Objective: To analyze the epidemiological characteristics and influencing factors of severe fever with thrombocytopenia syndrome (SFTS) in Zhejiang Province from 2019 to 2023, so as to provide the reference for strengthening SFTS prevention and control. Methods: Data on laboratory-confirmed SFTS cases in Zhejiang Province from 2019 to 2023 were collected through the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System. Meteorological data, geographic environment and socioeconomic factors during the same period were collected from the fifth-generation European Centre for Medium-Range Weather Forecasts, Geospatial Data Cloud, and Zhejiang Statistical Yearbook, respectively. Descriptive epidemiological methods were used to analyze the epidemiological characteristics of SFTS from 2019 to 2023, and a Bayesian spatio-temporal model was constructed to analyze the influencing factors of SFTS incidence. Results: A total of 578 SFTS cases were reported in Zhejiang Province from 2019 to 2023, with an annual average incidence of 0.23/105. The peak period was from May to July, accounting for 52.60%. There were 309 males and 269 females, with a male-to-female ratio of 1.15∶1. The cases were mainly aged 50-<80 years, farmers, and in rural areas, accounting for 82.53%, 77.34%, and 75.43%, respectively. Taizhou City and Shaoxing City reported more SFTS cases, while Shaoxing City and Zhoushan City had higher annual average incidences of SFTS. The Bayesian spatio-temporal interaction model showed good goodness of fit. The results showed that mean temperature (RR=1.626, 95%CI: 1.111-2.378) and mean wind speed (RR=1.814, 95%CI: 1.321-2.492) were positively correlated with SFTS risk, while altitude (RR=0.432, 95%CI: 0.230-0.829) and population density (RR=0.443, 95%CI: 0.207-0.964) were negatively correlated with SFTS risk. Conclusions SFTS in Zhejiang Province peaks from May to July. Middle-aged and elderly people and farmers are high-risk populations. Taizhou City, Shaoxing City, and Zhoushan City are high-incidence areas. Mean temperature, mean wind speed, altitude, and population density can all affect the risk of SFTS incidence.

ObjectiveTo analyze the protective effect of different types of influenza vaccines (InfV) against influenza A among the individuals aged between 3‒17 years old, and to provide a scientific basis for the prevention and control of influenza in the future. MethodsA retrospective cohort study was conducted to collect data on the incidence and InfV vaccination of the individuals aged between 3‒17 years during the influenza epidemic season from 2022 to 2023. Vaccine effectiveness (VE) was calculated, and a log-binomial regression model was used to calculate the corrected VE. ResultsThe incidence rate of influenza in InfV vaccinated and un-vaccinated groups was 7.32% (1 937/ 26 446) and 9.65% (4 421/45 837), respectively. After adjusting for age and gender factors, the unadjusted VE (95%CI) was 54.57% (52.24%‒56.78%). The unadjusted VE (95%CI) was 53.66% (50.36%‒56.74%) for males and 55.60% (52.24%‒58.72%) for females, respectively. The unadjusted VE (95%CI) for the age group of 3‒ years, 6‒ years, 9‒ years, 12‒ years, and 15‒17 years were 64.08% (60.89%‒67.01%), 57.40% (53.71%‒60.80%), 57.77% (52.49%‒62.47%), 24.36% (9.49%‒36.79%), and 24.09% (-17.59%‒51.00%), respectively. The unadjusted VE (95%CI) for quadrivalent split-virion inactivated influenza vaccine, trivalent split-virion inactivated influenza vaccine, trivalent subunit influenza vaccine, and trivalent live attenuated influenza vaccine were 53.84% (51.32%‒56.24%), 62.17% (56.28%‒67.26%), 79.83% (69.94%‒86.46%), and 31.59% (19.07%‒42.18%), respectively. ConclusionThe InfV used during the 2022‒2023 influenza season had a good protective effect against influenza A among the individuals aged between 3‒17 years old, especially in those aged between 3‒11 years old.

Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder characterized by recurrent and unpredictable episodes of edema. Currently, there is no effective cure available, which seriously affects patients′ quality of life. Gene therapy intervenes in the disease at the genetic level, offering new perspectives for the treatment of HAE. This article summarizes the current research progress in gene therapy for HAE, including gene editing, transgenic therapy, and RNA therapy. It aims to draw the attention of researchers in this field, and provide references and insights for clinicians.

Aconitum (Ranunculaceae) has a long-standing history in traditional Chinese medicine (TCM), where it has been widely used to treat conditions such as rheumatoid arthritis (RA), myocardial infarction, and heart failure. However, the potency of Aconitum alkaloids, the primary active components of Aconitum, also confers substantial toxicity. Therefore, assessing the efficacy and toxicity of these Aconitum alkaloids is crucial for ensuring clinical effectiveness and safety. Metabolomics, a quantitative method for analyzing low-molecular-weight metabolites involved in metabolic pathways, provides a comprehensive view of the metabolic state across multiple systems in vivo. This approach has become a vital investigative tool for facilitating the evaluation of their efficacy and toxicity, identifying potential sensitive biomarkers, and offering a promising avenue for elucidating the pharmacological and toxicological mechanisms underlying TCM. This review focuses on the applications of metabolomics in pharmacological and toxicological studies of Aconitum alkaloids in recent years and highlights the significant role of metabolomics in exploring compatibility detoxification and the mechanisms of TCM processing, aiming to identify more viable methods for characterizing toxic medicinal plants.
Aconitum/metabolism* ; Metabolomics/methods* ; Alkaloids/metabolism* ; Humans ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional

Rice is the world's largest food crop, and its yield and quality are directly related to food security and human health. Grain size, as one of the important factors determining the rice yield, has been widely concerned by breeders and researchers for a long time. To decipher the regulatory mechanism of rice grain size, we obtained a multi-tiller, dwarf, and small-grain mutant htd1 by ethyl methanesulfonate (EMS) mutation from the Japonica rice cultivar 'Zhonghua 11' ('ZH11'). Genetic analysis indicated that the phenotype of htd1 was controlled by a single recessive gene. Using the mutation site map (Mutmap) method, we identified the candidate gene OsHTD1, which encoded a carotenoid cleavage dioxygenase involved in the biosynthesis of strigolactone (SL). The SL content in htd1 was significantly lower than that in 'ZH11'. Cytological analysis showed that the grain size of the mutant decreased due to the reductions in the length and width of glume cells. The function of htd1 was further verified by the CRISPR/cas9 gene editing technology. The plants with the gene knockout exhibited similar grain size to the mutant. In addition, gene expression analysis showed that the expression levels of multiple grain size-related genes in the mutant changed significantly, suggesting that HTD1 may interact with other genes regulating grain size. This study provides a new theoretical basis for research on the regulatory mechanism of rice grain size and potential genetic resources for breeding the rice cultivars with high yields.
Oryza/growth & development* ; Mutation ; Edible Grain/growth & development* ; Alleles ; Plant Proteins/genetics* ; Dioxygenases/genetics* ; Lactones/metabolism* ; Gene Expression Regulation, Plant ; Genes, Plant ; Gene Editing ; CRISPR-Cas Systems ; Phenotype

Objective:To investigate the expression of protein kinase D2(PRKD2)in bladder cancer(BLCA)tissue using bioinformatics analysis method and its effect on the prognosis of BLCA patients,and to clarify the role of PRKD2 in the occurrence and development of BLCA.Methods:The data from 9 normal bladder samples,19 BLCA paracancerous samples,and 407 BLCA tumor samples were downloaded from the UCSC Cancer Genome Database.The Mann-Whitney U test was applied to analyze the difference in expression of PRKD2 mRNA in BLCA tumor and normal bladder tissues,and the Human Protein Atlas(HPA)database was used for proteomic validation.DESeq2 package in R software was applied to screen the differentially expressed genes(DEGs)in BLCA tissue in PRKD2 low-and high-expression groups.The co-expression heatmaps of PRKD2 were plotted using the ggplot2 package,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used for functional annotation analysis and pathway enrichment analysis of DEGs,and Gene Set Enrichment Analysis(GSEA)was used to obtain the gene sets that were significantly enriched for DEGs.The BLCA samples were divided into low-and high-expression groups according to the expression level of PRKD2,and the correlations between PRKD2 expression and immune cell infiltration in the BLCA patients were analyzed with GSVA package.The relationship between PRKD2 and prognosis of BLCA patients was further analyzed using the survival package and the survminer package.The PRKD2 gene mutations in BLCA tissue were analyzed using the cBioPortal database.The cystitis,bladder polyp and BLCA tissues were collected,and the expression levels of interleukin-17F(IL-17F)protein in BLCA and control tissues were detected using immunohistochemical staining technique.Results:PRKD2 was highly expressed in a variety of malignant tumors,and the expression levels of PRKD2 mRNA and protein in BLCA tissue were significantly increased compared with those in normal bladder tissue(P＜0.05).Single gene differential analysis of PRKD2 yielded a total of 1 058 DEGs,of which a total of 29 genes were up-regulated and 1 029 were down-regulated.The results of GO functional enrichment analysis showed that DEGs were mainly enriched in the biological process(BP),such as chemical stimuli involved in sensory perception,Cajal body,and endopeptidase inhibitor activity.The results of KEGG pathway analysis showed that DEGs were mainly enriched in the pathway of Staphylococcus aureus infection and the pathway of maturity onset diabetes of the young.GSEA analysis showed that DEGs were mainly enriched in the Notch signaling pathway,the retinoic acid-inducible gene-Ⅰ(RIG-Ⅰ)-like receptor signaling pathway,the cytoplasmic DNA screening pathway,the base excision repair signaling pathway,natural killer(NK)cell-mediated cytotoxicity signaling pathway and T cell receptor signaling pathway.The results of immune infiltration analysis indicated that the expression of PRKD2 was positively correlated with five types of cells,such as activated dendritic cells(aDC),NK CD56dim cells and central memory T cells(Tcm)(P＜0.05),and negatively correlated with three types of immune cells,including macrophages,effector memory T cells(Tem)and plasmacytoid dendritic cells(pDC)(P＜0.05).The clinical characteristic subgroup analysis results showed that the expression levels of PRKD2 mRNA in BLCA patients who were over 70 years old and developed lymphovascular invasion were decreased(P＜0.05);the overall survival(OS),disease-specific survival(DSS)and progression-free interval(PFI)in the BLCA patients with PRKD2 high expression were significantly longer than those with PRKD2 low expression(P＜0.05).The univariate and multivariate Cox analyses indicated that distant metastasis,primary therapy outcome and clinicopathologic stage were the important factors affecting BLCA prognosis.About 9％patients had PRKD2 gene mutations,including missense mutation,gene amplification,mRNA low or high expression,and multi-motif mutation.The immunohistochemistry results showed that the expression level of IL-17F protein in BLCA tissue was significantly higher than that in cystitis tissue(P＜0.05).Conclusion:The expression level of PRKD2 in BLCA tissue is obviously increased,which could up-regulate the expression of IL-17F protein,and the decrease of PRKD2 protein expression may be a potential factor for the poor prognosis of BLCA patients.

Objective:To analyze the role of interleukin-33(IL-33)in the occurrence and development of glioma and its related mechanism by bioinformatics technology,and to validate it through histopathological experiments,and to discuss the possibility of IL-33 as an auxiliary marker for the diagnosis and treatment of brain glioma.Methods:The glioblastoma multiforme/lower grade glioma(GBMLGG)case data were downloaded from the UCSC XENA database,including data of 689 glioma samples,5 paracancerous samples,and 1 152 normal brain tissue samples;Mann-Whitney U test was used to analyze the difference in the expression of IL-33 mRNA between the GBMLGG samples and the normal brain tissues;according to the expression level of IL-33 in GBMLGG tissue,the tumor samples were divided into IL-33 low expression group and IL-33 high expression group;the Human Protein Atlas(HPA)was used to validate the difference in the protein expression of IL-33 in the GBMLGG samples;the R language DESeq2(v.1.36.0)package was used to screen the differentially expressed genes(DEGs)in the GBMLGG tumor case samples;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were used to perform pathway analysis on the DEGs;Gene Set Enrichment Analysis(GSEA)was used to discuss the pathways significantly enriched by IL-33 in the GBMLGG tissues;GSVA package was used to analyze the immune infiltration in the GBMLGG samples;survival package and survminer package were used to analyze the effect of IL-33 expression level on the survival of the patients in different clinical subgroups of GBMLGG;univariate and multivariate Cox proportional hazards regression models were used to analyze the relationship between IL-33 expression and the clinicopathological characteristics of the GBMLGG patients;the GBMLGG and control tissue samples were collected;immunohistochemical staining was used to detect the expression levels of IL-33 and its receptor suppression of tumorigenicity 2(ST2)in the GBMLGG and normal brain tissue samples.Results:The expression levels of IL-33 mRNA and protein in the GBMLGG tissues were significantly increased compared with those in normal brain tissues;there were 634 DEGs in total between the IL-33 low and high expression groups,including 283 up-regulated DEGs and 351 down-regulated DEGs;the GO functional enrichment analysis and KEGG signaling pathway enrichment analysis results showed that the DEGs were associated with biological behaviors such as activation of the classical pathway of complement,immunoglobulin complex formation,and mediated immunoglobulin receptor binding;in the course of GBMLGG development,high expression of IL-33 could degrade valine,leucine,and isoleucine,induce limonene and pinene degradation,promote propanoate metabolism,and simultaneously activate the Leishmania infection pathway,NOD-like receptor signaling pathway,and allograft rejection pathway;the infiltration levels of dendritic cell(DC)and mast cell in the IL-33 high expression group were higher than those in IL-33 low expression group;the infiltration levels of eosinophil,helper T cell,and central memory T cell(Tcm)were lower than those in IL-33 low expression group;the expression level of IL-33 was positively correlated with the infiltration of γδT cell(Tgd),helperT cell,macrophage,eosinophil,Tcm,and effector memory T cell(Tem)(P＜0.05);it was negatively correlated with the infiltration levels of DC,natural killer cell(NK),CD8+T cell,and CD56bright NK cell(P＜0.05).There were no significant differences in the overall survival(OS),disease-specific survival(DSS),and disease-free interval(DFI)of the GBMLGG patients between IL-33 high expression group and IL-33 low expression group(P＞0.05);the clinical subgroup analysis results showed that the expression level of IL-33 in oligodendrocytoma tissues was lower than those in astrocytoma and oligoastrocytoma tissues,and the expression level of IL-33 in glioblastoma tissues was higher than that in oligodendroglioma tissues.World Health Organization(WHO)stage and age were risk factors affecting the prognosis of the GBMLGG patients,and IDH mutation and primary treatment effect were protective factors affecting the prognosis;The immunohistochemical staining results showed that compared with normal brain tissues,the expression levels of IL-33 and its receptor ST2 proteins in the malignant glioma tissues were significantly increased(P＜0.05),and their expression levels were positively correlated in both normal brain tissues and malignant glioma tissues(P＜0.05).Conclusion:The expression level of IL-33 in the glioma tissue is significantly increased,and high expression of IL-33 may be a potential factor for poor prognosis in the glioma patients.

Objective:To investigate the therapeutic efficacy and safety of conditioning regimen with oral melphalan in tandem autologous hematopoieticstem cell transplantation (ASCT) for patients with malignant plasma cell diseases.Methods:A retrospective case series study was conducted. The clinical data of 13 patients with malignant plasma cell diseases who underwent tandem ASCT between October 2019 and March 2024 in the First Affiliated Hospital of Xi'an Jiaotong University were collected. Compared with the use of intravenous melphalan as conditioning regimen for the first ASCT, hematopoietic reconstruction after transplantation, the therapeutic effects, adverse reactions after drug usage and survival of conditioning regimen with oral melphalan after tandem ASCT were analyzed.Results:Among the 13 patients, there were 10 males and 3 females, with a median age [ M ( Q1, Q3)] of 53 (48, 61) years; 11 cases were multiple myeloma and 2 cases were plasma cell leukemia. Before the first ASCT, tandem ASCT was performed 2-6 months later. The median reconstruction time of neutrophils after the first and second ASCT were both 9 (9, 10) d, and the median reconstruction time of platelets after the first and second ASCT were both 10 (9, 11) d, and there were no statistically significant differences in reconstruction rate of granulocytes on day 9 [69.2% (9/13) vs. 61.5% (8/13)] and platelets on day 10 [46.2% (6/13) vs. 53.8% (7/13)] between the first and second transplantation (all P > 0.05). There were 4 cases of strict complete remission (sCR), 3 cases of complete remission (CR), 4 cases of very good partial remission (VGPR), and 2 cases of partial remission (PR) before the first ASCT. After the first ASCT 1 month later, 1 case achieved VGPR, 1 case achieved PR, 11 cases achieved sCR; all 13 patients achieved sCR at 6 months after second ASCT. Compared with conditioning regimen of intravenous melphalan for the first ASCT, the non-hematological adverse reactions such as nausea (7 cases vs. 9 cases), vomiting (4 cases vs. 13 cases), diarrhea (4 cases vs. 13 cases) and oral mucositis (2 cases vs. 9 cases) in the conditioning regimen of oral melphalan after the second ASCT was reduced, and the differences were statistically significant (all P < 0.01). After the 2 transplantation conditioning regimen with melphalan, Ⅳ degree myelosuppression occurred in 13 cases. After the second ASCT, the median follow-up time was 14 (10, 22) months, 7 patients received maintenance therapy containing lenalidomide, 3 patients received maintenance therapy containing bortezomib, 2 patients received pomalidomide maintenance therapy, and 1 patient received maintenance therapy containing CD38 monoclonal antibody. At the last follow-up, all patients survived, among which 6 multiple myeloma patients relapsed; and the median recurrence time was 13 (10, 22) months after the second ASCT. The estimated 5-year progression-free survival rate was 28.6%. Conclusions:Conditioning regimen with oral melphalan for the second ASCT is safe and well tolerated, and it may further improve the efficacy of the first transplantation.

BACKGROUND: Lung cancer is the leading malignancy in China in terms of both incidence and mortality. With increased health awareness and the widespread use of low-dose computed tomography (CT), early diagnosis rates have been steadily improving. Surgical intervention remains the primary treatment option for early-stage lung cancer, and video-assisted thoracoscopic surgery (VATS) has become a common approach due to its minimal invasiveness and rapid recovery. However, post-discharge recovery remains incomplete, underscoring the importance of postoperative care. Traditional follow-up methods, lack standardization, consume significant medical resources, and increase the burden of the patients. Artificial intelligence (AI)-driven disease management platforms offer a novel solution to optimize postoperative follow-up. This study followed 463 lung cancer surgery patients using an AI-based platform, aiming to identify common postoperative issues, propose solutions, improve quality of life, reduce recurrence-related costs, and promote AI integration in healthcare. METHODS: Using the AI disease management platform, this study integrated educational videos, collaboration between healthcare teams and AI assistants, daily health logs, health assessment forms, and personalized interventions to monitor postoperative recovery. The postoperative rehabilitation status of the patients was assessed by the Leicester Cough Questionnaire (LCQ-MC). Two independent t-test and one-way ANOVA were used to analyze the causes of postoperative cough in lung cancer. RESULTS: Most issues occurred within 7 d post-discharge, significantly declined on 14 d post-discharge. Factors such as gender, smoking history, and surgical approaches were found to influence cough recovery. The incidence of cough on 7 d post-discharge in females was higher than that in males (P<0.01), while the incidence of cough on 14 d post-discharge in elderly patients was lower than that in young patients (P=0.03). The AI-based platform effectively addressed cough, pain, and sleep disturbances through phased interventions. CONCLUSIONS The AI-based platform significantly enhanced postoperative management efficiency and the self-care capabilities of the patients, particularly in phased cough management. Future integration with wearable devices could enable more precise and personalized postoperative care, further advancing the application of AI technology across multidisciplinary healthcare domains.
Humans ; Lung Neoplasms/rehabilitation* ; Male ; Female ; Middle Aged ; Aged ; Patient Discharge ; Artificial Intelligence ; Adult ; Postoperative Care ; Postoperative Period ; Disease Management ; Quality of Life

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.