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1.
Anesth Analg ; 136(1): 60-69, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36301724

RESUMO

BACKGROUND: The effect of anesthesia regimens on postoperative delirium after on-pump cardiac valve surgery is yet undetermined. This study aimed to evaluate the effect of volatile anesthesia compared with propofol-based total intravenous anesthesia (TIVA) on the occurrence of delirium after on-pump cardiac valve surgery. METHODS: This randomized clinical trial was conducted at a university academic hospital in China, from February 2019 to January 2021. Patients scheduled for on-pump cardiac valve surgery or combined valve with coronary artery bypass grafting (CABG) surgeries were randomly assigned to receive anesthesia maintenance with either a volatile anesthetic (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was the incidence of delirium during the first 7 days after surgery, assessed using the confusion assessment method for the intensive care unit (ICU). The secondary outcomes included duration of delirium, subtypes of delirium, 30-day mortality, pain score, major morbidity (including cerebral infarction, respiratory failure, and pneumonia), duration of mechanical ventilation, and lengths of ICU and hospital stay. The statistical analysis of the primary outcome variable was by Pearson's χ 2 test. RESULTS: Among the 684 patients analyzed (mean age, 53.8 years; 381 [55.7%] women), 676 were assessed for the primary outcome. Postoperative delirium occurred in 63 of 337 (18.7%) patients receiving volatile anesthesia versus 76 of 339 (22.4%) patients receiving propofol-based TIVA (relative risk, 0.80; 95% confidence interval [CI], 0.55-1.16; P = .231). There were no significant differences between the groups in any of the secondary outcomes. CONCLUSIONS: Among patients undergoing on-pump cardiac valve surgery, anesthesia maintenance with a volatile agent did not result in significantly fewer occurrences of postoperative delirium than propofol-based TIVA.


Assuntos
Anestésicos Inalatórios , Procedimentos Cirúrgicos Cardíacos , Delírio do Despertar , Propofol , Humanos , Adulto , Feminino , Pessoa de Meia-Idade , Masculino , Propofol/efeitos adversos , Delírio do Despertar/etiologia , Anestesia Intravenosa/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Valvas Cardíacas , Anestésicos Intravenosos/efeitos adversos
2.
J Cardiothorac Vasc Anesth ; 36(10): 3758-3765, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35863984

RESUMO

OBJECTIVES: The purpose of this study was to evaluate the effect of volatile anesthesia and propofol-based total intravenous anesthesia (TIVA) on postoperative pulmonary complications (PPCs) among patients undergoing cardiac surgery. DESIGN: Parallel-group, randomized controlled trial. SETTING: Single-center tertiary care hospital. PARTICIPANTS: Five hundred twenty-four patients undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: The patients were assigned randomly (1:1) to receive anesthesia maintenance with a volatile anesthetic (sevoflurane or desflurane) or propofol-based TIVA. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite of postoperative pulmonary complications within the first 7 postoperative days. The PPCs occurred in 118 of 262 patients (45.0%) in the volatile anesthesia group compared with 105 of 262 patients (40.1%) in the propofol-based intravenous anesthesia group (relative risk: 1.17 [95% CI 0.96-1.42], p = 0.123). There were no significant differences in the severity of PPCs within 7 days postoperatively, the occurrence and severity grade of PPCs within 30 days, the incidence of hypoxia, and 30-day mortality. CONCLUSIONS: In adult patients undergoing cardiac surgery with cardiopulmonary bypass, general anesthesia with a volatile anesthetic compared with propofol-based TIVA had not reduced pulmonary complications within the first 7 days after surgery.


Assuntos
Anestésicos Inalatórios , Procedimentos Cirúrgicos Cardíacos , Propofol , Adulto , Anestesia Geral , Anestesia Intravenosa/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Anestésicos Intravenosos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Propofol/efeitos adversos
3.
Zhongguo Zhong Yao Za Zhi ; 47(7): 1881-1887, 2022 Apr.
Artigo em Zh | MEDLINE | ID: mdl-35534258

RESUMO

This study employed Box-Behnken design combined with flux attenuation to explore the nanofiltration conditions for separation of alcohol precipitation liquid during the preparation of Reduning Injection and discussed the applicability of nanofiltration in the separation of the liquid with high-concentration ethanol. The effects of nanofiltration molecular weight cut-off(MWCO) and pH on the rejection of chlorogenic acid, 3,5-dicaffeoylquinic acid, and 4,5-dicaffeoylquinic acid were consistent with the principles of pore size sieving and charge effect, respectively. The rejection of the three phenolic acids was reduced by concentration polarization effect caused by trans-membrane pressure(TMP). The swelling of membrane surface decreased the pore size and membrane flux for effective separation. Chlorogenic acid and 4,5-dicaffeoylquinic acid were more sensitive to pH and ethanol concentration than 3,5-dicaffeoylquinic acid. A certain correlation existed between the compound structure and the separation factors of nanofiltration, and the separation rules were associated with the comprehensive effect of charge effect, pore size sieving, concentration polarization, steric hindrance and so on.


Assuntos
Ácido Clorogênico , Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/química , Etanol , Injeções
4.
J Cardiothorac Vasc Anesth ; 35(8): 2438-2446, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33183935

RESUMO

OBJECTIVES: Sternal incisions can generate persistent and intense post-sternotomy pain. Propofol has been shown to improve postoperative analgesia, but the preventive effect on persistent pain after cardiac surgery is unknown. The hypothesis of the present study was that intraoperative propofol-based anesthesia compared with volatile anesthesia could reduce the risk of chronic pain after cardiac surgery. DESIGN: A single-center, two-arm, patient-and-evaluator-blinded, randomized controlled trial. SETTING: A single major urban teaching and university hospital. PATIENTS: Five-hundred adult patients undergoing cardiac surgery via sternotomy randomly were assigned. With six withdrawals from the study and five from surgery, 244 in the total intravenous anesthesia group and 245 in the volatile group were included in the modified intention-to-treat analysis. INTERVENTIONS: Patients randomly were assigned to receive either propofol-based total intravenous anesthesia or volatile anesthesia during surgery. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were the incidence of pain at three, six, and 12 months after surgery defined as pain score >0 on the numeric rating scale. The secondary outcomes included acute pain, opioid use during the first 72 hours after surgery, and quality of life. The use of propofol did not significantly affect chronic pain at three months (55.4% v 52.9%, difference 2.5%, 95% confidence interval [CI] -6.6 to 11.6; p = 0.656), six months (35.5% v 37.5%, difference -2.0%, 95% CI -10.9 to 6.9; p = 0.657), or 12 months (18.2% v 20.7%, difference -2.5%, 95% CI -9.8 to 4.8; p = 0.495) compared with volatile anesthetics. Furthermore, there were no differences in acute pain score; morphine-equivalent consumption during the first 72 hours; and quality of life at three, six, and 12 months after surgery. CONCLUSIONS: Intraoperative administration of propofol did not reduce persistent pain after cardiac surgery compared with volatile anesthetics.


Assuntos
Dor Aguda , Anestésicos Inalatórios , Procedimentos Cirúrgicos Cardíacos , Propofol , Adulto , Anestésicos Inalatórios/efeitos adversos , Anestésicos Intravenosos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Humanos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Qualidade de Vida
5.
Hemoglobin ; 45(5): 318-321, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35514176

RESUMO

ß-Thalassemia (ß-thal), one of the most common form of single-gene inheritable blood diseases in the world, is highly prevalent in southern China, especially in the Guangxi Zhuang Autonomous Region. To update the ß-thal mutation spectrum in this region, we performed hematological and genetic analyses on 888 ß-thal major (ß-TM), ß-thal intermedia (ß-TI) and ß-thal carrier patients, aged 0-15 years old, from different parts of Guangxi Province. We identified 55 genotypes and 18 ß-thal mutations. The codons 41/42 (-TTCT) (HBB: c.126_129delCTTT) (43.97%), codon 17 (A>T) (HBB: c.52A>T) (25.43%), -28(A>G) (HBB: c.-78A>G) (8.18%), IVS-II-654 (C>T) (HBB: c.316-197C>T) (7.85%) and codon 26 (G>A) (HBB: c.79G>A) (5.02%) were the five most common, accounting for more than 90.0%. The results of our study are providing an up-to-date ß-thal mutation spectrum in the 0-15-year-old pediatric population, which will help genetic counseling and prevention of ß-TM in mainland China's most endemic region, Guangxi Zhuang Autonomous Region.


Assuntos
Talassemia beta , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Códon , Frequência do Gene , Genótipo , Humanos , Lactente , Recém-Nascido , Mutação , Globinas beta/genética , Talassemia beta/epidemiologia , Talassemia beta/genética
6.
Pharmacol Res ; 159: 105031, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32562816

RESUMO

Thrombosis initiated by abnormal platelet aggregation is a pivotal pathological event that precedes most cases of cardiovascular diseases (CVD). Recently, growing evidence indicates that platelet could be a potential target for CVD prevention. However, as the conventional antithrombotic management strategy, applications of current antiplatelet agents are somewhat limited by their various side effects, such as bleeding risk and drug resistance. Hence, efforts have been made to search for agents as complementary therapies. Ginsenoside, the principal active component extracted from Panax ginseng, has gained much attention for its regulations on multiple crucial events of platelet aggregation. From structural characteristics to clinical applications, this review anatomized the intrinsic structure-function relationship of antiplatelet potency of ginsenosides, and the involved signal pathways were specifically summarized. Additionally, the emphasis was placed on clinical studies that investigate the antithrombotic efficacy of ginsenosides in the treatment of CVD. Further, a broad overview of approaches for improving the bioavailability of ginsenosides was concluded. Limitations and prospects of current studies were also discussed. This study may provide some new insights into the systematic understanding of ginsenosides in CVD treatment and lay a foundation for future research.


Assuntos
Plaquetas/efeitos dos fármacos , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Ginsenosídeos/uso terapêutico , Músculo Liso Vascular/efeitos dos fármacos , Neointima , Inibidores da Agregação Plaquetária/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Remodelação Vascular/efeitos dos fármacos , Animais , Disponibilidade Biológica , Plaquetas/metabolismo , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/farmacocinética , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/patologia , Ginsenosídeos/efeitos adversos , Ginsenosídeos/farmacocinética , Humanos , Estrutura Molecular , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/farmacocinética , Transdução de Sinais , Relação Estrutura-Atividade
7.
Water Res ; 231: 119657, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36709568

RESUMO

Anaerobic digestion of lipid-rich wastewater generally suffers from foaming induced by long chain fatty acid (LCFA). However, a systematic understanding of LCFA inhibition, especially the physical inhibition on interfacial interaction still remains unclear. Here, we combined bubble probe atomic force microscope and impinging-jet technique to unravel the interfacial interactions controlled by long chain fatty acids in anaerobic digestion. We showed that LCFA had a significant inhibition on methane production in anaerobic reactors for the inhibition of the conversion of VFAs to methane. By measuring the LCFA influence on methanogenic archaea Methanosarcina acetivorans C2A, the results demonstrated that methanogenesis was limited for substrates utilization but not metabolic pathways. The impinging-jet technique results indicated that LCFA enhanced bubble separation from anaerobic granules and reduced the bubble-bubble coalescence probability. In addition, the bubble probe atomic force microscope (AFM) revealed that LCFA enhanced the adhesion force between bubbles by enhancing electrical double layer (EDL) repulsion and decreasing hydrophobic interactions. Overall, these results complement framework of LCFA inhibition in anerobic digestion and provide a nanomechanical insight into the fundamental interfacial interactions related to bubbles in anaerobic reactors.


Assuntos
Ácidos Graxos , Águas Residuárias , Anaerobiose , Ácidos Graxos/metabolismo , Metano/metabolismo , Reatores Biológicos , Esgotos/química
8.
Am J Chin Med ; 50(3): 749-772, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35450513

RESUMO

The endothelium covers the internal lumen of the entire circulatory system and plays an important modulatory role in vascular homeostasis. Endothelium dysfunction, characterized by a vasoconstrictive, pro-inflammatory, and pro-coagulant state, usually manifests as a significant pathological process of vascular diseases, including hypertension, atherosclerosis (AS), stroke, diabetes mellitus, coronary artery disease, and cancer. Therefore, there is an urgent necessity to seek promising therapeutic drugs or remedies to ameliorate endothelial dysfunction-induced vascular ailments and complications. Recently, much attention has been attached to ginsenosides, the most significant active components of ginseng, which have always been referred to as "all-healing" and widely used for its extensively medicinal value. Surprisingly, ginsenosides have diverse biological activity which might be related to inflammation, apoptosis, oxidative stress, and angiogenesis. In this review, a brief introduction about endothelial dysfunction and ginsenosides was demonstrated, and the emphasis was put on summarizing multi-faceted pharmacological effects and underlying molecular mechanisms of ginsenosides on the endothelium, including vasorelaxation, anti-oxidation, anti-inflammation, and angio-modulation. Beyond that, nanotechnology to improve efficacy and the existing clinical trials of ginsenosides were concluded. Hopefully, our work will give suggestions for promoting clinical application of traditional Chinese medicine, e.g., hypertension, AS, diabetes, ischemic stroke, and cancer. This review provides a comprehensive base of knowledge for ginsenosides to prevention and treatment of vascular injury- related diseases with clinical significance.


Assuntos
Ginsenosídeos , Hipertensão , Neoplasias , Panax , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Neoplasias/tratamento farmacológico , Preparações Farmacêuticas
9.
Biomater Sci ; 10(21): 6267-6281, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36128848

RESUMO

Conventional treatments for cancer, such as chemotherapy, surgical resection, and radiotherapy, have shown limited therapeutic efficacy, with severe side effects, lack of targeting and drug resistance for monotherapies, which limit their clinical application. Therefore, combinatorial strategies have been widely investigated in the battle against cancer. Herein, we fabricated a dual-targeted nanoscale drug delivery system based on EpCAM aptamer- and lactic acid-modified low-polyamidoamine dendrimers to co-deliver the FDA-approved agent disulfiram and photosensitizer indocyanine green, combining the imaging and therapeutic functions in a single platform. The multifunctional nanoparticles with uniform size had high drug-loading payload, sustained release, as well as excellent photothermal conversion. The integrated nanoplatform showed a superior synergistic effect in vitro and possessed precise spatial delivery to HepG2 cells with the dual-targeting nanocarrier. Intriguingly, a robust anticancer response of chemo-phototherapy was achieved; chemotherapy combined with the efficacy of phototherapy to cause cellular apoptosis of HepG2 cells (>35%) and inhibit the regrowth of damaged cells. Furthermore, the theranostic nanosystem displayed fluorescence imaging in vivo, attributed to its splendid accumulation in the tumor site, and it provided exceptional tumor inhibition rate against liver cancer cells (>76%). Overall, our research presents a promising multifunctional theranostic nanoplatform for the development of synergistic therapeutics for tumors in further applications.


Assuntos
Dendrímeros , Hipertermia Induzida , Nanopartículas , Neoplasias , Humanos , Verde de Indocianina/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Molécula de Adesão da Célula Epitelial , Doxorrubicina/farmacologia , Preparações de Ação Retardada , Medicina de Precisão , Dissulfiram , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/terapia , Ácido Láctico , Hipertermia Induzida/métodos , Liberação Controlada de Fármacos , Nanomedicina Teranóstica/métodos , Linhagem Celular Tumoral
10.
Des Monomers Polym ; 24(1): 259-264, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34434071

RESUMO

Through the reaction between HTrz and Cd(NO3)2 · 4H2O, a new Cd(II) compound of [Cd(Trz) 2] n (1, HTrz = 1,2,4-triazole) can be obtained, which has been studied with diffraction analysis by single crystal X-ray as well as powder X-ray diffraction. The structure of 1 can be stable up to 265°C, and the solid samples of 1 emit intense blue luminescence at room temperature. Along with the evaluation of tuberculosis treatment and clinical nursing, related mechanism was also studied here. Firstly, ELISA assay was conducted and the IL-10 and IL-18 released into the alveolar lavage fluid was determined. Apart from this, the real-time RT-PCR was used to reflect surviving gene's relative expression of Mycobacterium tuberculosis after compound treatment.

11.
Carbohydr Polym ; 257: 117642, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33541666

RESUMO

Carrageenan (CRG) is a kind of linear sulfated polysaccharide that emerging as a promising substituent in food, pharmaceutics, and cosmetics. In recent years, biological properties of CRG polysaccharides such as antiviral, immunomodulatory, anticoagulant, antioxidant, and anticancer have been broadly studied, however, systematical summary of their structure-property relationships is scarce. Moreover, chemical modification is of great significance to explore biological and physiochemical properties of CRG polysaccharides which should be focused on. Chemical modification of CRG polysaccharides, e.g., carboxymethylation, thiolation, acetylation, phosphorylation, oversulfation, oxidization, and cationic or other derivatives, can improve their bioactivities and facilitate their applications in different biological systems. Hence, this review aims to elucidate structure-property relationships of CRG and its chemically modified derivatives with different structures and bioactivities, so as toxicity of CRG as food additive for the guidance of its clinical application.


Assuntos
Carragenina/química , Sistemas de Liberação de Medicamentos , Polissacarídeos/química , Rodófitas/metabolismo , Sulfatos/química , Animais , Anticoagulantes/química , Antineoplásicos/farmacologia , Antioxidantes/química , Cátions , Desenho de Fármacos , Aditivos Alimentares , Humanos , Camundongos , Fosforilação , Relação Estrutura-Atividade
12.
Int J Pharm ; 605: 120784, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34111544

RESUMO

Diabetes is a metabolic disease caused by insufficient insulin secretion, action or resistance, in which insulin plays an irreplaceable role in the its treatment. However, traditional administration of insulin requires continuous subcutaneous injections, which is accompanied by inevitable pain, local tissue necrosis and hypoglycemia. Herein, a green and safe nanoformulation with unique permeability composed of insulin and ginsenosides is developed for transdermal delivery to reduce above-mentioned side effects. The ginsenosides are self-assembled to form shells to protect insulin from hydrolysis and improve the stability of nanoparticles. The nanoparticles can temporarily permeate into cells in 5 min and promptly excrete from the cell for deeper penetration. The insulin permeation is related to the disorder of stratum corneum lipids caused by ginsenosides. The skin acting as drug depot mantains the nanoparticles released continuously, therefore the body keeps euglycemic for 48 h. Encouraged by its long-lasting and effective transdermal therapy, ginsenosides-based nano-system is expected to deliver other less permeable drugs like proteins and peptides and benefit those who are with chronic diseases that need long-term medication.


Assuntos
Ginsenosídeos , Nanopartículas , Administração Cutânea , Sistemas de Liberação de Medicamentos , Insulina , Permeabilidade , Pele
13.
J Clin Anesth ; 67: 110009, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32836188

RESUMO

STUDY OBJECTIVE: Intraoperative lung-protective ventilation strategy has been recommended to reduce postoperative pulmonary complications (PPCs). However, the role of inspiratory oxygen fraction (FiO2) in this protection remains highly uncertain. We aimed to evaluate the effect of intraoperative low (30%) versus high (80%) FiO2 in the context of lung-protective ventilation strategy on PPCs in patients undergoing abdominal surgery. DESIGN: Prospective, two-arm, randomized controlled trial. SETTING: Tertiary university hospital in China. PATIENTS: A total of ASA I-III 252 patients aged ≥18, who were scheduled for elective abdominal surgery under general anesthesia were included in the study. INTERVENTION: Patients were randomly assigned to receive either 30% or 80% FiO2 during the intraoperative period. All patients received volume-controlled mechanical ventilation with lung-protective ventilation approach, which included a tidal volume of 8 ml kg-1 of predicted body weight, a positive end-expiratory pressure level of 6-8 cmH2O, and repeated recruitment maneuvers. MEASUREMENTS: The primary outcome was a composite of postoperative pulmonary complications within the first 7 postoperative days, consisting of respiratory infection, respiratory failure, bronchospasm, atelectasis, pleural effusion, pneumothorax, and aspiration pneumonitis. The severity grade of PPCs was measured as a key secondary outcome. MAIN RESULTS: Two hundred and fifty-one patients completed the trial. PPCs occurred in 43 of 125 (34.4%) patients assigned to receive 30% FiO2 compared with 59 of 126 (46.8%) patients receiving 80% FiO2 (relative risk 0.74, 97.5% confidence interval, 0.51-1.02, p = 0.045, > 0.025). The severity of PPCs within the first 7 days following surgery was attenuated significantly in the low (30%) FiO2 group (p = 0.001). CONCLUSIONS: Among patients undergoing abdominal surgery under general anesthesia, an intraoperative lung-protective ventilation strategy with 30% FiO2 compared with 80% FiO2 did not reduce the incidence of PPCs. And the use of 30% FiO2 resulted in less severe pulmonary complications.


Assuntos
Oxigênio , Respiração Artificial , China , Humanos , Pulmão , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Respiração Artificial/efeitos adversos , Volume de Ventilação Pulmonar
14.
ACS Appl Mater Interfaces ; 12(40): 44789-44797, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32910643

RESUMO

Metallic glasses (MGs) with superior catalytic performance have recently been recognized as attractive candidates for wastewater treatment. However, further improving their performance will require knowledge of how to precisely regulate their electronic structures via compositional control. Here, two Fe-based MGs (Fe78Si9B13 and Fe80Si9B11) were prepared to compare how slightly altering boron content affected their electronic structure and catalytic performance. Density functional theory revealed that the Fe78Si9B13 MG with 2 atom % higher boron exhibits an attractive electron delocalization, a high persulfate adsorption energy, and a superb work function due to precise regulation of the electronic structure, leading to exceptional degradation performance for seven organic pollutants. Furthermore, it can be reused 23 times without significant deterioration of catalytic performance, amorphous structure, and surface morphology. This work provides a new paradigm for the fundamental theory explaining how electronic structure is controlled by composition, creating a solid foundation to explore novel catalysts for water treatment.

15.
ACS Appl Mater Interfaces ; 12(51): 57362-57372, 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33301289

RESUMO

The rapid development of CRISPR/Cas9 systems has opened up tantalizing prospects to sensitize cancers to chemotherapy using efficient targeted genome editing, but safety concerns and possible off-target effects of viral vectors remain a major obstacle for clinical application. Thus, the construction of novel nonviral tumor-targeting nanodelivery systems has great potential for the safe application of CRISPR/Cas9 systems for gene-chemo-combination therapy. Here, we report a polyamidoamine-aptamer-coated hollow mesoporous silica nanoparticle for the co-delivery of sorafenib and CRISPR/Cas9. The core-shell nanoparticles had good stability, enabled ultrahigh drug loading, targeted delivery, and controlled-release of the gene-drug combination. The nanocomplex showed >60% EGFR-editing efficiency without off-target effects in all nine similar sites, regulating the EGFR-PI3K-Akt pathway to inhibit angiogenesis, and exhibited a synergistic effect on cell proliferation. Importantly, the co-delivery nanosystem achieved efficient EGFR gene therapy and caused 85% tumor inhibition in a mouse model. Furthermore, the nanocomplex showed high accumulation at the tumor site in vivo and exhibited good safety with no damage to major organs. Due to these properties, the nanocomplex provides a versatile delivery approach for efficient co-loading of gene-drug combinations, allowing for precise gene editing and synergistic inhibition of tumor growth without apparent side effects on normal tissues.


Assuntos
Sistemas CRISPR-Cas , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/química , Dióxido de Silício/química , Sorafenibe/uso terapêutico , Animais , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/toxicidade , Proteína 9 Associada à CRISPR/genética , Linhagem Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Molécula de Adesão da Célula Epitelial/química , Receptores ErbB/genética , Receptores ErbB/metabolismo , Edição de Genes , Genes erbB-1 , Humanos , Camundongos , Nanopartículas/toxicidade , Poliaminas/química , Poliaminas/toxicidade , Porosidade , Transdução de Sinais/efeitos dos fármacos , Dióxido de Silício/toxicidade
16.
World J Gastrointest Endosc ; 12(11): 451-458, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33269054

RESUMO

BACKGROUND: Compared to traditional open surgery, laparoscopic surgery has become a standard approach for colorectal cancer due to its great superiorities including less postoperative pain, a shorter hospital stay, and better quality of life. In 2007, Whiteford et al reported the first natural orifice trans-anal endoscopic surgery (NOTES) sigmoidectomy using transanal endoscopic microsurgery. To date, all cases of NOTES colorectal resection have included a hybrid laparoscopic approach with the use of established rigid platforms. AIM: To introduce a novel technique of peroral external traction-assisted transanal NOTES rectosigmoidectomy followed by intracorporeal colorectal end-to-end anastomosis by using only currently available and flexible endoscopic instrumentation in a live porcine model. METHODS: Three female pigs weighing 25-30 kg underwent NOTES rectosigmoid resection. After preoperative work-up and bowel preparation, general anesthesia combined with endotracheal intubation was achieved. One dual-channel therapeutic endoscope was used. Carbon dioxide insufflation was performed during the operation. The procedure of trans-anal NOTES rectosigmoidectomy included the following eight steps: (1) The rectosigmoid colon was tattooed with India ink by submucosal injection; (2) Creation of gastrostomy by directed submucosal tunneling; (3) Peroral external traction using endoloop ligation; (4) Creation of rectostomy on the anterior rectal wall by directed 3 cm submucosal tunneling; (5) Peroral external traction-assisted dissection of the left side of the colon; (6) Trans-anal rectosigmoid specimen transection, where an anvil was inserted into the proximal segment after purse-string suturing; (7) Intracorporeal colorectal end-to-end anastomosis using a circular stapler by a single stapling technique; and (8) Closure of gastrostomy using endoscopic clips. All animals were euthanized immediately after the procedure, abdominal exploration was performed, and the air-under-water leak test was carried out. RESULTS: The procedure was completed in all three animals, with the operation time ranging from 193 min to 259 min. Neither major intraoperative complications nor hemodynamic instability occurred during the operation. The length of the resected specimen ranged from 7 cm to 13 cm. With the assistance of a trans-umbilical rigid grasper, intracorporeal colorectal, tension-free, end-to-end anastomosis was achieved in the three animals. CONCLUSION: Peroral traction-assisted transanal NOTES rectosigmoidectomy followed by intracorporeal colorectal end-to-end anastomosis is technically feasible and reproducible in an animal model and is worthy of further improvements.

17.
Int J Pharm ; 570: 118663, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31493497

RESUMO

Nanoformulations with advantages in drug delivery, safety and pharmacodynamics have been booming as a promising strategy for cancer therapy. However, the traditional nanocarrier still suffers from the low drug loading capacity, potential systematic toxicity, unclear metabolism, and other uncertainties. To overcome these issues, carrier-free nanodrugs with desirable bioactivity were developed rapidly and drawn considerable attention. Meanwhile, the multifunctional self-delivery nanoarcheticture fabricated by a simple and "green" method, has significant advantages in synergistic cancer therapy and inhibition of multidrug resistant (MDR). Till now, carrier-free nanoparticles for tumor theranostics, phototherapy, chemotherapy, diagnose and synergistic therapy, have made outstanding progress. In this review, we make an integrated and exhaustive overview of lately reports on carrier-free nanodrug delivery systems formed by several active agents. We summarize the self-assembly and modified strategies, with emphasis on application superiority of carrier-free nanocrystal, and give new insight into the establishment of ideal nanosystems for cancer treatment.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Portadores de Fármacos/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Animais , Sistemas de Liberação de Medicamentos/métodos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Humanos
18.
Trials ; 20(1): 619, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675982

RESUMO

BACKGROUND: Postoperative pulmonary complications (PPCs) are the most common perioperative complications following surgical site infection (SSI). They prolong the hospital stay and increase health care costs. A lung-protective ventilation strategy is considered better practice in abdominal surgery to prevent PPCs. However, the role of the inspiratory oxygen fraction (FiO2) in the strategy remains disputed. Previous trials have focused on reducing SSI by increasing the inhaled oxygen concentration but higher FiO2 (80%) was found to be associated with a greater incidence of atelectasis and mortality in recent research. The trial aims at evaluating the effect of different FiO2 added to the lung-protective ventilation strategy on the incidence of PPCs during general anesthesia for abdominal surgery. METHODS AND DESIGN: PROtective Ventilation with a low versus high Inspiratory Oxygen fraction trial (PROVIO) is a single-center, prospective, randomized controlled trial planning to recruit 252 patients undergoing abdominal surgery lasting for at least 2 h. The patients will be randomly assigned to (1) a low-FiO2 (30% FiO2) group and (2) a high-FiO2 (80% FiO2) group in the lung-protective ventilation strategy. The primary outcome of the study is the occurrence of PPCs within the postoperative 7 days. Secondary outcomes include the severity grade of PPCs, the occurrence of postoperative extrapulmonary complications and all-cause mortality within the postoperative 7 and 30 days. DISCUSSION: The PROVIO trial assesses the effect of low versus high FiO2 added to a lung-protective ventilation strategy on PPCs for abdominal surgery patients and the results should provide practical approaches to intraoperative oxygen management. TRIAL REGISTRATION: www.ChiCTR.org.cn , identifier: ChiCTR18 00014901 . Registered on 13 February 2018.


Assuntos
Pneumopatias/prevenção & controle , Oxigênio/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos
19.
Exp Ther Med ; 10(4): 1549-1555, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26622524

RESUMO

The aim of the present meta-analysis was to investigate the correlation of promoter methylation of the p16 and Ras association domain family 1 isoform A (RASSF1A) genes with the risk of the development of papillary thyroid cancer (PTC). A number of electronic databases were searched without language restrictions as follows: Medline (1966-2013), the Cochrane Library database (Issue 12, 2013), Embase (1980-2013), CINAHL (1982-2013), Web of Science (1945-2013) and the Chinese Biomedical Database (CBM; 1982-2013). A meta-analysis was performed with the use of Stata statistical software. The odds ratios (ORs), ratio differences (RDs) and 95% confidence intervals (95% CIs) were calculated. In the present meta-analysis, eleven clinical cohort studies with a total of 734 patients with PTC were included. The results of the current meta-analysis indicated that the frequency of promoter methylation of p16 in cancer tissues was significantly higher compared with that in normal, adjacent and benign tissues (cancer tissues vs. normal tissues: OR=7.14; 95% CI, 3.30-15.47; P<0.001; cancer tissues vs. adjacent tissues: OR=11.90; 95% CI, 5.55-25.52; P<0.001; cancer tissues vs. benign tissues: OR=2.25; 95% CI, 1.67-3.03; P<0.001, respectively). The results also suggest that RASSF1A promoter methylation may be implicated in the pathogenesis of PTC (cancer tissues vs. normal tissues: RD=0.53; 95% CI, 0.42-0.64; P<0.001; cancer tissues vs. adjacent tissues: RD=0.39; 95% CI, 0.31-0.48; P<0.001; cancer tissues vs. benign tissues: RD=0.39; 95% CI, 0.31-0.47; P<0.001; respectively). Thus, the present meta-analysis indicates that aberrant promoter methylation of p16 and RASSF1A genes may play a crucial role in the pathogenesis of PTC.

20.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 24(2): 178-80, 2002 Apr.
Artigo em Zh | MEDLINE | ID: mdl-12905798

RESUMO

OBJECTIVE: To evaluate the features of gastroesophageal reflux disease (GERD) in elderly patients. METHODS: 72 patients with GERD were investigated for the history of illness and the results of gastroscopy and 24 hours esophageal bile monitoring of 54 patients were simultaneously randomized to undergo ambulatory pH monitoring. The degrees of esophagitis were graded according to endoscopic findings. RESULTS: Obesity was found in 48% of the elderly group (more than 65 years old) and 49% of the control group (less than 65 years old). There were longer acid and bile reflux time and higher frequency (65%) of hiatal hernia in the elderly, and more patients (35%) had complicated severe grade esophagitis. There were longer time of bile reflux and the higher incidence (76%) of both acid and bile reflux in elderly group than in control group (P < 0.05). But the acid reflux time (%) was similar in two groups (P > 0.05). CONCLUSIONS: The GERD in elderly patients may be associated with obesity and hiatal hernia. The features of elderly GERD patients are high frequency of erosive esophagitis, and high frequency of both acid and bile reflux, as well as longer history of bile reflux time.


Assuntos
Refluxo Gastroesofágico/diagnóstico , Fatores Etários , Idoso , Refluxo Biliar/complicações , Esofagite Péptica/diagnóstico , Feminino , Refluxo Gastroesofágico/etiologia , Gastroscopia , Hérnia Hiatal/complicações , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial , Obesidade/complicações
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