Chikungunya virus (CHIKV), which is primarily transmitted by Aedes aegypti and Ae. albopictus, has recently rapidly spread across the world, which poses a huge threat to public health. Chikungunya fever (CHIKF), caused by CHIKV infection, typically manifests as acute febrile illness with severe polyarthralgia that may persist for months to years. A few severe CHIKF cases may be accompanied by serious neurological complications, even resulting in death. The accelerating global expansion of CHIKV is closely associated with genetic variations of the virus, and mutated genes in CHIKV may augment the virus adaptability to Aedes vectors and transmission efficiency. Currently, the diagnosis of the CHIKV infection primarily relies on molecular and serological assays; however, there are still multiple challenges for early and differential diagnosis of CHIKV infections due to co-infections with arboviruses and nonspecific early symptoms. The first prophylactic vaccine for CHIKF has been recently approved in the United States; however, the large-scale application still awaits further validations. More importantly, there are no licensed antiviral therapies against CHIKV until now. This review describes the structure and pathogenesis of CHIKV, summarizes the latest epidemiology and advances in the diagnosis of CHIKV infections, and depicts the current status and prospects of antiviral agents and vaccine development, so as to inform evidence-based prevention and control strategies.

The accurate segmentation of breast ultrasound images is an important precondition for the lesion determination. The existing segmentation approaches embrace massive parameters, sluggish inference speed, and huge memory consumption. To tackle this problem, we propose T ²KD Attention U-Net (dual-Teacher Knowledge Distillation Attention U-Net), a lightweight semantic segmentation method combined double-path joint distillation in breast ultrasound images. Primarily, we designed two teacher models to learn the fine-grained features from each class of images according to different feature representation and semantic information of benign and malignant breast lesions. Then we leveraged the joint distillation to train a lightweight student model. Finally, we constructed a novel weight balance loss to focus on the semantic feature of small objection, solving the unbalance problem of tumor and background. Specifically, the extensive experiments conducted on Dataset BUSI and Dataset B demonstrated that the T ²KD Attention U-Net outperformed various knowledge distillation counterparts. Concretely, the accuracy, recall, precision, Dice, and mIoU of proposed method were 95.26%, 86.23%, 85.09%, 83.59%and 77.78% on Dataset BUSI, respectively. And these performance indexes were 97.95%, 92.80%, 88.33%, 88.40% and 82.42% on Dataset B, respectively. Compared with other models, the performance of this model was significantly improved. Meanwhile, compared with the teacher model, the number, size, and complexity of student model were significantly reduced (2.2×10 ⁶ vs. 106.1×10 ⁶, 8.4 MB vs. 414 MB, 16.59 GFLOPs vs. 205.98 GFLOPs, respectively). Indeedy, the proposed model guarantees the performances while greatly decreasing the amount of computation, which provides a new method for the deployment of clinical medical scenarios.
Humans ; Breast Neoplasms/diagnostic imaging* ; Female ; Ultrasonography, Mammary/methods* ; Image Processing, Computer-Assisted/methods* ; Algorithms ; Neural Networks, Computer ; Breast/diagnostic imaging*

OBJECTIVES: To study clinical manifestations and gene mutation features of neonates with centronuclear myopathy. METHODS: A retrospective analysis was conducted on the medical data of 5 neonates with centronuclear myopathy diagnosed in the Neonatal Intensive Care Unit of Children's Hospital, Zhejiang University School of Medicine from January 2020 to August 2024. The data included gender, gestational age, birth weight, Apgar score, clinical manifestations, creatine kinase level, electromyography, genetic testing results and the outcomes of the infants. RESULTS: All 5 male neonates had a history of postpartum asphyxia and resuscitation. They all presented with hypotonia, myasthenia, and respiratory failure; two neonates also had swallowing dysfunction. Of the five neonates, three had normal creatine kinase levels, while two had slightly elevated levels. Electromyography was performed for three neonates, among whom two had myogenic damage. MTM1 gene mutations were identified by genetic testing in all five neonates, including two nonsense mutations and three missense mutations, among which one variant had not been previously reported. Four mutations were inherited from the mother, and the other one was a de novo mutation. The five neonates showed no clinical improvement following treatment, failed weaning from mechanical ventilation, and ultimately died after withdrawal of life-sustaining therapy. CONCLUSIONS Centronuclear myopathy caused by MTM1 gene mutation often has a severe phenotype and a poor prognosis, and it should be considered for neonates with hypotonia and myasthenia after birth. Genetic testing should be performed as soon as possible.
Humans ; Myopathies, Structural, Congenital/genetics* ; Male ; Infant, Newborn ; Retrospective Studies ; Mutation ; Female ; Protein Tyrosine Phosphatases, Non-Receptor/genetics*

Patients with periodontal disease often require combined periodontal-orthodontic interventions to restore periodontal health, function, and aesthetics, ensuring both patient satisfaction and long-term stability. Managing these patients involving orthodontic tooth movement can be particularly challenging due to compromised periodontal soft and hard tissues, especially in severe cases. Therefore, close collaboration between orthodontists and periodontists for comprehensive diagnosis and sequential treatment, along with diligent patient compliance throughout the entire process, is crucial for achieving favorable treatment outcomes. Moreover, long-term orthodontic retention and periodontal follow-up are essential to sustain treatment success. This expert consensus, informed by the latest clinical research and practical experience, addresses clinical considerations for orthodontic treatment of periodontal patients, delineating indications, objectives, procedures, and principles with the aim of providing clear and practical guidance for clinical practitioners.
Humans ; Consensus ; Orthodontics, Corrective/standards* ; Periodontal Diseases/complications* ; Tooth Movement Techniques/methods* ; Practice Guidelines as Topic

Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis. However, mechanisms associated with stem cell senescence require further investigation. In this study, we conducted a proteomic analysis of human dental pulp stem cells (HDPSCs) obtained from individuals of various ages. Our findings showed that the expression of NUP62 was decreased in aged HDPSCs. We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo. Conversely, the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs. Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression, we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1. This, in turn, stimulates the transcription of the epigenetic enzyme NSD2. Finally, the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes (HMGA1, HMGA2, and SIRT6). Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
Humans ; Dental Pulp/cytology* ; Nuclear Pore Complex Proteins/genetics* ; Cellular Senescence/genetics* ; Stem Cells/metabolism* ; Epigenesis, Genetic ; Cell Proliferation ; Cell Differentiation ; Histone-Lysine N-Methyltransferase/metabolism* ; Cells, Cultured ; Cellular Reprogramming ; Cell Movement ; Proteomics

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 compare the interaction efficiency of three human-machine interaction modes with hand-touch control,eye movement control and voice control,based on a multi-channel human-machine interaction system in flight mission scenarios.Methods 20 pilots took part in the study and completed the first level(relatively simple)and second level(relatively complex)interactive experimental tasks in three human-computer interaction modes based on specific flight mission scenarios.The interaction efficiency indicators included the system's interaction time,response time,fusion calculation time,and number of errors.After the experiment was completed,the pilots conducted a subjective evaluation,which included the suitability of the interaction mode to the task,consistency with expected usage,fault-tolerance,effective feedback,and the tendency of the interaction mode to be applied in future flight fields.Results There were generally significant differences in interaction efficiency between hand-touch control,voice control,and eye movement control in flight mission scenarios,but the differences differed in first-level and second-level interaction tasks.Based on the comprehensive interaction experimental tasks at all levels,the experimental results obtained included:(1)the interaction time of hand-touch control was the shortest,the interaction time of voice control was the longest,and the main effect of the interaction mode was significant(F=18.214,P<0.001,η2=0.565);(2)The response time of hand-touch control was the shortest,while the response time of eye movement control was the longest.The main effect of interaction mode was significant(F=153.085,P<0.001,η2=0.944);(3)The fusion calculation time for hand-touch control was the shortest,while the fusion calculation time for voice control was the longest.The main effect of the interaction mode was significant(F=41.702,P<0.001,η2=0.777);(4)The errors in voice control were the least,while those in eye movement control were the most.The main effect of interaction mode was significant(χ2=22.845,P<0.001,φ=1.097);(5)The subjective evaluation scores of pilots on voice control were higher than those on eye movement control,and all had statistical significance(P<0.001,P<0.01).Conclusions This study focuses on flight interaction tasks and compares the interaction efficiency of three interaction modes of hand-touch control,voice control,and eye movement control,through a combination of experiments and subjective evaluations.The differences in various interaction efficiency indicators among different interaction modes are found,and the interaction modes have a significant impact on interaction efficiency.Hand-touch control has a significant advantage in interaction time efficiency,voice control has an advantage in accuracy for simple tasks,while eye movement control has relatively weak time efficiency and accuracy;Compared to eye movement control,pilots exhibit higher evaluations and tendencies towards voice control.The research results can provide reference for the future design,evaluation,and application of multi-modal interaction systems.

Objective To investigate the mechanism underlying gasdermin E(GSDME)-mediated pyroptosis in radiation-induced intestinal injury and to find out whether gasdermin(GSDM)family members regulate pyroptosis through similar signaling pathways.Methods Human normal colon epithelial cells(NCM460)and human colon cancer cells(HT-29)were exposed to radiation of different doses and durations before pyroptosis indicators were evaluated by observing pyroptotic bubbles,cell survival,and the cleavage of pyroptosis execution proteins.HT-29 cells overexpressing GSDME were subjected to radiation,followed by enrichment analysis of pyroptosis-related differentially expressed genes using RNA-seq.Results Radiation induced substantial pyroptosis in NCM460 cells.Overexpression of GSDME in HT-29 cells resulted in substantial radiation-induced pyroptosis.The pyroptosis state of human intestinal cells was simulated in the HT-29 model cell line.Overexpressions of GSDME-N and GSDMD-N resulted in the expression of more than 50％ of the differentially expressed genes in the pyroptosis state.Sequencing analysis showed that the genes in the pyroptosis state were mainly overrepresented in immune response,inflammatory response,and Rapl signaling pathway.Conclusion GSDME activation can mediate radiation-induced pyroptosis by producing GSDME-N fragments.GSDM family members participate in pyroptosis in a similar mode of regulation.Furthermore,radiation-induced activation of GSDME/D may regulate pyroptosis through immune response,inflammatory response,and Rap1 signaling pathway.

Objective To investigate the protective effect and mechanism of glutathione peroxidase 3-(GPx3)modified mesenchymal stem cells(MSC)against radiation-induced lung injury(RILI).Methods GPx3-modified MSCs were injected into the tail vein of mice whose lungs were irradiated with 20 Gy.Lung tissues were collected and sections were stained to observe pathological changes.The expression levels of inflammation-related factors were detected by real time quantitative PCR(qPCR),while the levels of malondialdehyde(MDA),H2O2,and 8-hydroxyguanine(8-OHG)were detected via biochemical experiments.Additionally,RNA damage was assessed by reverse transcription blocking combining with double primer PCR.Results GPx3-modified MSCs significantly improved the pathological damage in post-radiation lung tissues and inhibited the fibrosis process and inflammatory response.GPx3-modified MSCs were able to scavenge reactive oxygen species(ROS)more effectively,resulting in a reduction of lipid peroxidation products such as MDA and oxidative damage to RNA formation of 8-OHG.Conclusion By decreasing ROS accumulation,GPx3-modified MSCs can potentially reduce oxidative damage and attenuate RILI.GPx3-modified MSCs can improve the therapeutic efficacy against RILI.

Objective:To evaluate the value of metagenomic Next Generation Sequencing (mNGS) for the pathogenetic diagnosis of bloodstream infections in patients with sepsis.Methods:A retrospective analysis was performed on 105 sepsis cases who received blood mNGS and blood culture tests during their hospitalization in the Intensive Care Department of the Affiliated Hospital of North Sichuan Medical College from September 2021 to August 2023, and the results were compared and analyzed. According to mNGS and blood culture results, the cases were divided into the positive group and negative group.The distribution of pathogens in the enrolled patients were analyzed, and the diagnostic performance and consistency of blood culture and mNGS were compared. The differences in clinical characteristics of patients in each group were analyzed, and the pathogenic diagnostic value of mNGS for bloodstream infections in patients with sepsis was evaluated.Results:①Among 105 blood samples, 61 cases (58.10%) had positive results of mNGS, and 32 cases (30.48%) had positive results of blood culture. The positive rate of mNGS was higher than that of blood culture, and the difference was statistically significant ( P < 0.05).The accuracy of mNGS was lower than that of blood culture②The mean values of ESR, PCT and CRP in positive group were higher than those in negative group, and the proportion of septic shock was higher than that in negative group, and the differences were statistically significant ( P < 0.05). There was no significant difference in 28-day mortality rate between the two groups ( P > 0.05). Conclusions:mNGS is beneficial to the etiological diagnosis and treatment of bloodstream infection in patients with sepsis.