Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Objective:To investigate, for multi-sensitized allergic rhinitis (AR) patients allergic to dust mites combined with other allergens (pollen, mold, animal dander, etc.), whether the single dust mite subcutaneous immunotherapy (SCIT) can improve the specific symptoms caused by other allergens in the patients, and to analyze the relationship between the effectiveness of symptom improvement in these patients and the type, quantity and severity of the allergens.Methods:A multicenter retrospective study was conducted to collect mul-sensitized AR patients from allergy or respiratory departments of 5 hospitals who received house dust mite allergen preparation SCIT for 12 to 36 months and met other inclusion and exclusion criteria from February to July 2024. General clinical data were collected and the perennial or seasonal symptoms before and after treatment were evaluated with visual analogue scale (VAS) to assess whether there was an perennial or allergen-specific symptom improvement (VAS score decrease ≥30%), by which the patients were divided into effective group and ineffective. R software was used to analyze the differences between groups by using Fisher′s exact test and Mann-Whitney U test. Results:A total of 62 patients were enrolled, and the treatment were effective in 39 of them, with an effective rate of 62.9%. For allergen-specific symptoms, the median age of the effective group was higher than that of the ineffective group (12 years old vs. 8 years old, P=0.039), and the effective rate in dust mite specific immunoglobin E (sIgE) grade ≤5 group was higher than that in sIgE grade >5 group (81.6% vs. 45.5%, P=0.008), and the effective rate of mold sIgE grade ≤2 group was higher than that of sIgE grade >2 group (83.3% vs. 28.6%, P=0.045), and there was no statistically significant correlation between the other allergen grades and the effective rate ( P>0.05). For perennial symptoms, the effective rate in the mold grade ≤2 group was higher than that in the sIgE grade >2 group (91.3% vs. 28.6%, P=0.010), and there was no statistically significant correlation between the other allergen grades and the effective rate ( P>0.05). There was no significant correlation between the treatment effectiveness of perennial or allergen-specific symptoms and the number of combined allergens, the grade of skin test, and the difference between the grade of combined allergens and that of dust mites ( P>0.05). Conclusion:Among the patients with multi-sensitized AR allergic to dust mites included in this study, single dust mite SCIT is effective in some of them, and for allergen-specific symptoms, the effective group was elder, and dust mite sIgE grade 6 and mold sIgE grade ≥2 was related to the low effective rate of SCIT. The present results are insufficient for selecting single or multiple AIT in any type of multi-sensitized patients.

Designation of ideological and political teaching of Medical Immunology courses focuses on"cultivate talent for Party and the State",and adheres to goal of"build morality and cultivate people".From perspective of big ideology and politics,with basic foundation of"major guiding,disciplines supporting and curriculum shaping",principle of"six combinations"is applied to con-struct ideological and political cases of Medical Immunology courses,to create an infiltrating teaching pattern,which simultaneously cultivate talent for the Party and the State,and forms a synergistic effect of professional course learning and ideological and political learning.

Objective To establish a flow cytometry method for detecting C1s protein on platelet surface and preliminarily explore its potential application value in the auxiliary diagnosis of primary immune thrombocytopenia(ITP).Methods C1s-conjugated 2 μm car-boxylated magnetic beads(C1s beads)were prepared and used as quality control particles.Fluorescein isothiocyanate(FITC)-labeled anti-C1s antibody was employed as the detection antibody to develop a flow cytometric assay for detecting C1s protein expression on platelets.The intra-assay and inter-assay precision,as well as the dilution linearity of the method,were evaluated.Subsequently,the expression levels of C1 s protein on the surface of platelets were compared among the ITP group,the non-ITP thrombocytopenia group,and the healthy control group.Results Light microscopy showed that both unconjugated carboxylated magnetic beads(blank beads)and C1s-conjugated beads were uniformly dispersed without aggregation.Under fluorescence microscopy,C1s beads exhibited strong yellow-green fluorescence,whereas the blank beads showed no fluorescence signal.The established flow cytometry assay exhibited ac-ceptable precision,with intra-assay coefficient of variation(CV)values of 7.02％,7.12％,and 3.91％for low,medium,and high con-centrations of C1s beads,respectively,and inter-assay CV values of 13.49％,6.15％,and 0.78％,respectively.The dilution linearity was satisfactory,coefficient of determination(R2)=0.998 8.Clinical sample testing revealed that the proportion of C1s-positive plate-lets in ITP group(2.56±0.79)％was significantly higher than that in healthy control group(0.23±0.18)％and the non-ITP thrombo-cytopenia control group(0.22±0.10)％,with statistically significant differences(both P＜0.05).Conclusion This study successfully established a stable and reliable flow-cytometry method for quantifying C1s expression on platelet surface and preliminarily demonstrated that C1s expression is significantly elevated on platelets of ITP patients,suggesting that C1s could serve as a potential auxiliary diag-nostic marker for ITP.

Objective:To construct a rat model of non-alcoholic fatty liver disease(NAFLD)by choline-deficient high fat diet(CDHFD),and to observe the association between feeding cycle and antioxidant pathway.Methods:The study lasted 16 weeks and was divided into 4 cycles.Detection of pathological changes and expression of antioxidant enzymes in rats liver in different cycles.Results:The early stage of liver steatosis and inflammation in model rats was 2～4 weeks,non-alcoholic steatohepatitis(NASH)stage was 4～8 weeks,and liver fibrosis progression was 8～16 weeks.Mechanistic studies had shown that the expressions of antioxidant enzymes Nrf2,SOD and GSH-Px in the liver of NAFLD rats gradually decreased with the extension of the feeding cycle.Conclusion:Different modeling cycles can successfully induce the pathological changes of steatosis,inflammation and liver fibrosis in rat liver,and the pathological changes are time-dependent with the expressions of antioxidant enzymes.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

Objective:To analyze the changes and significance in clinical cardiac indicators of early cardiac myocardial dysfunction and cardiac substructure dose during conventional radiotherapy for N 2-N 3 non-small cell lung cancer (NSCLC) with mediastinal lymph node metastases. Methods:The data of 34 NSCLC patients with lymph node metastases in regions 4-8 admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to August 2023 were observed and analyzed. All patients were treated with volumetric modulated arc therapy with a prescribed dose of 60-70 Gy. Cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at 6 time points: within 1 week before radiotherapy ( t0); when the cumulative radiotherapy dose reaches 20 Gy ( t20), 40 Gy ( t40), 60 Gy ( t60) during radiotherapy; within 1 week after radiotherapy ( tp); 1 month after radiotherapy( tp1). Left ventricular global longitudinal strain (LVGLS) and left atrial global longitudinal strain (LAGLS) were assessed at 4 time points: t0, t40, tp and tp1, respectively. The changes in cardiac indicators at different time points during radiotherapy and their correlation with substructure doses were analyzed using analysis of variance, linear regression analysis, and Pearson correlation. Results:The correlation between cardiac substructure dose and mean heart dose (MHD) in the study cohort in the descending order was as follows: left ventricle ( B=0.43, P<0.001), right ventricle ( B=0.37, P=0.002), left atrium ( B=0.16, P<0.001), and right atrium ( B=0.15, P=0.001). There were significant differences in the changes of LVGLS and LAGLS across different time points ( F=3.13, P=0.029; F=17.18, P<0.001). At 1 month after radiation, LAGLS was significantly decreased compared to pre-radiation levels ( P=0.009), whereas no significant difference was observed in LVGLS ( P=1.000). No significant differences were observed in the changes of cTnT and NT-proBNP across different time points (all P>0.05). Significant correlations were identified between cTnT and right ventricle mean dose at t40 ( r=0.38, P=0.025), as well as between NT-proBNP and right atrium mean dose at t60 and tp ( r=0.54, P=0.001; r=0.41, P=0.016). Conclusions:At present, there is no significant difference between the sensitive serum markers of myocardial injury and LVGLS in detecting early myocardial injury. LAGLS may hold substantial clinical value. There is uncertainty about radiation injury and repair of various cardiac substructures.

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*