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1.
Micromachines (Basel) ; 15(5)2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38793210

RESUMEN

Improving measurement accuracy is the core issue with surface acoustic wave (SAW) micro-force sensors. An electrode transducer can stimulate not only the SAW but also the bulk acoustic wave (BAW). A portion of the BAW can be picked up by the receiving transducer, leading to an unwanted or spurious signal. This can harm the device's frequency response characteristics, thereby potentially reducing the precision of the micro-force sensor's measurements. This paper examines the influence of anisotropy on wave propagation, and it also performs a phase-matching analysis between interdigital transducers (IDTs) and bulk waves. Two solutions are shown to reduce the influence of BAW for SAW micro sensors, which are arranged with acoustic absorbers at the ends of the substrate and in grooving in the piezoelectric substrate. Three different types of sensors were manufactured, and the test results showed that the sidelobes of the SAW micro-force sensor could be effectively inhibited (3.32 dB), thereby enhancing the sensitivity and performance of sensor detection. The SAW micro-force sensor manufactured using the new process was tested and the following results were obtained: the center frequency was 59.83 MHz, the fractional bandwidth was 1.33%, the range was 0-1000 mN, the linearity was 1.02%, the hysteresis was 0.59%, the repeatability was 1.11%, and the accuracy was 1.34%.

2.
Int J Chron Obstruct Pulmon Dis ; 19: 1141-1151, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38817823

RESUMEN

Background: This study sought to explore the underlying mechanism of miR-21 mediated apoptosis and inflammation in chronic obstructive pulmonary disease (COPD) induced by cigarette smoke (CS). Methods: We detected levels and PTEN/Akt/NF-κB axis protein levels in peripheral lung tissues of COPD patients and CS-exposed mice and HBE cells. Western blotting assay was used to determine the expression of cleaved caspase-3. IL-6 and IL-8 protein was detected in cell supernatant from cells by ELISA. HBE cells were transfected with a miR-21 inhibitor, and co-culture with A549. Results: Increased miR-21 expression, reduced PTEN expression and following activation of Akt in in peripheral lung tissues of COPD patients and CS-exposed mice and HBE cells. Inhibition of miR-21 showed enhanced PTEN levels and reduced the expression of phosphorylated form of Akt and NF-κB. Decreased expression of cleaved caspase-3, IL-6 and IL-8 in A549 cells co cultured with HBE cells transfected with miR-21 inhibitor compared with transfected with miR-21 control inhibitor. Conclusion: MiR-21 contributes to COPD pathogenesis by modulating apoptosis and inflammation through the PTEN/Akt/NF-κB pathway. Targeting miR-21 may increase PTEN expression and inhibit Akt/NF-κB pathway, offering potential diagnostic and therapeutic value in COPD management.


Asunto(s)
Apoptosis , Modelos Animales de Enfermedad , Pulmón , MicroARNs , FN-kappa B , Fosfohidrolasa PTEN , Proteínas Proto-Oncogénicas c-akt , Enfermedad Pulmonar Obstructiva Crónica , Transducción de Señal , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/patología , MicroARNs/metabolismo , MicroARNs/genética , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , FN-kappa B/metabolismo , Células A549 , Pulmón/patología , Pulmón/metabolismo , Masculino , Persona de Mediana Edad , Femenino , Ratones Endogámicos C57BL , Interleucina-8/metabolismo , Mediadores de Inflamación/metabolismo , Interleucina-6/metabolismo , Fosforilación , Fumar Cigarrillos/efectos adversos , Estudios de Casos y Controles , Anciano
3.
J Inflamm Res ; 16: 5647-5665, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38050560

RESUMEN

Background: This study aims to investigate the association between immune cells and the development of COPD, while providing a new method for the diagnosis of COPD according to the changes in immune microenvironment. Methods: In this study, the "CIBERSORT" algorithm was used to estimate the tissue infiltration of 22 types of immune cells in GSE20257 and GSE10006. The "limma" package was used for differentially expressed analysis. The key modules associated with vital immune cells were identified using WGCNA. GO and KEGG enrichment analysis revealed the biological functions of the candidate genes. Ultimately, a novel diagnostic prediction model was constructed via machine learning methods and multivariate logistic regression analysis based on GSE20257. Furthermore, we examined the stability of the model on one internal test set (GSE10006), three external test sets (GSE8545, GSE57148 and GSE76925), one single-cell transcriptome dataset (GSE167295), macrophages (THP-M cells) and lung tissue from COPD patients. Results: M0 macrophages (AUC > 0.7 in GSE20257 and GSE10006) were considered as the most important immune cells through exploring the immune microenvironment landscapes in COPD patients and healthy controls. The differentially expressed genes from GSE20257 and GSE10006 were divided into six and five modules via WGCNA, respectively. The green module in GSE20257 (cor = 0.41, P < 0.001) and the brown module in GSE10006 (cor = 0.67, P < 0.001) were highly correlated with M0 macrophages and were selected as key modules. Forty-one intersected genes obtained from two modules were primarily involved in regulation of cytokine production, regulation of innate immune response, specific granule, phagosome, lysosome, ferroptosis, and other biological processes. On the basis of the candidate genetic markers further characterized via the "Boruta" and "LASSO" algorithm for COPD, a diagnostic model comprising CLEC5A, FTL and SLC2A3 was constructed, which could accurately distinguish COPD patients from healthy controls in multiple datasets. GSE20257 as the training set has an AUC of 0.916. The AUCs of the internal test set and three external test sets were 0.873, 0.932, 0.675 and 0.688, respectively. Single-cell sequencing analysis suggested that CLEC5A, FTL and SLC2A3 were expressed in macrophages from COPD patients. The expressions of CLEC5A, FTL and SLC2A3 were up-regulated in THP-M cells and lung tissue from COPD patients. Conclusion: According to the variations of immune microenvironment in COPD patients, we constructed and validated a novel macrophage M0-associated diagnostic model with satisfactory predictive value. CLEC5A, FTL and SLC2A3 are expected to be promising targets of immunotherapy in COPD.

4.
Micromachines (Basel) ; 14(11)2023 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-38004950

RESUMEN

In this paper, a SAW winding tension sensor is designed and data fusion technology is used to improve its measurement accuracy. To design a high-measurement precision SAW winding tension sensor, the unbalanced split-electrode interdigital transducers (IDTs) were used to design the input IDTs and output IDTs, and the electrode-overlap envelope was adopted to design the input IDT. To improve the measurement accuracy of the sensor, the particle swarm optimization-least squares support vector machine (PSO-LSSVM) algorithm was used to compensate for the temperature error. After temperature compensation, the sensitivity temperature coefficient αs of the SAW winding tension sensor was decreased by an order of magnitude, thus significantly improving its measurement accuracy. Finally, the error with actually applied tension was calculated, the same in the LSSVM and PSO-LSSVM. By multiple comparisons of the same sample data set overall, as well as the local accuracy of the forecasted results, which is 5.95%, it is easy to confirm that the output error predicted by the PSO-LSSVM model is 0.50%, much smaller relative to the LSSVM's 1.42%. As a result, a new way for performing data analysis of the SAW winding tension sensor is provided.

5.
Nanoscale ; 15(20): 9076-9093, 2023 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-37129436

RESUMEN

Articular cartilage injury repair remains a challenge for clinicians and researchers. Mesenchymal stem cells (MSCs) have multiple differentiation potentials and can be induced to differentiate into the chondrogenic lineage for cartilage defect repair; however, the insufficient capacity of chondrogenic differentiation and excess reactive oxygen species (ROS)-mediated oxidative stress, which always lead to differentiation into hypertrophic chondrocytes, still need to be resolved. Accordingly, kartogenin (KGN), which can promote chondrogenic differentiation of MSCs, has shown promise in promoting infected cartilage repair. However, realizing controllable release to prolong its action time and avoid hypertrophic differentiation is critical. We herein developed a mesoporous Prussian blue nanoparticle (mPB)-based near-infrared (NIR) light-responsive controlled nanosystem. KGN was encapsulated in temperature-stimulated responsive phase change materials (PCMs), which were used as excellent gating materials (KGN-PCM@mPBs). In addition, the mPBs could efficiently scavenge ROS by their enzyme-like antioxidative activities. Our study demonstrates that the nanocomposites could efficiently promote chondrogenic differentiation and successfully inhibit the hypertrophic differentiation of MSCs. By intra-articular injection of KGN-PCM@mPBs and NIR-triggered precisely controlled release, satisfactory cartilage repair effects can be achieved in a rat chondral defect model. Thus, this constructed NIR-mediated KGN-PCM@mPB nanoplatform may represent an effective cartilage repair strategy with satisfactory biosafety in clinical applications.


Asunto(s)
Cartílago Articular , Ácidos Ftálicos , Ratas , Animales , Especies Reactivas de Oxígeno/farmacología , Condrocitos , Ácidos Ftálicos/farmacología , Diferenciación Celular , Condrogénesis
6.
J Thorac Dis ; 15(12): 6928-6945, 2023 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-38249902

RESUMEN

Background: Lung cancer is the leading cause of morbidity and mortality among all cancer types, with lung adenocarcinoma (LUAD) being the most prevalent subtype. DNA damage repair (DDR)-related genes are closely associated with cancer progression and treatment, with emerging evidence highlighting their correlation with tumor development. However, the relationship between LUAD prognosis and DDR-related genes remains unclear. Methods: RNA sequencing (RNA-seq) data and clinical information were obtained from The Cancer Genome Atlas (TCGA) database. The GSE31210 dataset, utilized for external validation, was retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed DDR genes were identified, and a DDR-related prognostic model was established and validated using Kaplan-Meier (KM) survival analysis, time-dependent receiver operating characteristic (ROC) curves, gene set enrichment analysis (GSEA), tumor mutational burden (TMB) analysis, and immune cell infiltration. A P value of less than 0.05 was considered statistically significant. Results: A total of 514 patients with LUAD from TCGA database were divided into distinct subtypes to characterize the diversity within the DDR pathway. DDR-activated and DDR-suppressed subgroups showed distinct clinical characteristics, molecular characteristics, and immune profiles. Nine genes were identified as hub DDR-related genes, including CASP14, DKK1, ECT2, FLNC, HMMR, IGFBP1, KRT6A, TYMS, and FCER2. By using the expression levels of these selected genes, the corresponding risk scores for each sample was predicted. In the training group, KM survival analysis revealed that the high-risk group exhibited significantly diminished overall survival (OS) [hazard ratio (HR) =3.341, P=1.38e-08]. The corresponding area under the curve (AUC) values for the 1-year follow-up periods was 0.767, respectively. Upon validation in the external cohort, patients with higher risk scores manifested significantly reduced OS (HR =2.372, P=1.87e-03). The AUC values of the ROC curves for the 1-year OS in the validation cohort was 0.87, respectively. Moreover, advanced DDR risk score was correlated with increased TMB scores, a heightened frequency of TP53 mutations, an increased abundance of cancer-testicular antigens (CTAs), and a lower tumor immune dysfunction and exclusion (TIDE) score in patients with LUAD (P<0.05). Conclusions: A nine-gene risk signature associated with DDR in LUAD was effectively developed, demonstrating its potential as a robust and reliable classification tool for clinical practice. This model exhibited the capability to accurately predict the prognosis and survival outcomes of LUAD patients.

7.
J Thorac Dis ; 14(9): 3488-3499, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36245582

RESUMEN

Background: Lung adenocarcinoma (LUAD) is the most important subtype of lung cancer and usually metastasizes. Patients with LUAD usually had a poor prognosis. Identifying viable molecular markers for diagnostic and prognostic prediction among individuals with LUAD is critical for the future management of this disease. This study aimed to determine and verify a correlation between the glycolysis-related phosphoglucomutase 2 (PGM2) gene and dissatisfactory results and deficient infiltration of immune cells in LUAD. Methods: The expression of PGM2 in LUAD and adjoining normal tissues was screened from The Cancer Genome Atlas (TCGA) data and human protein atlas (HPA), and validatied by quantative reverse transcription polymerase chain reaction (qRT-PCR). We examined the correlation between PGM2 expression and clinicopathologic characteristics (including pathological stage, gender, M stage, smoker, age, N stage, race, and number pack years smoked) by multivariable approaches and Kaplan-Meier survival curves. The proteins network with PGM2 was built using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The correlation between PGM2 expression and infiltration of immune cells, along with the corresponding gene marker sets, was investigated through the Gene Expression Profiling Interactive Analysis (GEPIA) and Tumor Immune Estimation Resource (TIMER) databases. We evaluated the possible correlation between PGM2 expression and progression-free interval (PFI), disease-specific survival (DSS), and overall survival (OS) in LUAD patients. Results: Expression of PGM2 was up-regulated in LUAD tissues (P=0.003). According to the multivariate logistic regression analysis, the elevated expression level of PGM2 exhibited a remarkable correlation with advanced tumor-node-metastasis (TNM) stage, high-grade malignancy, and primary therapeutic outcome . Overexpression of PGM2 was shown to be correlated with an unfavorable prognosis including OS (P=0.004, HR =1.54), DSS (P=0.003, HR =1.77), and PFI (P=0.003, HR =1.5) in LUAD. The proteins PGM1 and UGP2 were shown to have a significant correlation with PGM2. Additionally, PGM2 was associated with the lack of infiltrating immune cells as well as their associated gene marker sets in LUAD. Conclusions: Overexpression of PGM2 was shown to be associated with the progression and an unfavorable prognosis of LUAD, as well as with inefficient immune cell infiltration. PGM2 was expected to be a potential biological marker for predicting the prognosis of patients with LUAD.

8.
Open Life Sci ; 17(1): 811-815, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35993095

RESUMEN

A 49-year-old woman was admitted to our hospital because of haemoptysis for 6 days. This patient claimed no medical history except high blood sugar. Chest computed tomography (CT) showed infection and multiple nodules on both sides of the lung. Blood tests showed no obvious abnormalities. Tracheoscopy showed haemorrhagic discharge in the left upper lobe and an old thrombus obstructing the lumen in the anterior basal segment of the right lower lobe. Then, CT-guided percutaneous lung biopsy was performed. The pathological results suggested multiple nodular-like lesions in the submitted tissues, and tumour cells were round or short fusiform, forming a solid nest structure, visible mitosis, and a vascular cavity-like structure containing red blood cells. Immunohistochemistry revealed positive staining for Vimentin, Bcl-2, CD31, and CD34; negative staining for CD68, SMA, CR, and D2-40; and 40% Ki67+ positivity. Based on the earlier data, the patient was diagnosed with pulmonary epithelioid haemangioendothelioma. This patient did not receive any treatment for several reasons. Unfortunately, the patient died 8 weeks after diagnosis. In conclusion, we present a case featuring the rapid death due to PEH.

9.
Front Cell Dev Biol ; 9: 690307, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34604211

RESUMEN

Background: The involvement of dysregulated circular RNAs (circRNAs) in human diseases has been increasingly recognized. In this study, we focused on the function of a newly screened circRNA, circ_0006349, in the progression of non-small-cell lung cancer (NSCLC) and the molecules of action. Methods: The NSCLC circRNA dataset GSE101684, microRNA (miRNA) dataset GSE29250, and mRNA dataset GSE51852 obtained from the GEO database were used to identify the differentially expressed genes in NSCLC samples. Tumor and normal tissues were collected from 59 patients with NSCLC. The expression of circ_0006349, miR-98, and MAP kinase phosphatase 1 (MKP1) in collected tissue samples and in acquired cells was determined. The binding relationships between miR-98 and circ_0006349/MKP1 were predicted and validated. Altered expression of circ_0006349, miR-98, and MKP1 was introduced in NSCLC cells to examine their roles in cell growth, apoptosis, and glycolysis. Results: Circ_0006349 and MKP1 were upregulated, and miR-98 was poorly expressed in the collected tumor tissues and the acquired NSCLC cell lines. Circ_0006349 was identified as a sponge for miR-98 to elevate MKP1 expression. Silencing of circ_0006349 suppressed proliferation and increased apoptosis of Calu-3 and H1299 cells, and it reduced glycolysis, glucose uptake, and the production of lactate in cells. Upon circ_0006349 knockdown, further downregulation of miR-98 or upregulation of MKP1 restored the malignant behaviors of cells. Conclusion: This research demonstrated that circ_0006349 derepressed MKP1 expression by absorbing miR-98, which augmented the proliferation and glycolysis of NSCLC cells and promoted cancer development.

10.
Lab Invest ; 101(8): 1060-1070, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33850295

RESUMEN

The membranous receptor syndecan-4 (SDC-4) and the nuclear transcription factor hypoxia-induced factor-2α (HIF-2α) play critical roles in the pathogenesis of osteoarthritis (OA). The aim of this study was to determine whether SDC-4 inhibition downregulates HIF-2a expression by microRNA-96-5p (miR-96-5p) in murine chondrocyte and cartilage tissue. The OA model was induced surgically in mice, and SDC-4 polyclonal antibody, HIF-2α small interfering RNA (siRNA) and its control, miR-96-5p mimics and its scrambled controls or anti-miR-96-5p and its control were then injected into the knee joints. At 2 and 4 weeks after surgery, OA progression was evaluated microscopically, histologically, radiographically and immunohistochemically in these mice. Real-time polymerase chain reaction (RT-PCR) and western blotting were performed after treating with antibody and transfecting with miRNA mimic or siRNA to determine their effects on OA-related mediators. The potential miRNAs related to OA development were identified by using miRNA microarray analysis. Whether miRNAs play a pivotal role in OA development in vivo or in vitro was also investigated. MiR-96-5p expression was upregulated by SDC-4-specific antibodies in chondrocytes and cartilage tissue, and miR-96-5p directly targeted the 3'-UTR of HIF-2α to inhibit HIF-2α signaling in murine chondrocytes. Moreover, we demonstrated that anti-SDC-4-attenuated IL-1ß-induced chondrocyte hypertrophy and cartilage degradation by inhibiting HIF-2α signaling by a miR-96-5p-dependent mechanism. Our study revealed that the inhibition of SDC-4 exerts its effects on both cartilage homeostasis and the chondrocyte hypertrophy phenotype by inducing miR-96-5p expression, which results in targeting HIF-2α 3'-UTR sequences and inhibiting HIF-2α in murine cartilage tissue and chondrocytes.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Cartílago Articular , MicroARNs , Osteoartritis , Sindecano-4 , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Cartílago Articular/metabolismo , Cartílago Articular/patología , Condrocitos/metabolismo , Regulación hacia Abajo/genética , Masculino , Ratones , Ratones Endogámicos ICR , MicroARNs/genética , MicroARNs/metabolismo , Osteoartritis/genética , Osteoartritis/metabolismo , Osteoartritis/patología , Sindecano-4/antagonistas & inhibidores , Sindecano-4/genética , Sindecano-4/metabolismo
11.
Int J Gen Med ; 14: 571-580, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33654424

RESUMEN

PURPOSE: Exhaled nitric oxide has been used as a marker of airway inflammation. The NO concentration in the central and peripheral airway/alveolar can be measured by a slow and fast exhalation flow rate to evaluate inflammation in different divisions within the respiratory tract. We hypothesized that FeNO200 (exhaled NO at a flow rate of 200mL/s) could be used as an evaluation tool for peripheral airway/alveolar inflammation and corticosteroid therapy in chronic obstructive pulmonary disease (COPD) patients. METHODS: We recruited 171 subjects into the study: 73 healthy controls, 59 stable COPD patients, and 39 acute exacerbations of COPD (AECOPD) patients. Exhaled nitric oxide (FeNO50 (exhaled NO at a flow rate of 50mL/s)), FeNO200 and CaNO (peripheral concentration of NO/alveolar NO) and clinical variables including pulmonary function, COPD Assessment Test (CAT), C-reactive protein concentration (CRP) and circulating eosinophil count were measured among the recruited participants. FeNO50, FeNO200 and CaNO were repeatedly evaluated in 39 AECOPD patients after corticosteroid treatment. RESULTS: FeNO200 was significantly higher in stable COPD and AECOPD patients than in healthy controls. Nevertheless, CaNO could not differentiate COPD from healthy controls. No correlation was found between circulating eosinophil counts or FEV1 and exhaled nitric oxide (FeNO50, FeNO200, CaNO) in COPD patients. For AECOPD patients, 64% of patients had eosinophil counts >100 cells/µL; 59% of patients had FeNO200 >10 ppb; only 31% of patients had FeNO50 > 25 ppb. Among AECOPD patients, the high FeNO50 and FeNO200 groups' levels were significantly lower than their baseline levels, and significant improvements in CAT were seen in the two groups after corticosteroid treatment. These implied a good corticosteroid response in AECOPD patients with FeNO200>10ppb. CONCLUSION: FeNO200 is a straightforward and feasible method to evaluate the peripheral NO concentration in COPD. FeNO200 can be a type 2 inflammation biomarker and a useful tool for predicting corticosteroid therapy in COPD.

12.
J Orthop Surg Res ; 16(1): 76, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33482875

RESUMEN

BACKGROUND: The risk factors of postoperative delirium (POD), a serious while preventable complication, developed by patients undergoing knee and replacement surgery are still under investigation. In this systematic review and meta-analysis, we identified risk factors associated with POD in knee and hip replacement. METHODS: PubMed, Ovid MEDLINE, and Ovid EMBASE were used to identify original researches. The studies evaluating the risk factors of POD after knee and hip replacement were reviewed, and the qualities of the included studies were assessed with Newcastle-Ottawa Scale. Data were extracted, pooled, and a meta-analysis was completed RESULT: Twenty-two studies were finally included with a total of 11934 patients who underwent knee or hip replacement and 1841 developed POD with an incidence of 17.6% (95% confidential interval (CI) 13.2-22.0%). Eighteen significant risk factors were identified including advanced age (odds ratio (OR) 1.15 95% CI 1.08-1.22), cognitive impairment (OR 6.84, 95% CI 3.27-14.33), history of cerebrovascular events (OR 2.51, 95% CI 1.28-4.91), knee replacement (OR 1.42, 95% CI 1.00-2.02), blood loss (standardized mean difference (SMD) 0.30, 95% CI 0.15-0.44), dementia (OR 3.09, 95% CI 2.10-4.56), neurologic disorders (OR 2.26, 95% CI 1.23-4.15), psychiatric illness (OR 2.74, 95% CI 1.34-5.62), and obstructive sleep apnea (OR 4.17, 95% CI 1.72-10.09) along with several comorbidity evaluation scores and laboratory markers. CONCLUSION: We identified risk factors consistently associated with the incidence of POD in knee and hip replacement. Strategies and interventions should be implemented to the patients receiving knee or hip replacement with potential risk factors identified in this meta-analysis.


Asunto(s)
Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Delirio/etiología , Complicaciones Posoperatorias/etiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Pérdida de Sangre Quirúrgica , Disfunción Cognitiva , Delirio/epidemiología , Demencia , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Factores de Riesgo , Apnea Obstructiva del Sueño , Accidente Cerebrovascular
13.
Mol Genet Genomic Med ; 8(10): e1395, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32757330

RESUMEN

BACKGROUND: ß3-αC loop is a highly conserved structural domain across oncogene families, which is a switch for kinase activity. There have been numerous researches on mutations within ß3-αC loop in EGFR, but relatively less in ERBB2, BRAF, and MAP2K1. In addition, previous studies mainly focus on ß3-αC deletion in EGFR, which is the most common type affecting kinase activity and driving lung cancer. Other mutation types are not well studied. METHODS: Here we analyzed the profile of ß3-αC loop mutations in a total of 10,000 tumor biopsy and/or ctDNA patient samples using hybridization capture-based next-generation sequencing. RESULTS: We identified 1616 mutations within ß3-αC loop in this cohort. Most mutations were located in EGFR, with less percentage in ERBB2, BRAF, and MAP2K1. EGFR ß3-αC deletions occurred at a high percentage of 96.7% and were all drug-relevant. We also detected rare EGFR ß3-αC insertions and point mutations, most of which were related to EGFR TKIs resistance. ERBB2 ß3-αC deletions were only found in breast cancers and sensitive to EGFR/ERBB2 inhibitor. Moreover, BRAF and MAP2K1 mutations within ß3-αC loop also demonstrated drugs relevance. CONCLUSION: Our study showed that oncogenic mutations within the ß3-αC loop of ERBB2, MAP2K1, and BRAF are analogous to that of EGFR, which have profound effect on drug response. Understanding the mutation profile within the ß3-αC loop is critical for targeted therapies.


Asunto(s)
Resistencia a Antineoplásicos , MAP Quinasa Quinasa 1/genética , Mutación , Neoplasias/genética , Proteínas Proto-Oncogénicas B-raf/genética , Receptor ErbB-2/genética , Antineoplásicos/uso terapéutico , Secuencia Conservada , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/química , Receptores ErbB/genética , Humanos , MAP Quinasa Quinasa 1/antagonistas & inhibidores , MAP Quinasa Quinasa 1/química , Neoplasias/tratamiento farmacológico , Dominios Proteicos , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Proteínas Proto-Oncogénicas B-raf/química , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/química
14.
Transplantation ; 103(12): 2634-2644, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31283687

RESUMEN

BACKGROUND: Both bilateral lung transplantation (BLT) and single lung transplantation (SLT) are commonly used, but which method is better remains controversial. This meta-analysis was conducted to compare the 2 surgical procedures to identify a better clinical choice. METHODS: Cohort studies comparing SLT and BLT were identified by conducting searches of databases and screening references of retrieved articles. Survival, pulmonary function, surgical indicators, and complications were compared between the 2 groups. RESULTS: Thirty studies (1980 recipients in the SLT group and 2112 recipients in the BLT group) were pooled in the meta-analysis. The long-term overall survival rate (OSR) (OSR-4y and OSR-5y), bronchiolitis obliterans syndrome (BOS)-free survival, BOS-free survival rate (BFSR) (2-5 y), 6-minute walking distance, forced expiratory volume in 1 second (%), forced vital capacity (%), oxygenation index, pulmonary arterial pressure, Arterial partial pressure of oxygen (Pao2), diffusing capacity of the lung for carbon monoxide (Dlco), and BOS were better in the BLT group than in the SLT group. The advantages shown in the BLT group compared with the SLT group in regard to these variables increased with the prolongation of survival time. However, surgical time, ischemic time, postoperative intensive care unit days, and postoperative hospital days were shorter in the SLT group than in the BLT group. Overall survival, short-term OSR (1-3 y), BSFR-1y, in-hospital mortality, postoperative ventilator days, and postoperative complications (except BOS) were similar between the 2 groups. Bacterial pneumonia, graft failure, fungal infection, cardiac arrhythmia, and hemorrhage were the top 5 causes of in-hospital mortality. CONCLUSIONS: BLT appears to be associated with better long-term survival, better postoperative lung function, and less BOS compared with SLT. In-hospital mortality and postoperative complications (except BOS) were similar between the 2 groups.


Asunto(s)
Trasplante de Pulmón/métodos , Pulmón/fisiopatología , Complicaciones Posoperatorias/epidemiología , Causas de Muerte/tendencias , Volumen Espiratorio Forzado , Salud Global , Mortalidad Hospitalaria/tendencias , Humanos , Incidencia , Complicaciones Posoperatorias/fisiopatología , Insuficiencia Respiratoria/cirugía , Tasa de Supervivencia/tendencias
15.
BMC Musculoskelet Disord ; 19(1): 357, 2018 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-30290765

RESUMEN

BACKGROUND: Compression therapy is commonly used to reduce lower limb swelling and blood loss after knee surgery. This study was performed to investigate whether modified Robert Jones bandage (MRJB) as a postoperative compression therapy is necessary for enhanced-recovery primary total knee arthroplasty without the tourniquet application. METHODS: In this prospective randomized controlled trial, 90 patients were grouped into 2 groups randomly. The experimental group received compression therapy with MRJB from toes to thigh for 24 h and the control group received no compression therapy. Knee swelling, blood loss, range of motion (ROM), pain, patient reported comfort level and complications were recorded. RESULTS: No significant differences were observed between the two groups when we compared knee swelling. Similarly, no significant difference on postoperative blood loss, pain, ROM, complications was found. However, patients in control group had significantly higher comfort ratings than compression group during the first 24 h. CONCLUSIONS: MRJB is not routinely indicated in enhanced-recovery primary total knee arthroplasty without tourniquet application. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR-INR-16010177 ) dated 18th December 2016.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/efectos adversos , Vendajes de Compresión , Edema/prevención & control , Articulación de la Rodilla/cirugía , Anciano , Fenómenos Biomecánicos , China , Edema/diagnóstico por imagen , Edema/etiología , Edema/fisiopatología , Femenino , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Rango del Movimiento Articular , Recuperación de la Función , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
16.
Int J Surg ; 53: 312-319, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29656129

RESUMEN

BACKGROUND: The debate over the use of cemented or cementless fixation in total knee arthroplasty (TKA) has never stopped since cementless fixation was introduced. We undertook a systematic review and meta-analysis to evaluate the optimal mode of fixation (full-cementless vs. full-cemented) in TKA. METHODS: PubMed, Embase, and the Cochrane Library databases up to July 2017 were searched to identify randomised controlled trials (RCTs) and quasi-RCTs comparing full-cementless TKA and full-cemented TKA. The primary outcome was implant survivorship. Secondary outcomes included radiological outcomes (maximum total point-motion [MTPM], radiolucent line, rotation degree) and clinical outcomes (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] score, Knee Society Score [KSS] score, postoperative range of movement, blood loss and complications). RESULTS: Seven studies were included in the systematic review and meta-analysis. The mean follow-up was 7.1 years (range from 2 to 16.6 years). There was no difference in implant survivorship (RR, 0.98; 95% CI, 0.95-1.01; p = 0.25; I2 = 0%), MTPM (weighted mean difference [WMD], 0.13 mm; 95% CI, -0.69-0.95; p = 0.75; I2 = 89.3%) and radiolucent line (RR, 1.36; 95% CI, 0.57-3.23; p = 0.48; I2 = 54%) between the cementless and cemented methods. There was a mean 0.22° more rotation in the full-cementless fixation group (95% CI, 0.13-0.32; p < 0.01; I2 = 28.5%). There were no significant differences relating to clinical outcomes (WOMAC score, KSS score, postoperative range of movement, blood loss and complications) between the two fixation groups. CONCLUSIONS: Although more overall component rotation is found in full-cementless fixation, the implant survivorship and clinical efficacy are likely similar between full-cementless and full-cemented fixation. However, future RCTs with similar cementless prosthetic coating and longer-term follow-up are still needed to confirm our findings.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/métodos , Cementos para Huesos , Prótesis de la Rodilla , Diseño de Prótesis , Falla de Prótesis , Humanos , Articulación de la Rodilla/cirugía
17.
Int J Surg ; 50: 87-93, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29329788

RESUMEN

BACKGROUND: Proper limb alignment and implant positioning are important for successful total knee arthroplasty (TKA). Whether any differences exist in restoration of limb alignment for valgus knees between fixed and individual femoral valgus correction angle (VCA) for distal femoral resection remains unknown. METHODS: The PubMed, Medline, Embase, and Wangfang databases were searched to identify studies comparing individualized VCA and fixed VCA in the distal femoral valgus resection. The primary outcomes were the mechanical femorotibial angle (MFT angle) and the proportion of postoperative alignment deviation within ±3°. The secondary outcomes were femoral valgus correction angle (VCA), component angle (α angle and ß angle). RESULTS: Six studies with 1167 TKAs were analyzed quantitatively. The coronal limb alignments in individualized group were closer to neutral than fixed group with a mean 0.77° difference (95% CI, -1.43 to -0.11; P = .022; I2 = 71.0%). Moreover, there were more patients' postoperative alignment deviation within neutral ±3° in the individualized group (RR, 1.23; 95% CI, 1.09 to 1.38; P = .00; I2 = 36.4%). The α angle were closer to neutral in the individualized group, and there's 1.2° more deviation from neutral in the fixed group (95% CI, 0.99 to 1.41; P = .00; I2 = 0%). No difference was found in the ß angle between groups (WMD, 0.85; 95% CI, -0.09 to 1.78; P = .075; I2 = 88.3%). CONCLUSIONS: This systematic review and meta-analysis demonstrated that the individualized VCA for distal femoral resection could enhance the accuracy of postoperative limb alignment and femoral component alignment in the coronal plane. However, further high-quality RCTs and well-designed trials are still needed.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/métodos , Anciano , Artritis Reumatoide/cirugía , Femenino , Fémur/cirugía , Humanos , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/cirugía , Tibia/cirugía , Resultado del Tratamiento
18.
Orthop Surg ; 8(2): 226-33, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27384732

RESUMEN

OBJECTIVE: To evaluate whether closed suction drainage (CSD) is associated with early recovery of knee function in patients undergoing total knee arthroplasty (TKA). METHODS: Between January 2015 and September 2015, 80 consecutive patients were prospectively randomized into two groups: a CSD group (40 cases; average age, 66.9 ± 8.6 years; male, 8; female, 32) and a non-CSD group (40 cases; average age, 66.8 ± 10.1 years; male, 9; female, 31). Local inflammation outcomes (assessed by a visual analog scale [VAS], swelling and skin temperature), calculated total blood loss (CBL), hidden blood loss (HBL), blood transfusion requirements and hemoglobin concentrations were recorded. Hospital for Special Surgery (HSS) knee scores, range of motion (ROM), limb swelling, tension vesicles, ecchymosis, time to regaining straight leg raising and duration of hospital stay were documented. All surgeries were performed by the same surgeon and followed up for 3 months. RESULTS: The peri-wound skin temperature and knee VAS pain scores were lower in the non-CSD group. Patients in the non-CSD group had significantly better knee ROM (P = 0.028). The time to regaining active straight leg raising was significantly shorter in the non-CSD groupN than in the CSD group (P = 0.014). In addition, patients in the non-CSD group had a shorter length of hospital stay (P = 0.004) than those in the CSD group, indicating earlier recovery of knee function. HBL was significantly less in the CSD group than the non-CSD group (P = 0.006) on postoperative day (POD) 5. However, CBL did not differ significantly between the two groups on POD5. There were no significant differences between two groups in all other assessed variables. CONCLUSION: In this randomized study, primary TKA without CSD was associated with faster recovery related to less local inflammation and better early knee function. Furthermore, use of a drain had no significant advantage with respect to other outcome measures and may have increased costs. Based on these data, CSD after primary TKA is not routinely indicated.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/rehabilitación , Drenaje/métodos , Articulación de la Rodilla/fisiopatología , Osteoartritis de la Rodilla/cirugía , Recuperación de la Función , Anciano , Femenino , Estudios de Seguimiento , Humanos , Articulación de la Rodilla/cirugía , Masculino , Osteoartritis de la Rodilla/fisiopatología , Estudios Prospectivos , Succión/métodos , Factores de Tiempo
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