Virtual sketching-based dental anatomy module improves learners' abilities to use computer-aided design to create dental restorations and prostheses.

Dental anatomy education for dental technology students should be developed in alignment with digital dental laboratory practices. We hypothesized that a virtually assisted sketching-based dental anatomy teaching module could improve students' acquisition of skills essential for digital restoration design. The second-year dental technology curriculum included a novel virtual technology-assisted sketching-based module for dental anatomy education. Pre- and post-course assessments evaluated students' skill sets and knowledge bases. Computer-aided design (CAD) scores were analyzed after one year to assess how the skills students developed through this module impacted their subsequent CAD performance. Participants who undertook the dental sketching-based teaching module demonstrated significantly improved theoretical knowledge of dental anatomy, dental aesthetic perception, and spatial reasoning skills. A partial least squares structural equation model indicated that the positive effects of this module on subsequent CAD performance were indirectly mediated by dental aesthetic perception, spatial reasoning, and practice time. A virtually assisted sketching-based dental anatomy teaching module significantly improved students' acquisition of skills and knowledge and positively mediated dental technology students' CAD performance.

Efficacy of a Virtual 3D Simulation-Based Digital Training Module for Building Dental Technology Students' Long-Term Competency in Removable Partial Denture Design: Prospective Cohort Study.

Background: Removable partial denture (RPD) design is crucial to long-term success in dental treatment, but shortcomings in RPD design training and competency acquisition among dental students have persisted for decades. Digital production is increasing in prevalence in stomatology, and a digital RPD (D-RPD) module, under the framework of the certified Objective Manipulative Skill Examination of Dental Technicians (OMEDT) system reported in our previous work, may improve on existing RPD training models for students. Objective: We aimed to determine the efficacy of a virtual 3D simulation-based progressive digital training module for RPD design compared to traditional training. Methods: We developed a prospective cohort study including dental technology students at the Stomatology College of Chongqing Medical University. Cohort 1 received traditional RPD design training (7 wk). Cohort 2 received D-RPD module training based on text and 2D sketches (7 wk). Cohort 3 received D-RPD module pilot training based on text and 2D sketches (4 wk) and continued to receive training based on 3D virtual casts of real patients (3 wk). RPD design tests based on virtual casts were conducted at 1 month and 1 year after training. We collected RPD design scores and the time spent to perform each assessment. Results: We collected the RPD design scores and the time spent to perform each assessment at 1 month and 1 year after training. The study recruited 109 students, including 58 (53.2%) female and 51 male (56.8%) students. Cohort 1 scored the lowest and cohort 3 scored the highest in both tests (cohorts 1-3 at 1 mo: mean score 65.8, SD 21.5; mean score 81.9, SD 6.88; and mean score 85.3, SD 8.55, respectively; P<.001; cohorts 1-3 at 1 y: mean score 60.3, SD 16.7; mean score 75.5, SD 3.90; and mean score 90.9, SD 4.3, respectively; P<.001). The difference between cohorts in the time spent was not statistically significant at 1 month (cohorts 1-3: mean 2407.8, SD 1370.3 s; mean 1835.0, SD 1329.2 s; and mean 1790.3, SD 1195.5 s, respectively; P=.06) but was statistically significant at 1 year (cohorts 1-3: mean 2049.16, SD 1099.0 s; mean 1857.33, SD 587.39 s; and mean 2524.3, SD 566.37 s, respectively; P<.001). Intracohort comparisons indicated that the differences in scores at 1 month and 1 year were not statistically significant for cohort 1 (95% CI -2.1 to 13.0; P=.16), while cohort 3 obtained significantly higher scores 1 year later (95% CI 2.5-8.7; P=.001), and cohort 2 obtained significantly lower scores 1 year later (95% CI -8.8 to -3.9; P<.001). Conclusions: Cohort 3 obtained the highest score at both time points with retention of competency at 1 year, indicating that progressive D-RPD training including virtual 3D simulation facilitated improved competency in RPD design. The adoption of D-RPD training may benefit learning outcomes.

Identifying endoplasmic reticulum stress-related genes as new diagnostic and prognostic biomarkers in clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most common cancers worldwide, and its incidence is increasing every year. Endoplasmic reticulum stress (ERS) caused by protein misfolding has broad and profound effects on the progression and metastasis of various cancers. Accumulating evidence suggests that ERS is closely related to the occurrence and progression of ccRCC. This study aimed to identify ERS-related genes for evaluating the prognosis of ccRCC. Methods: Transcriptomic expression profiles were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), and clinical data were downloaded from the TCGA. First, the differentially expressed genes (DEGs) were analyzed using the limma package, and the DEGs related to ERS (ERS-DEGs) were identified from the GeneCards database. Second, a function and pathway enrichment analysis and a Gene Set Enrichment Analysis (GSEA) were performed. Third, a protein-protein interaction (PPI) network was constructed to identify the hub genes, and a gene-micro RNA (miRNA) network and gene-transcription factor (TF) network were established using the hub genes. Finally, a least absolute shrinkage and selection operator (LASSO) regression analysis was conducted to establish a diagnostic model, and a Cox analysis was used to analyze the correlations between the expression of the characteristic genes and the clinical characteristics. Results: We identified 11 signature genes and established a diagnostic model. Further, the Cox analysis results revealed a correlation between the expression levels of the signature genes and the clinical characteristics. Ultimately, five signature genes (i.e., TNFSF13B, APOL1, COL5A3, and CDH5) were found to be associated with a poor prognosis. Conclusions: This study suggests that TNFSF13B, APOL1, COL5A3, and CDH5 may have potential as prognostic biomarkers in ccRCC and may provide new evidence to support targeted therapy in ccRCC.

SIRT1 Promotes Cisplatin Resistance in Bladder Cancer via Beclin1 Deacetylation-Mediated Autophagy.

Autophagy-dependent cisplatin resistance poses a challenge in bladder cancer treatment. SIRT1, a protein deacetylase, is involved in autophagy regulation. However, the precise mechanism through which SIRT1 mediates cisplatin resistance in bladder cancer via autophagy remains unclear. In this study, we developed a cisplatin-resistant T24/DDP cell line to investigate this mechanism. The apoptosis rate and cell viability were assessed using flow cytometry and the CCK8 method. The expression levels of the relevant RNA and protein were determined using RT-qPCR and a Western blot analysis, respectively. Immunoprecipitation was utilized to validate the interaction between SIRT1 and Beclin1, as well as to determine the acetylation level of Beclin1. The findings indicated the successful construction of the T24/DDP cell line, which exhibited autophagy-dependent cisplatin resistance. Inhibiting autophagy significantly reduced the drug resistance index of these cells. The T24/DDP cell line showed a high SIRT1 expression level. The overexpression of SIRT1 activated autophagy, thereby further promoting cisplatin resistance in the T24/DDP cell line. Conversely, inhibiting autophagy counteracted the cisplatin-resistance-promoting effects of SIRT1. Silencing SIRT1 led to increased acetylation of Beclin1, the inhibition of autophagy, and a reduction in the cisplatin resistance of the T24/DDP cell line. Introducing a double mutation (lysine 430 and 437 to arginine, 2KR) in Beclin-1 inhibited acetylation and activated autophagy, effectively reversing the decreased cisplatin resistance resulting from SIRT1 silencing. In summary, our study elucidated that SIRT1 promotes cisplatin resistance in human bladder cancer T24 cells through Beclin1-deacetylation-mediated autophagy activation. These findings suggest a potential new strategy for reversing cisplatin resistance in bladder cancer.

Prognostic significance of HER2 status evaluation using immunohistochemistry in patients with urothelial carcinoma of the bladder: A retrospective single­center experience.

In recent years, antibody-drug conjugate (ADC) therapy targeting human epidermal growth factor receptor 2 (HER2) has been proven to be beneficial in patients with advanced urothelial carcinoma of the bladder (UCB); however, the role of HER2 in UCB remains obscure. Thus, the present retrospective single-center study was performed to evaluate the expression of HER2 in UCB and its prognostic significance. The HER2 status of 108 patients with UCB who underwent radical cystectomy was assessed using immunohistochemistry, and its association with the recurrence and survival rates of patients was analyzed. HER2 overexpression was observed in 57.4% of the patients; this was significantly associated with higher tumor grades (P=0.006) and stages (P<0.001). Kaplan-Meier analysis suggested that patients with HER2 overexpression had a shorter 5-year overall survival rate (P=0.005) and recurrence-free survival rate (P=0.003). Multivariate Cox regression analysis indicated that HER2 overexpression was a high-risk independent predictor of UCB recurrence (hazard ratio, 3.61; 95% confidence interval, 1.07-12.18; P=0.039). On the whole, these findings demonstrate that evaluating the HER2 status may improve the prediction of cancer recurrence and may thus guide the selection of patients that will benefit the most from HER2-ADC therapies.

EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation.

Bladder cancer is a highly heterogeneous and aggressive malignancy with a poor prognosis. EGF/EGFR activation causes the detachment of SHC-binding protein 1 (SHCBP1) from SHC adapter protein 1 (SHC1), which subsequently translocates into the nucleus and promotes cancer development via multiple signaling pathways. However, the role of the EGF-SHCBP1 axis in bladder cancer progression remains unexplored. Herein, we report that SHCBP1 is upregulated in bladder cancer tissues and cells, with cytoplasmic or nuclear localization. Released SHCBP1 responds to EGF stimulation by translocating into the nucleus following Ser273 phosphorylation. Depletion of SHCBP1 reduces EGF-induced cell migration and invasiveness of bladder cancer cells. Mechanistically, SHCBP1 binds to RACGAP1 via its N-terminal domain of amino acids 1 ~ 428, and this interaction is enhanced following EGF treatment. Furthermore, SHCBP1 facilitates cell migration by inhibiting RACGAP-mediated GTP-RAC1 inactivation, whose activity is indispensable for cell movement. Collectively, we demonstrate that the EGF-SHCBP1-RACGAP1-RAC1 axis acts as a novel regulatory mechanism of bladder cancer progression, which offers a new clinical therapeutic strategy to combat bladder cancer.

Starvation induced autophagy promotes the progression of bladder cancer by LDHA mediated metabolic reprogramming.

BACKGROUND: Aberrant autophagy and preternatural elevated glycolysis are prevalent in bladder cancer (BLCA) and are both related to malignant progression. However, the regulatory relationship between autophagy and glycolytic metabolism remains largely unknown. We imitated starvation conditions in the tumour microenvironment and found significantly increased levels of autophagy and aerobic glycolysis, which both regulated the progression of BLCA cells. We further explored the regulatory relationships and mechanisms between them. METHODS: We used immunoblotting, immunofluorescence and transmission electron microscopy to detect autophagy levels in BLCA cells under different treatments. Lactate and glucose concentration detection demonstrated changes in glycolysis. The expression of lactate dehydrogenase A (LDHA) was detected at the transcriptional and translational levels and was also silenced by small interfering RNA, and the effects on malignant progression were further tested. The underlying mechanisms of signalling pathways were evaluated by western blot, immunofluorescence and immunoprecipitation assays. RESULTS: Starvation induced autophagy, regulated glycolysis by upregulating the expression of LDHA and caused progressive changes in BLCA cells. Mechanistically, after starvation, the ubiquitination modification of Axin1 increased, and Axin1 combined with P62 was further degraded by the autophagy-lysosome pathway. Liberated ß-catenin nuclear translocation increased, binding with LEF1/TCF4 and promoting LDHA transcriptional expression. Additionally, high expression of LDHA was observed in cancer tissues and was positively related to progression. CONCLUSION: Our study demonstrated that starvation-induced autophagy modulates glucose metabolic reprogramming by enhancing Axin1 degradation and ß-catenin nuclear translocation in BLCA, which promotes the transcriptional expression of LDHA and further malignant progression.

An epithelial-mesenchymal transition-related long noncoding RNA signature correlates with the prognosis and progression in patients with bladder cancer.

Bladder cancer is a common malignant tumour worldwide. Epithelial-mesenchymal transition (EMT)-related biomarkers can be used for early diagnosis and prognosis of cancer patients. To explore, accurate prediction models are essential to the diagnosis and treatment for bladder cancer. In the present study, an EMT-related long noncoding RNA (lncRNA) model was developed to predict the prognosis of patients with bladder cancer. Firstly, the EMT-related lncRNAs were identified by Pearson correlation analysis, and a prognostic EMT-related lncRNA signature was constructed through univariate and multivariate Cox regression analyses. Then, the diagnostic efficacy and the clinically predictive capacity of the signature were assessed. Finally, Gene set enrichment analysis (GSEA) and functional enrichment analysis were carried out with bioinformatics. An EMT-related lncRNA signature consisting of TTC28-AS1, LINC02446, AL662844.4, AC105942.1, AL049840.3, SNHG26, USP30-AS1, PSMB8-AS1, AL031775.1, AC073534.1, U62317.2, C5orf56, AJ271736.1, and AL139385.1 was constructed. The diagnostic efficacy of the signature was evaluated by the time-dependent receiver-operating characteristic (ROC) curves, in which all the values of the area under the ROC (AUC) were more than 0.73. A nomogram established by integrating clinical variables and the risk score confirmed that the signature had a good clinically predict capacity. GSEA analysis revealed that some cancer-related and EMT-related pathways were enriched in high-risk groups, while immune-related pathways were enriched in low-risk groups. Functional enrichment analysis showed that EMT was associated with abundant GO terms or signaling pathways. In short, our research showed that the 14 EMT-related lncRNA signature may predict the prognosis and progression of patients with bladder cancer.

Barriers to using personal protective equipment by healthcare staff during the COVID-19 outbreak in China.

The spread of coronavirus disease 2019 (COVID-19) around the world has put a heavy burden on human society and is also a great challenge facing medical staff. This study aimed to assess the difficulties faced by health care personnel (HCP) in using personal protective equipment (PPE) in clinical practice during the COVID-19 outbreak in Wuhan, China. One hundred twenty medical staff from the First Affiliated Hospital of Chongqing Medical University presented to the Wuhan First Hospital to provide medical assistance, from whom 20 HCP volunteered to participate in a focus group discussion attended by infection control nurse leaders. Participants' responses and discussions were recorded, and the content was analyzed for themes. Observed difficulties included inappropriate PPE sizes, the design of the PPE and its complexity of use, doubts related to the quality and effectiveness of PPE, potential risks during doffing, space layout between clean and contaminated area, and poor comfort with PPE use. Other factors, such as the support environment, management, processes, preparedness, HCP, and equipment can also have a positive or negative impact on the use of PPE. Future efforts to optimize PPE use should focus on strengthening training for HCP using real items for increasing compliance with standardized protocols, improving PPE design, and performing further research on the risks, benefits, and best practices of PPE use.