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1.
J Chem Phys ; 160(16)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38651809

RESUMO

Chiral quantum dots (QDs) are promising materials applied in many areas, such as chiral molecular recognition and spin selective filter for charge transport, and can be prepared by facile ligand exchange approaches. However, ligand exchange leads to an increase in surface defects and reduces the efficiencies of radiative recombination and charge transport, which restricts further applications. Here, we investigate the light-induced photoluminescence (PL) enhancement in chiral L- and D-cysteine CdSe QD thin films, providing a strategy to increase the PL. The PL intensity of chiral CdSe QD films can be significantly enhanced over 100 times by continuous UV laser irradiation, indicating a strong passivation of surface defects upon laser irradiation. From the comparative measurements of the PL intensity evolutions in vacuum, dry oxygen, air, and humid nitrogen atmospheres, we conclude that the mechanism of PL enhancement is photo-induced surface passivation with the assistance of water molecules.

2.
Chem Biol Drug Des ; 102(6): 1618-1631, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37705133

RESUMO

The advancement of colorectal cancer (CRC) prevention, detection, and treatment is essential to ensure that survivors live longer and higher-quality lives. The field of cancer detection and therapy has undergone a revolution with the development of nanotechnology for targeted drug delivery. The significant problems with the delivery of cancer drugs are their solubility, stability, and nonspecific distribution. There is a challenge that the acidic and enzymatic environment in the digestive tract will modify or destroy the medication or the active pharmaceutical ingredient. To overcome the problems, nanoparticles have been widely employed during the past several years to increase the specificity, selectivity, and controlled release of drug delivery systems. The site-specific and targeted delivery leads to reduce toxicity and side effects. With respect to the capability and utilization of cyclodextrin-based nanoparticles in different aspects of the tumour microenvironment and gut microbiota, a survey of current research papers was conducted via looking through databases including GoogleScholar, PubMed, Web of Science, and Scopus. This review aims to summarize cutting-edge nanoparticulate-based technologies and therapies for CRC.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Ciclodextrinas , Nanopartículas , Humanos , Sistemas de Liberação de Medicamentos/métodos , Antineoplásicos/uso terapêutico , Preparações Farmacêuticas , Neoplasias Colorretais/tratamento farmacológico , Microambiente Tumoral
3.
Talanta ; 259: 124520, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37058943

RESUMO

Glutathione (GSH) is present in almost every cell in the body and plays various integral roles in many biological processes. The Golgi apparatus is a eukaryotic organelle for the biosynthesis, intracellular distribution, and secretion of various macromolecules; however, the mechanism of GSH in the Golgi apparatus has not been fully elucidated. Here, specific and sensitive sulfur-nitrogen co-doped carbon dots (SNCDs) with orange-red fluorescence was synthesized for the detection of GSH in the Golgi apparatus. The SNCDs have a Stokes shift of 147 nm and excellent fluorescence stability, and they exhibited excellent selectivity and high sensitivity to GSH. The linear response of the SNCDs to GSH was in the range of 10-460 µM (LOD = 0.25 µΜ). More importantly, we used SNCDs with excellent optical properties and low cytotoxicity as probes, and successfully realized golgi imaging in HeLa cells and GSH detection at the same time.


Assuntos
Corantes Fluorescentes , Pontos Quânticos , Humanos , Células HeLa , Corantes Fluorescentes/toxicidade , Pontos Quânticos/toxicidade , Carbono/toxicidade , Glutationa , Complexo de Golgi , Nitrogênio , Limite de Detecção
4.
Sci Rep ; 13(1): 2894, 2023 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-36807376

RESUMO

To investigate the potential mechanism of resveratrol in anti-fatigue by network pharmacology and molecular docking, and to investigate the anti-fatigue efficacy of resveratrol through in vitro animal experiments. Resveratrol action targets and fatigue-related targets were obtained using various databases. The anti-fatigue targets of resveratrol were obtained using the Venn diagram, uploaded to the String database, imported into Cytoscape 3.7.1, and constructed into a Protein-protein interaction network. The target genes were then subjected to Gene ontology and Kyoto encyclopedia of gene and genome enrichment analysis. Molecular docking verification was performed on the binding ability of the core target to resveratrol. Using swimming-trained mice as exercise models, exhaustive swimming time and fatigue-related biochemical parameters were used as indicators to investigate the effects of resveratrol on exercise endurance and energy metabolism. 104 anti-fatigue targets and 10 core target genes of resveratrol were obtained. KEGG analysis enrichment included AGE-RAGE signaling pathway in diabetic complications, Human cytomegalovirus infection, and Pathways in cancer. Molecular docking showed that the core target genes TP53, PIK3R1, AKT1, PIK3CA, and MAPK1 had good binding activity to resveratrol. Animal experiments showed that resveratrol could prolong the exhaustive swimming time of endurance-trained mice (P < 0.01), decrease aspartate aminotransferase, alanine aminotransferase, uric acid, blood lactate (P < 0.01), decrease blood urea nitrogen (P < 0.05), increase the liver glycogen, muscle glycogen (P < 0.01). Conclusion: Resveratrol has the characteristics of multiple targets and multiple pathways in anti-fatigue; resveratrol can enhance exercise endurance in mice.


Assuntos
Medicamentos de Ervas Chinesas , Farmacologia em Rede , Humanos , Animais , Camundongos , Simulação de Acoplamento Molecular , Resveratrol , Genes Reguladores , Mapas de Interação de Proteínas , Medicina Tradicional Chinesa
5.
Medicine (Baltimore) ; 102(3): e32467, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36701716

RESUMO

BACKGROUND: Recurrent patellar dislocation (RPD) occurs in people who have their own patellofemoral dysplasia and who have not been properly treated after their first patellar dislocation. For RPD where conservative treatment is ineffective, medial patellofemoral ligament (MPFL) reconstruction is the first choice for surgical treatment, but there are various and controversial ways of MPFL reconstruction and fixation. Initially, more scholars adopted the patellar lateral tunneling (PT) approach to contain and stabilize the graft, but with the newer materials and techniques, some experts adopted the lateral patellar anchor fixation (AF) of the graft, which can avoid the collateral damage caused by the patellar lateral tunneling and can obtain the same definite efficacy. Therefore, a meta-analysis must be performed to provide evidence whether there is a difference between AF and PT reconstruction of the MPFL in the treatment of RPD. METHODS: We will search, with no time restriction, without any restriction of language and status, the time from the establishment of the database to October 2022, on the following databases: PubMed (MEDLINE), Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Data (WF), Chinese Scientific Journals Database (VIP), and Chinese databases SinoMed (CBM) electronic databases. The electronic database search will be supplemented by a manual search of the reference lists of included articles. We will apply the risk-of-bias tool of the Cochrane Collaboration for randomized controlled trials to assess the methodological quality. Risk-of-Bias Assessment Tool for Non-randomized Studies was used to evaluate the quality of comparative studies. Statistical analysis will be conducted using RevMan 5.4 software. RESULTS: This systematic review and meta-analysis will evaluate the functional outcomes of the two fixation modalities, AF and PT, in reconstructing MPFL for RPD. CONCLUSION: The findings of this study will provide a basis for clinical judgment of whether there is a difference between the two forms of AF and PT reconstructed MPFL for RPD.


Assuntos
Instabilidade Articular , Luxação Patelar , Ligamento Patelar , Articulação Patelofemoral , Humanos , Luxação Patelar/cirurgia , Articulação Patelofemoral/cirurgia , Articulação do Joelho/cirurgia , Ligamentos Articulares/cirurgia , Patela , Ligamento Patelar/cirurgia , Revisões Sistemáticas como Assunto , Metanálise como Assunto
6.
Appl Biochem Biotechnol ; 195(2): 1122-1135, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36331690

RESUMO

Lung cancer is considered one of the most prevalent cancers worldwide and also has a high death rate. The prevalence of lung cancer is high in developed countries than in developing countries due to the lifestyle changes and quality of air. Coronarin D is a diterpene, which is isolated from the Hedychium coronarium. It demonstrated several pharmacological properties such as anti-allergic, anti-inflammatory, antimicrobial, and anticancer activities. In the current investigation, the potential of Coronarin D on the B(a)P-induced lung cancer was studied in the experimental mice model. The B(a)P-administrated animals exhibited a reduced level of immune cells, IgG, IgM, immune complexes, SOD, and CAT. The B(a)P-administrated animals expressed high levels of IgA, LPO, xenobiotic markers, tissue marker, tumor marker, and proinflammatory cytokines. On treatment with Coronarin D, the level of neutrophils, lymphocytes, leucocytes, and absolute neutrophils was elevated in the B(a)P-administered mice. The immune complex was augmented in the Coronarin D-treated animals in comparison with B(a)P-treated mice. The level of IgG and IgM was increased, whereas the level of IgA was reduced in the Coronarin D-treated animals. The level of LPO was downregulated, whereas the level of SOD and CAT was upregulated in Coronarin D-treated animals. The expression level of xenobiotic markers, tissue marker, tumor marker, and proinflammatory cytokines was reduced in the Coronarin D-treated animals. The histopathological results revealed that lung tissues of Coronarin D-treated animals had less alveolar damage with decreased hyperplasia. These findings suggest that the Coronarin D can be utilized as a potent chemopreventive agent for treating lung cancer in the future.


Assuntos
Diterpenos , Neoplasias Pulmonares , Animais , Camundongos , Benzo(a)pireno/toxicidade , Xenobióticos/efeitos adversos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/prevenção & controle , Citocinas/metabolismo , Diterpenos/efeitos adversos , Superóxido Dismutase , Biomarcadores Tumorais , Imunoglobulina A , Imunoglobulina G , Imunoglobulina M/efeitos adversos
7.
Medicine (Baltimore) ; 101(48): e32135, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36482518

RESUMO

BACKGROUND: Wound infection (WI) is a disease in which pathogenic bacteria invade and multiply in a wound after trauma or surgery, causing a systemic inflammatory response. WI triggers an immune response in the body, resulting in inflammation and tissue damage, as well as slowing down the healing process. The traditional Chinese medicine prescription of Wuwei Xiaodu Drink (WWXDD) has been widely used in clinical practice with good results. However, there is no high-level evidence to support this result. The purpose of this study was to evaluate the efficacy and safety of WWXDD in the treatment of WI. METHODS: We will search articles in 7 electronic databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang Data (WF), Chinese Scientific Journals Database (VIP), Chinese databases SinoMed (CBM), PubMed, Embase, and Cochrane Library databases. All the publications, with no time restrictions, will be searched without any restriction on language and status, the time from the establishment of the database to October 2022. Two reviewers will independently assess the quality of the selected studies, NoteExpress and Excel software will be used to extract data, and the content will be stored in an electronic chart. Different researchers will separately screen the titles and abstracts of records acquired potential eligibility which comes from the electronic databases. Full-text screening and data extraction will be conducted afterward independently. Statistical analysis will be conducted using RevMan 5.4 software (Cochrane Collaboration). RESULTS: What this study will do is evaluate the efficacy and safety of WWXDD in the treatment of WI in order to provide high quality, evidence-based clinical recommendations. CONCLUSION: This research provides a trusted clinical foundation for the treatment of WI with WWXDD.


Assuntos
Medicamentos de Ervas Chinesas , Infecção dos Ferimentos , Humanos , Metanálise como Assunto , Extratos Vegetais , Revisões Sistemáticas como Assunto , Infecção dos Ferimentos/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico
8.
J Anaesthesiol Clin Pharmacol ; 38(3): 391-398, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505186

RESUMO

Post-operative nausea and vomiting (PONV) is an event of multifactorial origin with an incidence of 30% in the general population. Opioids such as fentanyl are being used as adjuvant to local anesthetic for its antiemetic effect. In this context, with this study we aimed to evaluate the impact of spinal fentanyl as an adjuvant on the incidence of PONV compared with a placebo, and shivering. A systematic search of randomized controlled trials that evaluated the use of spinal fentanyl in the prevention of PONV and shivering was conducted in different databases, of which 32 studies met the inclusion criteria. A total of 2116 patients scheduled for various surgeries, including cesarean section, orthopedic surgery in the lower limb, hysterectomy, and transurethral resection of the prostate, were included in the final analysis. The meta-analysis estimated the relative risk of incidence of PONV in the first 24 hours after surgery and secondary outcomes included the shivering symptom. The use of intrathecal fentanyl was associated with lower incidence of PONV, but not statistically significant when compared to the placebo (RR: 0.74 CI95%: 0.55-1.01 P = 0.06). Subgroup analysis showed a statistically significant reduction in PONV incidences with lower doses between 10 and 15 µg (RR: 0.44 CI95%: 0.35-0.55 P < 0.00001, I2 = 0%) but not with higher doses 20-25 µg. Secondary outcomes showed a decrease in incidence with the use of fentanyl vs the placebo (RR: 0.49, CI95% 0.33-0.72 P = 0.0003). Current evidence shows that the use of spinal fentanyl decreases the incidence of PONV, an effect favored using low doses.

9.
Am J Transl Res ; 14(1): 406-413, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35173859

RESUMO

OBJECTIVE: To investigate the risk factors of brain metastases and its influence on the prognosis of patients with complete resected non-small cell lung cancer (NSCLC). METHODS: The clinical data of 190 patients with completely resected NSCLC were retrospectively analyzed. The effect of brain metastasis on prognosis in patients with NSCLC after complete resection was investigated. The identification of risk factors for brain metastases was conducted by single-factor and Cox multivariate regression analysis. RESULTS: Among 190 patients, 9 patients were lost to follow up. Finally, 181 patients were included in this study. The median survival time of brain metastases patients (64 cases) was 700 days. At 1 year, 3 years, and 5 years after surgery, the survival rates of patients with brain metastases were 62.5%, 28.13% and 7.81% respectively. Compared with those in patients without brain metastases, significant differences were found for median survival time and survival rates (P < 0.05). The Single-factor and multivariate Cox regression analysis indicated that the level of preoperative carcinoembryonic antigen (CEA), the lymph node ratio (≥ 30%) and non-squamous carcinoma type were risk factors for brain metastasis (P < 0.05). CONCLUSIONS: Brain metastasis is a risk factor for mortality in NSCLC patients after complete resection. Preoperative CEA levels, lymph node ratio (≥ 30%), and type of non-squamous cell carcinoma were risk factors for brain metastases.

10.
Medicine (Baltimore) ; 101(1): e28454, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35029892

RESUMO

BACKGROUND: Many studies have reported a relationship between the vascular endothelial growth factor receptor 2 single nucleotide polymorphism (SNP) rs2305948 and glioma, but their conclusions have been controversial. A meta-analysis was performed to assess the association between rs2305948 and glioma susceptibility. METHODS: Inclusion criteria and a strategy for screening of original literature were created. Eligible articles on the correlation between the SNP rs2305948 and glioma were identified in the PubMed, Embase, Web of Science, Cochrane Library, CNKI and Wanfang databases. After extracting the data, Stata 12. 0 software was used to perform statistical analysis under 5 genetic models and to calculate the combined odds ratio (OR) value and its 95% confidence interval (CI). RESULTS: Four case-control studies including 1595 cases and 1657 controls were entered into the study. The overall analysis showed that no obvious association existed between rs2305948 and glioma risk (allele: OR = 1.20, 95% CI = 0.93-1.54, P = .162; dominant: OR = 1.17, 95% CI = 0.93-1.46, P = .174; recessive: OR = 1.72, 95% CI = 0.94-3.15, P = .076; heterozygous: OR = 1.11, 95% CI = 0.94-1.30, P = .226; homozygous: OR = 1.74, 95% CI = 0.92-3.29, P = .088). The subgroup analysis suggested that the SNP rs2305948 was related to glioma susceptibility under allele, dominant, recessive and homozygote models in the Asian population (allele: OR = 1.34, 95% CI = 1.16-1.55, P < .001; recessive: OR = 2.24, 95% CI = 1.49-3.36, P < .001; homozygous: OR = 2.32, 95% CI = 1.54-3.50, P < .001). CONCLUSION: The vascular endothelial growth factor receptor 2 rs2305948 gene polymorphism may be related to glioma susceptibility in the Asian population. However, the association is not clear in non-Asian populations, for which there has been less research.


Assuntos
Glioma/genética , Polimorfismo de Nucleotídeo Único , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Povo Asiático , Predisposição Genética para Doença , Glioma/metabolismo , Humanos , Fatores de Risco , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
11.
Biochem Biophys Res Commun ; 594: 153-160, 2022 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-35085892

RESUMO

Colorectal cancer (CRC) is a commonly seen malignant tumor manifesting itself in the digestive tract, but it remains unclear what is the molecular mechanism behind its occurrence and development, which can have a significant impact on the clinical diagnosis and treatment of CRC. According to some studies, microRNA (miRNA) plays an essential role in the occurrence and development of cancer. In spite of this, there are still many miRNAs that play an important role in the progression of CRC but have yet to be reported. In our research, it was found out that the expression of mir-4746 is significantly down-regulated in CRC tissues and cells, and that its expression level is closely associated with the tumor size and prognosis of clinical patients. As revealed by function and mechanism experiments, targeting CCND1 mRNA 3'-UTR, mir-4746 can promote the degradation of CCND1 mRNA, thus reducing the protein level of CCND1, leading to cell G0-G1 phase arrest, and ultimately inhibiting the proliferation of CRC cells. For the first time, our study reported the biological functions of mir-4746 and its preliminary mechanism of action, in addition to demonstrating that mir-4746 can be applied as both a potential prognostic marker and the therapeutic target for CRC.


Assuntos
Proliferação de Células , Neoplasias Colorretais/metabolismo , Ciclina D1/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Animais , Apoptose/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Progressão da Doença , Regulação para Baixo , Feminino , Humanos , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos BALB C
12.
J Clin Nurs ; 31(17-18): 2584-2592, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34750903

RESUMO

BACKGROUND: Hypothermia is a common clinical issue during the perioperative period. The patients with perioperative inadvertent hypothermia are associated with higher risk of postoperative complications and higher hospitalisation costs. AIMS: The aim of this study is to explore the prevalence of and predictors for hypothermia in patients entering postanaesthesia care unit. DESIGN: Retrospective cohort study. METHODS: A rigorous retrospective cohort study was conducted according to the STROBE reporting checklist. A total of 7216 patients were enrolled in this study. The perioperative variables potentially related to hypothermia were collected. Univariate analysis and multivariate logistic regression analysis were performed to investigate the contributing factors. RESULTS: The overall prevalence of inadvertent hypothermia in postanaesthesia care unit was 21.3% (n = 1505). The multivariate logistic regression analysis showed that age >65 (OR = 1.561, 95% CI 1.371-1.778, p < .001), non-supine position [lateral decubitus position (OR = 1.341, 95% CI 1.133-1.586, p = .001), lithotomy position (OR = 1.639, 95% CI 1.295-2.075, p < .001)], non-superficial surgery (OR = 2.195, 95% CI 1.566-3.077, p < .001), non-open surgery [laparoscopic surgery (OR = 1.205, 95% CI 1.020-1.423, p = .029), endoscopic surgery (OR = 1.430, 95%CI 1.084-1.887, p = .011)], the volume of intravenous infusion fluid >1000 ml (OR = 1.814, 95% CI 1.500-2.194, p < .001), blood transfusion (OR = 1.552, 95% CI 1.159-2.078, p = .003), operation performed in the summer or fall (OR = 1.874, 95%CI 1.656-2.122, p < .001) and use of dexmedetomidine (OR = 1.147, 95%CI 1.015-1.296, p = .028) were associated with increased risk of hypothermia. In contrast, our finding showed that body mass index ≥25 kg/m2 (OR = 0.556, 95%CI 0.491-0.630, p < .001), higher baseline body temperature (OR = 0.641, 95%CI 0.541-0.761, p < .001) and duration of fasting ≥18 h (OR = 0.487, 95%CI 0.345-0.689, p < .001) were associated with decreased risk of hypothermia. Compared with non-hypothermic patients, patients with hypothermia were associated with prolonged length of hospital days (5 vs. 4 days, p < .001). CONCLUSION: For patients admitted to postanaesthesia care unit after elective procedures, old age, non-supine position, non-open surgery, non-superficial surgery, large volume of intravenous infusion fluid, dexmedetomidine, blood transfusion and Summer or Fall operative season were associated with increased risk of hypothermia, whereas high body mass index, high baseline body temperature and long fasting duration were associated with decreased risk of hypothermia. RELEVANCE TO CLINICAL PRACTICE: The outcomes of this study will raise the concerns of perioperative care team on hypothermia in surgical patients. Measures should be taken to improve perioperative hypothermia and clinical outcome.


Assuntos
Dexmedetomidina , Hipotermia , Temperatura Corporal , Humanos , Hipotermia/epidemiologia , Hipotermia/etiologia , Complicações Intraoperatórias , Assistência Perioperatória/métodos , Prevalência , Estudos Retrospectivos
13.
J Anaesthesiol Clin Pharmacol ; 38(4): 529-536, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36778826

RESUMO

Post-operative nausea and vomiting (PONV) is an event of multifactorial origin with an incidence of 30% in the general population. Opioids such as fentanyl are being used as adjuvant to local anesthetic for its antiemetic effect. In this context, with this study we aimed to evaluate the impact of spinal fentanyl as an adjuvant on the incidence of PONV compared with a placebo, and shivering. A systematic search of randomized controlled trials that evaluated the use of spinal fentanyl in the prevention of PONV and shivering was conducted in different databases, of which 32 studies met the inclusion criteria. A total of 2116 patients scheduled for various surgeries, including cesarean section, orthopedic surgery in the lower limb, hysterectomy, and transurethral resection of the prostate, were included in the final analysis. The meta-analysis estimated the relative risk of incidence of PONV in the first 24 hours after surgery and secondary outcomes included the shivering symptom. The use of intrathecal fentanyl was associated with lower incidence of PONV, but not statistically significant when compared to the placebo (RR: 0.74 CI95%: 0.55-1.01 P = 0.06). Subgroup analysis showed a statistically significant reduction in PONV incidences with lower doses between 10 and 15 µg (RR: 0.44 CI95%: 0.35-0.55 P < 0.00001, I2 = 0%) but not with higher doses 20-25 µg. Secondary outcomes showed a decrease in incidence with the use of fentanyl vs the placebo (RR: 0.49, CI95% 0.33-0.72 P = 0.0003). Current evidence shows that the use of spinal fentanyl decreases the incidence of PONV, an effect favored using low doses.

14.
Am J Transl Res ; 13(10): 11209-11222, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34786052

RESUMO

OBJECTIVE: Colorectal cancer is a common malignancy worldwide. This research aimed to investigate the role of α-ketoglutarate-dependent dioxygenase alkB homologue 5 (ALKBH5), a N6-methyladenosine (m(6)A) demethylase, on the cell proliferation and metastasis of colorectal cancer. METHODS: The interaction relationship between FOXO3, miR-21, and SPRY2 were predicted by starBase 2.0 and determined using RIP, CHIP, and dual-luciferase reporter assays. Quantitative reverse transcription PCR (RT-qPCR) and western blot were used to measure the gene and miRNA expressions of ALKBH5, FOXO3, miR-21, and SPRY2. The cell proliferation was determined using CCK8 and colony formation assays. The metastatic abilities were measured using wound healing and transwell assays. RESULTS: In colorectal cancer, downregulated ALKBH5 is related to poor prognosis. Rescued ALKBH5 suppresses the proliferation and metastasis of colorectal cancer cells. The role of ALKBH5 is achieved by reducing the m(6)A modification of forkhead box O3 (FOXO3), which enhances its stability. FOXO3 targets miR-21 and increases the SPRY2 expressions. The antitumor effects of ALKBH5 can be blocked by FOXO3 knockdown, which is reversed by the miR-21 inhibitor. CONCLUSION: ALKBH5 plays an antitumor role in colorectal cancer by regulating the FOXO3/miR-21/SPRY2 axis, providing a new direction for colorectal cancer therapy.

15.
N Engl J Med ; 385(22): 2025-2035, 2021 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-34623788

RESUMO

BACKGROUND: The effects of spinal anesthesia as compared with general anesthesia on the ability to walk in older adults undergoing surgery for hip fracture have not been well studied. METHODS: We conducted a pragmatic, randomized superiority trial to evaluate spinal anesthesia as compared with general anesthesia in previously ambulatory patients 50 years of age or older who were undergoing surgery for hip fracture at 46 U.S. and Canadian hospitals. Patients were randomly assigned in a 1:1 ratio to receive spinal or general anesthesia. The primary outcome was a composite of death or an inability to walk approximately 10 ft (3 m) independently or with a walker or cane at 60 days after randomization. Secondary outcomes included death within 60 days, delirium, time to discharge, and ambulation at 60 days. RESULTS: A total of 1600 patients were enrolled; 795 were assigned to receive spinal anesthesia and 805 to receive general anesthesia. The mean age was 78 years, and 67.0% of the patients were women. A total of 666 patients (83.8%) assigned to spinal anesthesia and 769 patients (95.5%) assigned to general anesthesia received their assigned anesthesia. Among patients in the modified intention-to-treat population for whom data were available, the composite primary outcome occurred in 132 of 712 patients (18.5%) in the spinal anesthesia group and 132 of 733 (18.0%) in the general anesthesia group (relative risk, 1.03; 95% confidence interval [CI], 0.84 to 1.27; P = 0.83). An inability to walk independently at 60 days was reported in 104 of 684 patients (15.2%) and 101 of 702 patients (14.4%), respectively (relative risk, 1.06; 95% CI, 0.82 to 1.36), and death within 60 days occurred in 30 of 768 (3.9%) and 32 of 784 (4.1%), respectively (relative risk, 0.97; 95% CI, 0.59 to 1.57). Delirium occurred in 130 of 633 patients (20.5%) in the spinal anesthesia group and in 124 of 629 (19.7%) in the general anesthesia group (relative risk, 1.04; 95% CI, 0.84 to 1.30). CONCLUSIONS: Spinal anesthesia for hip-fracture surgery in older adults was not superior to general anesthesia with respect to survival and recovery of ambulation at 60 days. The incidence of postoperative delirium was similar with the two types of anesthesia. (Funded by the Patient-Centered Outcomes Research Institute; REGAIN ClinicalTrials.gov number, NCT02507505.).


Assuntos
Anestesia Geral , Raquianestesia , Delírio/etiologia , Fraturas do Quadril/cirurgia , Idoso , Idoso de 80 Anos ou mais , Anestesia Geral/efeitos adversos , Raquianestesia/efeitos adversos , Delírio/epidemiologia , Feminino , Fraturas do Quadril/mortalidade , Fraturas do Quadril/fisiopatologia , Humanos , Incidência , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Recuperação de Função Fisiológica
16.
J Pain Res ; 14: 2717-2727, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512011

RESUMO

BACKGROUND: Spine surgery causes severe pain and can be associated with significant opioid utilization; however, the evidence for opioid-sparing analgesic techniques such as erector spinae plane (ESP) block from controlled studies is limited. We aimed to investigate the analgesic effects of ESP block in lumbar laminoplasty. METHODS: In this prospective, double-blind, controlled single-center trial, 62 consecutive elective lumbar laminoplasty patients were randomized into either a control group (Group G, N=32) or a treatment group (Group E, N=30). Group G received general anesthesia and multimodal analgesia, similar to group E, while Group E received additional bilateral ESP block after induction of general anesthesia. The primary outcome was postoperative pain scores for the first 48 h after surgery, and the secondary outcomes analyzed included intraoperative anesthetic usage, perioperative analgesic consumption, return of bowel function and satisfaction for acute pain management indicated by overall benefit of analgesia score (OBAS). RESULTS: Significant differences in pain scores over time were found between the two groups (P=0.010), with Group E patients having significantly lower pain scores than Group G during the first six hours (P=0.000). The opioid consumption in Group G was significantly higher than in Group E both intraoperatively (P=0.000) and postoperatively (P=0.0005). Group E patients had lower intraoperative sevoflurane requirement, improved satisfaction with pain management, and earlier return of bowel function than Group G patients. CONCLUSION: ESP block is effective in reducing postoperative pain scores and lowering opioid utilization (both intraoperatively and postoperatively), resulting in improved patient satisfaction for pain management in lumbar laminoplasty.

17.
Proc Natl Acad Sci U S A ; 118(5)2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33495330

RESUMO

Multiplex assays, involving the simultaneous use of multiple circulating tumor DNA (ctDNA) markers, can improve the performance of liquid biopsies so that they are highly predictive of cancer recurrence. We have developed a single-tube methylation-specific quantitative PCR assay (mqMSP) that uses 10 different methylation markers and is capable of quantitative analysis of plasma samples with as little as 0.05% tumor DNA. In a cohort of 179 plasma samples from colorectal cancer (CRC) patients, adenoma patients, and healthy controls, the sensitivity and specificity of the mqMSP assay were 84.9% and 83.3%, respectively. In a head-to-head comparative study, the mqMSP assay also performed better for detecting early-stage (stage I and II) and premalignant polyps than a published SEPT9 assay. In an independent longitudinal cohort of 182 plasma samples (preoperative, postoperative, and follow-up) from 82 CRC patients, the mqMSP assay detected ctDNA in 73 (89.0%) of the preoperative plasma samples. Postoperative detection of ctDNA (within 2 wk of surgery) identified 11 of the 20 recurrence patients and was associated with poorer recurrence-free survival (hazard ratio, 4.20; P = 0.0005). With subsequent longitudinal monitoring, 14 patients (70%) had detectable ctDNA before recurrence, with a median lead time of 8.0 mo earlier than seen with radiologic imaging. The mqMSP assay is cost-effective and easily implementable for routine clinical monitoring of CRC recurrence, which can lead to better patient management after surgery.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Colo/genética , Neoplasias do Colo/cirurgia , Metilação de DNA/genética , Biópsia Líquida , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Antígeno Carcinoembrionário/metabolismo , DNA Tumoral Circulante/sangue , Estudos de Coortes , Neoplasias do Colo/sangue , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mutação/genética , Cuidados Pós-Operatórios , Reprodutibilidade dos Testes , Septinas/genética
18.
Clin Chem Lab Med ; 59(1): 91-99, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32673280

RESUMO

Objectives: Colorectal cancer (CRC) screening using stool samples is now in routine use where tumor DNA methylation analysis for leading markers such as NDRG4 and SDC2 is an integral part of the test. However, processing stool samples for reproducible and efficient extraction of human genomic DNA remains a bottleneck for further research into better biomarkers and assays. Methods: We systematically evaluated several factors involved in the processing of stool samples and extraction of DNA. These factors include: stool processing (solid and homogenized samples), preparation of DNA from supernatant and pellets, and DNA extraction with column and magnetic beads-based methods. Furthermore, SDC2 and NDRG4 methylation levels were used to evaluate the clinical performance of the optimal protocol. Results: The yield of total and human genomic DNA (hgDNA) was not reproducible when solid stool scraping is used, possibly due to sampling variations. More reproducible results were obtained from homogenized stool samples. Magnetic beads-based DNA extraction using the supernatant from the homogenized stool was chosen for further analysis due to better reproducibility, higher hgDNA yield, lower non-hgDNA background, and the potential for automation. With this protocol, a combination of SDC2 and NDRG4 methylation signals with a linear regression model achieved a sensitivity and specificity of 81.82 and 93.75%, respectively. Conclusions: Through the systematic evaluation of different stool processing and DNA extraction methods, we established a reproducible protocol for analyzing tumor DNA methylation markers in stool samples for colorectal cancer screening.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Colorretais/diagnóstico , DNA/análise , Testes Diagnósticos de Rotina/métodos , Detecção Precoce de Câncer/métodos , Fezes/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/química , DNA/química , Metilação de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/genética , Proteínas do Tecido Nervoso/genética , Reprodutibilidade dos Testes , Manejo de Espécimes/métodos , Sindecana-2/genética
19.
Amino Acids ; 52(3): 361-369, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31875260

RESUMO

Breast cancer susceptibility gene 2 (BRCA2) is an important tumor suppressor, which is participated in repair of damaged DNA by its highly conserved BRC repeat motifs regulating RAD51 protein homologous recombination and thereby preventing cell carcinogenesis. In this study, the BRCA2(1524-1548)-RAD51(241-260) complex structure was obtained based on PDB bank data 1N0W, which provided the basis for site-specific mutation of BRCA2(1524-1548). The BRC4 and BRC4 analogous peptides were synthesized, and the interaction between BRC peptide and RAD51(241-260) was studied by fluorescence spectroscopy, circular dichroism spectroscopy and microscale thermophoresis (MST). The results of circular dichroism showed that the changes in secondary structures of RAD51(241-260) occurred after adding BRC4 analogous peptides, and the α-helix content increased significantly. Fluorescence spectral data demonstrated that the model of BRC peptide binding to RAD51(241-260) was static quenching, and the binding constants of BRC4, P1, P2, P4 with RAD51(241-260) were 1.647 × 10-4 L mol-1, 2.532 × 10-4 L mol-1, 3.161 × 10-4 L mol-1, 1.705 × 10-4 L mol-1, respectively. The results of MST indicated that P2 and RAD51(241-260) have better affinity for dissociation constant 44.286 µM. The strongest affinity between P2 and RAD51(241-260) indicated that the mutation of amino acid residue constituting BRC α-helix affects the structure and interaction of BRC peptide and RAD51(241-260).


Assuntos
Proteína BRCA2 , Fragmentos de Peptídeos , Rad51 Recombinase/química , Substituição de Aminoácidos , Proteína BRCA2/síntese química , Proteína BRCA2/química , Proteína BRCA2/genética , Dicroísmo Circular , Humanos , Mutação , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/química , Conformação Proteica em alfa-Hélice/genética , Espectrometria de Fluorescência
20.
Cureus ; 11(11): e6085, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31853436

RESUMO

Proper perioperative pain control with opioid-sparing techniques that extend into post-discharge arena is desirable yet hard to accomplish in breast cancer patients. We here reported a case where we took advantage of long-acting local anesthetics in conjunction with glucocorticoids of different hydrophilic/lipophilic properties and achieved prolonged analgesia for days after single administration thoracic paravertebral blockade. Further exploration into the potential effects of long-acting glucocorticoids in breast cancer patients through peripheral nerve blockage is warranted.

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