1.Serpina3c Mitigates Adipose Tissue Inflammation by Inhibiting the HIF1α-Mediated Endoplasmic Reticulum Overoxidation in Adipocytes
Yu JIANG ; Jia-Qi GUO ; Ya WU ; Peng ZHENG ; Shao-Fan WANG ; Meng-Chen YANG ; Gen-Shan MA ; Yu-Yu YAO
Diabetes & Metabolism Journal 2026;50(1):62-76
Background:
Visceral white adipose tissue (vWAT) inflammation is a critical pathology of obesity-caused heart damage and is closely associated with adipocyte endoplasmic reticulum (ER) dysfunction. Serine (or cysteine) peptidase inhibitor, clade A, member 3C (Serpina3c) has been identified as an adipokine with anti-vWAT inflammatory effects. However, it remains unclear whether Serpina3c deficiency promotion of vWAT inflammation involves adipocyte ER dysfunction and whether it further contributes to heart damage in obesity.
Methods:
Wild type and Serpina3c knockout (Serpina3c–/–) mice were fed a high-fat diet (HFD) for 12 weeks. An adeno-associated virus (AAV) was injected locally into epididymal white adipose tissue (eWAT) of Serpina3c–/– mice to induce eWAT-adipocyte- specific overexpression of Serpina3c (AAV-Serpina3c) or knockdown of hypoxia-inducible factor 1α (AAV-shHIF1α). In vitro experiments were performed in 3T3-L1 adipocytes.
Results:
Serpina3c–/– mice exhibited more severe eWAT, serum and heart inflammation after HFD feeding. Consistently, these adverse phenotypes were mitigated in AAV-Serpina3c and AAV-shHIF1α mice. Mechanistically, ER oxidoreductase 1α (Ero1α) and protein disulfide isomerase (PDI) family members PDIA3 and PDIA4 were found to be target genes of HIF1α. In the obese mice, Serpina3c deficiency caused adipocyte more hypertrophy, and activated HIF1α-Ero1α/PDI mediated ER overoxidation and ER stress in eWAT. Subsequently, this led to increased adipocyte apoptosis and chemokine production and decreased adiponectin expression, which promoted macrophage infiltration and M1 polarization in eWAT, thus exacerbating eWAT inflammation and ultimately facilitating serum and distal heart inflammation.
Conclusion
These findings indicate that Serpina3c is a significant regulator of adipocyte ER redox homeostasis, thus highlighting Serpina3c as a potential therapeutic target for obesity-related eWAT inflammation and heart damage.
2.Efficacy of 3D-nnU-Net model of CT virtual monoenergetic images,non-linear blending images and mixed-energy images for automatically segmenting advanced gastric cancer
Bowen LIU ; Xiaoxiao WANG ; Chao LU ; Zhixuan WANG ; Jiulou ZHANG ; Zehui WANG ; Siyuan LU ; Xiaoyue JIANG ; Mingyao QI ; Donggang PAN ; Xiuhong SHAN
Chinese Journal of Medical Imaging Technology 2025;41(5):753-758
Objective To compare the segmenting efficacy of automatic segmentation models for advanced gastric cancer(AGC)on CT virtual monoenergetic images(VMI),non-linear blending images(NLBI)and mixed-energy images(MEI)based on 3D-nnU-Net.Methods Totally 216 cases of AGC were retrospectively enrolled,among them 185 cases were used to construct,train and validate models and divided into training set(n=154)and test set(n=31)at the ratio of 5∶1,while the other 31 cases were used as validation set to evaluate the generalization of the models.The 70 keV energy level VMI(VMI70 keV),NLBI and MEI were reconstructed with whole-abdominal dual-energy mode venous CT,and automatic segmentation models of AGC,including VMI70 keV,NLBI and MEI models were constructed using 3D-nnU-Net,respectively.Taken manually segmented results as golden standards,the efficacy of each model for segmenting all lesions and T2 stage lesions in test set and validation set were evaluated using Dice similarity coefficient(DSC),intersection over union(IoU)and average symmetric surface distance(ASSD).Results For all lesions in test and validation sets,DSC of 3 models were all>0.80.DSC and IoU of VMI70 keV and NLBI models were both higher,while their ASSD was lower than those of MEI model(all P<0.05).For T2 stage AGC in both test set and validation set(each n=5),DSC of MEI model was lower than that of VMI70 keV and NLBI models(both P<0.05),while IoU of MEI model was lower than that of VMI70 keV model(P<0.05),and its ASSD was higher than that of NLBI model(P<0.05).Conclusion All 3D-nnU-Net-based VMI70 keV,NLBI and MEI models could effectively segment AGC on dual-energy CT images,and the segmentation efficacy of the former two were better.
3.Clinical Features and Prognosis of Primary Tonsil Lymphoma
Dan LUO ; Qi-Miao SHAN ; Hua DING ; Jiao LIU ; Zi-Qing HUANG ; Feng ZHU
Journal of Experimental Hematology 2025;33(4):1042-1046
Objective:To investigate the clinical features and prognostic factors of primary tonsil lymphoma(PTL).Methods:The clinical data of 41 patients diagnosed with PTL and treated in the Affiliated Hospital of Xuzhou Medical University from January 2015 to December 2022 were collected and retrospectively analyzed.Their clinical features and prognostic factors were analyzed.Results:All the 41 patients were newly diagnosed with PTL,and the median age of onset was 58(19-85)years.Among them,19 patients started with pharyngeal pain,12 patients presented with dysphagia,8 patients presented with pharyngeal mass,and 2 patients presented with blurred articulation.The most common pathological type was diffuse large B-cell lymphoma(24 cases,58.54%).All patients received chemotherapy,and 3 patients were combined with hematopoietic stem cell transplantation.Among 41 patients,11(26.83%)achieved complete response,14(34.15%)achieved partial response,and the total response rate was 60.98%(25/41).The median follow-up time was 37(6-107)months,the 5-year overall survival(OS)rate was 70.81%and 5-year progression-free survival(PFS)rate was 66.20%.Univariate analysis showed that B symptoms,Ki-67,β2-MG and IPI score had significant effects on PFS and OS of patients(all P<0.05).Multivariate analysis showed that IPI score was an independent risk factor for PFS and OS of patients(P<0.05).Conclusion:The clinical manifestations of PTL lack specificity,and the prognosis is relatively good.Most patients can achieve long-term survival after treatment.IPI score is related to the prognosis.
4.Construction and validation of nomogram diagnosis model for EBV co-infection in children with Mycoplasma pneumoniae pneumonia
Qi LIU ; Hui MENG ; Mingfeng SHAN
Chinese Journal of Nosocomiology 2025;35(12):1824-1828
OBJECTIVE To construct a nomogram diagnosis model for Epstein-Barr virus(EBV)co-infection in children with Mycoplasma pneumoniae pneumonia(MPP).METHODS Clinical data of 427 children with MPP ad-mitted to the Children's Hospital of Nanjing Medical University from Jul.2020 to Jul.2024 were retrospectively analyzed.The children were divided into a modeling group(n=299)and a validation group(n=128).The model-ing group was further categorized into an MPP group(n=235)and an MPP co-infection group(n=64)based on EBV infection status.Multivariate logistic regression was used to identify risk factors for EBV co-infection in chil-dren with MPP,and a nomogram diagnosis model was constructed.The diagnostic value and clinical application value of the model were evaluated by receiver operating characteristic(ROC)curves,calibration curves and deci-sion curve analysis(DCA).RESULTS The white blood cell count(WBC)in the MPP co-infection group was(12.37±2.32)× 109/L,significantly higher than that in the MPP group(P<0.05).Platelet count(PLT)and hemoglobin(Hb)levels were(197.95±32.85)× 109/L and(102.58±13.74)g/L,respectively,lower than those in the MPP group(P<0.05).Additionally,the MPP co-infection group exhibited higher proportions of fe-ver duration ≥10 days,dyspnea and pleural effusion compared to the MPP group(P<0.05).Multivariate logistic regression analysis revealed that WBC(OR=1.514),PLT(OR=0.970),Hb(OR=0.959),fever duration(OR=4.790),dyspnea(OR=3.777)and pleural effusion(OR=4.795)were significantly associated with EBV infection in children with MPP(P<0.05).The nomogram demonstrated that when the total model score reached 219 points,the probability of EBV infection in children with MMP was 0.9.The areas under the ROC curve for the modeling group and validation group were 0.882(95%CI:0.836-0.927)and 0.943(95%CI:0.902-0.984),respectively,with sensitivities of 76.56%and 91.30%,respectively,and specificities of 82.55%and 85.71%,respectively.The Hosmer-Lemeshow goodness-of-fit test showed x2=4.124,P=0.846 for the modeling group and x2=4.203,P=0.838 for the validation group.DCA curve indicated high clinical applica-tion value of the model.CONCLUSIONS WBC,PLT,Hb levels,fever duration,dyspnea and pleural effusion have diagnostic values for EBV co-infection in children with MPP.The nomogram model constructed based on these six factors demonstrates excellent diagnostic performance.
5.Comparing the efficacy and safety of cyclophosphamide and ritux-imab in idiopathic membranous nephropathy
Shan WU ; Qi YU ; Qin YANG ; Wenjing WANG ; Yangyang ZHANG ; Yan LIU ; Yanlang YANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(5):657-664
AIM:To explore the efficacy and safe-ty of two drugs in diagnosed idiopathic membra-nous nephropathy(IMN).METHODS:A retrospec-tive study was conducted on 113 patients diag-nosed with IMN by renal biopsy or PLA2R antibody positive at the department of nephrology,yijishan hospital,wannan medical college from november 2019 to July 2024,of whom 55 received cyclophos-phamide treatment and 58 received rituximab treatment,and follow-up was ≥6 months.RESULTS:At 6 months,38 patients(69.09%)in the cyclophos-phamide treatment group and 36 patients(62.07%)in the rituximab treatment group had achieved a combined response(complete or partial response).At 12 and 18 months,there was no statistical differ-ence in the combined response rate between the two groups(70.83%vs.83.87%,P=0.186 and 73.68%vs.73.68%,P=1.000),but at 12 months,the combined response rate in the rituximab group was higher than that in the cyclophosphamide group.In IMN patients with eGFR<60 mL/(min·1.73 m2),rituximab significantly improved renal function(P=0.008).Over the entire follow-up peri-od,the total number of adverse events was higher in the cyclophosphamide group than in the ritux-imab group(57 vs..45),and the incidence of non-serious adverse events was higher than in the ritux-imab group(P=0.039).CONCLUSION:The efficacy of rituximab in the treatment of IMN is not inferior to that of cyclophosphamide,and it has better safety.Rituximab improved renal function better than cy-clophosphamide in patients with eGFR<60 mL/(min·1.73 m2)IMN.
6.Establishment of an indicator system for entrustable professional activities in general practice stage of pediatric specialist physician training
Shan LI ; Danyu SONG ; Xifang RU ; Xiaoyu LIU ; Lili LIU ; Xin QI ; Mi YAO ; Jianguang QI
Chinese Journal of Medical Education Research 2025;24(4):466-472
Objective:To construct an indicator system for entrustable professional activities (EPAs) in the general practice enhancement stage of pediatric specialist physician training.Methods:A draft indicator system for EPAs in the general practice enhancement stage of pediatric physician training was developed through core EPAs working group discussion, literature review, nominal group discussion, and expert consultation. Subsequently, the indicator system was preliminarily implemented and revised.Results:The core EPAs working group consisted of nine specialist physician trainers. In the initial brainstorming stage, a "potential list" of 30 activities was established. After literature review and collation, the draft indicator system included eight EPAs. Through nominal group discussion, the connotation of the draft was enriched, and the importance of the EPAs was ranked and modified. Finally, through expert consultation, the EPAs for the general practice enhancement stage of pediatric specialist physician training were determined. These included basic operations for the treatment of critically ill children, identification and management of critical illnesses, referral of critically ill children, perioperative management, in-hospital consultation, medical and teaching management and system improvement, doctor-patient communication and dispute handling, and response to public health events. During the preliminary implementation stage, a total of nine specialist physicians who participated in the training were evaluated. Based on the problems found in the pre-evaluation, the indicators of EPAs were revised, and a corresponding curriculum training system was developed.Conclusions:Through multiple rounds of nominal group discussion and expert consultation, the indicator system for EPAs in the general practice enhancement stage of pediatric specialist physician training was formulated. The system was preliminarily implemented and revised, and a curriculum system was constructed.
7.Carthami Flos-Lycopodii Herba ameliorates cartilage inflammation in knee osteoarthritis by inhibiting TLR4/MyD88/NF-κB signaling pathway
Li-kai YU ; Zi-shan SU ; Di TIAN ; Ze-en WANG ; Shang-qi LIU ; Pei-min WANG ; Nong-shan ZHANG
Chinese Pharmacological Bulletin 2025;41(7):1382-1390
Aim To verify the mechanism of action of Carthami Flos-Lycopodii Herba in treating KOA carti-lage inflammation based on network pharmacology and in vitro and in vivo experiments.Methods The effec-tive ingredients of Carthami Flos-Lycopodii Herba were screened through the database,the core targets of"drug disease"were analyzed,and pathway enrichment analy-sis and molecular docking verification were conducted.Experimental verification:Primary chondrocytes were extracted from mice and divided into the control group,IL-1β group,treatment group,and treatment+TLR4 agonist group.CCK-8 method was used to screen the optimal intervention concentration of Carthami Flos-Ly-copodii Herba.ELISA was used to detect the content of inflammatory factors in chondrocytes.Western blot was employed to detect the protein expression related to cellular pathways.Subsequently,a KOA mouse model was constructed using the DMM method.After admin-istration,the knee joint injury of mice was evaluated u-sing safranin O-green staining.ELISA was used to de-tect the levels of inflammatory factors in serum.West-ern blot was employed to detect collagen Ⅱ,MMP13,Aggrecan,and apoptosis related protein expression in cartilage tissue.TUNEL staining was used to detect the apoptosis rate of cells.Results A total of 26 active ingredients of Carthami Flos-Lycopodii Herba were screened,as well as 123 potential targets for treating KOA.The enrichment analysis results indicated that it mainly involved mechanisms such as Toll like receptors and cell apoptosis.The experimental results showed that Carthami Flos-Lycopodii Herba alleviated the in-flammatory response of chondrocytes and affected the expression of pathway related proteins.Compared with KOA mice,safflower stretched muscle grass could im-prove cartilage damage and reduce the concentration of serum inflammatory factors,regulate the expression of collagen Ⅱ,MMP13,Aggrecan,and apoptosis related proteins in cartilage tissue,and reduce the fluorescence intensity of TUNEL staining in the tissue.Conclusions Carthami Flos-Lycopodii Herba can improve KOA cartilage inflammation,and its mechanism may be relat-ed to the TLR4/MyD88/NF-κB signaling pathway.
8.Construction of a clinical competence index system for general practitioners based on CIPP evaluation model
Shan CAI ; Qi HAN ; Lin LIU ; Qipei GAO ; Chaowei TIAN
Chinese Journal of Medical Education Research 2025;24(3):315-319
Objective:To explore the construction of clinical competence index system for general practitioners based on CIPP(context evaluation, input evaluation, process evaluation, product evaluation) evaluation model.Methods:Based on the CIPP evaluation model, a research team was established to conduct a literature review. Research articles were retrieved, screened, and analyzed to formulate the primary clinical competence index system for general practitioners based on CIPP evaluation model and the expert consultation questionnaire. The Delphi method was employed to finalize the clinical competence index system for general practitioners based on CIPP evaluation model.Results:A total of 24 experts from grade A tertiary hospitals in several provinces and cities in China participated in two rounds of consultation. The effective recovery rate for both rounds was 100.00%. The authority coefficients were 0.905 and 0.912, respectively. After the consultations, the coefficients of variation of indexes at all levels were <0.25. The Kendall's W of all indexes ranged between 0.769 and 0.814 in the first round and between 0.867 and 0.905 in the second round of expert consultation ( P<0.001). The final clinical competence index system for general practitioners based on CIPP evaluation model included 4 first-level indexes, 12 second-level indexes, and 42 third-level indicators. Conclusions:The clinical competence index system for general practitioners based on CIPP evaluation model established in this study has reference significance for further research on the training assessment and evaluation index system of clinical competence for general practitioners in China, and has important practical significance for the evaluation tool of clinical work performance of general practitioners.
9.The construction and risk stratification study of a hepatocellular carcinoma prognosis model based on automatic segmentation and radiomics of gadoxetate disodium-enhanced MRI
Can YU ; Qi ZHANG ; Yueqi WANG ; Tiantian FAN ; Huiying LI ; Shan CONG ; Yang ZHOU
Chinese Journal of Radiology 2025;59(6):681-687
Objective:To explore the efficacy of deep learning-based automatic segmentation technology in the segmentation of hepatocellular carcinoma (HCC) lesions using gadoxetate disodium-enhanced MRI (EOB-MRI), and to investigate the prognostic value of radiomics analysis in predicting patient outcomes.Methods:This was a cross-sectional, retrospective study that collected data from 352 patients with solitary HCC who underwent imaging at the Harbin Medical University Cancer Hospital between June 2015 and May 2023. The patients were randomly divided into a training set ( n=213) and a validation set ( n=139) in a 3∶2 ratio using weighted random sampling. Two radiologists manually annotated the lesions. Hepatobiliary-phase EOB-MRI images were standardized, and six deep learning models,nnU-Net, nnFormer, UnetR, Swin-UnetR, UnetR++ and MedNeXt,were trained for automatic segmentation on the training set. The segmentation performance was evaluated on the validation set, and the segmentation efficacy was assessed using the Dice coefficient and 95% Hausdorff distance (HD 95), identifying of the optimal model. Radiomics features were extracted from both manual and automatic segmentation regions, and the radiomics score (Radscore) was calculated to stratify patients into high-risk and low-risk groups. Kaplan-Meier curves and log-rank tests were used to analyze the differences in relapse-free survival (RFS) and overall survival (OS) between the different stratified groups. Results:Among the automatic segmentation models, the MedNeXt model performed best in the validation set, with a Dice coefficient of 76.0%, HD 95 of 7.2, and a segmentation success rate of 90.6% (126/139). The nnFormer model was the second-best, with a Dice coefficient of 75.3%, HD 95 of 10.1, and a segmentation success rate of 89.9% (125/139). Other models showed Dice coefficients ranging from 66.3% to 74.1%. A MedNext-nnF model was established by combining the MedNeXt and nnFormer models, achieving a Dice coefficient of 78.2%, HD 95 of 5.9, and a segmentation success rate of 92.1% (128/139) in the validation group. After constructing the automatic segmentation radiomics prognostic model, patients were stratified by Radscore. Both manual and automatic segmentation models showed statistically significant differences in RFS and OS between different risk groups ( P<0.001). Conclusions:The Mednext-nnF fusion model enables efficient and automated segmentation of HCC lesions in EOB-MRI. The radiomics model constructed based on the automated segmentation demonstrates strong performance in predicting and stratifying prognostic risk.
10.Comparison of active constituent contents and their biological activities of Buzhong Yiqi Recipe with different dosage forms
Yan-ran HE ; Jing WANG ; Jia-qiang XU ; Zhao-zhao XIA ; Ying-jiao LIU ; Zi-shu DONG ; Liang-shan MING ; Hong-ning LIU ; Qi-meng FAN
Chinese Traditional Patent Medicine 2025;47(2):357-364
AIM To compare total sugar,total protein,total phenol,total flavonoid,calycosin-7-O-β-D-glucoside,liquiritin,lobetyolin,quercetin,isoferulic acid,hesperidin,glycyrrhizic acid contents and their antioxidant activities,hypoglycemic activities of big honey pill,small honey pill,water pill,concentrated pill,granule,mixture and decoction of Buzhong Yiqi Recipe.METHODS Anthraquinone-sulfuric acid method,Coomassie brilliant blue method,Folin-phenol colorimetry method,sodium nitrite-aluminum nitrate method and HPLC were adopted in the content determination of total sugar,total protein,total phenol,total flavonoid and seven constituents,respectively,after which the scavenging capacities,reducing powers on DPPH·free radical,ABTS+free radical,hydroxyl free radical,and inhibition capacity on α-glucosidase activity were detected.Subsequently,correlation analysis was performed.RESULTS Total sugar,total protein,total phenol and total flavonoid contents demonstrated significant differences among different dosage forms(P<0.05,P<0.01).Calycosin-7-O-β-D-glucoside,glycyrrhizin,codonoside and quercetin displayed the highest contents in the decoction,while those of isoferulic acid,hesperidin and glycyrrhizin were observable in the mixture.The water pill exhibited the strongest antioxidant activity,while those of the concentrated pill and mixture were weak;the big honey pill exhibited the strongest hypoglycemic activity,while that of the decoction was the weakest.Total protein,total phenol,total flavonoid and liquiritin contents displayed significant positive correlations between antioxidant activity(P<0.05,P<0.01),while hesperidin content displayed significant negative correlation between the latter(P<0.05);total protein,calycosin-7-O-β-D-glucoside,codonoside and quercetin contents displayed significant negative correlations between hypoglycemic activity(P<0.05,P<0.01).CONCLUSION Active constituent contents and their biological activities of Buzhong Yiqi Recipe with different dosage forms exist differences,total sugar,total protein,total flavonoids,calycosin-7-O-β-D-glucoside,licorice glycoside,hesperidin,codonoside and quercetin can be taken as quality control indices for this prescription.

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