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1.
OTJR (Thorofare N J) ; : 15394492241246233, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38654665

RESUMO

RATIONALE: Stigma permeates disability experiences and compounds disability-related challenges. OBJECTIVE: Identify individual and environmental factors of stigmatizing experiences of college students with learning disabilities (LDs) and attention-deficit/hyperactivity disorder (ADHD). METHODOLOGY: A qualitative descriptive design was used with a thematic analysis of 30 transcripts from group discussions among four cohorts of undergraduates with LD/ADHD (N = 52). The Person-Environment-Occupation-Performance Model was used in interpreting the stigmatizing experiences. FINDINGS: The themes Perceived Misconceptions and Stigmatizing Actions describe key social-environmental factors. The theme Overcoming Stigmatizing Experiences elucidates key skills and processes for developing stigma resilience. These skills and processes were anchored in self-awareness and personally contextualized understanding of disability-related challenges and strengths, which were fostered during positive interactions with supportive others, such as instructors and mentors. IMPLICATIONS: Findings illustrate the biopsychosocial nature of stigma and highlight the role of individual and social-environmental factors in building stigma resilience among young adults with LD/ADHD.


Understanding Stigma and Resilience Among College Students with Learning Disabilities and ADHDWe studied how college students with learning disabilities (LDs) and attention-deficit/hyperactivity disorder (ADHD) experience stigma, which means feeling judged or treated unfairly because of their disabilities. We talked to 52 undergraduates in four groups to understand their experiences and found three main things related to stigma. First, students feel like others have wrong ideas about them and their disabilities. Second, they experience actions from others that make them feel stigmatized. Third, they develop ways to overcome these experiences. Students became more resilient to stigma when they understood themselves better and had support from others like teachers and mentors. Stigma is not just a personal thing for students with LD/ADHD; but it is also influenced by the people around them and how they see themselves.

2.
J Org Chem ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607334

RESUMO

We report a step-economic strategy for the direct synthesis of spiro polycyclic N-heterocycles and indolecarbazole-fused naphthoquinones by merging oxidative coupling and cascade palladium-catalyzed intramolecular oxidative cyclization. In the protocol, bi-indolylnaphthoquinones were first synthesized by oxidative coupling of indoles and naphthoquinones. Subsequent cascade palladium-catalyzed intramolecular oxidative cyclization of bi-indolylnaphthoquinones gave spiro polycyclic N-heterocycles and indolecarbazoles. The intramolecular oxidative cyclization approach could also be realized by the presence or absence of iron catalysts under standard conditions. This protocol is featured with moderate to excellent yields, a wide substrate scope, and divergent structures of products.

3.
Clin Interv Aging ; 19: 367-373, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476831

RESUMO

Medication reconciliation (MR) is the process of comparing a patient's medication orders to all of the medications that the patient has been taking in order to identify and resolve medication discrepancies. It is an effective means of risk management to avoid medication errors (eg, omissions, duplication, dosage errors, or drug interactions). Some guidelines explicitly state that MR is a pharmacist-led transition of care; however, there is a shortage of qualified pharmacists to meet the increasing clinical needs, and clinical nurses' roles have not been clearly described. This paper aimed to enable nurses to gain confidence in contributing to MR at discharge and to make the industry aware of the potential risks if nurses do not actively intervene in this area. A narrative approach was used to introduce experiences in identifying discrepancies and medication errors through MR at discharge in a geriatric ward of an academic medical center hospital in China. The nurses' main roles in MR involve chasing, checking, and education. Clinical nurses, an untapped hospital resource, can actively engage in MR at discharge if they receive effective training and motivation. Multidisciplinary collaboration at discharge allowed many discrepancies to be reconciled before harming older patients. It is worth conducting further research in MR when discharging older adults, such as the cost-effectiveness of nurses' efforts, the value of electronic tools and the impact of MR-targeted education and training for nursing students and nursing staff.


Assuntos
Reconciliação de Medicamentos , Alta do Paciente , Humanos , Idoso , Erros de Medicação , Centros Médicos Acadêmicos , Hospitais , Farmacêuticos
4.
Genomics ; 116(2): 110806, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38325533

RESUMO

BACKGROUND: Cell differentiation agent II (CDA-II) exhibits potent anti-proliferative and apoptosis-inducing properties against a variety of cancer cells. However, its mechanism of action in chronic myeloid leukemia (CML) remains unclear. METHODS: Cell counting Kit 8 (CCK-8) and flow cytometry were used to investigate the effects of CDA-II on the biological characteristics of K562 cells. Gene (mRNA and lncRNA) expression profiles were analyzed by bioinformatics to screen differentially expressed genes and to perform enrichment analysis. The Pearson correlation coefficients of lncRNAs and mRNAs were calculated using gene expression values, and a lncRNA/mRNA co-expression network was constructed. The MCODE and cytoHubba plugins were used to analyze the co-expression network. RESULTS: The Results, derived from CCK-8 and flow cytometry, indicated that CDA-II exerts dual effects on K562 cells: it inhibits their proliferation and induces apoptosis. From bioinformatics analysis, we identified 316 mRNAs and 32 lncRNAs. These mRNAs were predominantly related to the meiotic cell cycle, DNA methylation, transporter complex and peptidase regulator activity, complement and coagulation cascades, protein digestion and absorption, and cell adhesion molecule signaling pathways. The co-expression network comprised of 163 lncRNA/mRNA interaction pairs. Notably, our analysis results implicated clustered histone gene families and five lncRNAs in the biological effects of CDA-II on K562 cells. CONCLUSION: This study highlights the hub gene and lncRNA/mRNA co-expression network as crucial elements in the context of CDA-II treatment of CML. This insight not only enriches our understanding of CDA-II's mechanism of action but also might provide valuable clues for subsequent experimental studies of CDA-II, and potentially contribute to the discovery of new therapeutic targets for CML.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Peptídeos , Fenilacetatos , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Perfilação da Expressão Gênica , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , RNA Mensageiro/metabolismo , Redes Reguladoras de Genes
5.
Oral Oncol ; 150: 106695, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38262250

RESUMO

PURPOSE: Initial treatment for Recurrent/Metastatic Nasopharyngeal Carcinoma (R/M NPC) often involves Gemcitabine plus cisplatin with or without PD-1 inhibitors. However, PD-1 inhibitors' effectiveness varies, prompting for better treatments. This study explores effect and safety of combining PD-1 inhibitors with chemoradiotherapy for oligometastatic NPC patients. METHODS: Oligometastatic NPC patients underwent radical treatment with PD-1 inhibitors and chemotherapy, followed by concurrent PD-1 inhibitors and chemoradiotherapy, and then maintenance PD-1 inhibitors. Objective response rate (ORR) and disease control rate (DCR) were calculated by irRECIST-1.1, and CTCAE-4.0 was used to evaluate the toxicity. RESULTS: The study enrolled 47 patients with a median age of 46. The median follow-up lasted 16.5 months, with metastatic lesions receiving a median radiation dose of 45 Gy. The median courses of PD-1 inhibitors and chemotherapy were 9.5 and 5 respectively. The metastasis sites included lung (40.8 %), liver (21.1 %), mediastinal lymph node (7.9 %), abdominal lymph nodes (3.9 %), bone (21.1 %), adrenal gland (3.9 %), and brain (1.3 %). ORR and DCR were 85.1 % and 100 % at 3 months after radiotherapy. The median survival was not reached yet, and 1 and 2-year OS rates were 93.1 % and 78.4 %. The median PFS was 18 months, with 1 and 2-year PFS rates of 70.2 % and 47.7 % respectively. PD-L1 expression showed a positive correlation for PFS. Twenty-five patients experienced grade 3 or 4 adverse events (AE) that were possibly related to chemotherapy. No grade 5 AE was observed. CONCLUSIONS: The synergy of concurrent PD-1 inhibitors and chemoradiotherapy shows promising efficacy and an acceptable toxicity for oligometastasis NPC patients.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias Nasofaríngeas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Cisplatino , Desoxicitidina/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos
6.
Risk Manag Healthc Policy ; 16: 2531-2541, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38024501

RESUMO

Background: Infusion rate is one of the essential elements that should be included in all intravenous orders. Patients may experience adverse consequences or risks associated with inappropriate infusion. Meanwhile, there is growing pressure on the chemotherapy unit to deliver treatment quickly, efficiently, and safely, and thus it is very necessary to improve the chemotherapy process and service to cancer patients. Clinicians should consider how to further standardize infusion therapy, and innovate new infusion strategies to increase efficacy, reduce toxicity, improve patient satisfaction and save health resource costs. Sporadic studies have evaluated the effects of infusion rates of anticancer agents on clinical outcomes, economic benefits, and administration efficiency. However, an update review has not been available. Methods: Relevant literature was identified by search of PubMed until September 2023. Results: Infusion rates may have significant effect on the efficacy of anticancer agents (e.g., methotrexate, fluorouracil, and arsenic trioxide). Slow infusion is safer for platinum compounds, doxorubicin and carmustine, whereas fast infusion is safer than slow infusion of gemcitabine. Optimal flow rates of paclitaxel and fluorouracil are based on the balance between multiple risks of toxicity. Optimal infusion rate may bring economic benefits. If efficacy and safety are not compromised, shortened infusion may result in higher patient satisfaction, improved institutional efficiency and more nursing time available for other activities (e.g., biosimilar products, endostar). Other concerns about infusion rate include clinical indications (eg, paclitaxel and rituximab, methotrexate), severity and type of hypersensitivity reactions (e.g., platinum compounds), formulation features (e.g., paclitaxel, doxorubicin), and genetic polymorphism (e.g., gemcitabine, methotrexate). Conclusion: The latest knowledge of infusion rate concerns will enhance the appropriateness and accuracy in intravenous administration. Interdisciplinary teams should collaborate and implement relevant risk management and healthcare policy. It is worthwhile to conduct comparative studies of intravenous therapy with different infusion speeds.

7.
Epilepsy Behav ; 147: 109438, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37716327

RESUMO

OBJECTIVE: To evaluate the reliability and validity the Chinese version of 19-item Epilepsy Surgery Satisfaction Questionnaire (C-ESSQ-19) in Chinese mainland patients. METHODS: Patients with epilepsy who had epilepsy surgery in our hospital one year earlier were included. Internal consistency and test-retest reliability were assessed by using Cronbach alpha and intraclass correlation coefficient (ICC). Confirmatory factor analysis was used for construct validity. Discriminant validity was assessed using receiver operating characteristic curve analysis. RESULTS: A total of 132 patients participated in our study, consisting of 59 females and 73 males. The C-ESSQ-19 yielded a median summary score of 86.5 (IQR=72.7-98.0). The Cronbach's alpha of the four domains of the C-ESSQ-19 ranged from 0.746 to 0.973. The test-retest reliability evaluated by ICC were good to excellent, ranging from 0.71 to 0.90 (P < 0.001). The C-ESSQ-19 demonstrated excellent construct validity, as indicated by the satisfactory goodness-of-fit of the data (SRMR = 0.046; CFI = 1.000). It exhibited acceptable discriminant validity for differentiating between patients excised or not (AUC = 0.72; 95% CI = 0.59-0.86) and self-rated severity of epilepsy (AUC = 0.76, 95% CI = 0.67-0.86), but poor discriminant validity for other factors, such as being seizure-free or not (AUC = 0.66, CI = 0.56-0.75), depressed or not (AUC = 0.66, 95% CI = 0.54-0.79), and self-rated disability related to seizures (AUC = 0.65, 95% CI = 0.50-0.80). CONCLUSIONS: The C-ESSQ-19 has proven to be a reliable and valid self-rated questionnaire for assessing the satisfaction of Chinese mainland epilepsy patients with surgery.


Assuntos
Reprodutibilidade dos Testes , Masculino , Feminino , Humanos , Inquéritos e Questionários , Curva ROC , Análise Fatorial , Psicometria , China
8.
Cancer Res ; 83(18): 3131-3144, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37433041

RESUMO

Neoadjuvant chemoimmunotherapy (NACI) has shown promise in the treatment of resectable esophageal squamous cell carcinoma (ESCC). The microbiomes of patients can impact therapy response, and previous studies have demonstrated that intestinal microbiota influences cancer immunotherapy by activating gut immunity. Here, we investigated the effects of intratumoral microbiota on the response of patients with ESCC to NACI. Intratumoral microbiota signatures of ß-diversity were disparate and predicted the treatment efficiency of NACI. The enrichment of Streptococcus positively correlated with GrzB+ and CD8+ T-cell infiltration in tumor tissues. The abundance of Streptococcus could predict prolonged disease-free survival in ESCC. Single-cell RNA sequencing demonstrated that responders displayed a higher proportion of CD8+ effector memory T cells but a lower proportion of CD4+ regulatory T cells. Mice that underwent fecal microbial transplantation or intestinal colonization with Streptococcus from responders showed enrichment of Streptococcus in tumor tissues, elevated tumor-infiltrating CD8+ T cells, and a favorable response to anti-PD-1 treatment. Collectively, this study suggests that intratumoral Streptococcus signatures could predict NACI response and sheds light on the potential clinical utility of intratumoral microbiota for cancer immunotherapy. SIGNIFICANCE: Analysis of intratumoral microbiota in patients with esophageal cancer identifies a microbiota signature that is associated with chemoimmunotherapy response and reveals that Streptococcus induces a favorable response by stimulating CD8+ T-cell infiltration. See related commentary by Sfanos, p. 2985.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Microbiota , Animais , Camundongos , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/terapia , Linfócitos T CD8-Positivos , Imunoterapia , Microambiente Tumoral
9.
Radiat Oncol ; 18(1): 109, 2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37403098

RESUMO

BACKGROUND: Programmed cell death-1 (PD-1) inhibitor was proven to be useful for the recurrent/metastatic head and neck squamous carcinoma (R/M HNSCC) patients. Though both PD-1 inhibitor alone and combination with chemotherapy showed some benefit for PFS and OS, the survival outcome was still not satisfactory. Some studies showed the possible benefit for PD-1 inhibitors combination with radiation for head and neck squamous carcinoma, however there was few studies concerned about synergy of concurrent PD-1 inhibitor combination with chemoradiotherapy for R/M HNSCC. So, we aimed to explore the potential effect and toxicity of the concurrent PD-1 inhibitor and chemoradiotherapy for R/M HNSCC. METHODS: We consecutively enrolled the R/M HNSCC patients treated with concurrent PD-1 inhibitor and chemoradiotherapy from August 2018 to April 2022 in Sichuan Cancer hospital. All the patients received the combination of PD-1 inhibitor and chemotherapy, and followed with synergy of concurrent PD-1 inhibitor and chemoradiotherapy, then maintenance PD-1 inhibitor. ORR and DCR was calculated by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST-1.1), and Common terminology criteria for adverse events (CTCAE-4.0) was used to evaluate the toxicity.The Kaplan-Meier method was used to analyze OS and PFS. RESULTS: 40 R/M HNSCC patients were enrolled in our stuty. The median follow up time was 14 months. 22 patients had recurrent disease only, 16 patients had metastatic disease only, and 2 patients had both recurrence and metastasis disease. For the recurrent lesions, 23 patients received a median radiation dose of 64 Gy (range 50-70 Gy). 18 patients received a median dose of 45 Gy (range 30-66 Gy) for metastatic lesions. The median courses of PD-1 inhibitors and chemotherapy were 8 and 5 respectively. After the treatment, the ORR and DCR were 70.0% and 100%. The median OS was 19 months (range 6.3-31.7 months), with 1 and 2-years OS rates of 72.8% and 33.3%. The median PFS was 9 months (range 3.1-14.9 months), with 6 and 12 months PFS rates of 75.5% and 41.4% respectively. The PFS had no statistical significance in PD-L1 negative and positive group (7 vs 12 months, p = 0.059). The most common grade 3 or 4 adverse events(AE) were leucopenia (25.0%), neutropenia (17.5%), anemia (10.0%), thrombocytopenia (5.0%), hyponatremia (2.5%), and pneumonia(2.5%). No grade 5 AE was observed. CONCLUSIONS: The synergy of concurrent PD-1 inhibitor treatment with chemoradiotherapy shows promise as a treatment strategy and an acceptable toxicity for the R/M HNSCC patients.


Recurrent/metastatic head and neck squamous carcinoma (R/M HNSCC) patients face limited treatment choices and poor prognosis. As a new treatment method, immune checkpoint inhibitor plays an important role for the R/M HNSCC patients recently. However, there were still some controversies for the combination of chemoradiotherapy and immunotherapy, such as timing, radiation dose, fractionation, and et al. In our study, the synergy of concurrent chemoradiotherapy with PD-1 inhibitor showed a promising results for the R/M HNSCC patients, with improved objective response rate (ORR) (70.0%, 95% CI 55.8% to 84.2%) and disease control rate (DCR) (100%, 95% CI 100% to 100%). The median progression-free survival (PFS) and overall survival (OS) were prolonged to 9 months (range 3.1­14.9 months) and 19 months (range 6.3­31.7 months) respectively. The toxicity was tolerable during the treatment, the total incidence rate of grade 3 or 4 adverse events were 65%, similar with other study.


Assuntos
Antineoplásicos Imunológicos , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Receptor de Morte Celular Programada 1 , Inibidores de Checkpoint Imunológico/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Recidiva Local de Neoplasia/etiologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Quimiorradioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose
10.
Plant Mol Biol ; 112(6): 325-340, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37380791

RESUMO

The contrasting genome size between homosporous and heterosporous plants is fascinating. Different from the heterosporous seed plants and mainly homosporous ferns, the lycophytes are either heterosporous (Isoetales and Selaginellales) or homosporous (Lycopodiales). Many lycophytes are the resource plants of Huperzine A (HupA) which is invaluable for treating Alzheimer's disease. For the seed-free vascular plants, several high-quality genomes of heterosporous Selaginella, homosporous ferns (maidenhair fern, monkey spider tree fern), and heterosporous ferns (Azolla) have been published and provided important insights into the origin and evolution of early land plants. However, the homosporous lycophyte genome has not been decoded. Here, we assembled the first homosporous lycophyte genome and conducted comparative genomic analyses by applying a reformed pipeline for filtering out non-plant sequences. The obtained genome size of Lycopodium clavatum is 2.30 Gb, distinguished in more than 85% repetitive elements of which 62% is long terminal repeat (LTR). This study disclosed a high birth rate and a low death rate of the LTR-RTs in homosporous lycophytes, but the opposite occurs in heterosporous lycophytes. we propose that the recent activity of LTR-RT is responsible for the immense genome size variation between homosporous and heterosporous lycophytes. By combing Ks analysis with a phylogenetic approach, we discovered two whole genome duplications (WGD). Morover, we identified all the five recognized key enzymes for the HupA biosynthetic pathway in the L. clavatum genome, but found this pathway incomplete in other major lineages of land plants. Overall, this study is of great importance for the medicinal utilization of lycophytes and the decoded genome data will be a key cornerstone to elucidate the evolution and biology of early vascular land plants.


Assuntos
Embriófitas , Gleiquênias , Filogenia , Tamanho do Genoma , Plantas/genética , Gleiquênias/genética , Embriófitas/genética , Sequências Repetidas Terminais , Evolução Molecular
11.
Healthcare (Basel) ; 11(8)2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-37107989

RESUMO

Taiwan had the second highest number globally of end-stage renal disease patients undergoing treatment in 2018. A meta-analysis of Chen et al. (2021) showed the incidence and mortality rates of COVID-19 were 7.7% and 22.4%, respectively. Few studies have explored the effects of patients' self-participation and perceptions of hemodialysis on their quality of life. This study aimed to explore the factors related to hemodialysis patients' quality of life during the COVID-19 pandemic. This study was a descriptive correlational study. Patients were recruited (n = 298) from the hemodialysis unit of a medical center in northern Taiwan. Variables included patients' sociodemographic, psychological, spiritual, and clinical characteristics (i.e., perceived health level, comorbidities, hemodialysis duration, weekly frequency, transportation, and accompaniment during hemodialysis), perceptions of hemodialysis, self-participation in hemodialysis, and health-related quality of life (KDQOL-36 scale). Data were analyzed using descriptive and bivariate and multivariate linear regression. Multivariate linear regression, after adjusting for covariates, showed that anxiety, self-perceived health status, two vs. four comorbidities, and self-participation in hemodialysis were significantly associated with quality of life. The overall model was significant and accounted for 52.2% (R2 = 0.522) of the variance in quality of life during hemodialysis (adjusted R2 = 0.480). In conclusion, the quality of life of hemodialysis patients with mild, moderate, or severe anxiety was poorer, whereas that of patients with fewer comorbidities, higher self-perceived health status, and higher self-participation in hemodialysis was better.

12.
BMC Plant Biol ; 23(1): 128, 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36882696

RESUMO

BACKGROUND: Chinese cabbage is one of the most widely grown leafy vegetables in China. Cytoplasmic male sterility (CMS) is a maternally inherited trait that produces abnormal pollen during anther development, which is commonly seen in cruciferous vegetables. However, the molecular mechanism of Chinese cabbage CMS is not clear. In this study, the metabolome and hormone profiles of Chinese cabbage male sterile line (CCR20000) and sterile maintainer line (CCR20001) were analyzed in flower buds during normal stamen development and abnormal stamen development, respectively. RESULTS: A total of 556 metabolites were detected based on UPLC-MS/MS detection platform and database search, and the changes of hormones such as auxin, cytokinins, abscisic acid, jasmonates, salicylic acid, gibberellin acid and ethylene were analyzed. The results showed that compared with the male fertile line (MF), the male sterile line (MS) significantly decreased the content of flavonoids and phenolamides metabolites in the stamen dysplasia stage, accompanied by a large accumulation of glucosinolate metabolites. Meanwhile, the contents of GA9, GA20, IBA, tZ and other hormones in MS were significantly lower than those in MF strains. Further, by comparing the metabolome changes of MF and MS during stamen dysplasia, it was found that flavonoid metabolites and amino acid metabolites were distinctly different. CONCLUSIONS: These results suggest that flavonoids, phenolamides and glucosinolate metabolites may be closely related to the sterility of MS strains. This study provides an effective basis for further research on the molecular mechanism of CMS in Chinese cabbage.


Assuntos
Brassica , Glucosinolatos , Cromatografia Líquida , Infertilidade das Plantas , Espectrometria de Massas em Tandem , Flavonoides , Brassica/genética
13.
Micromachines (Basel) ; 14(1)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36677205

RESUMO

Cell lysis is a key step for studying the structure and function of proteins in cells and an important intermediate step in drug screening, cancer diagnosis, and genome analysis. The current cell lysis methods still suffer from limitations, such as the need for large instruments, a long and time-consuming process, a large sample volume, chemical reagent contamination, and their unsuitability for the small amount of bacteria lysis required for point-of-care testing (POCT) devices. Therefore, a fast, chemical-free, portable, and non-invasive device needs to be developed. In the present study, we designed an integrated microfluidic chip to achieve E. coli lysis by applying an alternating current (AC) electric field and investigated the effects of voltage, frequency, and flow rate on the lysis. The results showed that the lysis efficiency of the bacteria was increased with a higher voltage, lower frequency, and lower flow rate. When the voltage was at 10 Vp-p, the lysis efficiency was close to 100%. The study provided a simple, rapid, reagent-free, and high-efficiency cleavage method for biology and biomedical applications involving bacteria lysis.

15.
Int J Mol Sci ; 23(20)2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36293001

RESUMO

Immunotherapy, such as immune checkpoint inhibitors (ICIs), is a validated strategy for treating lung adenocarcinoma (LUAD) patients. One of the main challenges in ICIs treatment is the lack of efficient biomarkers for predicting response or resistance. Metabolic reprogramming has been proven to remodel the tumor microenvironment, altering the response to ICIs. We constructed a prognostic model as metabolism-related gene (MRG) of four genes by using weighted gene co-expression network analysis (WGCNA), the nonnegative matrix factorization (NMF), and Cox regression analysis of a LUAD dataset (n = 500) from The Cancer Genome Atlas (TCGA), which was validated with three Gene Expression Omnibus (GEO) datasets (n = 442, n = 226 and n = 127). The MRG was constructed based on BIRC5, PLK1, CDKN3, and CYP4B1 genes. MRG-high patients had a worse survival probability than MRG-low patients. Furthermore, the MRG-high subgroup was more associated with cell cycle-related pathways; high infiltration of activated memory CD4+T cells, M0 macrophages, and neutrophils; and showed better response to ICIs. Contrarily, the MRG-low subgroup was associated with fatty acid metabolism, high infiltration of dendric cells, and resting mast cells, and showed poor response to ICIs. MRG is a promising prognostic index for predicting survival and response to ICIs and other therapeutic agents in LUAD, which might provide insights on strategies with ICIs alone or combined with other agents.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Imunoterapia , Biomarcadores , Ácidos Graxos , Microambiente Tumoral/genética
16.
World J Gastroenterol ; 28(24): 2733-2747, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35979164

RESUMO

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) remains poor and relapse occurs in more than half of patients within 2 years after hepatectomy. In terms of recent studies, microvascular invasion (MVI) is one of the potential predictors of recurrence. Accurate preoperative prediction of MVI is potentially beneficial to the optimization of treatment planning. AIM: To develop a radiomic analysis model based on pre-operative magnetic resonance imaging (MRI) data to predict MVI in HCC. METHODS: A total of 113 patients recruited to this study have been diagnosed as having HCC with histological confirmation, among whom 73 were found to have MVI and 40 were not. All the patients received preoperative examination by Gd-enhanced MRI and then curative hepatectomy. We manually delineated the tumor lesion on the largest cross-sectional area of the tumor and the adjacent two images on MRI, namely, the regions of interest. Quantitative analyses included most discriminant factors (MDFs) developed using linear discriminant analysis algorithm and histogram analysis with MaZda software. Independent significant variables of clinical and radiological features and MDFs for the prediction of MVI were estimated and a discriminant model was established by univariate and multivariate logistic regression analysis. Prediction ability of the above-mentioned parameters or model was then evaluated by receiver operating characteristic (ROC) curve analysis. Five-fold cross-validation was also applied via R software. RESULTS: The area under the ROC curve (AUC) of the MDF (0.77-0.85) outperformed that of histogram parameters (0.51-0.74). After multivariate analysis, MDF values of the arterial and portal venous phase, and peritumoral hypointensity in the hepatobiliary phase were identified to be independent predictors of MVI (P < 0.05). The AUC value of the model was 0.939 [95% confidence interval (CI): 0.893-0.984, standard error: 0.023]. The result of internal five-fold cross-validation (AUC: 0.912, 95%CI: 0.841-0.959, standard error: 0.0298) also showed favorable predictive efficacy. CONCLUSION: Noninvasive MRI radiomic model based on MDF values and imaging biomarkers may be useful to make preoperative prediction of MVI in patients with primary HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética/métodos , Microvasos/diagnóstico por imagem , Microvasos/patologia , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos
17.
Pak J Pharm Sci ; 35(3): 755-760, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35791473

RESUMO

This study aims to explore the effect of the Rubus extract on the TLR4/NF-κB signaling pathway in alcoholic liver fibrosis rats. The alcoholic liver rat model was established by continuous ethanol gavage administration. Rats were divided randomly into six groups (i.e., blank control, model, 0.05g/kg Rubus extract, 0.125g/kg Rubus extract, 0.259 g/kg Rubus extract and positive control groups). Liver tissue and blood were collected after treatment for four weeks. The pathological changes in the liver were observed by HE and Masson staining methods. The hyaluronic acid (HA), TNF-α and IL-6 levels were determined by ELISA kits. The TLR4 and p-p65 protein expression levels in liver were detected by Western blot. The liver lesion degree was significantly decreased in the Rubus extract group, and a high concentration of the Rubus extract indicated a significant improvement. The TNF-α, HA and IL-6 levels in the Rubus extract and positive control groups were significantly lower than those of the model group (P<0.05). The TLR4 and p-p65 protein expression levels were also significantly decreased in the Rubus extract and positive control groups (P< 0.05) with a concentration dependence of Rubus extract. The Rubus extract could delay the development of alcoholic liver fibrosis through inhibiting the TLR4/NF-κB pathway activity.


Assuntos
NF-kappa B , Rubus , Animais , Interleucina-6/farmacologia , Cirrose Hepática , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Ratos , Rubus/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-35409569

RESUMO

Background. This retrospective observational study attempted to examine the prevalence of abnormal blood aluminum levels in dialysis patients, and to explore the association of pathogenic factors, such as demographic, clinical, laboratory as well as the use of phosphate binding drugs, drugs for secondary hyperparathyroidism and erythropoiesis-stimulating drugs with the blood aluminum levels. Methods. The study included 1175 patients (874 hemodialysis and 301 peritoneal dialysis), recruited from Chang Gung Memorial Hospital in November 2020. Patients were stratified into two groups by their blood aluminum levels, as normal (<2 µg/dL, n = 1150) or abnormal (≥2 µg/dL, n = 25). Results. The patients aged 60.4 ± 13.2 years and were dialyzed for 8.6 ± 8.1 years. The average blood aluminum level was 1.0 ± 0.4 µg/dL. Patients with abnormal blood aluminum levels received more sevelamer than patients with normal blood aluminum level (p = 0.014). Patients with abnormal blood aluminum levels had higher platelet count (p = 0.001), triglyceride (p < 0.001) and total iron binding capacity (p = 0.003) than patients with normal blood aluminum levels. Moreover, the cardiothoracic ratio was higher in patients with abnormal blood aluminum levels than patients with normal blood aluminum levels (p = 0.003). Conclusions. The prevalence of abnormal blood aluminum levels was low at 2.2%. Nevertheless, the linking of cardiothoracic ratio of more than 0.5 as well as elevated blood platelet count and triglyceride level with blood aluminum levels are interesting, and warranted more researches in this area.


Assuntos
Falência Renal Crônica , Diálise Peritoneal , Alumínio , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Diálise Renal , Triglicerídeos
19.
J Oncol ; 2022: 4586729, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35356251

RESUMO

Low serum sodium levels have been associated with poor prognoses for several cancers. However, the prognostic value of low serum sodium levels in esophageal carcinoma (EC) has not been well elucidated. We examined the prognostic value of low baseline serum sodium levels before radiotherapy or chemoradiotherapy for EC patients. A retrospective analysis of data from EC patients who received radiotherapy or chemoradiotherapy at a single cancer center was performed. Patients were divided into low serum sodium level (≤140.0 mmol/L) or high serum sodium level (>140.0 mmol/L) groups according to the median pretreatment serum sodium level. The Kaplan-Meier model and Cox proportional hazards model were used for survival analyses. The 5-year progression-free survival (PFS) and overall survival (OS) rates in the whole group were 16.9% and 21.8%, respectively. The PFS and OS rates of patients in the low serum sodium levels group were significantly lower than those in the high serum sodium levels group (p < 0.001). A similar association between PFS/OS and sodium levels was observed in the treatment subgroups. The univariate analysis showed that low serum sodium levels, Karnofsky performance status (KPS), clinical N stage, tumor site, clinical stage, and treatment mode were the influencing factors of OS. Multivariate analyses indicated that low baseline serum sodium levels were an independent prognostic marker of poor PFS (HR, 1.744; 95% CI, 1.248-2.437; p = 0.001) and OS (hazard ratio (HR), 2.125; 95% confidence interval (CI), 1.555-2.904; p < 0.001). Pretreatment levels of low serum sodium could be a new and helpful serum biomarker of the prognosis of EC patients receiving radiotherapy or chemoradiotherapy.

20.
PLoS One ; 17(3): e0266231, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35358262

RESUMO

INTRODUCTION: Diabetic patients normally have enlarged or normal-sized kidneys throughout their lifetime, but some diabetic uremic patients have small kidneys. It is uncertain if kidney size could have any negative impact on outcome in hemodialysis patients. METHODS: This longitudinal, observational cohort study recruited 301 diabetic hemodialysis patients in 2015, and followed until 2019. Patients were stratified into two subgroups according to their kidney sizes before dialysis, as small (n = 32) or enlarged or normal (n = 269). Baseline demographic, hematological, biochemical, nutritional, inflammatory and dialysis related data were collected for analysis. RESULTS: Patients with small kidney size were not only older (P<0.001) and had lower body mass index (P = 0.016), but had also higher blood uric acid concentration (P<0.001) compared with patients with enlarged or normal kidney size. All patients received adequate doses of hemodialysis since the Kt/V and urea reduction ratio was 1.7±0.3 and 0.7±0.1, respectively. Patients with small size kidneys received higher erythropoietin dose than patients with enlarged or normal kidney size (P = 0.031). At the end of analysis, 92 (30.6%) patients expired. Kaplan-Meier analysis revealed no survival difference between both groups (P = 0.753). In a multivariate logistic regression model, it was demonstrated that age (P<0.001), dialysis duration (P<0.001), as well as blood albumin (P = 0.012) and low-density lipoprotein (P = 0.009) concentrations were significantly correlated with mortality. CONCLUSIONS: Small kidney size on starting hemodialysis was not related with an augmented risk for death in diabetic patients receiving hemodialysis. Further studies are necessary.


Assuntos
Diabetes Mellitus , Falência Renal Crônica , Diabetes Mellitus/etiologia , Humanos , Rim , Estudos Longitudinais , Diálise Renal/efeitos adversos
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