Objective:To investigate the underlying mechanism behind the significant reduction in intracellular virus loads after respiratory syncytial virus (RSV) and influenza viruses infect respiratory epithelial cells overexpressing the chemokine (C-C motif) receptor 1 (CCR1).Methods:A549 cells were infected with respiratory syncytial virus (RSV), influenza A viruses (H1N1, H3N2), or influenza B virus (FluB), and the expression of chemokine (C-C motif) ligand 5 (CCL5) and CCR1 were detected by qRT-PCR, ELISA, and Western blot. After overexpressing or knocking down CCR1 in A549 cells, these cells were infected with RSV, H1N1, H3N2, or FluB, and the expression of CCR1, heat shock protein 90 (HSP90), cyclin-dependent kinase 1 (CDK1), and viral proteins were detected by qRT-PCR and Western blot. After stimulating CCR1-overexpressed A549 cells with CCL5, Western blot was used to detect the expression of HSP90 and CDK1, and co-immunoprecipitation was used to detect the interaction between HSP90 and CCR1. CCR1 -/- mice were infected with RSV, H1N1, or H3N2 to observe the changes in the expression of HSP90, CDK1, and viral proteins with Western blot, and the inflammation in lung tissues with HE staining. One-way analysis of variance and t test were used for statistical analysis. Results:RSV, H1N1, H3N2, and FluB infections induced high expression of CCL5 in A549 cells ( P<0.05), but the expression of CCR1 showed an overall downward trend. After activating its receptor CCR1, CCL5 inhibited the replication of RSV and influenza viruses by suppressing the activity of HSP90 ( P<0.05). The experiments conducted on CCR1 -/- mice confirmed that the enhanced activity of HSP90 facilitated the replication of RSV and influenza viruses. Conclusion:RSV and influenza viruses may reduce the binding of CCL5 to CCR1 by downregulating the expression of CCR1 in respiratory epithelial cells, thereby weakening the inhibitory effect of CCR1 on HSP90 activity, which enables them to evade host immune defense.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective·To investigate the causal relationship between type 2 diabetes mellitus(T2DM)and cognitive dysfunction using two-sample Mendelian randomisation(MR).Methods·Instrumental variables associated with T2DM were pooled from a large-scale genome-wide association study(GWAS)dataset.Inverse variance weighting was used as the primary analytical technique,supplemented by MR-Egger regression,weighted median and simple median analyses.Meta-analysis was jointly applied to combine different endpoints and to analyse the possibility of a causal relationship between T2DM and dementia,Alzheimer's disease,and Parkinson's dementia.Horizontal pleiotropy was examined by MR-PRESSO global test and MR-Egger analysis.Results·There was a causal relationship between genetically predicted T2DM and dementia(OR=1.11,95%CI 1.02～1.20,P=1.96×10-2)and AD(OR=1.16,95%CI 1.04～1.30,P=8.41×10-3).Meta-analysis also supported the association between T2DM and cognitive impairment(OR=1.12,95%CI 1.05～1.20,P=4.22×10-4).A series of sensitivity analyses suggested the absence of heterogeneity and horizontal pleiotropy.Reverse MR analysis showed no significant causal relationship of various types of dementia on T2DM.Conclusion·T2DM is positively associated with the risk of developing various types of dementia,suggesting that T2DM may be an important risk factor for cognitive impairment.

Objective·To investigate the causal relationship between type 2 diabetes mellitus(T2DM)and cognitive dysfunction using two-sample Mendelian randomisation(MR).Methods·Instrumental variables associated with T2DM were pooled from a large-scale genome-wide association study(GWAS)dataset.Inverse variance weighting was used as the primary analytical technique,supplemented by MR-Egger regression,weighted median and simple median analyses.Meta-analysis was jointly applied to combine different endpoints and to analyse the possibility of a causal relationship between T2DM and dementia,Alzheimer's disease,and Parkinson's dementia.Horizontal pleiotropy was examined by MR-PRESSO global test and MR-Egger analysis.Results·There was a causal relationship between genetically predicted T2DM and dementia(OR=1.11,95%CI 1.02～1.20,P=1.96×10-2)and AD(OR=1.16,95%CI 1.04～1.30,P=8.41×10-3).Meta-analysis also supported the association between T2DM and cognitive impairment(OR=1.12,95%CI 1.05～1.20,P=4.22×10-4).A series of sensitivity analyses suggested the absence of heterogeneity and horizontal pleiotropy.Reverse MR analysis showed no significant causal relationship of various types of dementia on T2DM.Conclusion·T2DM is positively associated with the risk of developing various types of dementia,suggesting that T2DM may be an important risk factor for cognitive impairment.

Objective:To investigate the underlying mechanism behind the significant reduction in intracellular virus loads after respiratory syncytial virus (RSV) and influenza viruses infect respiratory epithelial cells overexpressing the chemokine (C-C motif) receptor 1 (CCR1).Methods:A549 cells were infected with respiratory syncytial virus (RSV), influenza A viruses (H1N1, H3N2), or influenza B virus (FluB), and the expression of chemokine (C-C motif) ligand 5 (CCL5) and CCR1 were detected by qRT-PCR, ELISA, and Western blot. After overexpressing or knocking down CCR1 in A549 cells, these cells were infected with RSV, H1N1, H3N2, or FluB, and the expression of CCR1, heat shock protein 90 (HSP90), cyclin-dependent kinase 1 (CDK1), and viral proteins were detected by qRT-PCR and Western blot. After stimulating CCR1-overexpressed A549 cells with CCL5, Western blot was used to detect the expression of HSP90 and CDK1, and co-immunoprecipitation was used to detect the interaction between HSP90 and CCR1. CCR1 -/- mice were infected with RSV, H1N1, or H3N2 to observe the changes in the expression of HSP90, CDK1, and viral proteins with Western blot, and the inflammation in lung tissues with HE staining. One-way analysis of variance and t test were used for statistical analysis. Results:RSV, H1N1, H3N2, and FluB infections induced high expression of CCL5 in A549 cells ( P<0.05), but the expression of CCR1 showed an overall downward trend. After activating its receptor CCR1, CCL5 inhibited the replication of RSV and influenza viruses by suppressing the activity of HSP90 ( P<0.05). The experiments conducted on CCR1 -/- mice confirmed that the enhanced activity of HSP90 facilitated the replication of RSV and influenza viruses. Conclusion:RSV and influenza viruses may reduce the binding of CCL5 to CCR1 by downregulating the expression of CCR1 in respiratory epithelial cells, thereby weakening the inhibitory effect of CCR1 on HSP90 activity, which enables them to evade host immune defense.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

The correct working posture of dentists is not only the premise of clinical diagnosis, treatment quality and safety but also an important guarantee for the occupational health of dentists. Presently, research on the working posture of dental professionals and related influencing factors is relatively mature internationally. Still, the dental curriculums in our country have not systematically introduced theoretical knowledge and standards related to working posture. This review analyzes and summarizes previous literature on the importance of dental working posture, criteria, assessment methods, and influencing factors, in hopes of providing references and theoretical supports for future guidelines and standards.

Objective:The present study was designed to strengthen the education of research integrity, and to improve the awareness of academic misconduct and academic literacy of medical post-graduate students.Methods:A questionnaire survey was conducted with master post-graduate students of a university affiliated hospital, and statistical analysis on the education of research integrity and the perception of academic misconduct among the survey respondents was performed.Results:Academic master post-graduate students′ cognitions of the misconduct in scientific research process and overall academic misconduct were better than that of professional master post-graduate students, and there were significant differences ( P<0.05). The more times of participation in research integrity training, the better cognition of misconduct of scientific research process, research results publication process, and overall academic misconduct, with significant differences ( P<0.05). Conclusions:The education on scientific research integrity of medical post-graduates should be carried out systematically, while the content should be improved and the form should be enriched for scientific research integrity education, so that the medical post-graduates can have a deeper understanding of the code of academic practices, and an education model of scientific research integrity for medical post-graduate which is suitable for China′s national conditions can be gradually developed.

Objective:To analyze the research hotspots and frontiers of hospital research management research from 1981 to 2022.Methods:The relevant literature in the field of hospital scientific research management was retrieved from the CNKI database to explore the trends of publications in this research field. A scientific knowledge graph was drawn and a visualization analysis of the information of authors, issuing units, and research institutions were conducted by Cite Space.5.8.R3.Research hotspots were discussed based on keyword emergence, cluster analysis, and keyword time zone graph.Results:The publication trend in this field was generally policy-oriented, but the cooperation among authors and institutions was relatively loose, and the research hotspots were gradually shifting from scientific research funding management to discipline construction, talent training, translational medicine, and informatization. Cluster analysis found that the main content of hospital scientific research management was scientific research funding and clinical scientific research management and the main management objects were the medical and nursing staff.Conclusions:Hospital scientific research managers must adhere to the policy-oriented approach, strengthen the cooperation and exchanges in scientific research management, innovate the scientific research management mode around the research hotspots and development trends, and promote the quality and efficiency of scientific research management.

Based on the characteristics of medical specialty, this research group has developed the virtual simulation experiment teaching project of Chinese revolutionary morality (red medicine spirit). This project uses 3D simulation technology and OpenGL technology to build a virtual experimental learning environment based on WebGL, learn general Fu Lianzhang's glorious deeds and immersive experience of the inheritance and development of the spirit of red medicine by contemporary "heroes in harms way" in the fight against the COVID-19 epidemic in the form of 3D animation interaction. Through research, it is found that virtual simulation teaching is conducive to promoting students' understanding and mastery of medical humanities and improving students' satisfaction with teaching, with good popularization value.