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1.
Pract Lab Med ; 40: e00416, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38989481

RESUMO

Objectives: Rapid antigen test (RAT) and polymerase chain reaction (PCR) using nasopharyngeal (NP) or oropharyngeal (OP) swab specimens are the two main testing techniques used for laboratory diagnosis of influenza in clinical practice. However, performance variations have been observed not only between techniques, but also between different specimens. This study evaluated the differences in performance between specimens and testing techniques to identify the best combination in clinical practice. Methods: Both NP and OP samples from suspected influenza patients collected in the 2023/4-2023/5 Flu-season in Xiamen, China, were tested for RAT and quantitative PCR. The testing performance of the different specimens and testing techniques were recorded and evaluated. Results: Compared to PCR, RAT showed 58.9 % and 10.3 % sensitivity for NP and OP swabs, respectively. The Limit of Detection (LoD) was 28.71 the Median Tissue Culture Infectious Dose (TCID50)/mL. Compared with PCR using NP swabs, PCR with OP swabs showed 89.5 % sensitivity and 95.4 % specificity. Conclusions: There were no significant differences in performance between the specimens when PCR was used to test for influenza. However, a decrease in sensitivity was observed when the RAT was used, regardless of the specimen type. Therefore, to avoid false-negative results, PCR may be a better choice when OP swabs are used as specimens. In contrast, NP swabs should be the recommended specimens for RAT.

2.
Front Neurorobot ; 18: 1293992, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38298467

RESUMO

With the development of deep learning, synthetic aperture radar (SAR) ship detection and recognition based on deep learning have gained widespread application and advancement. However, there are still challenging issues, manifesting in two primary facets: firstly, the imaging mechanism of SAR results in significant noise interference, making it difficult to separate background noise from ship target features in complex backgrounds such as ports and urban areas; secondly, the heterogeneous scales of ship target features result in the susceptibility of smaller targets to information loss, rendering them elusive to detection. In this article, we propose a context-aware one-stage ship detection network that exhibits heightened sensitivity to scale variations and robust resistance to noise interference. Then we introduce a Local feature refinement module (LFRM), which utilizes multiple receptive fields of different sizes to extract local multi-scale information, followed by a two-branch channel-wise attention approach to obtain local cross-channel interactions. To minimize the effect of a complex background on the target, we design the global context aggregation module (GCAM) to enhance the feature representation of the target and suppress the interference of noise by acquiring long-range dependencies. Finally, we validate the effectiveness of our method on three publicly available SAR ship detection datasets, SAR-Ship-Dataset, high-resolution SAR images dataset (HRSID), and SAR ship detection dataset (SSDD). The experimental results show that our method is more competitive, with AP50s of 96.3, 93.3, and 96.2% on the three publicly available datasets, respectively.

3.
ACS Appl Mater Interfaces ; 15(39): 46226-46235, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37738374

RESUMO

Much can be learned from the research and development of scintillator crystals for improving the scintillation performance of glasses. Relying on the concept of "embedding crystalline order in glass", we have demonstrated that the scintillation properties of Ce3+-doped nanoglass composites (nano-GCs) can be optimized via the synergistic effects of Gd3+-sublattice sensitization and band-gap engineering. The nano-GCs host a large volume fraction of KYxGd1-xF4 mixed-type fluoride nanocrystals (NCs) and still retain reasonably good transparency at Ce3+-emitting wavelengths. The light yield of 3455 ± 20 ph/MeV is found, which is the largest value ever reported in fluoride NC-embedded nano-GCs. A comprehensive study is given on the highly selective doping of Ce3+ in the NCs and its positive effect on the scintillation properties. The favorable influence of the Y3+/Gd3+ mixing on the suppression of defects is accounted for by density functional theory and borne out experimentally. As a proof-of-concept, X-ray imaging with a good spatial resolution (7.9 lp/mm) is demonstrated by employing Ce3+-doped nano-GCs. The superior radiation hardness, repeatability, and thermal stability of the designed scintillators bode well for their long-term practical applications.

4.
Appl Opt ; 62(23): 6234-6240, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37707092

RESUMO

A low F-number and 100% cold stop efficiency are beneficial for improving the performance of optical systems and have a wide range of applications in various thermal imaging scenarios. The cooled infrared coaxial four-mirror system can meet these two requirements, improve system integration, and reduce adjustment costs and difficulties. However, the secondary obstruction caused by the central hole of the third mirror will generate potential stray light. A structure model is proposed in which the primary mirror and the quaternary mirror are processed on the same mirror blank. In this model, a method is given to calculate system parameters using the obstruction ratio and magnification of each mirror. To evaluate the performance of the method, two design examples with different F-numbers (1.4, 1.0) were constructed. The influence of initial structural constraints on the exit pupil position and secondary obstruction was analyzed based on the design objectives of the examples. The aberrations were optimized by targeting the spot. In the optimization process, the incident coordinates and directions of the restricted edge field rays in the tertiary mirror and the quaternary mirror were limited to achieve control of the obstruction caused by the holes in the center of the mirrors. In the results, the RMS spot radius of the two design examples is smaller than the Airy disk radius, and the axial beam wavefront deviation RMS values are 0.026λ and 0.024λ, respectively. Moreover, the obstruction caused by the central holes of the mirrors is controlled within the given field of view. The results show that the proposed model and method can be used to design a low F-number cooled infrared coaxial four-mirror system and have good application prospects.

5.
Front Pharmacol ; 14: 1266782, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37745050

RESUMO

Background: Small cell lung cancer (SCLC) is characterized by extreme invasiveness and lethality. There have been very few developments in its diagnosis and treatment over the past decades. It is urgently needed to explore potential novel biomarkers and drug targets for SCLC. Methods: Two-sample Mendelian Randomization (MR) was performed to investigate causal associations between SCLC and plasma proteins using genome-wide association studies (GWAS) summary statistics of SCLC from Transdisciplinary Research Into Cancer of the Lung Consortium (nCase = 2,791 vs. nControl = 20,580), and was validated in another cohort (nCase = 2,664 vs. nControl = 21,444). 734 plasma proteins and their genetic instruments of cis-acting protein quantitative trait loci (pQTL) were used, whereas external plasma proteome data was retrieved from deCODE database. Bidirectional MR, Steiger filtering and phenotype scanning were applied to further verify the associations. Results: Seven significant (p < 6.81 × 10-5) plasma protein-SCLC pairs were identified by MR analysis, including ACP5 (OR = 0.76, 95% CI: 0.67-0.86), CPB2 (OR = 0.90, 95% CI: 0.86-0.95), GSTM3 (OR = 0.45, 95% CI: 0.33-0.63), SHMT1 (OR = 0.74, 95% CI: 0.64-0.86), CTSB (OR = 0.79, 95% CI: 0.71-0.88), NTNG1 (OR = 0.81, 95% CI: 0.74-0.90) and FAM171B (OR = 1.40, 95% CI: 1.21-1.62). The external validation confirmed that CPB2, GSTM3 and NTNG1 had protective effects against SCLC, while FAM171B increased SCLC risk. However, the reverse causality analysis revealed that SCLC caused significant changes in plasma levels of most of these proteins, including decreases of ACP5, CPB2, GSTM3 and NTNG1, and the increase of FAM171B. Conclusion: This integrative analysis firstly suggested the causal associations between SCLC and plasma proteins, and the identified several proteins may be promising novel drug targets or biomarkers for SCLC.

6.
Comput Biol Med ; 158: 106836, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37031511

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and has the highest proportion of homologous recombination deficiency (HRD). HRD has been considered a biomarker of response to immune checkpoint inhibitors (ICIs), but the reality is more complicated. A comprehensive comparison of the tumor microenvironment (TME) in HRD and non-HRD TNBC samples may be helpful. METHODS: Datasets from single-cell, spatial, and bulk RNA-sequencing were collected to explore the role of HRD in the development of TME at multiple scales. Based on the findings in the TME, machine learning algorithms were used to construct a response prediction model in eleven ICI therapy cohorts. RESULTS: A more exhausted phenotype of T cells and a more tolerogenic phenotype of dendritic cells were found in the non-HRD group. HRD reprograms the predominant phenotype of cancer-associated fibroblasts (CAFs) from myofibroblastic CAFs to inflammatory-like CAFs. As interactions between myofibroblastic CAFs and other cells, DPP4-chemokines associated with reduced immune cell recruitment were unique in the non-HRD group. The prediction model based on DPP4-related genes had acceptable performance in predicting response, prognosis, and immune cell content. Higher HRD scores in bulk RNA-sequencing samples indicated more activated immune cell function, but not higher immune cell content, which may be affected by factors such as antigen-presenting capacity. CONCLUSIONS: Based on multi-scale transcriptomics, our findings comprehensively reveal differences in the TME between HRD and non-HRD samples. Combining HRD with the prediction model or other methods for assessing immune cell content, may better predict response to ICIs in TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/terapia , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral/genética , Dipeptidil Peptidase 4/genética , Transcriptoma/genética , Proteína BRCA1/genética , Recombinação Homóloga , Imunoterapia , RNA
7.
Rev Sci Instrum ; 94(1): 015110, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36725570

RESUMO

When the load and speed of rotating machinery change, the vibration signal of rolling bearing presents an obvious nonstationary characteristic. Stochastic resonance (SR) mainly is convenient to analyze the stationary feature of vibration signals with high signal-to-noise ratio. However, it is difficult for SR to extract the nonstationary feature of rolling bearings under strong noise background. For one thing, the frequency change of nonstationary signals makes the occurrence of SR very difficult. For another, the features of rolling bearings are large parameters and further prevent the SR method from performing well. Therefore, combined with order analysis (OA), adaptive frequency-shift SR is presented in this paper. To solve the problem of frequency change, OA is used to convert the nonstationary feature into stationary feature, which resamples the nonstationary signal in the time domain to stationary signal in the angular domain. To solve the other problem, the frequency-shift method based on Fourier transform is adopted to move the fault feature frequency to low frequency, and thus SR is more likely to occur under small parameter conditions. The simulated and experimental results indicate that not only the amplitude of fault feature but also the signal-to-noise ratio is significantly improved. These demonstrate that the fault features of rolling bearing in variable speed conditions are extracted successfully.

8.
Biomolecules ; 13(1)2023 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-36671569

RESUMO

Brain metastasis (BM) occurs commonly in patients with lung adenocarcinomas. Limited evidence indicates safety and efficacy of immunotherapy for this metastatic tumor, though immune checkpoint blockade has become the front-line treatment for primary advanced non-small cell lung cancer. We aim to comprehensively compare tumor microenvironments (TME) between primary tumors (PT) and BM at single-cell resolution. Single-cell RNA transcriptomics from tumor samples of PT (N = 23) and BM (N = 16) and bulk sequencing data were analyzed to explore potential differences in immunotherapeutic efficacy between PT and BM of lung adenocarcinomas. Multiple machine learning algorithms were used to develop and validate models that predict responses to immunotherapy using the external cohorts. We found obviously less infiltration of immune cells in BM than PT, characterized specifically by deletion of anti-cancer CD8+ Trm cells and more dysfunctional CD8+ Tem cells in BM tumors. Meanwhile, macrophages and dendritic cells within BM demonstrated more pro-tumoral and anti-inflammatory effects, represented by distinct distribution and function of SPP1+ and C1Qs+ tumor-associated microphages, and inhibited antigen presentation capacity and HLA-I gene expression, respectively. Besides, we also found the lack of inflammatory-like CAFs and enrichment of pericytes within BM tumors, which may be critical factors in shaping inhibitory TME. Cell communication analysis further revealed mechanisms of the immunosuppressive effects associated with the activation of some unfavorable pathways, such as TGFß signaling, highlighting the important roles of stromal cells in the anti-inflammatory microenvironment, especially specific pericytes. Furthermore, pericyte-related genes were identified to optimally predict immunotherapeutic responses by machine learning models with great predictive performance. Overall, various factors contribute to the immunosuppressive TME within BM tumors, represented by the lack of critical anti-cancer immune cells. Meanwhile, pericytes may help shape the TME and targeting the associated mechanisms may enhance immunotherapy efficacy for BM tumors in patients with lung adenocarcinomas.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Microambiente Tumoral , Neoplasias Encefálicas/metabolismo , Imunoterapia , Adenocarcinoma de Pulmão/tratamento farmacológico , Anti-Inflamatórios/farmacologia
9.
Front Plant Sci ; 14: 1303667, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38169626

RESUMO

Increasing biotic and abiotic stresses are seriously impeding the growth and yield of staple crops and threatening global food security. As one of the largest classes of regulators in vascular plants, WRKY transcription factors play critical roles governing flavonoid biosynthesis during stress responses. By binding major W-box cis-elements (TGACCA/T) in target promoters, WRKYs modulate diverse signaling pathways. In this review, we optimized existing WRKY phylogenetic trees by incorporating additional plant species with WRKY proteins implicated in stress tolerance and flavonoid regulation. Based on the improved frameworks and documented results, we aim to deduce unifying themes of distinct WRKY subfamilies governing specific stress responses and flavonoid metabolism. These analyses will generate experimentally testable hypotheses regarding the putative functions of uncharacterized WRKY homologs in tuning flavonoid accumulation to enhance stress resilience.

10.
Front Oncol ; 12: 933672, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36185268

RESUMO

Objectives: To explore the clinical and prognostic characteristics of thymic lymphoma and the effects of current treatments on the prognosis. Methods: Patients diagnosed as primary thymic lymphoma between 1975 and 2018 from the nine states of the US were identified, including Atlanta, Connecticut, Detroit, Hawaii, Iowa, New Mexico, San Francisco-Oakland, Seattle-Puget Sound, and Utah. Incidence and mortality rates were analyzed using SEER*Stat 8.3.9 software. Univariate and multivariate Cox regressions were performed to identify prognostic factors. The Kaplan-Meier curve and log-rank test were used to compare overall survival (OS) among different treatments. Results: A total of 233 patients diagnosed as thymic lymphoma were identified, and eight of them were lost to follow-up or died upon diagnosis. The incidence of thymic lymphoma was 2.032 per ten million (95% CI: 1.777-2.312), and the mortality rate was 0.649 per ten million (95% CI: 0.508-0.817). Among the 225 patients with definite follow-up, 98 were males and 127 were females, with a median age of 33 years. The Cox regression results showed that age and pathological type were independent risk prognostic factors. The 5-, 10-, and 20-year OS were 80.0%, 77.5%, and 70.9%, respectively. For Ann Arbor stage I and II patients, there was no significant difference between the surgical group (N = 78) and the non-operative group (N = 65; P = 0.270). The radiotherapy group (N = 79) had better OS than the non-radiotherapy group (N = 64) in the first 25 years, and the prognosis in the later years was not significantly different (P = 0.051). The chemotherapy group (N = 37) had a significantly better prognosis than the non-chemotherapy group (N = 37; P = 0.020). Patients who received postoperative radiotherapy (N = 45) or who only received radiotherapy (N = 34) seemed to have better OS than that of patients who only received surgery (N = 33), although the difference was not significant (P = 0.063). Conclusions: Age and pathological type were independent prognostic factors for thymic lymphoma. Surgical treatment had limited effects on OS, while both radiotherapy and chemotherapy could significantly improve the survival outcome.

11.
Surg Today ; 52(9): 1358-1372, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35522343

RESUMO

BACKGROUND AND PURPOSE: The wide application of low-dose computed tomography (CT) has led to an increase in the detection of small lung cancer lesions. Moreover, surgical recommendations for second primary non-small cell lung cancer (NSCLC) lesions ≤ 2 cm are obscure. This study compares the efficacy of wedge resection, lobectomy, and segmentectomy for small second primary NSCLC lesions. METHODS: The cohort was established based on the SEER database. Univariate and multivariate cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression, and restricted mean survival time (RMST) values were applied to identify prognostic factors. We used the Kaplan-Meier method to plot the survival curves of the different subgroups according to propensity score matching (PSM) analysis to then compare the therapeutic efficacy of the surgical procedures. RESULTS: A total of 568 patients were enrolled in this study. Age, sex, grade, and lymph node ratio were selected as independent prognostic factors (p < 0.05). No significant differences were observed in survival probabilities among the groups of patients who underwent segmentectomy, wedge resection, or lobectomy (p > 0.05). We also established a nomogram model based on the four prognostic factors to guide clinical treatment. CONCLUSIONS: Based on the findings of our study, segmentectomy was more appropriate than lobectomy for patients with a second primary NSCLC lesion ≤ 2 cm in diameter. The evidence to support other recommendations is insufficient.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Estadiamento de Neoplasias , Pneumonectomia/métodos , Pontuação de Propensão
12.
PeerJ ; 10: e12936, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35186502

RESUMO

BACKGROUND: No postoperative cardiopulmonary morbidity models have been developed or validated in Chinese patients with lung resection. This study aims to externally validate five predictive models, including Eurolung models, the Brunelli model and the Age-adjusted Charlson Comorbidity Index, in a Chinese population. METHODS: Patients with lung cancer who underwent anatomic lung resection between 2018/09/01 and 2019/08/31 in our center were involved. Model discrimination was assessed by the area under the receiver operating characteristic curve. Model calibration was evaluated by the Hosmer-Lemeshow test. Calibration curves were plotted. Specificity, sensitivity, negative predictive value, positive predictive value and accuracy were calculated. Model updating was achieved by re-estimating the intercept and/or the slope of the linear predictor and re-estimating all coefficients. RESULTS: Among 1085 patients, 91 patients had postoperative cardiopulmonary complications defined by the European Society of Thoracic Surgeons. For original models, only parsimonious Eurolung1 had acceptable discrimination (area under the receiver operating characteristic curve = 0.688, 95% confidence interval 0.630-0.745) and calibration (p = 0.23 > 0.05) abilities simultaneously. Its sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 0.700, 0.649, 0.153, 0.960 and 0.653, respectively. In the secondary analysis, increased pleural effusion (n = 94), which was nonchylous and nonpurulent, was labeled as a kind of postoperative complication. The area under the receiver operating characteristic curve of the models increased slightly, but all models were miscalibrated. The original Eurolung1 model had the highest discrimination ability but poor calibration, and thus it was updated by three methods. After model updating, new models showed good calibration and small improvements in discrimination. The discrimination ability was still merely acceptable. CONCLUSIONS: Overall, none of the models performed well on postoperative cardiopulmonary morbidity prediction in this Chinese population. The original parsimonious Eurolung1 and the updated Eurolung1 were the best-performing models on morbidity prediction, but their discrimination ability only achieved an acceptable level. A multicenter study with more relevant variables and sophisticated statistical methods is warranted to develop new models among Chinese patients in the future.


Assuntos
População do Leste Asiático , Pulmão , Humanos , Morbidade , Valor Preditivo dos Testes , Curva ROC , Pulmão/cirurgia
13.
Gen Thorac Cardiovasc Surg ; 70(5): 463-471, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35112288

RESUMO

OBJECTIVE: Our study aimed to reveal the prognostic factors of second primary lung cancer and explore the optimal surgical procedure for Stage II/IIIA second primary lung cancer patients with prior non-small cell lung cancer. METHODS: Patients with Stage II/IIIA second primary lung cancer were collected from the Surveillance, Epidemiology and End Results database from 2004 to 2016. Lasso regression, along with univariate and multivariate Cox regression, was used to screen prognostic factors. The propensity score matching was used to minimize baseline differences, and restricted mean survival time was used to compare overall survival and cancer-specific survival of different groups. RESULTS: A total of 579 patients were enrolled in the study. After data was screened by lasso regression and univariate Cox regression, multivariate Cox regression revealed that age, sex, race, tumor size of initial primary lung cancer, tumor size, histological grade, T stage, N stage and surgical procedure of second primary lung cancer were independent prognostic factors. Further analysis showed that surgery, especially lobectomy, provided better survival in Stage II/IIIA second primary lung cancer. CONCLUSIONS: Our study identified nine independent prognostic factors of Stage II/IIIA second primary lung cancer. Surgery can provide a better prognosis, and lobectomy might be the optimal surgical procedure for these patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Segunda Neoplasia Primária , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Segunda Neoplasia Primária/cirurgia , Prognóstico
14.
J Thorac Dis ; 13(10): 5863-5874, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34795935

RESUMO

BACKGROUND: With the improvement of cancer therapy, a second primary malignancy (SPM) occurs more commonly among cancer survivors. At present, it remains unclear whether the radiation therapy for the initial lung cancer will increase the risk of developing a SPM. This study aims to investigate the long-term risk of a SPM attributable to the radiation therapy in patients with the initial lung cancer. METHODS: Patients initially diagnosed with lung cancer between January 1975 and November 2011 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. SPM was defined as the occurrence of a second cancer at least five years after the diagnosis of the initial lung cancer. Age- and propensity score matching (PSM)-adjusted competing risk analyses were performed to compare the risk of SPM. RESULTS: Of 47,911 patients, 9,162 (19.1%) underwent radiotherapy for the initial lung cancer. The PSM-adjusted competing risk analyses showed that radiation therapy was associated with a lower overall risk of SPM (HR: 0.89, 95% CI: 0.84-0.94, P<0.001). Specifically, the risk of second primary melanoma (HR: 0.49, 95% CI: 0.29-0.81, P=0.006), second primary female breast cancer (HR: 0.65, 95% CI: 0.50-0.85, P=0.001), second primary prostate cancer (HR: 0.69, 95% CI: 0.58-0.84, P<0.001) and second primary thyroid cancer (HR: 0.23, 95% CI: 0.07-0.77, P=0.017) was found to decrease, while the risk for second primary esophageal cancer dramatically increased (HR: 1.76, 95% CI: 1.26-2.45, P<0.001). CONCLUSIONS: In patients who received radiotherapy for the initial lung cancer, the risk decreased for second primary melanoma as well as for second primary cancers of female breast, prostate and thyroid gland but increased for second primary cancer of esophagus. On the whole, radiation therapy for initial lung cancer may not increase the overall risk of SPM.

15.
Int Immunopharmacol ; 101(Pt B): 108376, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34815191

RESUMO

High incidence of recurrency had been a significant threat among glioma patients. Moreover, the performance of traditional therapies among recurrent gliomas was far from satisfying. Advances in the tumor microenvironment (TME) and immune responses on the brain inspired immunotherapy researches. Nevertheless, verification of classic PD-1/PD-L1 inhibitors failed in phase III clinical trials. Additional gene targets were required for future studies among glioma patients. Immune cell infiltration (ICI) scores, defined based on multiple prognostic genes, were proved as the marker for the sensitivity of immunotherapies in many tumors. However, relevant results were not reported in gliomas. In the study, a retrospective cohort of 495 patients was classified into two ICI score subgroups. High ICI scores were closely related to high tumor mutation burden (TMB) values, indicating a high instability of genes. Furthermore, ICI scores were proved as reliable prognostic predictors. And a predictive model was built based on the ICI scores and multiple clinical features. The model showed its superiority through both internal validation and external validation. The ICI scores and the predictive model showed significant clinical values through decision curve analysis (DCA) since high ICI scores were related to high sensitivity for treatment. The prognostic immune-related gene list provided targets for immunotherapy researches.


Assuntos
Biomarcadores Tumorais/genética , Marcadores Genéticos , Instabilidade Genômica , Genômica/métodos , Glioma/classificação , Glioma/genética , Humanos
16.
Int Immunopharmacol ; 96: 107610, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33848908

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been used as a novel treatment for diffuse gliomas, but the efficacy varies with patients, which may be associated with the tumor mutational burden (TMB) and immune infiltration. We aimed to explore the relationship between the two and their impacts on the prognosis. METHODS: The data of the training set were downloaded from The Cancer Genome Atlas (TCGA). "DESeq2" R package was used for differential analysis and identification of differentially expressed genes (DEGs). A gene risk score model was constructed based on DEGs, and a nomogram was developed combined with clinical features. With the CIBERSORT algorithm, the relationship between TMB and immune infiltration was analyzed, and an immune risk score model was constructed. Two models were verification in the validation set downloaded from the Chinese Glioma Genome Atlas (CGGA). RESULTS: Higher TMB was related to worse prognosis, older age, higher grade, and higher immune checkpoint expression. The gene risk score model was constructed based on BIRC5, SAA1, and TNFRSF11B, and their expressions were all negatively correlated with prognosis. The nomogram was developed combined with age and grade. The immune risk score model was constructed based on M0 macrophages, neutrophils, naïve CD4+ T cells, and activated mast cells. The proportions of the first two were higher in the high-TMB group and correlated with worse prognosis, while the latter two were precisely opposite. CONCLUSIONS: In diffuse gliomas, TMB was negatively correlated with prognosis. The association of immune infiltration with TMB and prognosis varied with the type of immune cells. The nomogram and risk score models can accurately predict prognosis. The results can help identify patients suitable for ICIs and potential therapeutic targets, thus improve the treatment of diffuse gliomas.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Regulação Neoplásica da Expressão Gênica/imunologia , Glioma/genética , Glioma/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Adulto , Fatores Etários , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/diagnóstico , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Glioma/diagnóstico , Humanos , Proteínas de Checkpoint Imunológico/genética , Evasão da Resposta Imune , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Mutação , Nomogramas , Prognóstico , Fatores de Risco , Análise de Sobrevida
17.
Future Oncol ; 17(16): 2005-2013, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33784826

RESUMO

Background: Previous researches had not proposed any prediction models for occult lymph node metastasis (OLNM). Considering the occurrence of OLNM and the importance of OLNM management, we aimed to develop a nomogram to predict OLNM of patients with lung adenocarcinoma ≤2 cm. Methods: Characteristics of patients with lung adenocarcinoma of ≤2 cm diameter at the Peking Union Medical College Hospital were retrospectively reviewed. Univariate and multivariate logistic regressions were performed. A nomogram model was developed. The concordance index (C-index) and calibration and decision curves were used to evaluate the predictive ability. Results: A total of 473 patients were enrolled, with an OLNM incidence of 7.4%. Four factors were selected as risk factors. The model had a C-index of 0.932. Calibration and decision curves were determined. Conclusion: Patients with pure ground-glass opacity (pGGO) or noninvasive adenocarcinoma have significantly lower risk of OLNM. SUVmax, CEA, micropapillary and solid component were identified as independent risk factors. The nomogram model was effective in predicting OLNM preoperatively.


Lay abstract Lung cancer was once the leading cause of death among tumors. Today, as routine examination has become more common, the incidence of lung cancers ≤2 cm diameter has been increasing. Much research had explored treatment for these patients. Lobectomy and lymph node dissection in particular were recommended. Furthermore, lymph node dissection was strongly recommended for lymph-node-positive patients. During treatment, occult lymph node metastasis (OLNM) had been observed in some cases. And OLNM referred to a postoperative positive pathological result among preoperative imaging-negative cases. The study was designed to establish a model for predicting OLNM. In a cohort of 473 patients, we found certain risk factors for OLNM and established a predictive model. Relevant findings were shown in the 'Conclusion' section.


Assuntos
Adenocarcinoma de Pulmão/secundário , Neoplasias Pulmonares/patologia , Metástase Linfática/patologia , Nomogramas , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/terapia , Idoso , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Carga Tumoral
18.
Thorac Cancer ; 12(4): 426-443, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33295696

RESUMO

BACKGROUND: The therapeutic effect of chemotherapy is still unclear for clinical usage among second primary non-small cell lung cancer (NSCLC) patients. The aim of this study was to verify the therapeutic effect of chemotherapy and identify the prognostic factors among patients who had received chemotherapy for second primary NSCLC. METHODS: A retrospective cohort was constructed based on the Surveillance, Epidemiology and End Results (SEER) database. Through least absolute shrinkage and selection operator regression, univariate Cox and multivariate Cox regression, we identified the prognostic factors among clinicopathological features. Propensity score matching analysis was used to verify the therapeutic effect of chemotherapy. Survival curves were plotted among the subgroups of the selected factors. We further selected clinicopathological features that would affect the prognosis among patients who had received chemotherapy through a similar process. RESULTS: A total of 769 patients were enrolled to verify the therapeutic value of chemotherapy for second primary lung cancer. Significant differences were observed between the chemotherapy and nonchemotherapy group for cancer-specific survival. 215 patients who had received chemotherapy were analyzed to identify the factors that might influence outcome on the therapeutic effect of chemotherapy. Age, tumor size, histology and treatment were selected as significant factors. CONCLUSIONS: The therapeutic effect of chemotherapy for second primary NSCLC was found to be significant. Age, tumor size and histology were significant prognostic factors among patients who had received chemotherapy for second primary NSCLC. KEY POINTS: Significant findings of the study A significant therapeutic effect of chemotherapy for second primary non-small cell lung cancer was proven through univariate Cox regression and propensity score matching analysis. Prognostic factors for second primary non-small cell lung cancer patients who had received chemotherapy. What this study adds Chemotherapy could be applied in clinical practice as an additional therapeutic method for second primary non-small cell lung cancer patients. We selected prognostic factors for patients who had received chemotherapy to identify patients who were appropriate for chemotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Segunda Neoplasia Primária/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
19.
Nanotechnology ; 32(8): 085504, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33152726

RESUMO

Exosomal microRNAs (miRNAs) have attracted great attention as predictive and prognostic biomarkers of cancer. Profiling of miRNAs plays a key role in the effective diagnosis of cancers. However, simultaneous quantification of multiple miRNAs is challenging due to their homology and low abundance especially in exosomes. Here, we developed a sensitive detection method for multiple exosomal miRNAs with the help of rolling circle amplification (RCA). In contrast of the traditional ways, this method takes the advantages of both the multiplex sensing ability and the simplicity of RCA. Specifically, multiple exosomal miRNAs from different cell lines were replicated simultaneously through RCA and detected using designed molecular beacons (MBs). miRNA-21, miRNA-122 and miRNA-155 were chosen as the targets, which are overexpressed in cancers. Normalized fluorescence intensities of MB were used to imply the relative concentrations of these miRNAs. The obtained relative miRNAs expression levels could be used to distinguish the breast cancer exosome from normal one. If the varieties of the detected exosomal miRNAs are abundant enough, the concentration ratios of miRNAs could basically indicate the corresponding exosome and exosome screening could be realized. Such exosomal miRNA profiling and exosome screening can assist cancer diagnosis, which is promising in clinical application.


Assuntos
Exossomos/metabolismo , MicroRNAs/análise , Técnicas de Amplificação de Ácido Nucleico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Fluorescência , Células Endoteliais da Veia Umbilical Humana , Humanos , Limite de Detecção , Células MCF-7 , MicroRNAs/genética , MicroRNAs/metabolismo , Sondas Moleculares
20.
Front Surg ; 7: 580203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195388

RESUMO

Background: Lymph node metastasis (LNM) status is critical to the treatment. Fewer studies has focused on LNM in patients with small-size non-small cell lung cancer (NSCLC). This study aims to investigate clinicopathological characteristics associated with skip N2 (SN2) and non-skip N2 (NSN2) metastasis, and their metastatic patterns in NSCLC with tumor size of 1-2 cm. Methods: We reviewed the records of NSCLC patients with tumor size of 1-2 cm who underwent lobectomy with systematic lymph node dissection (LND) between January 2013 and June 2019. Clinical, radiographical, and pathological characteristics were compared among N1, SN2, and NSN2 groups. Metastatic patterns of mediastinal lymph node were analyzed based on final pathology. Results: A total of 63 NSCLC patients with tumor size of 1-2 cm were staged as pN2, including 25 (39.7%) SN2 and 38 (60.3%) NSN2. The incidence rates of SN2 and NSN2 were 2.8% (25/884) and 4.3% (38/884), respectively. For all clinicopathological characteristics, no significant difference was observed among the groups of N1, SN2, and NSN2. For the tumor located in each lobe, specific nodal drainage stations were identified: 2R/4R for right upper lobe; 2R/4R and subcarinal node (#7) for right middle lobe and right lower lobe; 4L and subaortic node (#5) for left upper lobe; #7 for left lower lobe. However, there were still a few patients (10.9%, 5/46) had the involvement of lower zone for tumors of upper lobe and the involvement of upper zone for lower lobe. Conclusions: SN2 occurs frequently in patients with small-size NSCLC. Whether lobe-specific selective LND is suitable for all small-size patients deserves more studies to confirm. Surgeons should be more careful when performing selective LND for tumors located in the lower and upper lobes.

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