Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.
Dermatitis, Atopic/genetics* ; Interleukins/metabolism* ; Animals ; Methicillin-Resistant Staphylococcus aureus/immunology* ; Mice ; Keratinocytes/microbiology* ; Humans ; Interleukin-33/immunology* ; Inflammation/microbiology* ; Staphylococcal Infections/microbiology* ; Disease Models, Animal ; Hypersensitivity/microbiology* ; Mice, Inbred C57BL

Background and Aims:Microsatellite-stable(MSS)colorectal cancer(CRC)generally exhibits poor responsiveness to immune checkpoint inhibitors(ICIs),and effective immunotherapy strategies remain lacking.Anti-angiogenic agents such as bevacizumab(BEV)can improve the tumor immune microenvironment and act synergistically with ICIs.This multicenter real-world study compared the efficacy of different immunotherapy-based combination regimens in patients with MSS/MSI-L/pMMR advanced CRC,aiming to identify the optimal treatment strategy.Methods:A total of 100 patients with MSS/MSI-L/pMMR advanced CRC who received systemic treatment between November 2019 and February 2025 at four tertiary hospitals in Hunan,China,were retrospectively enrolled.Patients were classified into six treatment groups:chemotherapy alone,chemotherapy+targeted therapy,immunotherapy alone,immunotherapy+chemotherapy,immunotherapy+targeted therapy,and immunotherapy+chemotherapy+targeted therapy.The primary endpoints were overall survival(OS)and progression-free survival(PFS),while secondary endpoints were objective response rate(ORR)and disease control rate(DCR).Additionally,among patients receiving immunotherapy,subgroup analysis was performed according to BEV administration.Results:Among all 100 patients,the immunotherapy+chemotherapy+targeted therapy group achieved the highest ORR(32.0%)and DCR(76.0%)and was the only regimen yielding a complete response(CR).Compared with chemotherapy or immunotherapy alone,the triplet regimen significantly improved OS(P<0.05);although PFS improvement did not reach statistical significance,a clear late-stage separation of survival curves was observed.In the immunotherapy subgroup,BEV-containing regimens achieved markedly better outcomes than non-BEV regimens,with DCR of 75.0%vs.48.8%,median OS of 18.9 vs.11.5 months,and median PFS of 13.8 vs.7.2 months(all P<0.001).Cox regression analysis showed that compared with chemotherapy alone,the triplet regimen significantly reduced the risk of death(HR=0.11)and disease progression(HR=0.25)(both P=0.002).Vascular invasion was identified as an adverse prognostic factor for PFS(HR=3.0,P=0.007).Conclusion:This multicenter real-world study demonstrated that combining immunotherapy with chemotherapy and targeted therapy significantly improves DCR and survival outcomes in patients with MSS/MSI-L/pMMR advanced CRC,with BEV-containing triplet regimens providing the most pronounced benefit.BEV may enhance immune responsiveness by modulating the tumor microenvironment and promoting effector T-cell infiltration,offering a promising therapeutic direction for"immune-cold"CRC.Prospective randomized studies are warranted to further validate its clinical value and define appropriate patient populations.

Background and Aims:Microsatellite-stable(MSS)colorectal cancer(CRC)generally exhibits poor responsiveness to immune checkpoint inhibitors(ICIs),and effective immunotherapy strategies remain lacking.Anti-angiogenic agents such as bevacizumab(BEV)can improve the tumor immune microenvironment and act synergistically with ICIs.This multicenter real-world study compared the efficacy of different immunotherapy-based combination regimens in patients with MSS/MSI-L/pMMR advanced CRC,aiming to identify the optimal treatment strategy.Methods:A total of 100 patients with MSS/MSI-L/pMMR advanced CRC who received systemic treatment between November 2019 and February 2025 at four tertiary hospitals in Hunan,China,were retrospectively enrolled.Patients were classified into six treatment groups:chemotherapy alone,chemotherapy+targeted therapy,immunotherapy alone,immunotherapy+chemotherapy,immunotherapy+targeted therapy,and immunotherapy+chemotherapy+targeted therapy.The primary endpoints were overall survival(OS)and progression-free survival(PFS),while secondary endpoints were objective response rate(ORR)and disease control rate(DCR).Additionally,among patients receiving immunotherapy,subgroup analysis was performed according to BEV administration.Results:Among all 100 patients,the immunotherapy+chemotherapy+targeted therapy group achieved the highest ORR(32.0%)and DCR(76.0%)and was the only regimen yielding a complete response(CR).Compared with chemotherapy or immunotherapy alone,the triplet regimen significantly improved OS(P<0.05);although PFS improvement did not reach statistical significance,a clear late-stage separation of survival curves was observed.In the immunotherapy subgroup,BEV-containing regimens achieved markedly better outcomes than non-BEV regimens,with DCR of 75.0%vs.48.8%,median OS of 18.9 vs.11.5 months,and median PFS of 13.8 vs.7.2 months(all P<0.001).Cox regression analysis showed that compared with chemotherapy alone,the triplet regimen significantly reduced the risk of death(HR=0.11)and disease progression(HR=0.25)(both P=0.002).Vascular invasion was identified as an adverse prognostic factor for PFS(HR=3.0,P=0.007).Conclusion:This multicenter real-world study demonstrated that combining immunotherapy with chemotherapy and targeted therapy significantly improves DCR and survival outcomes in patients with MSS/MSI-L/pMMR advanced CRC,with BEV-containing triplet regimens providing the most pronounced benefit.BEV may enhance immune responsiveness by modulating the tumor microenvironment and promoting effector T-cell infiltration,offering a promising therapeutic direction for"immune-cold"CRC.Prospective randomized studies are warranted to further validate its clinical value and define appropriate patient populations.

Drug-induced liver injury is caused by the drug itself and/or its metabolites during drug use or occurs due to hypersensitivity or reduced tolerance to the drug in a particular body type. In the last three years of the diagnosis and treatment of coronavirus disease 2019 （COVID-19）， antiviral drugs have played a very important role， but there are many reports on liver injury caused by anti-COVID-19 drugs in China and globally， with unknown pathogenesis of liver injury caused by such drugs. This article reviews the research advances in the types of antiviral drugs for COVID-19 and their mechanism in inducing liver injury， in order to promote the rational use of antiviral drugs.

Fertility preservation technology provides an effective method of protecting fertility resources for young patients with malignant tumors, allowing them to offspring after their fertility is impaired. However, the development of this technology has caused many social and ethical controversies. From the perspective of ethics, this paper discussed the ethical issues faced by young female patients in the implementation of fertility preservation, including whether it is necessary to preserve fertility, the ownership of the preserved fertility resources and the fair and equitable distribution of health resources involved in its implementation process, and identifies these issues and controversies from ethical view. In order to eliminate public doubts and misunderstandings about the technology of fertility preservation, ethical principles of benefit and non-harm, informed consent, prudent application, and ethical supervision have to be followed in the process of providing fertility preservation services, so as to promote the further development and application of fertility preservation technology.

Objective To understand the research status,hotspots and trends of Wuzhuyu Decoction;To provide reference for relevant research.Methods The literature related to Wuzhuyu Decoction was retrieved from CNKI,VIP,Wanfang Data and CBM databases from the establishment to February 28,2023.NoteExpress 3.6 was used to merge and deduplicate,and the author,organization and keywords were mapped and interpreted by CiteSpace 6.1.R6 software.Results A total of 822 articles were included,and the number of publications showed a wave upward trend;the top journals were New Chinese Medicine,Henan Traditional Chinese Medicine and Sichuan Traditional Chinese Medicine;the main research institutions were Beijing University of Chinese Medicine,China Academy of Chinese Medical Sciences and Shandong University of Traditional Chinese Medicine;a total of 566 authors were involved,and the authors with more publications included Wang Zhimin(12),Gong Muxin(9)and Bi Kaishun(5);high-frequency keywords included"headache","Shang Han Lun","TCM therapy"and so on.Conclusion Wuzhuyu Decoction is effective in treating chronic gastritis,hypertension and other primary diseases,which is a research hotspot in this field.It is a research trend in this field to explore its active components by high performance liquid chromatography and explain its action mechanism and target at the molecular level.

Objective To understand the research status,hotspots and trends of animal medicinal materials;To provide reference for future research.Methods The literature related to animal medicinal materials was retrieved from CNKI,VIP,Wanfang Data and CBM from January 1,2000 to April 30,2023.NoteExpress 3.6 was used to merge and deduplicate,and the author,institution and keywords were mapped and interpreted by CiteSpace 6.1.R6 software.Results A total of 1 169 articles were included,and the overall publication quantity in this field showed a stable fluctuation trend;the top journals were Lishizhen Medicine and Materia Medica Research,China Journal of Chinese Materia Medica and Modern Chinese Medicine;the main research institutions were China Academy of Chinese Medical Sciences,Changchun University of Chinese Medicine and Chinese Academy of Medical Sciences;a total of 676 authors were involved,and the authors with more publications included Zhang Hui(22),Liu Rui(15),Lin Zhe and Ma Shuangcheng(14);high-frequency keywords included"identification","TCM resources","clinical application"and so on.Conclusion Resource survey of animal medicinal materials,standardized breeding of medicinal animals,development of alternatives to rare medicinal animal resources,and construction of quality standard system for animal medicinal materials are the research hotspots in this field.The basic research of pharmacodynamic substances of animal medicinal materials based on the integrated analysis strategies of proteomics,peptideomics and transcriptomics,and the revelation of the signaling pathways and targets of animal medicinal materials from the molecular biology level are the research trends in this field.

Objective To investigate the oral health status and caries related influence factors in 3-year-old children in Shanghai.Methods A total of 1 709 3-year-old children in 29 kindergartens from Huangpu,Xuhui,Jiading,and Jing'an districts were selected for the survey by random cluster sampling in 2021.Oral clinical examinations and questionnaires were conducted according to the criteria of the Fourth National Oral Health Epidemiological Survey.EpiData 3.1 software was used to build the database,analyse the prevalence of caries and the mean dmft.Multivariate logistic regression model was used to evaluate the influence factors of caries.Results A total of 1 709 questionnaires were collected in this survey,of which 1469 were complete questionnaires,with a valid rate of 86.0%.The prevalence of caries was 27.8%,and the mean dmft was 1.09±2.49.The caries filling rate was 8.2%.Frequency of eating sweet food(P<0.001),eating before bedtime(P=0.016),a history of dental discomfort(P<0.001),no history of dental visits within six months(P=0.015),a history of dental visits for therapeutic purposes(P<0.001),caries status of mothers(P<0.001),and parent's education level(P=0.012)were influence factors of caries in 3-year-old children.Conclusion The prevalence of caries in 3-year-old children in Shanghai is lower than the national level,but more improvement is needed.The frequency of eating sweet food,eating before bedtime,and parent's cognition of oral health are the influence factors of children's caries.

Objective To investigate the distribution and antimicrobial resistance of clinical isolates in the First Affiliated Hospital of Xi'an Jiaotong University in 2022 for rational use of antibiotics in clinical practice.Methods Nonduplicate clinical isolates were collected from January 1,2022 to December 31,2022.Antimicrobial susceptibility testing was carried out using Kirby-Bauer method and automated systems.The data were analyzed using WHONET 5.6 software and interpreted according to the Clinical and Laboratory Standards Institute(CLSI)breakpoints(2021 Edition).Results Of the 8 638 clinical isolates,gram negative bacteria and gram positive bacteria accounted for 60.8％(5 253/8 638)and 39.2％(3 385/8 638),respectively.The prevalence of methicillin-resistant strains was 33.0％in S.aureus(MRSA),75.8％in S.epidermidis(MRSE),and 51.9％in other coagulase-negative Staphylococcus(MRCNS).No staphylococcal strains were found resistant to vancomycin.The prevalence of vancomycin-resistant E.faecium was 0.6％,and no vancomycin-resistant E.faecalis was found.E.faecalis strains showed higher resistance rate to linezolid(5.2％)than E.faecium(0.7％).The prevalence of carbapenem-resistant Enterobacterales(CRE)was 7.9％,specifically 12.1％for carbapenem-resistant K.pneumoniae(CRKP)and 1.6％for carbapenem-resistant E.coli(CREC).The prevalence of carbapenem-resistant P.aeruginosa(CRPA)and carbapenem-resistant A.baumannii(CRAB)was 30.9％and 77.0％,respectively.Conclusions Clinical microbiology laboratories should strengthen the collection and testing of clinical specimens from the sites of infection in order to improve pathogenic diagnosis and antimicrobial resistance surveillance.This is conducive to the rational use of antibiotics and reduce the further spread of multidrug-resistant bacteria.