
14.
Adv Sci (Weinh) ; 9(23): e2201232, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35712774

RESUMO

In the field of nanomedicine, there is a tendency of matching designed nanomaterials with a suitable type of orthotopic cancer model, not just a casual subcutaneous one. Under this condition, knowing the specific features of the chosen cancer model is the priority, then introducing a proper therapy strategy using designed nanomaterials. Here, the Fenton chemistry is combined with zinc peroxide nanoparticles in the treatment of orthotopic liver cancer which has a "chemical factory" including that liver is the main place for iron storage, metabolism, and also the main metabolic sites for the majority of ingested substances, guaranteeing customized and enhanced chemodynamic therapy and normal liver cells protection as well. The good results in vitro and in vivo can set an inspiring example for exploring and utilizing suitable nanomaterials in corresponding cancer models, ensuring well-fitness of nanomaterials for disease and satisfactory therapeutic effect.


Assuntos
Neoplasias Hepáticas , Nanopartículas , Nanoestruturas , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Nanomedicina/métodos , Fototerapia
15.
J Comput Assist Tomogr ; 46(3): 379-382, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35405710

RESUMO

OBJECTIVE: The clinical application of magnetic resonance imaging-guided focused ultrasound (MRgFUS) surgery for treatment of symptomatic uterine fibroids is often limited because of the bowel between the abdominal wall and uterus. If bowels are in the pathway of sonication path, firstly filling the bladder, then filling the rectum, and emptying the bladder subsequently can be used to avoid them in recent research. The purpose of this study was to evaluate whether the modified bowel displacement technique (rectal filling first and then bladder filling, with or without subsequent bladder emptying) was feasible to create secure acoustic window. METHODS: A total of 78 patients who had undergone MRgFUS treatment for uterine fibroids and adenomyosis from January 2020 to November 2020 were included in this retrospective study. Of the 78 patients, 19 patients were treated using a modified bowel displacement technique, whereas the rest of the patients did not require intestinal displacement. High-intensity focused ultrasound was performed using GE Sightec HDXT 1.5 Tesla MR and ExAblate high-intensity focused ultrasound system. RESULTS: Of the 19 patients requiring bowel displacement techniques, 17 patients successfully completed MRgFUS surgery. Magnetic resonance imaging-guided focused ultrasound surgery was feasible in 4 patients after rectal filling, bladder filling, and subsequent bladder emptying. The others received ablation through the extended bladder because of bowel descending after emptying the bladder. The surgery caused no intestinal or uterine complications and no serious discomfort to the patient. CONCLUSIONS: The modified bowel displacement technique was effective in displacing interposed bowels during MRgFUS treatment to create safe acoustic pathway for ablating uterine fibroids and adenomyosis.


Assuntos
Adenomiose , Leiomioma , Neoplasias Uterinas , Adenomiose/diagnóstico por imagem , Adenomiose/cirurgia , Feminino , Humanos , Leiomioma/diagnóstico por imagem , Leiomioma/cirurgia , Imageamento por Ressonância Magnética , Reto/patologia , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgia
16.
Eur Radiol ; 32(5): 3187-3198, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35133485

RESUMO

OBJECTIVES: To construct a radiomics nomogram based on multiparametric MRI data for predicting isocitrate dehydrogenase 1 mutation (IDH +) and loss of nuclear alpha thalassemia/mental retardation syndrome X-linked expression (ATRX -) in patients with lower-grade gliomas (LrGG; World Health Organization [WHO] 2016 grades II and III). METHODS: A total of 111 LrGG patients (76 mutated IDH and 35 wild-type IDH) were enrolled, divided into a training set (n = 78) and a validation set (n = 33) for predicting IDH mutation. IDH + LrGG patients were further stratified into the ATRX - (n = 38) and ATRX + (n = 38) subtypes. A total of 250 radiomics features were extracted from the region of interest of each tumor, including that from T2 fluid-attenuated inversion recovery (T2 FLAIR), contrast-enhanced T1 WI, ASL-derived cerebral blood flow (CBF), DWI-derived ADC, and exponential ADC (eADC). A radiomics signature was selected using the Elastic Net regression model, and a radiomics nomogram was finally constructed using the age, gender information, and above features. RESULTS: The radiomics nomogram identified LrGG patients for IDH mutation (C-index: training sets = 0.881, validation sets = 0.900) and ATRX loss (C-index: training sets = 0.863, validation sets = 0.840) with good calibration. Decision curve analysis further confirmed the clinical usefulness of the two nomograms for predicting IDH and ATRX status. CONCLUSIONS: The nomogram incorporating age, gender, and the radiomics signature provided a clinically useful approach in noninvasively predicting IDH and ATRX mutation status for LrGG patients. The proposed method could facilitate MRI-based clinical decision-making for the LrGG patients. KEY POINTS: • Non-invasive determination of IDH and ATRX gene status of LrGG patients can be obtained with a radiomics nomogram. • The proposed nomogram is constructed by radiomics signature selected from 250 radiomics features, combined with age and gender. • The proposed radiomics nomogram exhibited good calibration and discrimination for IDH and ATRX gene mutation stratification of LrGG patients in both training and validation sets.


Assuntos
Glioma , Nomogramas , Glioma/diagnóstico por imagem , Glioma/genética , Humanos , Imageamento por Ressonância Magnética/métodos , Mutação , Estudos Retrospectivos , Proteína Nuclear Ligada ao X/genética
17.
Adv Sci (Weinh) ; 8(11): e2002548, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34105274

RESUMO

Timely detection of liver fibrosis by X-ray computed tomography (CT) can prevent its progression to fatal liver diseases. However, it remains quite challenging because conventional CT can only identify the difference in density instead of X-ray attenuation characteristics. Spectral CT can generate monochromatic imaging to specify X-ray attenuation characteristics of the scanned matter. Herein, an X-ray energy-dependent attenuation strategy originated from bismuth (Bi)-based nanoprobes (BiF3 @PDA@HA) is proposed for the accurate diagnosis of liver fibrosis. Bi element in BiF3 @PDA@HA can exhibit characteristic attenuation depending on different levels of X-ray energy via spectral CT, and that is challenging for conventional CT. In this study, selectively accumulating BiF3 @PDA@HA nanoprobes in the hepatic fibrosis areas can significantly elevate CT value for 40 Hounsfield units on 70 keV monochromatic images, successfully differentiating from healthy livers and achieving the diagnosis of liver fibrosis. Furthermore, the enhancement produced by the BiF3 @PDA@HA nanoprobes in vivo increases as the monochromatic energy decreases from 70 to 40 keV, optimizing the conspicuity of the diseased areas. As a proof of concept, the strategically designed nanoprobes with energy-dependent attenuation characteristics not only expand the scope of CT application, but also hold excellent potential for precise imaging-based disease diagnosis.


Assuntos
Bismuto/farmacologia , Cirrose Hepática/diagnóstico , Nanopartículas/química , Tomografia Computadorizada por Raios X , Animais , Bismuto/química , Meios de Contraste/química , Meios de Contraste/farmacologia , Modelos Animais de Doenças , Humanos , Indóis/química , Fígado/diagnóstico por imagem , Fígado/efeitos dos fármacos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Camundongos , Nanopartículas/uso terapêutico , Imagens de Fantasmas , Polímeros/química , Intensificação de Imagem Radiográfica/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
19.
J Comput Assist Tomogr ; 45(2): 285-293, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33661150

RESUMO

PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial arteriopathy characterized by recurrent lacunar stroke, migraine, and depression. The mechanism of cognitive dysfunction in CADASIL is still uncertain. The aim of this study was to use tract-based spatial statistics (TBSS) to map voxelwise the spatial distribution of brain microstructural change revealed by DTI-derived indices in patients with CADASIL to further study the underlying neuropsychopathological mechanism of CADASIL. METHOD: Twelve patients with CADASIL and 11 age-, sex-matched healthy controls underwent magnetic resonance imaging at 3 T. Then we evaluated DTI-derived indices (fractional anisotropy [FA], mode of anisotropy [MO], mean diffusivity [MD], axial diffusivity [AD] and radial diffusivity [RD]) of brain white matter (WM) between CADASIL patients and healthy subjects through TBSS. RESULTS: Compared with healthy controls, patients with CADASIL showed extensive decreased FA, MO and increased RD, AD, and MD throughout the entire brain (mainly the WM of the temporal poles, inferior and superior longitudinal fasciculus, inferior fronto-occipital fasciculus, corpus callosum, uncinate fasciculus, internal capsule, external capsule, corona radiata, thalamic radiation, and cingulum). Furthermore, these WM microstructural alterations were significantly correlated with cognitive scores and Scheltens scores. Decreased FA values and MO values were positively correlated with Montreal Cognitive Assessment scores in CADASIL patients. Increased AD, RD, and MD values were significantly negatively correlated with Montreal Cognitive Assessment scores. CONCLUSIONS: Widespread WM abnormalities were clearly shown in CADASIL by using TBSS. Severity of microstructural changes correlates significantly with extension of T2 hyperintensity. Moreover, WM microstructural damage and cognitive impairment were significantly correlated. This study indicated that WM tract damage plays an important role in cognitive impairment in CADASIL.


Assuntos
Encéfalo/diagnóstico por imagem , CADASIL/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Imagem de Tensor de Difusão , Adulto , Encéfalo/patologia , CADASIL/complicações , CADASIL/patologia , Estudos de Casos e Controles , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Curr Med Res Opin ; 37(4): 693-701, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33534617

RESUMO

OBJECTIVES: To evaluate the efficacy and safety of oral sitafloxacin versus oral moxifloxacin in the treatment of Chinese adults with community-acquired pneumonia (CAP). PATIENTS AND METHODS: This is a multicenter, randomized, open-label, positive-controlled clinical trial (chinadrugtrials.org.cn identifier: CTR20130046). CAP patients received sitafloxacin tablets 100 mg once daily (qd) or 100 mg twice daily (bid) to compare with moxifloxacin tablets 400 mg qd, for 7-10 days. The primary outcome was non-inferiority of sitafloxacin to moxifloxacin in clinical cure rate at test of cure (TOC) visit in per-protocol set (PPS). RESULTS: A total of 343 patients were randomized (sitafloxacin 100 mg qd, n = 117; sitafloxacin 100 mg bid, n = 116; moxifloxacin, n = 110), 291 patients were included in the PPS (sitafloxacin 100 mg qd, n = 96; sitafloxacin 100 mg bid, n = 94; moxifloxacin, n = 101). The clinical cure rate was 94.8% in the sitafloxacin 100 mg qd group, 96.8% in the sitafloxacin 100 mg bid group and 95.0% in the moxifloxacin group. At the TOC visit, the microbiological success rate was 97.0% (32/33) in the sitafloxacin 100 mg qd group, 97.1% (34/35) in the sitafloxacin 100 mg bid group and 94.9% (37/39) in the moxifloxacin group in the microbiological evaluable set (MES). The incidence of study-drug-related adverse events (AEs) was 23.3% (27/116) in the sitafloxacin 100 mg qd group, 29.8% (34/114) in the sitafloxacin 100 mg bid group and 28.2% (31/110) in the moxifloxacin group (p > .05). The common AEs related to study drug were dizziness, nausea, diarrhea, increased platelet count and alanine transaminase (ALT) elevation. All the AEs resolved completely after discontinuation of study drug. CONCLUSION: Sitafloxacin 100 mg qd or 100 mg bid for 7-10 days is not inferior to moxifloxacin 400 mg qd for 7-10 days in clinical efficacy for adult CAP patients. Sitafloxacin provides a safety profile comparable to moxifloxacin.


Assuntos
Antibacterianos , Pneumonia , Adulto , Antibacterianos/efeitos adversos , Método Duplo-Cego , Fluoroquinolonas/efeitos adversos , Humanos , Moxifloxacina/efeitos adversos , Resultado do Tratamento
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