A metabolomics study on carcinogenesis of ground-glass nodules.

Objective: This study aimed to identify differential metabolites and key metabolic pathways between lung adenocarcinoma (LUAD) tissues and normal lung (NL) tissues using metabolomics techniques, to discover potential biomarkers for the early diagnosis of lung cancer. Material and Methods: Forty-five patients with primary ground-glass nodules (GGN) identified on computed tomography imaging and who were willing to undergo surgery at Shanghai General Hospital from December 2021 to December 2022 were recruited to the study. All participants underwent video thoracoscopy surgery with segmental or wedge resection of the lung. Tissue samples for pathological examination were collected from the site of ground-glass nodules (GGN) lesion and 3 cm away from the lesion (NL). The pathology results were 35 lung adenocarcinoma (LUAD) cases (13 invasive adenocarcinoma, 14 minimally invasive adenocarcinoma, and eight adenocarcinoma in situ), 10 benign samples, and 45 NL tissues. For the untargeted metabolomics technique, 25 LUAD samples were assigned as the case group and 30 NL tissues as the control group. For the targeted metabolomics technique, ten LUAD samples were assigned as the case group and 15 NL tissues as the control group. Samples were analyzed by untargeted and targeted metabolomics, with liquid chromatography-tandem mass spectrometry detection used as part of the experimental procedure. Results: Untargeted metabolomics revealed 164 differential metabolites between the case and control groups, comprising 110 up regulations and 54 down regulations. The main metabolic differences found by the untargeted method were organic acids and their derivatives. Targeted metabolomics revealed 77 differential metabolites between the case and control groups, comprising 69 up regulations and eight down regulations. The main metabolic changes found by the targeted method were fatty acids, amino acids, and organic acids. The levels of organic acids such as lactic acid, fumaric acid, and malic acid were significantly increased in LUAD tissue compared to NL. Specifically, an increased level of L-lactic acid was found by both untargeted (variable importance in projection [VIP] = 1.332, fold-change [FC] = 1.678, q = 0.000) and targeted metabolomics (VIP = 1.240, FC = 1.451, q = 0.043). Targeted metabolomics also revealed increased levels of fumaric acid (VIP = 1.481, FC = 1.764, q = 0.106) and L-malic acid (VIP = 1.376, FC = 1.562, q = 0.012). Most of the 20 differential fatty acids identified were downregulated, including dodecanoic acid (VIP = 1.416, FC = 0.378, q = 0.043) and tridecane acid (VIP = 0.880, FC = 0.780, q = 0.106). Furthermore, increased levels of differential amino acids were found in LUAD samples. Conclusion: Lung cancer is a complex and heterogeneous disease with diverse genetic alterations. The study of metabolic profiles is a promising research field in this cancer type. Targeted and untargeted metabolomics revealed significant differences in metabolites between LUAD and NL tissues, including elevated levels of organic acids, decreased levels of fatty acids, and increased levels of amino acids. These metabolic features provide valuable insights into LUAD pathogenesis and can potentially serve as biomarkers for prognosis and therapy response.

Evaluating personalized circulating tumor DNA detection for early-stage lung cancer.

Circulating tumor DNA (ctDNA) has been widely used as a minimally invasive biomarker in clinical routine. However, a number of factors such as panel design, sample quality, patients' disease stages are known to influence ctDNA detection sensitivity. In this study, we systematically evaluated common factors associated with the variability of ctDNA detection in plasma and investigated ctDNA abundance in bronchoalveolar lavage (BAL). Whole exome profiling was conducted on 61 tumor tissue samples to identify tumor-specific variants, which were then used to design personalized assay MarRyDa® for ctDNA detection. DNA extracted from BAL fluid and plasma were genotyped using MarRyDa® platform. Our analysis showed that histological subtypes and disease stages had significant differences in ctDNA detection rate. Furthermore, we found that DNA purified from BAL supernatants contains the highest levels of ctDNA compared with BAL precipitates and plasma; therefore, utilizing BAL supernatants for tumor detection might provide additional benefits. Finally, we demonstrated that tumor cellularity played significant roles in the design of personalized ctDNA panel which eventually impacts ctDNA detection sensitivity. We suggest setting a flexible criteria for sample quality control and utilization of BAL might benefit more patients in clinics.

[Retracted] MicroRNA­365b­3p represses the proliferation and promotes the apoptosis of non­small cell lung cancer cells by targeting PPP5C.

[This retracts the article DOI: 10.3892/ol.2021.12650.].

MRI-based radiomics for pretreatment prediction of response to concurrent chemoradiotherapy in locally advanced cervical squamous cell cancer.

PURPOSE: To investigate the value of magnetic resonance imaging (MRI)-based radiomics in predicting the treatment response to concurrent chemoradiotherapy (CCRT) in patients with locally advanced cervical squamous cell cancer (LACSC). METHODS: In total, 198 patients (training: n = 138; testing: n = 60) with LACSC treated with CCRT between January 2014 and December 2019 were retrospectively enrolled in this study. Responses were evaluated by MRI and clinical data performed at one month after completion of CCRT according to RECIST standards, and patients were divided into the residual group and nonresidual group. Overall, 200 radiomics features were extracted from T2-weighted imaging and apparent diffusion coefficient maps. The radiomics score (Rad-score) was constructed with a feature selection strategy. Logistic regression analysis was used for multivariate analysis of radiomics features and clinical variables. The performance of all models was assessed using receiver operating characteristic curves. RESULTS: Among the clinical variables, tumor grade and FIGO stage were independent risk factors, and the areas under the curve (AUCs) of the clinical model were 0.741 and 0.749 in the training and testing groups. The Rad-score, consisting of 4 radiomics features selected from 200 radiomics features, showed good predictive performance with an AUC of 0.819 in the training group and 0.776 in the testing group, which were higher than the clinical model, but the difference was not statistically significant. The combined model constructed with tumor grade, FIGO stage, and Rad-score achieved the best performance, with an AUC of 0.857 in the training group and 0.842 in the testing group, which were significantly higher than the clinical model. CONCLUSION: MRI-based radiomics features could be used as a noninvasive biomarker to improve the ability to predict the treatment response to CCRT in patients with LACSC.

Whole-lesion apparent diffusion coefficient (ADC) histogram as a quantitative biomarker to preoperatively differentiate stage IA endometrial carcinoma from benign endometrial lesions.

BACKGROUND: To assess the value of whole-lesion apparent diffusion coefficient (ADC) histogram analysis in differentiating stage IA endometrial carcinoma (EC) from benign endometrial lesions (BELs) and characterizing histopathologic features of stage IA EC preoperatively. METHODS: One hundred and six BEL and 126 stage IA EC patients were retrospectively enrolled. Eighteen volumetric histogram parameters were extracted from the ADC map of each lesion. The Mann-Whitney U or Student's t-test was used to compare the differences between the two groups. Models based on clinical parameters and histogram features were established using multivariate logistic regression. Receiver operating characteristic (ROC) analysis and calibration curves were used to assess the models. RESULTS: Stage IA EC showed lower ADC10th, ADC90th, ADCmin, ADCmax, ADCmean, ADCmedian, interquartile range, mean absolute deviation, robust mean absolute deviation (rMAD), root mean squared, energy, total energy, entropy, variance, and higher skewness, kurtosis and uniformity than BELs (all p < 0.05). ADCmedian yielded the highest area under the ROC curve (AUC) of 0.928 (95% confidence interval [CI] 0.895-0.960; cut-off value = 1.161 × 10-3 mm2/s) for differentiating stage IA EC from BELs. Moreover, multivariate analysis demonstrated that ADC-score (ADC10th + skewness + rMAD + total energy) was the only significant independent predictor (OR = 2.641, 95% CI 2.045-3.411; p < 0.001) for stage IA EC when considering clinical parameters. This ADC histogram model (ADC-score) achieved an AUC of 0.941 and a bias-corrected AUC of 0.937 after bootstrap resampling. The model performed well for both premenopausal (accuracy = 0.871) and postmenopausal (accuracy = 0.905) patients. Besides, ADCmin and ADC10th were significantly lower in Grade 3 than in Grade 1/2 stage IA EC (p = 0.022 and 0.047). At the same time, no correlation was found between ADC histogram parameters and the expression of Ki-67 in stage IA EC (all p > 0.05). CONCLUSIONS: Whole-lesion ADC histogram analysis could serve as an imaging biomarker for differentiating stage IA EC from BELs and assisting in tumor grading of stage IA EC, thus facilitating personalized clinical management for premenopausal and postmenopausal patients.

MRI-based radiomics value for predicting the survival of patients with locally advanced cervical squamous cell cancer treated with concurrent chemoradiotherapy.

BACKGROUND: To investigate the magnetic resonance imaging (MRI)-based radiomics value in predicting the survival of patients with locally advanced cervical squamous cell cancer (LACSC) treated with concurrent chemoradiotherapy (CCRT). METHODS: A total of 185 patients (training group: n = 128; testing group: n = 57) with LACSC treated with CCRT between January 2014 and December 2018 were retrospectively enrolled in this study. A total of 400 radiomics features were extracted from T2-weighted imaging, apparent diffusion coefficient map, arterial- and delayed-phase contrast-enhanced MRI. Univariate Cox regression and least absolute shrinkage and selection operator Cox regression was applied to select radiomics features and clinical characteristics that could independently predict progression-free survival (PFS) and overall survival (OS). The predictive capability of the prediction model was evaluated using Harrell's C-index. Nomograms and calibration curves were then generated. Survival curves were generated using the Kaplan-Meier method, and the log-rank test was used for comparison. RESULTS: The radiomics score achieved significantly better predictive performance for the estimation of PFS (C-index, 0.764 for training and 0.762 for testing) and OS (C-index, 0.793 for training and 0.750 for testing), compared with the 2018 FIGO staging system (C-index for PFS, 0.657 for training and 0.677 for testing; C-index for OS, 0.665 for training and 0.633 for testing) and clinical-predicting model (C-index for PFS, 0.731 for training and 0.725 for testing; C-index for OS, 0.708 for training and 0.693 for testing) (P < 0.05). The combined model constructed with T stage, lymph node metastasis position, and radiomics score achieved the best performance for the estimation of PFS (C-index, 0.792 for training and 0.809 for testing) and OS (C-index, 0.822 for training and 0.785 for testing), which were significantly higher than those of the radiomics score (P < 0.05). CONCLUSIONS: The MRI-based radiomics score could provide effective information in predicting the PFS and OS in patients with LACSC treated with CCRT. The combined model (including MRI-based radiomics score and clinical characteristics) showed the best prediction performance.

The Value of Whole-Tumor Texture Analysis of ADC in Predicting the Early Recurrence of Locally Advanced Cervical Squamous Cell Cancer Treated With Concurrent Chemoradiotherapy.

Objectives: To investigate the value of whole-tumor texture analysis of apparent diffusion coefficient (ADC) map in predicting the early recurrence of patients with locally advanced cervical squamous cell cancer (LACSC) treated with concurrent chemoradiotherapy (CCRT) and establish a combined prediction model including clinical variables and first-order texture features. Methods: In total, 219 patients (training: n = 153; testing: n = 66) with stage IIB-IVA LACSC treated by CCRT between January 2014 and December 2019 were retrospectively enrolled in this study. Clinical variables and 22 first-order texture features extracted from ADC map were collected. The Mann-Whitney U test or independent sample t test, chi-square test or Fisher's exact were used to analyze statistically significant parameters, logistic regression analysis was used for multivariate analysis, and receiver operating characteristic analysis was used to compare the diagnostic performance. Results: In the clinical variables, T stage and lymph node metastasis (LNM) were independent risk factors, and the areas under the curve (AUCs) of the clinical model were 0.697 and 0.667 in the training and testing cohorts, the sensitivity and specificity were 48.8% and 85.5% in the training cohort, and 84.1% and 51.1% in the testing cohort, respectively. In the first-order texture features, mean absolute deviation (MAD) was the independent protective factor, with an AUC of 0.756 in the training cohort and 0.783 in the testing cohort. The sensitivity and specificity were 95.3% and 52.7% in the training cohort and 94.7% and 53.2% in the testing cohort, respectively. The combined model (MAD, T stage, and LNM) was established, it exhibited the highest AUC of 0.804 in the training cohort and 0.821 in the testing cohort, which was significantly higher than the AUC of the clinical prediction model. The sensitivity and specificity were 67.4% and 85.5% in the training cohort and 94.7% and 70.2% in the testing cohort, respectively. Conclusions: The first-order texture features of the ADC map could be used along with clinical predictive biomarkers to predict early recurrence in patients with LACSC treated by CCRT.

Added-value of texture analysis of ADC in predicting the survival of patients with 2018 FIGO stage IIICr cervical cancer treated by concurrent chemoradiotherapy.

PURPOSE: To investigate the value of texture analysis of ADC in predicting the survival of patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IIICr cervical squamous cell cancer (CSCC) treated with concurrent chemoradiotherapy (CCRT). METHODS: A total of 91 patients with stage IIICr CSCC treated by CCRT between January 2014 and December 2018 were retrospectivelyenrolled in this study. Clinical variables and 21 first-order texture features extracted from ADC maps were collected. Univariate and multivariate Cox hazard regression analyses were performed to evaluate these parameters in predicting progression-free survival (PFS) and overall survival (OS). The independent variables were combined to build a prediction model and compared with the 2018 FIGO staging system. Survival curves were generated using the Kaplan-Meier method, and the log-rank test was used for comparison. RESULTS: Mean Absolute Deviation (MAD), T stage, and the number of lymph node metastasis (LNM) were independently associated with PFS, while MAD, energy, T stage, number of LNM, and tumor grade were independently associated with OS. The C-index values of the combined models for PFS and OS, which were respectively 0.750 and 0.832, were significantly higher compared to 2018 FIGO staging system values of 0.629 and 0.630, respectively (P < 0.05). CONCLUSIONS: The texture analysis of the ADC maps could be used along with clinical prognostic biomarkers to predict PFS and OS in patients with stage IIICr CSCC treated by CCRT.

Value of MRI and diffusion-weighted imaging in diagnosing normal-sized pelvic lymph nodes metastases in patients with cervical cancer.

OBJECTIVES: To investigate the value of conventional MRI and diffusion-weighted imaging (DWI) in diagnosing normal-sized pelvic lymph nodes metastases in patients with cervical cancer. METHODS: 102 patients with cervical cancer who underwent MRI and DWI scan were included. 137 lymph nodes were analyzed, including 44 metastatic lymph nodes (MLNs) and 93 non-metastatic lymph nodes (non-MLNs). The morphology and apparent diffusion coefficient (ADC) value of lymph nodes were measured including short-axis diameter (DS), long-axis diameter (DL), ratio of short-to-long-axis diameter (DR), fatty hilum, asymmetry, ADCmax, ADCmean and ADCmin. The Mann-Whitney U-test, independent sample t-test and Chi-square test were employed to compare the differences of all criteria between MLNs and non-MLNs. Logistic regression and decision tree were used to develop the combined diagnostic model. ROC analyses were used to evaluate the diagnostic performance. RESULTS: The DS and DR of MLNs were significantly higher than those of non-MLNs (p < 0.05), the ADCmax, ADCmean and ADCmin of MLNs were significantly lower than those of non-MLNs (p < 0.05). Presence of fatty hilum and asymmetric lymph nodes between MLNs and non-MLNs were significantly different (p＜0.05). Combined measurement of ADCmin, DS and DR had the highest AUC 0.937 with 90.9% sensitivity and 87.1% specificity. The accuracy of decision tree was 88.3%. CONCLUSION: MRI with DWI had potential in diagnosing normal-sized pelvic lymph nodes metastases in patients with cervical cancer. The combined evaluation of DS, DR and ADCmin of lymph nodes and decision tree of the combined measure showed better diagnostic performances than sole criteria. ADVANCES IN KNOWLEDGE: The short-axis diameter, ratio of short-to-long-axis diameter and ADCmin of lymph nodes have moderate value in the diagnosis of the metastases of the normal-sized lymph nodes for the patient with cervical cancer as the sole indices. The combined evaluation of DS, DR and ADCmin is much more valuable in the detection of metastatic lymph nodes.

The mechanism behind BAF60c in myocardial metabolism in rats with heart failure is through the PGC1α-PPARα-mTOR signaling pathway.

Metabolic remodeling in heart failure (HF) is a type of overload cardiomyopathy caused by insufficient energy supply or an imbalance of glucose and lipid metabolism. Therefore, metabolic pathways may serve as potential targets for HF treatment. BRM-associated factor (BAF) 60c (also known as smarcd3) promotes the transformation of oxidative muscle fibers to glycolytic muscle fibers. Our study aimed to test whether BAF60c and the PGC1α-PPARα-mTOR pathway interact to affect myocardial metabolism in HF rats. Established rat models of HF were injected with BAF60c low or overexpression plasmids to assess cardiac contractile proteins, energy metabolism, oxidative metabolism, glycolysis, high-energy phosphate content, mitochondrial function, and apoptosis. BAF60c overexpression/siRNA plasmid was transfected into H9C2 cells. These results suggest that HF rats present decreased levels of BAF60c, increased glycolysis, and reduced levels of cardiac contractile proteins, PGC1α, PPARα, and oxidative metabolism. Overexpression of BAF60c maintained the balance between oxidative metabolism and glycolysis and activated the PGC1α-PPARα-mTOR pathway. PGC1α interacted with BAF60c, and overexpression of PGC1α decreased BAF60c knockdown, damaging H9C2 cells. Collectively, overexpression of BAF60c activated the PGC1α-PPARα-mTOR pathway, maintained the oxidative metabolism/glycolysis balance, and improved mitochondrial function in HF rats. This study offers novel insights into HF treatment.

Potential of natural products as radioprotectors and radiosensitizers: opportunities and challenges.

Natural products can be used as natural radiosensitizers and radioprotectors, showing promising effects in cancer treatments in combination with radiotherapy, while reducing ionizing radiation (IR) damage to normal cells/tissues. The different effects of natural products on irradiated normal and tumor cells/tissues have attracted more and more researchers' interest. Nonetheless, the clinical applications of natural products in radiotherapy are few, which may be related to their low bioavailability in the human body. Here, we displayed the radiation protection and radiation sensitization of major natural products, highlighted the related molecular mechanisms of these bioactive substances combined with radiotherapy to treat cancer, and critically reviewed their deficiency and improved measures. Lastly, several clinical trials were presented to verify the clinical application of natural products as radiosensitizers and radioprotectors. Further clinical evaluation is still needed. This review provides a reference for the utilization of natural products as radiosensitizers and radioprotectors.

LOXL1­AS1 promotes thymoma and thymic carcinoma progression by regulating miR­525­5p­HSPA9.

Due to the lack of specific symptoms in early thymic epithelial tumours (TETs), patients are mostly in the advanced stage at the time of presentation. The aim of the present study was to explore the mechanism by which the long noncoding RNA (lncRNA) LOXL1­AS1 affects thymoma and thymic carcinoma progression by targeting the miR­525­5p­HSPA9 axis. Bioinformatics was used to analyse the process of LOXL1­AS1 targeting miR­525­5p­HSPA9 and its expression characteristics in TET. The relationships between LOXL1­AS1, miR­525­5p, HSPA9 and prognosis were analysed. The dual luciferase reporter assay was applied to verify targeting. The gene was knocked down or overexpressed by plasmid transfection. Cell counting kit 8 (CCK­8) assay, flow cytometry and Transwell assay were used to detect cell viability, apoptosis and invasion ability, respectively. Proteins and RNAs were examined by western blot analysis and qPCR, respectively. A tumour­burdened assay was used to perform in vivo verification. LOXL1­AS1 and HSPA9 were overexpressed in thymoma and thymic carcinoma; high levels of LOXL1­AS1 and HSPA9 were associated with poor prognosis, and there was a significant positive correlation between their levels. Downregulation of miR­525­5p expression was also associated with poor prognosis of patients. Clinical trials also demonstrated the same trends. miR­525­5p inhibited the expression of HSPA9 protein by targeting the 3'­untranslated region (UTR) of HSPA9 mRNA. LOXL1­AS1 promoted the expression of HSPA9 as a sponge targeting miR­525­5p. Animal experiment results also showed that knockdown of miR­525­5p promoted cancer by promoting the expression of HSPA9. In conclusion, LOXL1­AS1 and HSPA9 are highly expressed in thymoma and thymic carcinoma; miR­525­5p is expressed at low levels in thymoma and thymic carcinoma; and downregulation of miR­525­5p is associated with poor prognosis. In summary, this study demonstrates that LOXL1­AS1 acts as a sponge that targets miR­525­5p to promote HSPA9 expression, thereby promoting the growth and invasion and inhibiting apoptosis of thymoma and thymic carcinoma cells.

MicroRNA-365b-3p represses the proliferation and promotes the apoptosis of non-small cell lung cancer cells by targeting PPP5C.

MicroRNA (miR)-365b-3p has been recently reported to induce cell cycle arrest and apoptosis in retinoblastoma; however, its expression pattern and biological function in non-small cell lung cancer (NSCLC) remain unknown. The present study aimed to investigate the functional role of miR-365b-3p in NSCLC. The results demonstrated that miR-365b-3p expression level was significantly decreased in NSCLC tissues and cell lines compared with controls using reverse transcriptase quantitative PCR. Furthermore, miR-365b-3p expression level was overexpressed by miR-365b-3p mimics transfection in A549 cells, whereas it was downregulated following H1299 cell transfection with miR-365b-3p inhibitor. Restoration of miR-365b-3p inhibited cell proliferation, induced cell cycle G0/G1 arrest and stimulated apoptosis in A549 cells using CCK-8 assay, colony formation and flow cytometry assay. However, miR-365b-3p inhibitor had the opposite effects in H1299 cells. Furthermore, results from bioinformatics analysis and luciferase reporter assay confirmed that serine/threonine protein phosphatase 5 (PPP5C) was a direct target of miR-365b-3p. In addition, online Kaplan-Meier plotter software demonstrated that high PPP5C expression level was associated with lower overall survival and disease-free survival in patients with NSCLC. Furthermore, PPP5C knockdown imitated the effects of miR-365b-3p mimics on A549 cell proliferation, cell cycle distribution and apoptosis, whereas its overexpression rescued the effects of miR-365b-3p mimics on A549 cell proliferation, cell cycle distribution and apoptosis. In conclusion, the findings from the present study suggested that miR-365b-3p may partly suppress NSCLC cell behaviors by targeting PPP5C, which may represent a promising therapeutic target for patients with NSCLC.

The Role of Multiparametric Magnetic Resonance Imaging in the Study of Primary Tumor and Pelvic Lymph Node Metastasis in Stage IB1-IIA1 Cervical Cancer.

OBJECTIVE: The aim of this study was to investigate the value of multiparametric magnetic resonance imaging (MRI) in demonstrating the metastatic potential of primary tumor and differentiating metastatic lymph nodes (MLNs) from nonmetastatic lymph nodes (non-MLNs) in stage IB1-IIA1 cervical cancer. METHODS: Fifty-seven stage IB1-IIA1 subjects were included. The apparent diffusion coefficient (ADC) values and dynamic contrast-enhanced MRI (DCE-MRI) parameters of primary tumors and lymph nodes and the conventional imaging features of the lymph nodes were measured and analyzed. Mann-Whitney test and χ test were used to analyze statistically significant parameters, logistic regression was used for multivariate analysis, and receiver operating characteristic analysis was used to compare the diagnostic performance of the MLNs. RESULTS: Nineteen subjects had lymph node metastasis. A total of 94 lymph nodes were evaluated, including 30 MLNs and 64 non-MLNs. There were no significant difference in ADC and DCE-MRI parameters between metastatic and nonmetastatic primary tumors. The heterogeneous signal was more commonly seen in MLNs than in non-MLNs (P = 0.001). The values of ADCmean, ADCmin, and ADCmax of MLNs were lower than those of non-MLNs (P < 0.001). The values of short-axis diameter, K, Kep, and Ve of MLNs were higher than those of non-MLNs (P < 0.05). Compared with individual MRI parameters, the combined evaluation of short-axis diameter, ADCmean, and K showed the highest area under the curve of 0.930. CONCLUSIONS: Diffusion-weighted imaging and DCE-MRI could not demonstrate the metastatic potential of primary tumor in stage IB1-IIA1 cervical cancer. Compared with individual MRI parameters, the combination of multiparametric MRI could improve the diagnostic performance of lymph node metastasis.

Clinical Experience with Thymic Cystectomy: A Single-Institution Study of 117 Cases from 2013 to 2019.

BACKGROUND The aim of this study was to summarize the clinical experience of thymic cysts treatment from a single center. MATERIAL AND METHODS Clinical data, imaging, pathological results, and follow-up results of thymic cyst patients who underwent surgery from January 2013 to September 2019 were retrospectively reviewed. RESULTS A total of 117 patients were enrolled, including 76 asymptomatic patients and 41 symptomatic patients. The average diameter of thymic cysts, the cysts in asymptomatic patients, and those in symptomatic patients were 31.93±19.92 mm, 29.28±17.97 mm, and 36.85±22.50 mm, respectively. The number of cysts ranged from 1 to 3 cm, 3 to 6 cm, and >6 cm in 73 cases (62.4%), 32 cases (27.3%), and 12 cases (10.3%), respectively. There was no correlation between the size of thymic cysts and the presence or absence of symptoms. Only 20 cases (17.1%) were correctly diagnosed as thymic cysts before surgery. There were 67 patients (57.3%) who underwent video-assisted thoracic surgery (VATS) and 50 cases (42.7%) underwent open surgery. Cystectomy was performed in 93 cases (79.5%) and 24 cases (20.5%) underwent simultaneous resection of thymic cysts and other thoracic tumors. Compared with the thoracotomy group, the VATS group had shorter hospital stay and chest tube indwelling time. No serious complications occurred after surgery. The median follow-up time was 45.0 months (range 4.0-84.0 months) and there was no recurrence. CONCLUSIONS Attention should be paid to the accuracy of preoperative diagnosis of thymic cysts and the reduction of asymptomatic thymic cystectomy. For patients who have both thymic cysts and other thoracic tumors, simultaneous surgery is safe and feasible.

Binary mixtures of active and passive particles on a sphere.

We study the cooperation and segregation dynamics of binary mixtures of active and passive particles on a sphere. According to the competition between rotational diffusion and polar alignment, we find three distinct phases: a mixed phase and two different demixed phases. When rotational diffusion dominates the dynamics, the demixing is due to the aggregation of passive particles, where active and passive particles respectively occupy two hemispheres. When polar alignment is dominated, the demixing is caused by the aggregation of active particles, where active particles occupy the equator of the sphere and passive particles occupy the two poles of the sphere. In this case, there exist a circulating band cluster and two cambered surface clusters, which is a purely curvature-driven effect with no equivalent in the planar model. When rotational diffusion and polar alignment are comparable, particles are completely mixed. Our findings are relevant to the experimental pursuit of segregation dynamics of binary mixtures on curved surfaces.

EGCG enhances cancer cells sensitivity under 60Coγ radiation based on miR-34a/Sirt1/p53.

Ionizing radiation (IR) resistance and toxicity to normal cells are the main problems in radiotherapy for cancer. In this study, we demonstrated that epigallocatechin gallate (EGCG) could inhibit effectively IR-induced damage to mouse normal hepatic cells AML-12, and improve dramatically the radiosensitivity of mouse hepatoma cells H22 to 60Coγ. In addition, the different effects of EGCG and underlying molecular mechanisms based on microRNA-34a (miR-34a) and apoptosis-related proteins were investigated by cells viability analysis, quantitative realtime PCR (qRT-PCR), Western blot and cells transfection. The results indicated EGCG played the key role of radiosensitization on H22 cells by activating the miR-34a/Sirt1/p53 signaling pathway. Besides, EGCG could down-regulate the expression of anti-apoptotic protein Bcl-2, and up-regulate the expression of pro-apoptotic proteins Bax and Caspase-3 in H22 cells. Interestingly, EGCG showed contrary results on AML-12 cells. Therefore, radiation protection and radiosensitization of EGCG were associated with apoptosis regulated by miR-34a/Sirt1/p53 signaling pathway.

Angiotensin-converting enzyme 2 regulates autophagy in acute lung injury through AMPK/mTOR signaling.

Autophagy exerts a dual role in promoting cell death or survival. Recent studies have shown that it may play an important role in lipopolysaccharide (LPS)-induced acute lung injury (ALI). It was also suggested that angiotensin converting enzyme 2 (ACE2) may participate in the regulation of autophagy. The present study aims to investigate the role of autophagy in ALI and the involvement of ACE2. The regulation of the APMK/mTOR pathway was explored to clarify the underlying mechanism. The results showed that autophagy played an important role in ALI induced by LPS, as the autophagy inhibitor 3-methyladenine (3-MA) mitigated the severity of ALI. ACE2 activator resorcinolnaphthalein and inhibitor MLN-4760 significantly affected the histological appearance and wet/dry (W/D) ratio of the lung and altered the ACE2 activity of the lung, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels in bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) levels in lung tissue. Furthermore, LPS, resorcinolnaphthalein and MLN-4760 significantly affected the expression of autophagy proteins Beclin-1, LC3-I and LC3-II. To explore the mechanism of ACE2 on lung autophagy, we measured the phosphorylation of AMPK/mTOR after mice were treated with LPS and resorcinolnaphthalein or MLN-4760. The results revealed that resorcinolnaphthalein and MLN-4760 both significantly altered the phosphorylation of AMPK/mTOR. Finally, we found that AMPK inhibitor (8-bAMP) and mTOR activator (propranolol) both abolished the effects of ACE2 activator (resorcinolnaphthalein) on the expression of lung autophagy proteins Beclin-1, LC3-I and LC3-II. In conclusion, these findings suggest that ACE2 could alleviate the severity of ALI, inflammation and autophagy in lung tissue through the AMPK/mTOR pathway.

Flow and clogging of particles in shaking random obstacles.

Transport of three types of particles (passive particles, active particles, and polar particles) is investigated in a random obstacle array in the presence of a dc drift force. The obstacles are static or synchronously shake along the given direction. When the obstacles are static, the average velocity is a peaked function of the dc drift force (negative differential mobility) for low particle density, while the average velocity monotonically increases with the dc drift force (positive differential mobility) for high particle density. Under the same conditions, passive particles are most likely to pass through the obstacles, while polar particles are easily trapped by the obstacles. The polar alignment can strongly reduce the overall mobility of particles. When the obstacles shake along the given direction, the optimal shaking frequency or amplitude can maximize the average velocity. It is more effective to reduce clogging for the transverse shaking than that for the longitudinal shaking.

En Bloc Resection of Thoracic Tumors Invading the Spine: A Single-Center Experience.

BACKGROUND: Vertebral involvement by a thoracic tumor has long been considered as a limit to surgical treatment, and despite advances, such an invasive operation remains controversial. The aim of this study was to characterize a single-center cohort and to evaluate the outcome, focusing on survival and complications. METHODS: We retrospectively reviewed the data of all patients operated on for tumors involving the thoracic spine in an 8-year period. En bloc resection was generally performed by a double team involving thoracic and orthopedic surgeons. Distant follow-up was recorded for oncologic and functional analysis. RESULTS: There were 31 patients operated on. An induction therapy was administered in 20 patients. Spinal resection (mostly including ≥2 vertebral levels) was combined with lobectomy in 48.3% of the patients, and osteosynthesis was required in 22 patients. We observed no in-hospital death and a major complications rate of 32.3%, including 5 patients with early neurologic complications. There were 61.3% primary lung carcinomas, 12.9% extrapulmonary primaries, 9.7% metastases, and 16.1% benign tumors. Mean follow-up was 32.1 months. The 5-year overall survival rate was 81.3% in the entire cohort and 75.0% in patients with a malignant tumor. Occurrence of an early postoperative major complication was the only factor significantly associated with shorter overall survival (p = 0.03). The 5-year disease-free survival rate was 37.0% in malignancies. Delayed complications occurred in 35.5% of patients, including persistent neurologic deficit in 12.9%, instrumentation migration in 19.4%, and local infection in 12.9%. CONCLUSIONS: En bloc resection of spinal thoracic tumors offers long-term survival and few recurrences in highly selected patients but is associated with significant delayed mechanical or infectious complications.