Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

OBJECTIVE To explore the prognostic significance of the prognostic nutrition index(PNI)in patients with hypopharyngeal cancer undergoing surgical treatment.METHODS Clinical and pathological data of 117 patients with hypopharyngeal carcinoma who underwent surgical treatment at the center of Otolaryngology Head and Neck Surgery of Beijing Friendship Hospital,Capital Medical University from May 2014 to June 2022 were collected.The prognostic significance of hematological indicators such as PNI and neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),and systemic immune inflammation index(SⅡ)were investigated.The time-dependent receiver operating characteristic(tROC)curves were used to analyze the sensitivity and specificity of various hematological indicators and to determine their optimal cutoffvalues.The Kaplan-Meier method was used to plot the postoperative survival curve,and the Cox regression model was used to analyze the correlation between PNI and overall survival(OS)and disease-free survival(DFS).RESULTS 117 patients were enrolled in this cohort,of which 109 were clinically classified as advanced stage(Ⅲ-Ⅳ).63 cases underwent surgery to preserve laryngeal function.The 5-year OS is 46.07％.According to the analysis of the tROC curve,the optimal cutoffvalue for PNI is 46.75.PNI is correlated with tumor T staging,NLR,PLR,and SⅡ.Kaplan Meier univariate analysis showed that PNI was significantly correlated with OS and DFS(P<0.05).In addition,tumor N-stage,postoperative complications,adverse pathological prognostic factors,NLR,PLR,and SⅡ were all significantly correlated with OS(P<0.05).Tumor N-stage,laryngeal preservation,postoperative complications,NLR,and SⅡ were significantly correlated with DFS(P<0.05).The Cox multivariate analysis results indicated that PNI,tumor N-stage,and postoperative complications were independent factors affecting OS and DFS.CONCLUSION Preoperative PNI,tumor N-stage,and postoperative complications are independent risk factors for OS and DFS in patients with hypopharyngeal carcinoma.PNI,as a prognostic indicator for predicting hypopharyngeal cancer patients,is superior to other hematological indicators.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective:To develop a network-structured clinical pathway grouping rule based on the principles and methods of China healthcare security diagnosis related groups(CHS-DRG), for references for optimizing clinical pathway management.Methods:From August to November 2024, this study constructed a network-structured clinical pathway management framework, followed the grouping principles of CHS-DRG, and developed a network-structured clinical pathway grouping rule through literature analysis and expert discussions. 54 clinical specialists from the sample hospital were organized and grouped according to the rule for the normal magnification cases(139 218 cases) of DRG medical insurance settlement in the hospital in 2023. Using a stratified random sampling method, 205 physicians from 54 clinical specialties in the hospital were selected to quantitatively evaluate the rationality, homogeneity, and clarity of the grouping results. The Likert 5-level scoring method was wsed to assign scores.Results:The network-structured clinical pathway grouping rule and nomenclature was established. A total of 341 main pathways and 35 sub-pathways covering 169 adjacent diagnosis related groups were formed. The quantitative assessment scores for rationality, homogeneity, and clarity were 4.90, 4.87 and 4.87 points, respectively.Conclusions:The network-structured clinical pathway grouping rule based on CHS-DRG had good, feasibility and standardization, and could meet the practical needs of clinical applications.

Objective:To explore the relationship between childhood trauma and anxiety symptom among high school students,as well as the mediating role of social support and the moderating role of stressful life events.Methods:A total of 3 075 high school students were selected.The Short Form of the Childhood Trauma Questionnaire(CTQ-SF),Social Support Rate Scale(SSRS),Adolescent Self-Rating Life Events Checklist(ASLEC)and Chinese Secondary School Students Anxiety Scale(CSSAS)were used to assess the levels of child-hood trauma,social support,stressful life events,and anxiety symptom severity.The SPSS PROCESS 3.3 macropro-gram was used to test the mediating effect and moderated mediation effect.Results:The CTQ-SF scores were posi-tively correlated with CSSAS scores(r=0.26,P＜0.001).The SSRS scores and the subjective support(S2)scores and availability of support(S3)scores in the SSRS played partial mediating effects between CTQ-SF scores and CSSAS scores.The mediating effects were 0.11(95％CI:0.09-0.12,P＜0.001),0.08(95％CI:0.06-0.09,P＜0.001),0.04(95％CI:0.03-0.06,P＜0.001)respectively,which accounted for 44.00％,32.00％,16.00％of the total effect respectively.The ASLEC scores moderated the relationship between CTQ-SF scores and CSSAS scores(β=0.02,P=0.044),and the relationship between SSRS scores and CSSAS scores(β=0.08,P＜0.001).Conclusion:Among high school students,social support and the subjective support and availability of support in so-cial support play partial mediating effects between childhood trauma and anxiety symptom,and stressful life events moderates the relationship between childhood trauma,social support and anxiety symptom.

Objective:This study aimed to construct a prediction model for diagnosis of proliferative lupus nephritis based on a machine learning algorithm. Additionally, a user-friendly platform was developed to propose a non-invasive method to assist the pathologic classification of lupus nephritis.Methods:A retrospective analysis was conducted on clinical and pathological data of lupus nephritis patients confirmed by renal biopsy at Zhengzhou University People′s Hospital from January 2017 to August 2023. The study population was randomly divided into training and testing sets in a 7∶3 ratio. Utilizing six machine learning algorithms, classification models were developed. The predictive performance of each model was assessed using metrics such as accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC). The optimal model, once identified, was deployed as a web-based calculator for convenient model application. SPSS 25.0 and R 4.2.2 were used to analyze the data.Results:The study included a total of 212 patients, with 138 cases with proliferative lupus nephritis and 74 cases with non-proliferative lupus nephritis. The AUC values for the six models, namely logistic regression, decision tree, random forest, support vector machine, extreme gradient boosting, and light gradient boosting machine, were 0.79, 0.62, 0.79, 0.88, 0.81, and 0.77, respectively; the accuracy rates were 82.54%, 65.08%, 74.60%, 85.71%, 69.84%, 71.43%, respectively. Among them, the support vector machine model demonstrated the optimal performance. This model had deployed as a web-based calculator. Based on feature importance scores, the top 10 influencing factors were identified, including anti URNP antibody, immunoglobulin G, serum globulin, estimated glomerular filtration rate, anti Smith antibody, BMI index, anti dsDNA antibody, uric acid, anti-Rib.p antibody, and gender.Conclusion:A prediction model based on machine learning algorithms was successfully established, and a web calculator was developed to offer a simple and non-invasive method for diagnosing proliferative lupus nephritis. This can assist clinicians in evaluating the risk-benefit ratio of kidney biopsy in patients with lupus nephritis.

[Objective] To resolve the ambiguities of HLA genotyping generated by next generation sequencing (NGS) using nanopore sequencing technology. [Methods] A total of 38 samples with ambiguous HLA genotyping by NGS in our laboratory were collected, and HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1 and -DPB1 loci in these samples were amplified using primers in the same commercial NGS HLA genotyping kit, then subjected to third-generation library construction, and sequenced on the nanopore sequencer. The sequencing data were converted into Fastq files and analyzed by software, and the genotypes of 11 HLA loci were obtained. The ambiguities were counted directly. [Results] The high-resolution genotyping at the second domain of 11 HLA loci of 38 samples using the third generation sequencing (TGS) were consistent with the results of the NGS method at a rate of 100%. The genotypes for the HLA-A, -B, -C, -DRB3, -DRB4, -DQA1 and -DPA1 loci by TGS were all only one result, and the discrimination rate for ambiguities of the HLA-A, -B, -C, and -DQA1 loci (all caused by the difficulty in phasing due to the short NGS read length) was 100%. Among the HLA-DRB1, -DRB5, -DQB1 and -DPB1 loci, the discrimination rate of TGS for the ambiguities caused by non-amplification of exon 1 was 0% and by the short NGS read length was 100%. [Conclusion] Nanopore technology was used to identify the ambiguities of 11 HLA loci in this study, and the ambiguities caused by the short read length disadvantage of the NGS method could be solved effectively and the accuracy of HLA genotyping would be improved.

Avian infectious bronchitis(IB),a rapidly spreading and acute disease in chickens,is caused by the infectious bronchitis virus(IBV).IB is characterized by its remarkable genetic varia-bility.IBV has a high degree of mutation,and the existing means of immunization often fail to a-chieve good results,seriously affecting the development of the domestic poultry industry.This ar-ticle offers a comprehensive review of the current understanding of the immune response to IBV,focusing on three key areas:non-specific immunity,mucosal immunity,and specific immunity.By dissecting these aspects,the aim is to provide a theoretical reference for the study of the immune mechanism of IBV.

The endoplasmic reticulum quality control(ERQC)system is a core mechanism for maintaining cellular homeostasis,which primarily mediates the degradation of misfolded proteins in the endoplasmic reticulum(ER)through the ER-associated degradation(ERAD)and ER autophagy(ER-phagy)pathways.Tripartite motif 13(TRIM13)is a protein located on the ER membrane,which plays a critical role in ERAD via its E3 ubiquitin ligase activity.TRIM13 also acts as a non-classical ER-phagy receptor to mediate the occurrence of ER-phagy.TRIM13 has recently received extensive attention in the field of ERQC.Here we review the structure and function of TRIM 13 and the mechanisms by which it contributes to ERQC,and summarize its abnormal expression and regulatory role in diseases,with the aim of providing new strategies for the treatment of related diseases.

Objective : To explore the central role of interleukin(IL)-25 in allergy of eosinophil asthma. Methods : Forty 4-5 week-old C57BL/6 mice were used in this study(n=10). Mice were randomly divided into 4 groups: WT+shRNA NT group, WT+HDM group, IL-25 shRNA+IL-25 group, and IL-25 shRNA+IL-25+HDM group. According to each group′s treatment requirement, mice were treated with house dust mite and/or IL-25 by intranasal infusion. HE staining and PAS staining were used for lung tissue section staining and pathological analysis. The levels of type 2 cytokines in bronchoalveolar lavage fluid(BALF) were determined by ELISA. Flow cytometry(FCM) was used to determine the number of type 2 helper T(Th2) cells, the group 2 innate lymphoid cells(ILC2) and eosinophils in lung tissues. Mice were treated with FITC-labeled DQ-ovalbumin(DQ-OVA) by intranasal infusion to determine the antigen presentation ability of eosinophils infiltrated in the lungs. Results : HE staining and PAS staining results showed that, compared with WT+shRNA NT group, a large amount of mucus and a large number of eosinophil infiltration were found in the lungs, and subcutaneous thickening of inflammatory airway were observed in the pulmonary vessels, alveolar ducts and the whole alveoli in IL-25 shRNA+IL-25+HDM group. In the IL-25 shRNA+IL-25 group, only a small amount of mucus and a small amount of eosinophil infiltration were found in the lungs, and a small amount of subcutaneous thickening of inflammatory airway were observed in pulmonary vessels, alveolar ducts and the whole alveoli. There was no significant difference in WT+HDM group. Compared with WT+shRNA NT group, the levels of IL-25, IL-4,IL-5,IL-13, IL-33 and interferon-γ(IFN-γ) in BALF significantly increased; the levels of infiltrated Th2, ILC2 and eosinophils in the lung significantly increased; the fluorescence levels of FITC-labeled DQ-OVA in eosinophils infiltrated in lungs significantly increased in IL-25 shRNA+IL-25+HDM group(P<0.05). IL-25 shRNA+IL-25 group mice also showed an increase in the above measurements, but the amplitude were limited(P<0.05). WT+HDM group had no significant difference. Conclusion IL-25 plays an essential role in the allergy and eosinophil antigen presentation processes in eosinophil asthma mice.