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Abstract Background Lung cancer, a major global health concern, disproportionately impacts low socioeconomic status (SES) patients, who face suboptimal care and reduced survival. This study aimed to evaluate the prognostic performance of traditional Cox proportional hazards (CoxPH) regression and machine learning models, specifically Decision Tree (DT), Random Forest (RF), Support Vector Machine (SVM), and Extreme Gradient Boosting (XGBoost), in patients with advanced lung cancer with low SES. Design A retrospective study. Method The 949 patients with advanced lung cancer with low SES who entered the hospice ward of a tertiary hospital in Wuhan, China, from January 2012 to December 2021 were randomized into training and testing groups in a 3:1 ratio. CoxPH regression methods and four machine learning algorithms (DT, RF, SVM, and XGBoost) were used to construct prognostic risk prediction models. Results The CoxPH regression-based nomogram demonstrated reliable predictive accuracy for survival at 60, 90, and 120 days. Among the machine learning models, XGBoost showed the best performance, whereas RF had the lowest accuracy at 60 days, DT at 90 days, and SVM at 120 days. Key predictors across all models included Karnofsky Performance Status (KPS) score, quality of life (QOL) score, and cough symptoms. Conclusions CoxPH, DT, RF, SVM, and XGBoost models are effective in predicting mortality risk over 60–120 days in patients with advanced lung cancer with low SES. Monitoring KPS, QOL, and cough symptoms is crucial for identifying high-risk patients who may require intensified care. Clinicians should select models tailored to individual patient needs and preferences due to varying prediction accuracies. Reporting method This study was reported in strict compliance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline. Patient or public contribution No patient or public contribution.

Abstract Background The activity and number of immune cells in the tumor microenvironment are closely related to the overall survival of patients with hepatocellular carcinoma (HCC). The sex-determining region Y-box 4 (SOX4) gene is abnormally expressed in various tumor tissues and is critical for tumor development. However, the correlation between SOX4 expression in HCC and tumor immunity is unclear. Methods SOX4 expression was explored using data from The Cancer Genome Atlas, and UALCAN databases. Real-time reverse transcription quantitative and western blotting were used to analyze SOX4 expression in several liver cancer cell lines. Additionally, correlations among SOX4 expression, cancer immune characteristics, and infiltrated immune cell gene marker sets in patients with HCC were analyzed using data from the Tumor Immune Estimation Resource, Gene Expression Profiling Interactive Analysis, and Tumor-Immune System Interactions databases. Moreover, we evaluated SOX4 expression in HCC tissues and the correlation of SOX4 expression with survival rate. Subsequently, noncoding RNAs (ncRNAs) responsible for SOX4 overexpression were identified using expression, correlation, and survival analyses. Results SOX4 expression was significantly upregulated in HCC and correlated with a poor prognosis. Additionally, SOX4 upregulation in HCC positively correlated with immune cell infiltration, several biomarkers of immune cells, and immune checkpoint expression. Finally, the MCM3AP-AS1/hsa-miR-204-5p axis was identified as the most likely upstream ncRNA-related pathway for SOX4 in HCC. These results indicated that ncRNA-mediated upregulation of SOX4 correlated with the immune infiltration level and poor prognosis in HCC. Our findings provide new directions for the development of novel immunotherapeutic targets for HCC.

Este trabajo examina El honrado hermano, un drama histórico de Lope de Vega ambientada en la Antigua Roma, a partir de la construcción de sus cuatro personajes principales. Nuestro análisis muestra que la pareja protagonista, que forma parte de los vencedores —los romanos Horacio y Flavia— no cumplen con los rasgos típicos de galán y la dama en Lope, sino que son la pareja rival —Curiacio y Flavia— los que asumen como propias estas características. Se concluye que esta situación —que está potencialmente en la fuente principal de la obra, la Historia de Roma de Tito Livio— tiene que ver con una lectura política de la obra: el pasado de Roma se dramatiza desde una visión heroica, pero no plenamente positiva, que asumen los perdedores de la contienda: el pueblo albano. El reconocimiento y la asunción del derrotado se plantea como una condición para el desarrollo del imperio, una lectura que puede proyectarse a la creación de una identidad colectiva hispana.

Abstract Background Cell-free DNA (cfDNA) contains a large amount of molecular information that can be used for multi-cancer early detection (MCED), including changes in epigenetic status of cfDNA, such as cfDNA fragmentation profile. The fragmentation of cfDNA is non-random and may be related to cfDNA methylation. This study provides clinical evidence for the feasibility of inferring cfDNA methylation levels based on cfDNA fragmentation patterns. We performed whole-genome bisulfite sequencing and whole-genome sequencing (WGS) on both healthy individuals and cancer patients. Using the information of whole-genome methylation levels, we investigated cytosine–phosphate–guanine (CpG) cleavage profile and validated the method of predicting the methylation level of individual CpG sites using WGS data. Results We conducted CpG cleavage profile biomarker analysis on data from both healthy individuals and cancer patients. We obtained unique or shared potential biomarkers for each group and built models accordingly. The modeling results proved the feasibility to predict the methylation status of single CpG sites in cfDNA using cleavage profile model from WGS data. Conclusion By combining cfDNA cleavage profile of CpG sites with machine learning algorithms, we have identified specific CpG cleavage profile as biomarkers to predict the methylation status of individual CpG sites. Therefore, methylation profile, a widely used epigenetic biomarker, can be obtained from a single WGS assay for MCED.

Abstract Purpose To construct a radiomics-clinical nomogram model for predicting the risk of local and metastatic recurrence within 3 years after radical cystectomy (RC) of bladder cancer (BCa) based on the radiomics features and important clinical risk factors for arterial computed tomography (CT) images and to evaluate its efficacy. Methods Preoperative CT datasets of 134 BCa patients (24 recurrent) who underwent RC were collected and divided into training (n = 93) and validation sets (n = 41). Radiomics features were extracted from a 1.5 mm CT layer thickness image in the arterial phase. A radiomics score (Rad-Score) model was constructed using the feature dimension reduction method and a logistic regression model. Combined with important clinical factors, including gender, age, tumor size, tumor number and grade, pathologic T stage, lymph node stage and histology type of the archived lesion, and CT image signs, a radiomics-clinical nomogram was developed, and its performance was evaluated in the training and validation sets. Decision curve analyses (DCA) the potential clinical usefulness. Results The radiomics model is finally linear combined by 8 features screened by LASSO regression, and after coefficient weighting, achieved good predictive results. The radiomics nomogram developed by combining two independent predictors, Rad-Score and pathologic T stage, was developed in the training set [AUC, 0.840; 95% confidence interval (CI) 0.743–0.937] and validation set (AUC, 0.883; 95% CI 0.777–0.989). The calibration curve showed good agreement between the predicted probability of the radiomics-clinical model and the actual recurrence rate within 3 years after RC for BCa. DCA show the clinical application value of the radiomics-clinical model. Conclusion The radiomics-clinical nomogram model constructed based on the radiomics features of arterial CT images and important clinical risk factors is potentially feasible for predicting the risk of recurrence within 3 years after RC for BCa.

In this paper, Fe-3%Si ultra-thin ribbons prepared by the planar flow casting (PFC) technique were subjected to temper rolling and annealing treatments. The microstructure and texture evolution during this process were examined through experimental measurements coupled with crystal plasticity finite element (CPFE) simulation to assess the feasibility of preparing ultra-thin non-oriented silicon steel using PFC ribbons. The results indicate that the PFC ribbons exhibit a significant columnar crystal structure, and {001}-oriented grains comprise over 30%. After being annealed, the grains with different orientations grew uniformly, the texture components were basically unchanged, and the {001} texture was well preserved. When annealing was carried out after temper rolling with a reduction rate of 7%, uneven grain growth was observed, and the growth tendency of the {001} grains, especially, surpassed that of the {111} grains, with an elevated temperature which peaked at 950 °C, where the proportion of {001} grains was maximal. When being annealed after temper rolling to 15%, grains of other orientations showed significant growth at each temperature, while the {001} grains did not show an obvious growth advantage. Utilizing the CPFE, the deformation-stored energy distribution of each characteristic-oriented grain was simulated, and it was shown that compared to the 15% rolling reduction rate, the deformation-stored energy accumulation of {001}-oriented grains after being rolled to 7% reduction was significantly lower than that of {111}-oriented grains. It suggests that the larger stored energy difference makes {001} grains show a stronger growth advantage based on the SIBM mechanism during annealing, after being rolled with a reduction rate of 7%. Overall, for the synergistic optimization of microstructure and texture, rolling with a 7% reduction rate followed by annealing at 950 °C in a hydrogen atmosphere is most advantageous.

Hepatocellular carcinoma (HCC) is a malignant liver cancer characterized by aggressive progression, unfavorable prognosis, and an increasing global health burden. Therapies that precisely target immunological checkpoints and immune cells have gained significant attention as possible therapeutics in recent years. In truth, the efficacy of immunotherapy is heavily contingent upon the tumor microenvironment (TME). Recent studies have indicated that exosomes serve as a sophisticated means of communication among biomolecules, executing an essential part in the TME of immune suppression. Exosomal non-coding RNAs (ncRNAs) can induce the activation of tumor cells and immunosuppressive immune cells that suppress the immune system, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), CD+8 T cells, regulatory T cells (Tregs), and regulatory B cells (Bregs). This cell-cell crosstalk triggered by exosomal ncRNAs promotes tumor proliferation and metastasis, angiogenesis, malignant phenotype transformation, and drug resistance. Hence, it is imperative to comprehend how exosomal ncRNAs regulate tumor cells or immune cells within the TME to devise more comprehensive and productive immunotherapy programs. This study discusses the features of exosomal ncRNAs in HCC and how the activation of the exosomes redefines the tumor's immunosuppressive microenvironment, hence facilitating the advancement of HCC. Furthermore, we also explored the potential of exosomal ncRNAs as a viable biological target or natural vehicle for HCC therapy.

Abstract Peripheral blood mononuclear cell (PBMC) genes reflect the host immune status and could be suitable for evaluating the prognosis of patients with hepatocellular carcinoma (HCC), for which a reliable biomarker is unavailable and the host immune responses to cancer cells. This study aimed to investigate prognostically relevant genes in HCC PBMCs and assessed whether their expression represents tumor immune infiltration. Gene expression in PBMCs from patients with advanced or terminal HCC who had survived or died was examined. Correlations among FAT atypical cadherin 4 (FAT4) expression, cancer immune characteristics, and infiltrated immune cell gene marker sets were analyzed. FAT4 expression was lower in the PBMCs of patients with advanced or terminal HCC who had died than that in patients who survived. Kaplan–Meier analysis indicated that FAT4 downregulation was associated with a relatively poor prognosis while overexpression was positively correlated with immune cell infiltration, several immune cell markers, and immune checkpoint expression. Hsa-miR-93-5p represented the most probable upstream microRNA of FAT4. Thus, upregulated FAT4 in PBMCs and HCC tissues might indicate a favorable prognosis and increased immune cell infiltration, while miRNA-93-5p could be a modulator of FAT4 expression. Collectively, these findings suggest novel immunotherapy targets for HCC.

Twinning-induced plasticity (TWIP) steel is an ideal material for impact-resistant structures and energy absorption because of its high product of strength and elongation. However, compared with other advanced high-strength steels, the relatively low yield strength of TWIP steel is one of the important shortfalls that significantly limits its engineering applications. To enhance the comprehensive properties of TWIP steel, a machine learning design strategy that integrated comparative modelling, SHAP analysis, and multi-objective optimization were adopted in this study. Initially, various machine learning algorithms were compared for their predictive accuracy based on normalized data (273 entries) regarding the microstructure and properties of TWIP steel. Then, performance prediction models for yield strength, tensile strength, and elongation were established. SHAP analysis was subsequently employed to assess the significance and explicit laws of composition and microstructures in these three target properties, identifying key elements that enhance the overall performance. Furthermore, two new TWIP steels with high yield strengths and high products of strength and elongation were developed via multi-objective optimization. Under conventional hot forging + hot rolling + cold rolling + annealing processes, the two designed TWIP steels had yield strengths of 585 MPa and 560 MPa, tensile strengths of 1055 MPa and 1101 MPa, elongations of 55% and 58.5%, and products of strength and elongation of 58.0 GPa% and 66.4 GPa%, respectively. The yield strengths of the designed TWIP steels significantly improved while maintaining a reasonable product of strength and elongation. This work provides important references for the rational development of new TWIP steels.

Abstract Background Mitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of chronic kidney disease (CKD). Estimation of mitochondrial DNA copy number (mtDNA-CN) is considered a convenient method for representing mitochondrial function in large samples. However, no study has investigated the association between mtDNA-CN and CKD in older adults with the highest prevalence. The objective is to examine cross-sectional and prospective associations between mtDNA-CN values and CKD risk in older adults to determine whether mtDNA-CN represents a novel potential biomarker for the recognition of CKD risk. Patients and methods In a Chinese community-based cohort of over 65-year-olds, we included 14,467 participants (52.6% females). CKD was defined by eGFR

Abstract Background Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and is characterized by insidious onset, rapid progression, and poor prognosis. Immunotherapy is a first-line treatment for advanced HCC. The identification of immune-related prognostic markers may be an effective strategy to predict and improve clinical response rate of immunotherapy. Methods The DESeq2, edgeR, and limma R packages were used to compare the transcriptomes of HCC with different prognoses. Cancer-related databases such as UALCAN, TNMplot, GEPIA, muttarget and Human Protein Atlas (HPA), and the Kaplan–Meier Plotter platform were used to analyze the relationship between CLDN18 and the clinical characteristics, as well as prognosis of HCC. The co-expressed genes of CLDN18 were obtained from LinkedOmics platform, and GO functional enrichment and KEGG pathway analysis were performed. The CIBERSORT, TIMER, Timer 2.0 and TISIDB algorithms were used to analyze immune infiltration. Results CLDN18 was differentially expressed in HCC patients with different prognoses, and its expression level in PBMC was positively correlated with the stage of BCLC. In addition, CLDN18 was significantly overexpressed in HCC tumor tissues compared to adjacent non-tumor tissues, which was consistent with PBMC sequencing results and immunohistochemical data from human protein profiles. CLDN18 was also positively correlated with HCC staging and grading, and high expression levels of CLDN18 predicted shorter overall survival. Functional annotation of CLDN18 in HCC revealed enrichment of the cellular senescence and protein activation cascade, along with biological processes such as cell cycle, inflammatory response, and cellular ketone metabolism. In addition, CLDN18 was also associated with tumor infiltrating immune cells, suppressive immune cell markers, T lymphocyte depletion and activation of HCC, and low expression of CLDN18 was associated with higher CD8 + T cell infiltration and better survival rates. Conclusions CLDN18 is a potential prognostic marker and immunotherapeutic target for HCC.

Abstract Acute liver injury (ALI) is an acute inflammatory liver disease with a high mortality rate. Alternatively, activated macrophages (AAMs) have been linked to the inflammation and recovery of ALI. However, the mechanism underlying AAM death in ALI has not been studied sufficiently. We used liensinine (Lie) as a drug of choice after screening a library of small-molecule monomers with 1488 compounds from traditional Chinese remedies. In ALI, we evaluated the potential therapeutic effects and underlying mechanisms of action of the drug in ALI and found that it effectively inhibited RSL3-induced ferroptosis in AAM. Lie significantly reduced lipid peroxidation in RSL3-generated AAM. It also improved the survival rate of LPS/D-GalN-treated mice, reduced serum transaminase activity, suppressed inflammatory factor production, and may have lowered AAM ferroptosis in ALI. Lie also inhibited ferritinophagy and blocked Fe2+ synthesis. Following combined treatment with RSL3 and Lie, super-resolution microscopy revealed a close correlation between ferritin and LC3-positive vesicles in the AAM. The co-localization of ferritin and LC3 with LAMP1 was significantly reduced. These findings suggest that Lie may ameliorate ALI by inhibiting ferritinophagy and enhancing AMM resistance to ferroptosis by inhibiting autophagosome-lysosome fusion. Therefore, Lie may be used as a potential therapeutic agent for patients with ALI.

Drawing on social learning theory, this study presents a moderated mediation model to examine the role of proactive behavior and conformity value in the positive relationship between creative leadership and employees’ creativity. Two-wave data are collected from 230 employees and their leaders in an automobile manufacturing enterprise in China, in which employees are encouraged to be creative because they need to implement novel designs and proposals to attract consumers. Statistical analysis reveals that proactive behavior partially mediates the influence of creative leadership on employees’ creativity. Conformity value moderates not only the relationship between creative leadership and proactive behavior but also the indirect effect of creative leadership on employees’ creativity via proactive behavior. The relationship and the mediating mechanism are stronger in the presence of employees’ higher conformity value. We discuss the theoretical and practical implications as well as future research directions of the findings.

Background: Qizhu Anti-Cancer Recipe (QACR) is a traditional Chinese medicine widely used in treating several liver diseases. However, its function and the relevant mechanism underlying its effect in treating hepatocellular carcinoma (HCC) remain unknown. The aim of this study was to explore the effect of QACR in HCC, which are expected to be a potential therapeutic scheme for HCC. Materials and methods: The chemical compositions of QACR were determined by liquid chromatography/quadrupole time-of-fight mass spectrometry (LC-QTOF-MS). The anoikis-resistant HCC cell proliferation and angiopoiesis were detected using the cell counting kit 8 (CCK8) assay, trypan blue, calcein AM/EthD-1, flow cytometer, Western blot, and tube formation assays. An orthotopic xenograft mouse model was established to evaluate the in vivo effects of the QACR. The expression of proliferating cell nuclear antigen (PCNA), Bcl-2, CD31, caspase-3, caspase-8, caspase-9, PARP-1, DFF40, phospho-c-Jun NH2-terminal kinase (p-JNK), and JNK was assessed using Western blot and immunohistochemical analysis. Results: QACR reduced the growth and tube formation of anoikis-resistant HCC cells and enhanced cell apoptosis in vitro. In the orthotopic xenograft mouse models, QACR suppressed the tumorigenesis of HCC in vivo. Mechanistically, QACR modulated the JNK pathway. The JNK inhibitor (SP600125) reverses the inhibitory effects of QACR on anoikis-resistant HCC cell proliferation and angiopoiesis. Conclusion: Our study suggests that QACR suppresses the proliferation and angiopoiesis of anoikis-resistant HCC cells by activating the JNK pathway. Therefore, QACR is a promising new therapeutic strategy for treating hepatocellular carcinoma.

With the obesity epidemic, nonalcoholic steatohepatitis (NASH) is emerging as the fastest growing potential cause of hepatocellular carcinoma (HCC). NASH has been demonstrated to establish a tumor-prone liver microenvironment where both innate and adaptive immune systems are involved. As the most typical anti-tumor effector, the cell function of CD8+ T cells is remodeled by chronic inflammation, metabolic alteration, lipid toxicity and oxidative stress in the liver microenvironment along the NASH to HCC transition. Unexpectedly, NASH may blunt the effect of immune checkpoint inhibitor therapy against HCC due to the dysregulated CD8+ T cells. Growing evidence has supported that NASH is likely to facilitate the state transition of CD8+ T cells with changes in cell motility, effector function, metabolic reprogramming and gene transcription according to single-cell sequencing. However, the mechanistic insight of CD8+ T cell states in the NASH-driven HCC is not comprehensive. Herein, we focus on the characterization of state phenotypes of CD8+ T cells with both functional and metabolic signatures in NASH-driven fibrosis and HCC. The NASH-specific CD8+ T cells are speculated to mainly have a dualist effect, where its aberrant activated phenotype sustains chronic inflammation in NASH but subsequently triggers its exhaustion in HCC. As the exploration of CD8+ T cells on the distribution and phenotypic shifts will provide a new direction for the intervention strategies against HCC, we also discuss the implications for targeting different phenotypes of CD8+ T cells, shedding light on the personalized immunotherapy for NASH-driven HCC.

Abstract Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and has extremely high morbidity and mortality. Although many existing studies have focused on the identification of biomarkers, little information has been uncovered regarding the PBMC RNA profile of HCC. We attempted to create a profile throughout using expression of peripheral blood mononuclear cell (PBMC) RNA using RNA-seq technology and compared the transcriptome between HCC patients and healthy controls. Seventeen patients and 17 matched healthy controls were included in this study, and PBMC RNA was sequenced from all samples. Sequencing data were analyzed using bioinformatics tools, and quantitative reverse transcription PCR (qRT-PCR) was used for selected validation of DEGs. A total of 1,578 dysregulated genes were found in the PBMC samples, including 1,334 upregulated genes and 244 downregulated genes. GO enrichment and KEGG studies revealed that HCC is closely linked to differentially expressed genes (DEGs) implicated in the immune response. Expression of 6 selected genes (SELENBP1, SLC4A1, SLC26A8, HSPA8P4, CALM1, and RPL7p24) was confirmed by qRT-PCR, and higher sensitivity and specificity were obtained by ROC analysis of the 6 genes. CALM1 was found to gradually decrease as tumors enlarged. Nearly the opposite expression modes were obtained when compared to tumor sequencing data. Immune cell populations exhibited significant differences between HCC and controls. These findings suggest a potential biomarker for the diagnosis of HCC. This study provides new perspectives for liver cancer development and possible future successful clinical diagnosis.

Objective: To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy (MIRC) or open radical cystectomy (ORC). Methods: We identified patients with bladder cancer who underwent radical cystectomy (RC) in 13 centers of the Chinese Bladder Cancer Consortium (CBCC). Perioperative outcomes were compared between MIRC and ORC. The influence of surgical approaches on overall survival (OS) and cancer-specific survival (CSS) in the entire study group and subgroups classified according to pathologic stage or lymph node (LN) status was assessed with the log-rank test. Multivariable Cox proportional hazard models were used to evaluate the association among OS, CSS and risk factors of interest. Results: Of 2 098 patients who underwent RC, 1 243 patients underwent MIRC (1 087 laparoscopic RC and 156 robotic-assisted RC, respectively), while 855 patients underwent ORC. No significant differences were noted in positive surgical margin rate and 90-day postoperative mortality rate. MIRC was associated with less estimated blood loss, more LN yield, higher rate of neobladder diversion, longer operative time, and longer length of hospital stay. There was no significant difference in OS and CSS according to surgical approaches (p=0.653, and 0.816, respectively). Subgroup analysis revealed that OS and CSS were not significantly different regardless of the status of extravesical involvement or LN involvement. Multivariable Cox regression analyses showed that the surgical approach was not a significant predictor of OS and CSS. Conclusions: Our study showed that MIRC was comparable to conventional ORC in terms of OS and CSS.

Abstract Background A routine blood examination is one of the most rapid, convenient and inexpensive clinical examinations that can reflect a patient’s inflammatory status and other blood conditions, and the prognostic value of routine preoperative blood parameters in MIBC patients is still unclear, so we evaluated the prognostic value of routine preoperative blood parameters in muscle-invasive bladder cancer (MIBC) following radical cystectomy (RC). Methods Data on 202 patients with MIBC who underwent RC at our institution were retrospectively collected between October 2007 and August 2018. The median preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and hemoglobin (HGB) values were used as cutoffs to form the low and high NLR, low and high PLR, and low and high HGB groups, respectively. The clinicopathologic characteristics of each group were compared by chi-square and t tests. Kaplan-Meier survival and multivariate Cox regression analyses were used to analyze prognosis. Results The median NLR, PLR and HGB values were 2.42, 112 and 125 g/L, respectively. Kaplan-Meier results showed that the low HGB group had poor progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). A high NLR and high PLR groups correlated only with poor OS. Multivariate Cox analyses showed that pathological T3/4 stage, positive lymph node status and low HGB were independent risk factors for PFS, CSS and OS, and age was the only independent risk factor for OS. Conclusion Preoperative peripheral blood HGB is an independent risk factor for the prognosis of MIBC patients. These data suggest that HGB may be a useful prognostic marker for MIBC patients undergoing RC.

Abstract Background To evaluate the efficacy of submucosal injection of triamcinolone acetonide for the treatment of type II/III interstitial cystitis/bladder pain syndrome. Methods A retrospective analysis of the clinical data of type II/III interstitial cystitis/bladder pain syndrome patients treated in our department from April 2016 to August 2018 was conducted, and changes in International Prostate Symptom Scores and the Pelvic Pain and Urgency/Frequency symptom scale after surgery were evaluated to explore factors that may affect patient outcomes. Results A total of 27 female patients and 8 male patients were enrolled, with type II patients accounting for 62.9% of the sample, and the median follow-up duration was 31 months (range: 12–40 months). Twenty-two patients (74.3%) had significantly improved questionnaire scores at 4 weeks postoperatively. Treatment efficacy was sustained for at least 1 year in 15 patients, and persistent effectiveness was noted in 10 (28.6%) patients. Patients with an advanced age (p = 0.015), high pain scores (p = 0.040), and higher International Prostate Symptom Scores (p = 0.037) and Pelvic Pain and Urgency/Frequency symptom scale scores (p = 0.020) were more likely to benefit from submucosal injection of triamcinolone acetonide. Gender, disease duration, and the presence of Hunner’s lesions had no predictive value for treatment outcomes. Conclusion Submucosal injection of triamcinolone acetonide can improve the clinical symptoms and quality of life in both men and women with type II/III interstitial cystitis/bladder pain syndrome. Patients with an advanced age and more severe interstitial cystitis/bladder pain syndrome related symptoms may benefit more from triamcinolone acetonide injection.

In the field of 3D geologic modeling, researchers often pay more attention to modeling methods and workflows, but neglect the quantitative evaluation of models. If the evaluation is narrowed to the same reservoir type, the comparability and practicality of quantitative assessment will be emerging. The evaluation system should include three parts: data verification, geological understanding and process check. Data verification mainly involves testing the accuracy of local prediction with actual data, and geological understanding is to examine whether the global estimation honors geological principles and prior insights. Process check is also indispensable to avoid occasionality. To this end, we produced a set of assessment criteria, taking complex fault-block sandstone oil reservoir as an example. To be specific, thirteen characteristic parameters were totally selected, setting weights according to their rated importance, formulating three-level evaluation standards in a centesimal system for each characteristic parameter, and obtaining the final assessment based on the cumulative score. The results indicate that such evaluation can not only access the quality of the model objectively and comprehensively, but also identify the aspects in need of improvement through the deduction items. Key words: reservoir characterization, geological modeling, quality evaluation, characteristic parameter, reserves estimation, fault-block oil reservoir

System of Systems (SoS) is designed to deliver value to participant stakeholders in a dynamic and uncertain environment where new systems are added and current systems are removed continuously and on their own volition. This requires effective evolution management at the SoS architectural level with adequate support of process, methods, and tools. This paper follows the principle of Model-Based Systems Engineering (MBSE) and develops a holistic framework integrating MBSE conceptual representations and approximate dynamic programming (ADP) to support the SoS evolution. The conceptual models provide a common architectural representation to improve communication between various decision makers while the dynamic optimization method suggests evolution planning decisions from the analytical perspective. The Department of Defense Architecture Framework (DoDAF) models using Systems Modeling Language (SysML) are used as MBSE artifacts to connect with ADP modeling elements through DoDAF metamodels to increase information traceability and reduce unnecessary information loss. Using a surface warfare SoS as an example, this paper demonstrates and explains the procedures of developing DoDAF models, mapping DoDAF models to ADP elements, formulating ADP formulation, and generating evolutionary decisions. The effectiveness of using ADP in supporting evolution to achieve a near-optimal solution that can maximize the SoS capability over time is illustrated by comparing ADP solution to other alternative solutions. The entire framework also sheds light on bridging the DoDAF-based conceptual models and other mathematical optimization methods.

In virtual reality, users’ input and output interactions are carried out in a three-dimensional space, and bare-hand click interaction is one of the most common interaction methods. Apart from the limitations of the device, the movements of bare-hand click interaction in virtual reality involve head, eye, and hand movements. Consequently, clicking performance varies among locations in the binocular field of view. In this study, we explored the optimal interaction area of hand–eye coordination within the binocular field of view in a 3D virtual environment (VE), and implemented a bare-hand click experiment in a VE combining click performance data, namely, click accuracy and click duration, following a gradient descent method. The experimental results show that click performance is significantly influenced by the area where the target is located. The performance data and subjective preferences for clicks show a high degree of consistency. Combining reaction time and click accuracy, the optimal operating area for bare-hand clicking in virtual reality is from 20° to the left to 30° to the right horizontally and from 15° in the upward direction to 20° in the downward direction vertically. The results of this study have implications for guidelines and applications for bare-hand click interaction interface designs in the proximal space of virtual reality.

Chinese bayberry leaves proanthocyanidin (BLPs) contain epigallocatechin-3-O- gallate (EGCG) as its terminal unit and most of its extension units, which is unusual in the plant kingdom. The present study compared the antioxidant and anti-proliferative activities of BLPs prepared from different purification stages. Low-molecular-weight BLPs were prepared by ultrasonic treatment. Results revealed that the antioxidant activities of BLPs were strongly related to the content of total phenolics and proanthocyanidins; however, the cellular assay indicated that the mean degree of polymerization (mDP) played a vital role in the cellular antioxidant activity (CAA) of BLPs. The ultrasonic depolymerized BLPs with lower mDP (3.6 ± 0.3) exhibited a much higher CAA (EC50 = 0.042 ± 0.005 mg/mL) than other groups, which suggests that bioavailability is crucial to the cellular antioxidant potential of BLPs. Additionally, BLPs strongly inhibited HepG2 proliferation in a dose-dependent manner. Our results indicated that BLPs could be a valuable resource of bioactive compounds to promote consumer health.

Continuous movements of the hand contain discrete expressions of meaning, forming a variety of semantic gestures. For example, it is generally considered that the bending of the finger includes three semantic states of bending, half bending, and straightening. However, there is still no research on the number of semantic states that can be conveyed by each movement primitive of the hand, especially the interval of each semantic state and the representative movement angle. To clarify these issues, we conducted experiments of perception and expression. Experiments 1 and 2 focused on perceivable semantic levels and boundaries of different motion primitive units from the perspective of visual semantic perception. Experiment 3 verified and optimized the segmentation results obtained above and further determined the typical motion values of each semantic state. Furthermore, in Experiment 4, the empirical application of the above semantic state segmentation was illustrated by using Leap Motion as an example. We ended up with the discrete gesture semantic expression space both in the real world and Leap Motion Digital World, containing the clearly defined number of semantic states of each hand motion primitive unit and boundaries and typical motion angle values of each state. Construction of this quantitative semantic expression will play a role in guiding and advancing research in the fields of gesture coding, gesture recognition, and gesture design.

Background/Aims: Ginkgolide B (GB) is currently used as an anticancer drug for treatment of some malignant cancers. However, whether it may have therapeutic effects on bladder cancer remains unknown. Here, we studied the effects of GB on bladder cancer cells. Methods: Bladder cells were treated with different doses of GB, and the effects on ZEB1 and microRNA-223-3p (miR-223-3p) were analyzed by RT-qPCR and/or Western blot. Prediction of a regulatory relationship between miR-93 and 3'-UTR of Beclin-1 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. Results: We found that GB dose-dependently decreased ZEB1 protein, but not mRNA, in bladder cancer cells, resulting in suppression of cell invasion. Moreover, in bladder cancer cells, GB dose-dependently decreased the levels of miR-223-3p, which suppressed the protein translation of ZEB1 through binding to 3'-UTR of ZEB1 mRNA. Overexpression of miR-223-3p decreased ZEB1 protein, while depletion of miR-223-3p increased ZEB1 protein in bladder cancer cells. Conclusion: GB inhibits bladder cancer cell invasiveness through suppressing ZEB1 protein translation via upregulating miR-223-3p.

Object selection is the basis of natural user–computer interaction (NUI) in a virtual environment (VE). Among the three-dimensional object selection techniques employed in virtual reality (VR), bare hand-based finger clicking interaction and ray-casting are two convenient approaches with a high level of acceptance. This study involved 14 participants, constructed a virtual laboratory environment in VR, and compared the above two finger-based interaction techniques in terms of aspects of the task performance, including the success rate, total reaction time, operational deviation, and accuracy, at different spatial positions. The results indicated that the applicable distance range of finger clicking interaction and finger ray-casting was 0.2 to 1.4 m and over 0.4 m, respectively. Within the shared applicable distance, the finger clicking interaction achieved a shorter total reaction time and higher clicking accuracy. The performance of finger clicking interaction varied remarkably at the center and edge of the horizontal field of view, while no significant difference was found among ray-casting at various horizontal azimuths. The current findings could be directly applied to the application of bare-hand interaction in VR environments.

Flow maps are a common type of geographic information visualization in which lines that symbolize flow are typically varied in width to represent differences in the magnitude of the flow. An accurate perception of thickness is critical to numerical representation in flow maps. Previous studies have identified some of the factors, such as horizontal–vertical visual illusions and color size effects, that affect the perceived size of objects. However, the question of whether multiple visual variables that encode flow lines, such as length, orientation, and shape, interfere with their perceived thicknesses, remains unanswered. In this study, we performed a user study to determine the effect of length and orientation on thickness perception. The result indicates that the horizontal orientation is perceived to be thicker than the vertical orientation, and a short length is perceived to be thicker than a long length. Furthermore, we report and discuss other results (e.g., on adjustment direction) that are consistent with previous work. Although this study constitutes basic research, accumulating evidence on thickness perception is essential to this field of science. This study may contribute to our understanding of the factors that influence the perception of the thickness of lines on a flow map. We provide some concrete guidelines for the design of flow maps that may be beneficial to map designers.

Objectives To report on the treatment of urethral recurrence after orthotopic urinary diversion at our institution. Methods We retrospectively reviewed clinical information of urethral recurrence in patients who underwent radical cystectomy and orthotopic urinary diversion between January 1998 and January 2013. Results Of 341 patients, 282 presented for follow-up (median follow-up: 56 months; range: 1–174 months). Eight patients developed local recurrence of urothelial cancer after radical cystectomy. The rate of urethral recurrence (1.4%) in female patients who underwent orthotopic urinary diversion was lower than in male patients (3.3%). The median (range) time to recurrence was 33 (6–120) months after radical cystectomy and orthotopic urinary diversion. Recurrences were treated by transurethral resection of tumour, urethrectomy, neobladder resection, revision of urinary diversion, adjuvant chemotherapy, or radiation therapy, based on individual circumstances. Survival analysis showed that 5-year cancer-specific survival was significantly higher in patients with urethral recurrence alone (83.3%), compared with patients with other recurrences, including pelvic/abdomen recurrence and distant metastasis (26.8%). Conclusions En bloc urethrectomy and revision of urinary diversion remain the principle surgical choices. Selection of transurethral tumour resection was based on tumour stage and was used in carefully chosen patients. Cancer-specific survival might depend on multidisciplinary therapy.

Bladder cancer is the most common malignant tumor of urinary system, largely resulting from failure of repair of DNA damage to the environmental insults. The function of XPA in nucleotide excision repair pathway has been well documented. However, participation of XPA in the repair of DNA double-strand break remains unknown. Here, we reported that bladder cancer expressed low XPA levels compared to adjacent non-tumor bladder tissue, and this phenotype was closely associated with chromosomal aberrations. Moreover, downregulated XPA appeared to increase incidence of chromosome aberration. XPA reduction increased cell viability of a bladder cancer cell line RT4, while XPA re-expression decreased the cell viability of RT4 cells. Since high mutation frequency is the basis of mutations of oncogenes and anti-oncogenes, and may be the essence of bladder cancer susceptibility, our study suggests that downregulated XPA may promote carcinogenesis of bladder cancer via impairment of DNA repair.

Proanthocyanidins in Chinese bayberry leaves (PCBLs) were qualitatively analyzed. NMR data suggest that PCBLs are mostly composed of (epi)gallocatechin gallate units. Matrix-assisted laser desorption time-of-flight MS data indicate 95 possible prodelphinidin structures, ranging from dimers to tridecamers. Preparative normal-phase HPLC and further analysis by reverse-phase HPLC together with electrospray ionization MS enabled detection of 20 compounds, including seven newly identified compounds in Chinese bayberry leaves. The antioxidant capacity of PCBLs was evaluated by (1,1-diphenyl-2-picryl-hydrazyl), ferric-reducing antioxidant power, and oxygen radical absorption capacity assays. The EC50 of DPPH radical scavenging activities (as 50% decrease in the initial DPPH concentration) were 7.60 µg. The FRAP and ORAC values were 8859.33 ± 978.39 and 12991.61 ± 1553.34 µmol Trolox equivalents per gram, respectively. The results indicate the high antioxidant potency of PCBLs.