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Background and objective: Surgery is the primary therapy that crucially affects the survival of patients with kidney cancer (KC). However, pertinent surgical decision criteria for individuals with stage T2-3 KC are lacking. This study aimed to display the practical choices and evolving trends of surgical procedures and elucidate their implied value. Methods: Through the Surveillance, Epidemiology, and End Results (SEER) dataset, the levels and evolving trends of different surgical methods were examined to determine cancer-specific risk of death (CSRD). Additionally, stratification analysis and survival rate analysis were performed to explore the effectiveness of partial nephrectomy (PN). Results: In this study, 9.27% of patients opted for PN. Interestingly, an upward trend was observed in its decision, with an average annual percentage change (AAPC) of 7.0 (95% CI: 4.8-9.3, P < 0.05). Patients who underwent PN and were in a relatively less severe condition exhibited more favorable CSRD levels (0.17-0.36 vs. 0.50-0.67) and an improvement trend compared with those who underwent radical nephrectomy (RN) (AAPC: -1.9 vs. -0.8). Further analysis showed that the levels of CSRD and survival rates for patients opting for different surgical methods followed a similar pattern. Conclusions: This study showed that RN was still the most common surgical method. Patients with stage T2-3 KC had an increasing preference for PN and exhibited more favorable cancer-related survival outcomes, which underscores the need for further investigation and validation.
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PURPOSE: To investigate bilateral axial length (AL) growth patterns and interactions of myopic eyes in anisometropic children during unilateral orthokeratology (OK) treatment in their singularly myopic eyes (Eyes1), followed by bilateral treatment when their second eyes (Eyes2) developed myopia. METHODS: This study enrolled 94 eyes from 47 anisometropes (20 males). All patients had undergone monocular OK treatment for > 1 year followed by binocular treatment for > 1 year. Axial growth of Eyes1 and Eyes2 during the first year of monocular treatment (Stage 1), average annual axial elongation during the monocular treatment period, and axial elongation during the first year of binocular treatment (Stage 2) were respectively termed: S1E1 and S1E2, Annual E1 and Annual E2, and S2E1 and S2E2. Associations between AL growth and age, sex, interval time, and ocular parameters were analysed using correlation and generalised estimating equation (GEE) analysis. RESULTS: During the monocular period, Eyes1 showed less AL growth (S1E1: 0.05 ± 0.18 mm; Annual E1: 0.05 ± 0.21 mm) than Eyes2 (S1E2: 0.51 ± 0.24 mm; Annual E2: 0.52 ± 0.25 mm) (all p < 0.001). During the binocular period, there was no significant difference between S2E1 and S2E2(0.21 ± 0.14 mm v. 0.19 ± 0.17 mm, p = 0.951). Between monocular and binocular periods, Eyes1 had significantly higher S2E1 compared to S1E1 and Annual E1 (both p < 0.001), and Eyes2 had significantly lower S2E2 than S1E2 and Annual E2 (both p < 0.001). In the GEE model, spherical equivalent refraction (SER) and between periods interval time showed independently significant associations with AL growth after adjusting for age and sex. CONCLUSION: Orthokeratology can significantly control AL growth in unilateral myopia. AL growth of the initial myopic OK-treated eyes accelerated relative to the monocular period when contralateral eyes developed myopia and assumed OK treatment. During the binocular treatment phase, OK lenses showed moderate and comparable effects on AL retardation across both eyes.
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BACKGROUND: This study aimed to investigate the knowledge, attitudes, and practices (KAP) toward cardiovascular complications among end-stage renal disease patients undergoing maintenance hemodialysis. METHODS: This web-based cross-sectional study was conducted at Guangdong Provincial People's Hospital between December 2022, and May 2023. RESULTS: A total of 545 valid questionnaires were collected, with an average age of 57.72 ± 13.47 years. The mean knowledge, attitudes and practices scores were 8.17 ± 2.9 (possible range: 0-24), 37.63 ± 3.80 (possible range: 10-50), 33.07 ± 6.10 (possible range: 10-50) respectively. Multivariate logistic regression analysis showed that patients from non-urban area had lower knowledge compared to those from urban area (odds ratio (OR) = 0.411, 95% CI: 0.262-0.644, P < 0.001). Furthermore, higher levels of education were associated with better knowledge, as indicated by OR for college and above (OR = 4.858, 95% CI: 2.483-9.504), high school/vocational school (OR = 3.457, 95% CI: 1.930-6.192), junior high school (OR = 3.300, 95% CI: 1.945-5.598), with primary school and below as reference group (all P < 0.001). Besides, better knowledge (OR = 1.220, 95% CI: 1.132-1.316, P < 0.001) and higher educational levels were independently associated with positive attitudes. Specifically, individuals with a college degree and above (OR = 2.986, 95% CI: 1.411-6.321, P = 0.004) and those with high school/vocational school education (OR = 2.418, 95% CI: 1.314-4.451, P = 0.005) have more positive attitude, with primary school and below as reference group. Next, better attitude (OR = 1.174, 95% CI: 1.107-1.246, P < 0.001) and higher education were independently associated with proactive practices. Those with college and above (OR = 2.870, 95% CI: 1.359-6.059, P = 0.006), and those with high school/vocational school education (OR = 1.886, 95% CI: 1.032-3.447, P = 0.039) had more proactive practices, with primary school and below as reference group. CONCLUSIONS: End-stage renal disease patients undergoing maintenance hemodialysis demonstrated insufficient knowledge, positive attitudes, and moderate practices regarding cardiovascular complications. Targeted interventions should prioritize improving knowledge and attitudes, particularly among patients with lower educational levels and income, to enhance the management of cardiovascular complications in end-stage renal disease.
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Enfermedades Cardiovasculares , Conocimientos, Actitudes y Práctica en Salud , Fallo Renal Crónico , Diálisis Renal , Humanos , Masculino , Femenino , Diálisis Renal/psicología , Estudios Transversales , Fallo Renal Crónico/terapia , Fallo Renal Crónico/psicología , Persona de Mediana Edad , Adulto , Anciano , Encuestas y Cuestionarios , China/epidemiologíaRESUMEN
OBJECTIVES: Healthcare-associated infections (HAIs) represent a major threat to patient safety and are associated with significant economic burden. Calculating the costs attributable to HAIs is challenging given the various sources of bias. Although HAIs as a reasonably preventable medical harm should have been closely linked to medical insurance incentives, there was little linkage between HAIs and medicare in western China owing to the lack of economic evaluation data. The present study aimed to generate estimates of the attributable costs associated with HAIs and the magnitude of costs growth. METHODS: In this cohort study designed horizontally and vertically from 2016 to 2022, we compared outcomes of randomly sampling patients with HAIs and individually matched patients without HAIs in two cohorts at a 6-year interval at 34 hospitals in western China. The primary outcome was the direct medical cost for the entire hospital stay, converted to US dollars ($ for the benchmark year), discounted at 3% annually, and estimated separately in the full analysis set (FAS) and the per protocol set (PPS). We used multiple linear regression to adjust the discounted costs and to assess subgroups effects within each cohort. We nested a dynamic vertical comparison of costs attributable to HAIs between the front and rear cohorts. RESULTS: A total of 230 patients with HAIs in 2016 and 204 patients with HAIs in 2022 were enrolled. After a 1:1 match, all 431 pairs were recruited as FAS, of which 332 pairs as PPS met all matching restrictions. Compared to the 2016 cohort in FAS, the patients with HAIs in 2022 had a significantly older age (64.40 ± 16.45 years), higher repeat hospitalization rate (65 [32.02%] of 203), and lower immune function (69 [33.99%] of 203). The discounted costs and adjusted-discounted costs for patients with HAIs in the 2022 cohort were found to be significantly higher than those of patients without HAIs (discounted costs: $5484.60 [IQR 8426.03] vs $2554.04(4530.82), P < 0.001; adjusted-discounted costs: $5235.90 [3772.12] vs $3040.21(1823.36), P < 0.001, respectively), and also higher than those of patients with HAIs in the 2016 cohort (discounted costs: $5484.60 [8426.03] vs $3553.00 [6127.79], P < 0.001; adjusted-discounted costs: $5235.90 [3772.12] vs $3703.82 [3159.14], P < 0.001, respectively). In vertical comparison of PPS, the incremental costs of the 2022 cohort are 1.48 times higher than those of the 2016 cohort ($964.63(4076.15) vs $652.43 [2533.44], P = 0.084). CONCLUSIONS: This meticulously designed study in western China has successfully and accurately examined the economic burden attributable to HAIs. Their rapidly increasing tendency poses a serious challenge to patients, hospitals, and the medical insurance. A closer linkage between HAIs and ongoing motivating system changes is urgently needed in western China.
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Infección Hospitalaria , Estrés Financiero , Estados Unidos , Humanos , Anciano , Estudios de Cohortes , Estudios Prospectivos , Medicare , Infección Hospitalaria/epidemiología , Hospitales , China/epidemiología , Atención a la SaludRESUMEN
Background: The continuous exploration of oligometastatic disease has led to the remarkable achievements of local consolidative therapy (LCT) and favorable outcomes for this disease. Thus, this study investigated the potential benefits of LCT in patients with single-organ metastatic pancreatic ductal adenocarcinoma (PDAC). Methods: Patients with single-organ metastatic PDAC diagnosed between 2010 - 2019 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to minimize selection bias. Factors affecting survival were assessed by Cox regression analysis and Kaplan-Meier estimates. Results: A total of 12900 patients were identified from the database, including 635 patients who received chemotherapy combined with LCT with a 1:1 PSM with patients who received only chemotherapy. Patients with single-organ metastatic PDAC who received chemotherapy in combination with LCT demonstrated extended median overall survival (OS) by approximately 57%, more than those who underwent chemotherapy alone (11 vs. 7 months, p < 0.001). Furthermore, the multivariate Cox regression analysis revealed that patients that received LCT, younger age (< 65 years), smaller tumor size (< 50 mm), and lung metastasis (reference: liver) were favorable prognostic factors for patients with single-organ metastatic PDAC. Conclusion: The OS of patients with single-organ metastatic pancreatic cancer who received LCT may be prolonged compared to those who received only chemotherapy. Nevertheless, additional prospective randomized clinical trials are required to support these findings.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Anciano , Estudios Transversales , Puntaje de Propensión , Estudios Prospectivos , Neoplasias Pancreáticas/tratamiento farmacológico , Sistema de RegistrosRESUMEN
Objective: To analyze the prognostic factors of patients with cholangiocarcinoma (CCA) who were unresected and received radiotherapy to establish a nomogram model for the prediction of patient cancer-specific survival (CSS). Methods: Suitable patient cases were selected from the Surveillance, Epidemiology, and End Results (SEER) database, survival rates were calculated using the Kaplan-Meier method, prognostic factors were analyzed by Lasso, Cox regression, and nomogram was developed based on independent prognostic factors to predict 6 and 12 months CSS. The consistency index (C-index), calibration curve, and decision curve analysis (DCA) were tested for the predictive efficacy of the model, respectively. Results: The primary site, tumor size, T-stage, M-stage, and chemotherapy (P < 0.05) were identified as independent risk factors after Cox and Lasso regression analysis. Patients in training cohort had a 6 months CSS rates was 68.6 ± 2.6%, a 12-month CSS rates was 49.0 ± 2.8%. The median CSS time of 12.00 months (95% CI: 10.17-13.83 months). The C-index was 0.664 ± 0.039 for the training cohort and 0.645 ± 0.042 for the validation cohort. The nomogram predicted CSS and demonstrated satisfactory and consistent predictive performance in 6 (73.4 vs. 64.9%) and 12 months (72.2 vs. 64.9%), respectively. The external validation calibration plot is shown AUC for 6- and 12-month compared with AJCC stage was (71.2 vs. 63.0%) and (65.9 vs. 59.8%). Meanwhile, the calibration plot of the nomogram for the probability of CSS at 6 and 12 months indicates that the actual and nomogram predict that the CSS remains largely consistent. DCA showed that using a nomogram to predict CSS results in better clinical decisions compared to the AJCC staging system. Conclusion: A nomogram model based on clinical prognostic characteristics can be used to provide CSS prediction reference for patients with CCA who have not undergone surgery but have received radiotherapy.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Nomogramas , Factores de Riesgo , Conductos Biliares IntrahepáticosRESUMEN
BACKGROUND: Aberrant expression of circular RNA (circRNA) has been demonstrated to be related to atherosclerosis (AS) formation. However, the mechanism of circCHMP5 (also known as hsa_circ_0003575) in AS formation remains unclear. METHODS: Oxidized low-density lipoprotein (ox-LDL) was used to treat human umbilical vein endothelial cells (HUVECs) to construct a cell injury model. The expression level of circCHMP5, miR-532-5p, and Rho-associated protein kinase 2 (ROCK2) was measured using quantitative real-time PCR. Cell cycle, apoptosis, proliferation, and angiogenesis were determined by flow cytometry, 5-ethynyl-2'-deoxyuridine (EdU) assay, and tube formation assay. In addition, the protein expression of apoptosis markers, inflammation factors, and ROCK2 was detected by western blot analysis. The interaction between miR-532-5p and circCHMP5 or ROCK2 was assessed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULTS: Our results indicated that circCHMP5 was overexpressed in ox-LDL-induced HUVECs. CircCHMP5 knockdown promoted cell cycle, proliferation, and angiogenesis while inhibiting apoptosis and inflammation in ox-LDL-induced HUVECs. MiR-532-5p could be sponged by circCHMP5, and its inhibitor reversed the negative regulation of si-circCHMP5 on ox-LDL-induced HUVECs injury. ROCK2, a target of miR-532-5p, reversed the inhibition effect of miR-532-5p on ox-LDL-induced HUVECs injury. Furthermore, we confirmed that circCHMP5 upregulated ROCK2 by sponging miR-532-5p. CONCLUSION: To sum up, our data showed that circCHMP5 regulated the miR-532-5p/ROCK2 axis to accelerate ox-LDL-induced HUVECs injury, confirming that circCHMP5 might be a potential target for AS treatment.
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Aterosclerosis , MicroARNs , Humanos , Lipoproteínas LDL/toxicidad , Células Endoteliales de la Vena Umbilical Humana , Apoptosis , Aterosclerosis/genética , Inflamación , MicroARNs/genética , Proliferación Celular , Quinasas Asociadas a rhoRESUMEN
PURPOSE: To investigate the efficacy of myopia control by comparing the orthokeratology (Ortho-K) treated eyes and the emmetropic contralateral eyes in unilateral myopic children, and to identify the inter-individual influence factors. METHOD: In this retrospective study, 1566 medical records of children wearing Ortho-K lens were reviewed, and 62 children who received monocular Ortho-K lens for more than 1 year were analyzed. The change in axial length (AL) of the Ortho-K eyes and the emmetropic contralateral eyes was recorded. To evaluate the absolute and relative efficacy of myopia control, the intra-bilateral absolute reduction in AL growth (ibARAL) and the intra-bilateral relative reduction in AL growth (ibRRAL) were calculated as main outcomes. Association of the AL elongation, ibARAL and ibRRAL with age, sex and ocular parameters was analyzed by correlation analysis and generalized estimating equation (GEE) analysis. RESULT: The average initial wearing age was 10.76 ± 1.45 (ranged 8.5 to 15.8). The average baseline SER was - 2.15 ± 1.03 (ranged - 5.25 to -1.00) D in the Ortho-K eyes and - 0.01 ± 0.40 (ranged - 0.75 to 0.75) D in the contralateral eyes. At the 1-year follow-up, the average increased AL was significantly less in the Ortho-K eyes (0.07 ± 0.18 mm) than in the fellow eyes (0.48 ± 0.24 mm) (p < 0.001). The mean ibARAL was 0.41 ± 0.30 mm, and the mean ibRRAL was 83.4%±56.3%. In the GEE model, the AL change in Ortho-K eyes (ß = 0.051, p = 0.009, 95%CI: 0.012 to 0.090), the ibARAL (ß= -0.153, p = 0.000, 95%CI: -0.228 to -0.078) and the ibRRAL (ß= -0.196, p = 0.020, 95%CI: -0.361 to -0.030) were independently associated with the spherical equivalent refraction (SER) of the Ortho-K eyes, after adjusting for age, sex, and keratometry. CONCLUSION: In our study, the Ortho-K treatment was efficacious in controlling axial length growth in the monocular orthokeratology treated unilateral myopic eyes. The efficacy increased when the myopia was more severe. In the children from 8 to 16 years old, the effectiveness was independent of age and sex.
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Miopía , Procedimientos de Ortoqueratología , Humanos , Niño , Adolescente , Estudios Retrospectivos , Longitud Axial del Ojo , Miopía/terapia , Córnea , Refracción OcularRESUMEN
Background: There is a lack of studies regarding radiotherapy (RT) in patients with gallbladder cancer (GBC) on the survival benefit after surgery and nonsurgical treatment. Therefore, this study evaluated the impact of external beam RT on the overall survival (OS) of patients with GBC in a real-world setting. Methods: Patients with GBC enrolled from the Surveillance, Epidemiology, and End Results (SEER) database were examined through Kaplan-Meier survival curves and multivariable Cox regression analyses. Results: A total of 7,866 patients with GBC were screened for the current analysis, of whom 2,130 (27.1%) did not undergo RT or surgery, 209 (2.7%) underwent RT, 4,511 (57.3%) underwent surgery, and 1,016 (12.9%) underwent both RT and surgery. The median OS times were 4 months, 8 months, 16 months, and 22 months (p < 0.0001). OS was significantly different between adjuvant RT (p = 0.0002) and palliative RT (p < 0.0001). Multifactorial analysis (controlling for age, sex, year of diagnosis, marital status, race, grade, and stage) showed that both adjuvant RT (surgery and adjuvant RT vs. surgery alone; HR, 0.75; 95% CI, 0.69-0.82, p < 0.001) and palliative RT (RT alone vs. no treatment; HR, 0.80; 95% CI, 0.69-0.92, p = 0.003) had a significant impact on patient OS. The results remained stable following sensitivity analyses. Conclusion: The study results indicate that adjuvant and palliative radiation treatment was associated with a survival benefit. GBC patients can derive a survival benefit from external beam RT.
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Neoplasias de la Vesícula Biliar , Humanos , Neoplasias de la Vesícula Biliar/radioterapia , Radioterapia Adyuvante , Estimación de Kaplan-Meier , Análisis de RegresiónRESUMEN
Diabetic retinopathy (DR) is one of the leading causes of severe visual impairment worldwide. However, the role of adaptive immune inflammation driven by microglia/macrophages in DR is not yet well elucidated. Kdm6a is a histone demethylase that removes the trimethyl groups of histones H3K27 and plays important biological roles in activating target genes. To elucidate the role of Kdm6a in microglia/macrophages in diabetic retinas, we established diabetic animal models with conditional knockout mice to investigate the impacts of Kdm6a deficiency. The RNA-seq analysis, mass spectrum examination, immunohistochemistry and detection of enzyme activities were used to elucidate the effect of Kdm6a deletion on gene transcription in microglia/macrophages. The expression of Kdm6a was increased in the retinas of diabetic mice compared to the control group. Loss of Kdm6a in microglia/macrophages ameliorated the diabetes-induced retinal thickness decrease, inflammation, and visual impairment. Kdm6a in microglia/macrophages regulated Lcn2 expression in a demethylase activity-dependent manner and inhibited glycolysis progression in photoreceptor cells through Lcn2. These results suggest that Kdm6a in microglia/macrophages aggravated diabetic retinopathy by promoting the expression of Lcn2 and impairing glycolysis progression in photoreceptor cells.
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Diabetes Mellitus Experimental , Retinopatía Diabética , Histona Demetilasas , Lipocalina 2 , Animales , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Retinopatía Diabética/genética , Histona Demetilasas/genética , Histonas/metabolismo , Inflamación/genética , Inflamación/metabolismo , Lipocalina 2/genética , Lipocalina 2/metabolismo , Macrófagos/metabolismo , Ratones , Ratones Noqueados , Microglía/metabolismo , Células Fotorreceptoras/metabolismoRESUMEN
Clinical Relevance: A vergence formula may provide a simple and reliable calculation of the refractive status of aphakic eyes. Background: Measuring the refractive error of pediatric eyes with aphakia is difficult. This study investigated the accuracy and applicability of a vergence formula for estimating the refractive status of such eyes. Methods: A retrospective review of the medical records, created between January 2016 and December 2018, of pediatric patients with aphakia was conducted. A vergence formula, based on axial length, was used to calculate the refractive status of the aphakic eyes. The refractive values determined using retinoscopy, an automatic refractometer, and the vergence formula were compared. Results: A total of 72 eyes (47 patients) were analyzed. The spherical equivalents of the refractive errors (mean ± standard deviation) of the eyes were determined using retinoscopy (13.01 ± 3.27 D), automatic refractometry (12.90 ± 3.23 D), and the vergence formula (12.70 ± 3.4 D). The correlation coefficient between retinoscopy values determined using retinoscopy and the vergence formula, automatic refractometry and the vergence formula, and retinoscopy and automatic refractometry were 0.968, 0.987, and 0.979, respectively. The Bland-Altman consistency analysis revealed that the mean differences in the spherical equivalent values between retinoscopy and automatic refractometry, retinoscopy and the vergence formula, and automatic refractometry and the vergence formula were 0.11 D, 0.31 D, and 0.21 D, respectively, with 95% limits of agreement of-1.20 to 1.41 D,-1.37 to 2.00 D, and-0.90 to 1.31 D, respectively. Conclusion: The vergence formula was effective for evaluating the refractive status of aphakic eyes in pediatric patients.
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OBJECTIVE: The aim of this study was to investigate the efficacy and safety of combined applications of local consolidative radiation therapy (LCRT) and first-line tyrosine kinase inhibitors (TKIs) for the treatment of primary tumors and oligometastatic sites in oligometastatic NSCLC harboring Epidermal Growth Factor Receptor (EGFR) activating mutations. PATIENTS AND METHODS: Elderly patients with oligometastatic NSCLC (≤5 metastases) harboring EGFR activating mutations at the time of diagnosis were identified. They were treated with first-line TKIs alone or in combination with LCRT. Progression-free survival (PFS) and overall survival (OS) were estimated through the Kaplan-Meier method. RESULTS: A total of 122 elderly patients were enrolled between February 2010 and January 2018. Among them, 41.0% (n = 50) received TKIs combined with LCRT (TKIs + LCRT group), whereas 59.0% (n = 72) received TKIs monotherapy (TKIs alone group). Patients were followed up for a median length of 34 months (ranging from 7.0 to 64 months). The median PFS in TKIs + LCRT group was 17 months (95%CI: 15.37-18.63), which was significantly longer than that of the TKIs-alone group (12 months; 95%CI: 11.05-12.95) (p <0.001). Median OS in TKIs + LCRT group was 38 months (95%CI: 35.61-40.39), while that of the TKIs-alone group was 29 months (95%CI: 26.86-31.14) (p <0.001). Multivariate analyses revealed that LCRT, one to two metastases, and good ECOG PS were independent predictors for better PFS (p <0.001, p = 0.004, and p = 0.027). Moreover, LCRT, good ECOG PS, and T1-2 stage were independent predictors for better OS (p <0.001, p = 0.007 and p = 0.007). Most of the patients suffered from grade 1 to 2 toxicities, and treatment-related deaths were not recorded. CONCLUSION: First-line TKIs combined with LCRT may improve survival outcomes for elderly patients with oligometastatic NSCLC harboring EGFR activating mutations. This approach was not associated with much toxicity, therefore, it can be used for the treatment of elderly patients with oligometastatic disease.
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OBJECTIVES: Myocardial infarction (MI) is the leading cause of death worldwide. Histone deacetylases (HDACs) collectively participate in the initiation and progression of heart diseases, including MI. This study aimed to investigate the roles of histone deacetylase 9 (HDAC9) in the development of MI. METHODS: In vivo and in vitro assays were conducted to determine the effects of HDAC9 on heart function and MI. qRT-PCR was applied to determine the mRNA level. Western blot was performed for protein expression. Immunofluorescence was applied to detect the fluorescence tensity of Myog and Myod. CCK-8, flow cytometry and transwell assays were carried out for function analysis. KEY FINDINGS: HDAC9 was upregulated in MI models in vivo and in vitro. Downregulated HDAC9 modulated the changes in left ventricle ejection fraction (LVEF), left ventricle fractional shortening (LVFS) and left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD). Moreover, HDAC9 knockdown activated NFE2-related factor 2 (Nrf2)/Keap1/HO-1 pathways. Additionally, HDAC9/Nrf2 axis modulated the proliferation, apoptosis and myogenesis of cardiomyocytes. CONCLUSIONS: Taken together, HDAC9 knockout induced the activation of Nrf2 and protected heart from MI injury. Thus, the HDAC9/Nrf2 axis can be a novel marker for the treatment of MI.
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Histona Desacetilasas , Infarto del Miocardio , Factor 2 Relacionado con NF-E2 , Proteínas Represoras , Apoptosis , Histona Desacetilasas/metabolismo , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Infarto del Miocardio/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Proteínas Represoras/metabolismo , Volumen SistólicoRESUMEN
BACKGROUND AND PURPOSE: This study aimed to investigate the efficacy and safety of maintenance therapy combined with local radiotherapy at all oligometastatic sites (LRTOS) in elderly patients with metachronous oligometastatic cancers (MOC). PATIENTS AND METHODS: A total of 242 elderly patients with MOC (≤5 metastases) and primary tumor well controlled after definitive treatment was retrospectively analyzed between August 2014 and February 2020 at Beijing Geriatric Hospital and Air Force General Hospital. Patients were divided into maintenance therapy group (maintenance therapy alone) and local radiotherapy group (maintenance therapy combined with LRTOS). RESULTS: There were 86 patients in the local radiotherapy group and 156 patients in the maintenance therapy group. The median length of follow-up was 36 months (range, 8.0-62 months). Median overall survival (mOS) was 25 months (95% CI: 21.1-28.9) in the local radiotherapy group and 16 months (95% CI: 14.5-17.6) in the maintenance therapy group (p < 0.001). Multivariate analyses demonstrated that LRTOS (hazard ratio (HR) = 0.49, 95% confidence interval (CI): 0.35-0.67, p < 0.001), good Eastern Cooperative Oncology Group Performance Status (ECOG PS, HR = 0.69, 95% CI: 0.49-0.97, p = 0.032), longer duration between diagnosis of primary tumor and occurrence of progression (HR = 0.87, 95% CI: 0.78-0.97, p = 0.015), and subsequent systemic treatment (HR = 0.52, 95% CI: 0.38-0.72, p < 0.001) were independent predictors of good OS. In patients who did not receive subsequent systemic treatment, their mOS was 21 months (95% CI: 12.8-29.2) for those treated with LRTOS and 14 months (95% CI: 11.4-16.6) for those who did not receive local radiotherapy (p = 0.001). Further multivariate analysis showed that LRTOS was the only independent factor for predicting good OS (HR = 0.47, 95% CI: 0.26-0.83, p = 0.010). Patients with metachronous oligometastatic lung cancer, colorectal cancer, prostate cancer, and breast cancer had higher survival benefits following LRTOS. Most patients suffered from grade 1-2 toxicities, but no treatment-related death was recorded. CONCLUSION: This retrospective study shows that elderly patients with MOC treated with LRTOS may have better survival outcomes.
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OBJECTIVE: To study the surgical effects of medial rectus recession (MRR) on divergence insufficiency esotropia (DIE). METHODS: Nine DIE patients who were admitted to and had MRR at Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University between December 2017 and June 2020 were included in this retrospective study. All patients were followed up for 1 year at least. The postoperative esodeviation, near-distant disparity (NDD) and visual function were observed and compared. RESULTS: The mean age of the 9 patients was 28.8 years old (10-49 yr.), including 3 adolescent patients (≤18 yr.). The mean preoperative esodeviation was (19.8±13.2) PD for near and (32.6±15.3) PD at distance, while, the mean postoperative esodeviation 1 year after MMR was (-0.2±3.5) PD for near and (6.0±2.2) PD at distance, showing significant improvement over the mean preoperative esodeviation ( P=0.012, P=0.007). NDD dropped from (12.8±2.4) PD before the surgery to (6.0±2.2) PD 1 year after the surgery, showing significant improvement ( P=0.008), and remained stable 1 year after the surgery ( F=0.075, P=0.900). There was no significant improvement of near stereopsis ( P=0.306). Binocular function at distance was significantly improved after surgery (Worth 4 dots test : P=0.017; Bagolini striated glasses: P=0.035). The patients were divided into two groups, the adolescent group (age≤18 yr., n=3) and the adult group (age>18 yr., n=6). Prior to the operation, the mean spherical diopter of the adolescent group (OD -1.75 D, OS -1.92 D) was lower than that of the adult group (OD -6.17 D, OS -6.04 D) ( P=0.012). The average value of preoperative AC/A of the adolescent group was 4.33. It was 2.33 in the adult group, which was lower than the normal value, and significantly lower than that of the adolescent group ( P=0.12). There was no significant difference in esodeviation or NDD between the adolescent group and the adult group before and after operation. CONCLUSIONS: Medial rectus muscle recession can effectively improve the NDD and the binocular function at distance of patients with divergence insufficiency esotropia. Postoperative esodeviations both for near and at distance tend to regress after the surgery. Therefore, it is recommended that the amount of MRR be increased in the treatment of DIE.
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Esotropía , Adolescente , Adulto , China , Esotropía/cirugía , Humanos , Músculos Oculomotores/cirugía , Procedimientos Quirúrgicos Oftalmológicos , Estudios Retrospectivos , Resultado del Tratamiento , Visión BinocularRESUMEN
Forkhead-box O (FoxO) is the primary transcriptional effector of the insulin-like signaling pathway that enhances gluconeogenesis through transcriptional activation of PEPCK and G6Pase in mammals. We have previously demonstrated the involvement of phosphoenolpyruvate carboxykinase (BmPEPCK-2) in antiviral immunity against the multiplication of Bombyx mori nuclearpolyhedrosisvirus (BmNPV) in silkworm. Therefore, we speculated that BmFoxO might suppress BmNPV by regulating the expression of PEPCK in silkworm. In the present study, we found that the expression of BmFoxO decreased after BmNPV infection in Bombyx mori; this finding was consistent with BmPEPCK-2 expression. In addition, the expression of BmFoxO was altered, and it was found that reduced expression of BmFoxO (dsBmFoxO) downregulated the expression of BmPEPCK-2 and increased the viral fluorescence and content in silkworm embryonic cell line BmE cells, and vice versa. BmFoxO could upregulate the expression of BmPEPCK-2 by binding to the BmPEPCK-2 promoter. Moreover, overexpression of BmFoxO significantly increased the expression of autophagy genes ATG6/7/8 after infection with BmNPV, consistent with BmPEPCK-2. These results indicate that BmNPV downregulates transcription factor BmFoxO to elevate virus infection, and BmFoxO overexpression upregulates BmPEPCK-2 expression and enhances silkworm antiviral resistance.
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Bombyx/genética , Regulación hacia Abajo , Factores de Transcripción Forkhead/genética , Regulación de la Expresión Génica , Proteínas de Insectos/genética , Nucleopoliedrovirus/crecimiento & desarrollo , Animales , Autofagia/genética , Proteína 7 Relacionada con la Autofagia/genética , Proteína 7 Relacionada con la Autofagia/metabolismo , Familia de las Proteínas 8 Relacionadas con la Autofagia/genética , Familia de las Proteínas 8 Relacionadas con la Autofagia/metabolismo , Beclina-1/genética , Beclina-1/metabolismo , Bombyx/metabolismo , Bombyx/virología , Línea Celular , Factores de Transcripción Forkhead/metabolismo , Interacciones Huésped-Patógeno , Proteínas de Insectos/metabolismo , Nucleopoliedrovirus/fisiología , Fosfoenolpiruvato Carboxiquinasa (ATP)/genética , Fosfoenolpiruvato Carboxiquinasa (ATP)/metabolismo , Regiones Promotoras Genéticas/genética , Unión ProteicaRESUMEN
BACKGROUND: The aim of this study was to research the effects of glutamine synthetase (GS) and glutamate aspartate transporter (GLAST) in rat Müller cells and the effects of an adenosine A2AR antagonist (SCH 442416) on GS and GLAST in hypoxia both in vivo and in vitro. METHODS: This study used RT-PCR and Western blotting to quantify the expressions of GS and GLAST under different hypoxic conditions as well as the expressions of GS and GLAST at different drug concentrations. A cell viability assay was used to assess drug toxicity. RESULTS: mRNA and protein expression of GS and GLAST in hypoxia Group 24 h was significantly increased. mRNA and protein expressions of GS and GLAST both increased in Group 1 µM SCH 442416 compared with other groups. One micromolar SCH 442416 could upregulate GS and GLAST's activity in hypoxia both in vivo and in vitro. CONCLUSIONS: Hypoxia activates GS and GLAST in rat retinal Müller cells in a short time in vitro. (2) A2AR antagonists upregulate the activity of GS and GLAST in hypoxia both in vivo and in vitro.
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Antagonistas del Receptor de Adenosina A2/farmacología , Sistema de Transporte de Aminoácidos X-AG/genética , Glutamato-Amoníaco Ligasa/genética , Hipoxia/enzimología , Hipoxia/genética , Regulación hacia Arriba/efectos de los fármacos , Sistema de Transporte de Aminoácidos X-AG/metabolismo , Animales , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Células Ependimogliales/efectos de los fármacos , Células Ependimogliales/metabolismo , Glutamato-Amoníaco Ligasa/metabolismo , Pirazoles/farmacología , Pirazoles/toxicidad , Pirimidinas/farmacología , Pirimidinas/toxicidad , Ratas Sprague-DawleyRESUMEN
PURPOSE: We assessed the clinical outcomes and toxicities following hypofractionation with helical tomographic intensity-modulated radiotherapy technology (tomotherapy) in patients with stage III non-small cell lung cancer (NSCLC) who were not candidates for surgery or concurrent chemoradiation. METHODS: Forty-three patients with stage III NSCLC who were treated between 2011 and 2017 were enrolled. The prescription doses for gross target volume and clinical target volume were 70 Gy and 60 Gy (respectively) delivered in 15-25 fractions over 3-5 weeks. RESULTS: The median overall survival (OS) time was 34.23 (range 11.33-99.33) months. The estimated 1-, 2-, and 3-year OS rates were 97.7%, 74.4%, and 55.9%, respectively; the corresponding progression-free survival (PFS) rates were 79.1%, 53.5%, and 36.1%, respectively. The local disease recurrence, regional disease recurrence, and distant metastasis rates at 3 years were 4.7%, 11.62%, and 55.81%, respectively. On multivariate analysis, dose regimen (<19 f vs. ≥19 f) was an independent prognostic factor affecting OS, PFS, and DM (p < 0.05). Seven patients developed grade 1-2 acute radiation pneumonia (RP), 5 patients developed grade 1-2 late RP, while 3 patients developed grade 3 late RP. None of the patients developed grade 4-5 radiation lung injury. CONCLUSION: Tomotherapy may be an effective treatment option for patients with stage III NSCLC. It may be a viable alternative to surgery with lower incidence of side effects.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Radioterapia de Intensidad Modulada , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Quimioradioterapia , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/radioterapia , Masculino , Estadificación de Neoplasias , Supervivencia sin ProgresiónRESUMEN
Two chloroantimonate hybrids with isomeric bipyridyltriazoliums and similar packing patterns, {[2-bpt]2[(SbCl5)Cl2]}n (1) and {[4-bpt]2[(SbCl5)Cl2]}n (2) (2-bpt2+ = protonated 3,5-bis(pyridine-2-yl)-1,2,4-triazole, 4-bpt2+ = protonated 3,5-bis(pyridine-4-yl)-1,2,4-triazole), have been designed and synthesized. Distinct intermolecular electronic interactions and photochromic behaviors are attributed to the remarkable modulation of positional isomeric effect on the electron deficiency of the acceptors and donor-acceptor matching relationship. 1 is the first reported photochromic chloroantimonate hybrid.
RESUMEN
A novel divided solenoid with high homogeneity is designed through linear programming (LP) for actual guiding magnet application in high power microwave devices. During the LP process, current density, magnetic field homogeneity, and total volume of coils are set as variable, constraint condition, and objective function, respectively. The divided solenoid is designed after calculating current density in the available zone where the coil current exists. After comparing the electrical parameters and magnetic field distribution of the conventional and the new solenoid, it is concluded that the inhomogeneity of the new design is reduced from 10% to 0.7%, the central magnetic field is equal, and other factors are in the same range. The divided solenoid magnet designed by LP is able to achieve high uniformity by improving the winding process and mechanical structure, which also has strong generalization.