Objective To analyze the spatiotemporal distribution characteristics of and trends in the disease burden of dengue fever in China from 2005 to 2024, so as to provide insights into formulation of dengue fever control strategies. Methods Data pertaining to dengue fever cases in China from 2005 to 2024 were retrieved from the Infectious Disease Reporting Information System of Chinese Center for Disease Control and Prevention, and city population, gross domestic product (GDP), GDP per capita, and consumer price index in China were captured from the China Statistical Yearbook, National Bureau of Statistics of China, the China City Statistical Yearbook, and bureaus of statistics in each city. The disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) due to dengue fever were calculated in China from 2005 to 2024. The direct and indirect economic burdens of dengue fever were estimated to calculate the total economic burden. The trends in the disease burden of dengue fever were estimated in China from 2005 to 2024 using a Joinpoint regression model with the software Joinpoint 4.9.0.0, and the average annual percent change (AAPC) and its 95% confidence interval (CI) were calculated. In addition, the DALYs rate and economic burden of dengue fever in China were subjected to global and local spatial autocorrelation analyses using the software ArcGIS 10.8. Results The gross DALYs due to dengue fever were 5 558 person-years in China from 2005 to 2024, and the DALYs of dengue fever increased from 36 person-years in 2005 to 899 person-years in 2024, with an increase of 23.97 folds. The average annual DALYs rate of dengue fever was 0.02 person-years/10⁵ in China during the 20-year study period from 2005 to 2024, and the DALYs rate peaked in 2014 (0.13 person-years/10⁵) and reduced during the COVID-19 pandemic from 2020 to 2022. YLDs were the main contributor of DALYs due to dengue fever in China from 2005 to 2024, with a total of 5 354 person-years, accounting for 96.33% (5 354 person-years/5 558 person-years) of the gross DALYs. The gross DALYs of dengue fever were 2 982 person-years among men (53.66%) and 2 575 person-years among women (46.34%) in China from 2005 to 2024, and high DALYs of dengue fever were measured among residents at ages of 15 to 30 years (1 639 person-years), 30 to 45 years (1 857 person-years), and 45 to 60 years (1 204 person-years), respectively, accounting for 84.56% (4 700 person-years/5 558 person-years) of total DALYs due to dengue fever in China. The total economic burden of dengue fever was estimated to be 612 million Yuan in China from 2005 to 2024, with an average annual economic burden of 30.584 million Yuan. The economic burden of dengue fever increased from 196 000 Yuan in 2005 to 121 million Yuan in 2024 in China, with an increase of 616.35 folds, and the per capita economic burden increased from 3 322.21 Yuan in 2005 to 4 940.01 Yuan in 2024, with an increase of 48.70%. Dengue fever cases were reported in 274 cities (counties) across 31 provinces (autonomous regions, municipalities) in China from 2005 to 2024, with relatively higher DALYs in Guangdong Province and Yunnan Province. Spatial autocorrelation analysis revealed that the disease burden of dengue fever appeared positive aggregation in Chinese cities (counties) from 2005 to 2024 (global Moran’s I = 0.045, Z = 2.24, P < 0.05), with high-high clusters mainly concentrated in the Pearl River Delta region in Guangdong Province and Xishuangbanna Dai Autonomous Prefecture and Pu’er City in Yunnan Province, and the total economic burden (global Moran’s I = 0.032, Z = 9.55, P < 0.001), per capita economic burden (global Moran’s I = 0.208, Z = 27.34, P < 0.001), and the proportion of total economic burdens in GDP in 2024 (global Moran’s I = 0.017, Z = 5.91, P < 0.001) all presented positive aggregation, with relatively higher total economic burdens mainly concentrated in Guangdong Province and Yunnan Province. Joinpoint regression analysis showed that the gross DALYs rates of dengue fever appeared an overall tendency towards a rise in China from 2005 to 2024 (AAPC = 16.24%, P = 0.029), and the DALYs rate presented an overall tendency towards a rise among both men (AAPC = 14.75%, P = 0.028) and women (AAPC = 14.93%, P = 0.037) during the study period. The per capita direct economic burden appeared an overall tendency towards a rise among dengue fever patients in China from 2005 to 2024 (AAPC = 2.16%, P = 0.012); however, there was no significant difference in the trends in the per capita indirect economic burden (AAPC = 0.46%, P = 0.470). In addition, the DALYs rate of dengue fever appeared a tendency towards a rise in 84.67% (232/274) of cities (counties) in China from 2005 to 2024, and the per capita economic burden appeared a tendency towards a rise in 85.40% (234/274) of cities (counties), while the DALYs rate and per capita economic burden of dengue fever appeared a tendency towards a rise in 77.01% (211/274) of cities (counties). Conclusions The disease burden of dengue fever significantly increased in China from 2005 to 2024. It is recommended to reinforce integrated dengue fever control in high-risk areas and among high-risk populations, and to improve the surveillance of imported dengue fever cases and vector control.

This study systematically examined the effects of atomization as a transdermal permeation enhancer on the transdermal delivery of active ingredients with different physicochemical properties and investigated the underlying mechanisms. Porcine ear skin served as an in vitro model, and skin permeation experiments were conducted using Franz diffusion cells. Receptor fluids were collected at specific time points, and samples of the stratum corneum and viable epidermis–dermis were separated and prepared. Quantitative and visualization methods, including high-performance liquid chromatography, fluorescence derivatization, and confocal laser scanning microscopy, were used to compare skin retention and transdermal permeation of adenosine (AD), tranexamic acid (TXA), calcein (CAL), and tocopheryl acetate (TA) under atomized and non-atomized conditions. Additionally, transepidermal water loss (TEWL) measurements and attenuated total reflectance–Fourier transform infrared spectroscopy (ATR-FTIR) were employed to analyze the mechanism behind the penetration enhancement caused by atomization. The findings showed that atomization increased skin retention within the stratum corneum and viable epidermis–dermis, as well as the transdermal permeation of all four active ingredients to varying degrees. The most significant enhancement was observed for TXA, which has a relatively low molecular weight and moderate lipophilicity, while the enhancement effects for highly hydrophilic AD and highly lipophilic TA were comparatively limited; however, atomization significantly increased the skin retention of TA. TEWL results indicated that skin permeability increased within 4 hours after atomization and largely recovered within 8 hours. ATR-FTIR analysis suggested that atomization may facilitate transdermal delivery by disrupting the lipid order and keratin conformation in the stratum corneum.This study provides theoretical support and experimental references for the advancement of atomization transdermal delivery technology, as well as the design and development of related atomization products.

Exercise-induced muscle damage (EIMD) is a frequent form of skeletal muscle microdamage that occurs after high-intensity, prolonged, or unaccustomed exercise, especially exercise dominated by eccentric contractions. It is commonly characterized by delayed-onset muscle soreness, transient loss of muscle strength, local inflammation, structural disruption of myofibers, and delayed functional recovery. Although mild EIMD may serve as a stimulus for training adaptation, excessive or insufficiently recovered muscle damage can impair exercise performance, disturb training continuity, and reduce participation in physical activity. Therefore, clarifying the molecular mechanisms that underlie the initiation, amplification, and resolution of EIMD is important for optimizing athletic training, improving post-exercise recovery, and guiding evidence-based public fitness practice. Necroptosis is a regulated form of programmed cell death mediated primarily by the receptor-interacting protein kinase (RIPK) 1/RIPK3/mixed lineage kinase domain-like protein (MLKL) signaling axis. Recent studies have shown that necroptosis is closely involved in tissue injury, sterile inflammation, and repair remodeling. However, whether necroptosis acts as an initiating driver, a secondary damage amplifier, or an adaptive signal required for repair after EIMD remains unclear. This review aimed to summarize the potential role of necroptosis in EIMD and to establish a mechanistic framework linking regulated cell death, inflammatory amplification, immune regulation, and skeletal muscle repair. Relevant studies concerning EIMD, necroptosis, RIPK1/RIPK3/MLKL signaling, damage-associated molecular patterns (DAMPs), inflammatory responses, immune cell recruitment, extracellular matrix remodeling, and muscle regeneration were reviewed and integrated. On this basis, the possible temporal and functional involvement of necroptosis in different phases of EIMD was analyzed. The main evidence summarized in this review suggests that EIMD is not merely a consequence of primary mechanical disruption. Instead, it develops through a dynamic sequence that includes sarcolemmal instability, calcium overload, mitochondrial dysfunction, oxidative stress, inflammatory mediator production, immune cell infiltration, necrotic tissue clearance, and regeneration-associated remodeling. Necroptosis may participate in this process through at least two interconnected mechanisms. First, in the early or progressive phase of EIMD, activation of the RIPK1/RIPK3/MLKL signaling axis may promote MLKL phosphorylation and plasma membrane permeabilization, leading to the release of DAMPs such as high-mobility group box 1, ATP, mitochondrial DNA, and other intracellular components. These signals may activate innate immune pathways, amplify inflammatory cytokine production, and enhance the recruitment of neutrophils and macrophages, thereby aggravating secondary inflammation and extending muscle fiber injury. Second, during the resolution and repair phases, necroptosis-related signaling may also contribute indirectly to the formation of a regenerative microenvironment. By influencing the clearance of necrotic debris, the recruitment and phenotypic transition of immune cells, and the remodeling of extracellular matrix components, necroptosis may affect satellite cell activation, myogenic repair, and the eventual structural and functional recovery of injured skeletal muscle. Thus, the biological effect of necroptosis in EIMD may be context dependent rather than uniformly harmful. Its outcome may depend on exercise intensity, the extent of tissue damage, the timing of pathway activation, the involved cell types, inflammatory status, training background, age, and metabolic condition. In conclusion, necroptosis may represent an important molecular link between skeletal muscle injury, sterile inflammation, and tissue repair after damaging exercise. It may exert a dual role in EIMD by amplifying secondary damage while also contributing to repair coordination under appropriate temporal and microenvironmental conditions. Future studies should determine the activation pattern of RIPK1/RIPK3/MLKL signaling after different exercise protocols, identify the major cell populations undergoing necroptosis in injured skeletal muscle, and examine whether targeted modulation of necroptosis can reduce excessive inflammation without impairing necessary regenerative responses. This review provides a theoretical basis for understanding the pathogenesis of EIMD and for developing targeted strategies to improve skeletal muscle recovery after exercise-induced injury.

Objective:To explore the distribution of cardiovascular disease(CVD)and cardiovascular risk fac-tors(CVRF)in patients with epithelial ovarian cancer before treatment and their correlation with the histological type,stage and grade of ovarian cancer.Methods:A total of 401 newly diagnosed epithelial ovarian cancer pa-tients admitted to The First Affiliated Hospital of Dalian Medical University from January 1,2015 to December 31,2022 were enrolled.Analyze the distribution of CVD(including hypertension,coronary heart disease,stroke,etc.)and CVRF(including diabetes,dyslipidemia,high level of uric acid)in epithelial ovarian cancer patients.Univari-ate analysis and multivariate Logistic regression were performed on the association between CVD,CVRF and the histological type,grade and stage of epithelial ovarian cancer.Results:①Among 401 epithelial ovarian cancer pa-tients,43.6％had at least one CVD before therapy.The most common CVD was hypertension(41.1％),and the most common CVRF was dyslipidemia(57.9％).②Multivariate Logistic regression analysis showed that age ≥60 years was an independent risk factor for serous,high-grade,and advanced epithelial ovarian cancer(OR＞1,P＜0.05).Dyslipidemia was an independent risk factor for high-grade and advanced epithelial ovarian cancer(OR＞1,P＜0.05).High level of uric acid was an independent risk factor for advanced epithelial ovarian cancer(OR＞1,P＜0.05).③The proportion of high-density lipoprotein cholesterol(HDL-C)and lipoprotein A[Lp(A)]abnor-malities in patients with advanced epithelial ovarian cancer was significantly higher than in those with early stage epithelial ovarian cancer(P＜0.05),and the proportion of number of abnormal lipid components was higher in pa-tients with high grade and advanced epithelial ovarian cancer than in patients with low grade and early stage epi-thelial ovarian cancer,respectively(P＜0.05).Conclusions:Patients with epithelial ovarian cancer bear a signifi-cant burden of CVD and CVRF.Hypertension is the most common CVD,and dyslipidemia is the most common CVRF.Dyslipidemia was associated with epithelial ovarian cancer grade and stage.High level of uric acid was as-sociated with epithelial ovarian cancer stage.Active control of blood pressure and blood lipid levels is very impor-tant for epithelial ovarian cancer patients.

Tic disorder is a chronic neuropsychiatric disorder with complex etiology and diverse phenotypes,and its incidence has been increasing significantly in recent years.Most scholars believe that abnormalities in the cortico-striatal-thalamo-cortical circuit and its interconnected brain regions are closely related to the development of tic disorder.Chinese materia medica intervention in tic disorders is characterized by multi-targets,multi-mechanisms and holistic nature,and has a good prospect for research application.This article summarized the experimental studies of TCM compound intervention in tic disorder in recent years,which have shown that TCM compounds could reduce the damage of nerve cells through the regulation of neurotransmitters,inflammatory response,immune function and the"colony-gut-brain axis"to improve and prevent tic disorder,which could provide a reference for the research and development of new medicines for tic disorder and for the clinical research.

Objective:To explore the effects of diversified teaching combined with the affective-cognitive theory in neurology clerkship instruction.Methods:We enrolled 406 medical students on clerkship at the affiliated hospitals of Sun Yat-sen University from November 2023 to April 2024. They were randomly assigned by cluster to either observation group ( n=164) or control group ( n=242). The observation group received a diversified teaching model that selected context-appropriate teaching methods based on clinical scenarios, while using the affective-cognitive theory to optimize instructional pathways. The control group received traditional teaching. The effectiveness of teaching was evaluated through an objective structured clinical examination (OSCE; maximum score, 10 points) and a questionnaire survey. SPSS 22.0 was used to perform Mann-Whitney U test, chi-square test, and multiple linear regression analysis. NVivo 12.0 was employed to process open-ended questions. Results:In the OSCE, the observation group had a significantly higher mean score than the control group [9 (8, 10) points vs. 8 (7, 9) points, Z=-6.10, P<0.001]. The distribution difference across different score ranges between the two groups was also statistically significant ( Z=-5.94, P<0.001). Stratified analyses by sex and neurological theory test score demonstrated significantly higher mean scores in the observation group than in the control group ( P<0.001). The multiple linear regression analysis indicated an independent positive correlation between the novel teaching model and OSCE score ( P<0.001). The results of the questionnaires revealed that in the observation group, 98.57% reported that they were satisfied with the teaching model, and 90.72% reported that they accomplished the core teaching objectives; core competencies including knowledge and skills, communication and collaboration, and professionalism were improved; additionally, the participants of the observational group highly endorsed the practical content, the logical structure and richness of instruction, and the active classroom learning environment. Conclusions:The diversified teaching model integrated with the affective-cognitive theory significantly improves proficiency in core clinical skills across different groups of neurology clerks.

Gastric cancer, a highly malignant tumor, has seen a persistent rise in global incidence in recent years. Claudin 18.2, a protein with highly specific expression in gastric cancer, has emerged as a prominent research target in therapeutic development. The overexpression of Claudin 18.2 in gastric cancer cells and its abnormal surface exposure provide novel opportunities for targeted and immunotherapeutic interventions. Therapeutic approaches targeting Claudin 18.2 have shown promising initial results in clinical trials, primarily including monoclonal antibodies and chimeric antigen receptor T-cell therapies. The authors systematically summarize the biological characteristics, mechanism of action, clinical research progress, and future treatment prospects and challenges of Claudin 18.2.

BACKGROUND:Cellular autophagy maintains metabolism and in vivo homeostasis through the autophagosome-lysosome degradation pathway,which is closely related to the impaired cell death and functional recovery of distal neurons after spinal cord injury,and targeting cellular autophagy to promote the functional recovery of the spinal cord after spinal cord injury is a promising therapeutic direction.OBJECTIVE:To summarize the role of cellular autophagy in spinal cord injury,related regulatory mechanisms of cellular autophagy and therapeutic strategies.METHODS:PubMed and CNKI databases were searched with the search terms of"spinal cord injury,autophagy,regulatory mechanisms,autophagy pathway,therapeutic target"in English and Chinese,respectively.A total of 133 English and 4 Chinese articles were included for review.RESULTS AND CONCLUSION:(1)Autophagy,a form of programmed cell death,has been shown to play a crucial role in the progression and treatment of spinal cord injury.Most studies have shown that moderate activation or promotion of autophagy promotes neurological recovery by decreasing inflammatory responses and apoptosis.A few studies have reported that excessive activation of autophagy,on the contrary,impedes neurological recovery following spinal cord injury.(2)After spinal cord injury,PI3K/AKT/mTOR,MAPK,AMPK and p53 signaling pathways,and factors such as Beclin-1,ATG and LC3 regulate the initiation and development of cell autophagy in a positive or negative manner.(3)Promoting or inhibiting autophagy may be a promising therapeutic strategy to modulate the pathogenesis of traumatic spinal cord injury.And the drugs amlodipine,metformin,and minocycline,the Chinese medicines hawthorn leaf total flavonoids,betulinic acid,oxidized ginseng saponins,acupuncture,and extracellular vesicles of different cellular origins,exosomes and reactive oxygen species-responsive composite fibers as activators of cellular autophagy attenuate secondary injury in response to spinal cord injury by activating cellular autophagy,while the drugs insulin-like growth factor 1 and eladavone,Chinese medicine ginseng saponin,acupuncture,and hydrogel carrying basic fibroblast growth factor as inhibitors of cellular autophagy promote functional recovery after spinal cord injury by inhibiting excessive cellular autophagy.(4)The related regulators of cellular autophagy are interconnected,and the bi-directional effects of cellular autophagy on spinal cord injury make it necessary to further explore the dominant factors that regulate cellular autophagy.(5)Research on the use of autophagy as a therapeutic target for spinal cord injury is mostly carried out in animal models,but there are no autophagy-related drugs used in the clinical practice,and their safety and efficacy need to be further investigated in the clinical field.

BACKGROUND:Currently,spinal cord injury imposes a huge psychological and economic burden on patients and the National Health Service.The prevention,treatment,and rehabilitation of spinal cord injury have become an important topic in the field of medicine.Therefore,it is important to explore new effective therapeutic strategies based on an in-depth understanding of the underlying molecular mechanisms of spinal cord injury.OBJECTIVE:To review the research progress on the mechanism of action of mesenchymal stem cell-derived exosomes loaded with various miRNAs in improving the function of spinal cord injury,and based on the current status of clinical translation,to put forward a few thoughts and outlooks on their clinical use.METHODS:The first author searched CNKI and PubMed databases using"mesenchymal stem cells,exosomes,spinal cord injury,miRNA,pathophysiology,clinical translation,clinical trials,good manufacturing practice"as Chinese and English search terms.The types of literature included treatises and reviews,and the language types were English and Chinese.Finally,72 papers were screened and analyzed.RESULTS AND CONCLUSION:(1)This article outlines the biological properties of exosomes and the advantages that they can serve as good vectors for loading miRNAs.A variety of miRNAs mediated by mesenchymal stem cell-derived exosomes mainly promote the recovery of neuronal function by regulating the expression of nerve regeneration-associated proteins,repressing RAS homologous gene family member A,activating cyclophosphoadenosine effector-binding proteins,and signaling and transcriptional activation proteins 3,and regulating phosphoinositide and tensin homologue/programmed cell death factor 4 pathways.Inflammatory responses were improved by regulating endoplasmic reticulum-to-nucleus signaling 1,expression of interferon regulatory factor 5,Toll-like receptor 4/nuclear factor-kappa B pathway,and down-regulating related pro-inflammatory factors.Angiogenesis was promoted by inhibition of germination-associated domain 1-containing EVH1 and phosphatidylinositol 3-kinase regulatory subunit 2.(2)Further comparative analyses revealed that miR-216-5p,miR-145-5p,and miR-146b improved inflammatory responses by regulating related pathways.Combining these miRNAs may produce more significant effects;hypoxic preconditioning may be a preconditioning method to increase the efficacy of exosomal therapy.(3)There are currently no clinical trials applying mesenchymal stem cell-derived exosomes to spinal cord injury,which is related to the need to meet good manufacturing practices before they can be put into clinical use.Challenges such as the need for large-scale,high-volume cell production,the lack of an efficient and uniform method for isolating exosomes,and the need to pass a strict regulatory approval mechanism prior to clinical use have impeded the clinical entry.(4)miRNAs have great potential as exosomal contents of mesenchymal stem cells in the treatment of spinal cord injury,and their mechanism of action should be explored in depth as well as accelerated to the clinical trial stage in order to provide a new and effective method for the treatment of spinal cord injury.

Efficient screening constitutes a prerequisite for the research,development,generalization and application of characteristic external treatment techniques with Miao medicine featured by miscellaneous content as well as the coexistence of essence and dross,while the bottleneck lies in the absence of a screening indicators.Based on own features and current development status of characteristic external treatment techniques with Miao medicine,this study proposed a"three-stage"design thought involving qualitative exploration,tool research and development,and quantitative research in exploratory sequential design under the framework of mixed methods research.The present study systematically integrated qualitative and quantitative research methods as well as data to compensate for the shortcomings of single research paradigm-sourced data that was insufficient to comprehensively address various difficulties in the establishment of a screening indicators.It is expected to provide ideas and methodological references for establishing a screening indicators for characteristic external treatment techniques with Miao medicine.