1.Screening and validation of diagnostic biomarkers in metabolic dysfunction-associated fatty liver disease based on data-independent acquisition quantitative proteomics
Hongfei SONG ; Lijuan DAN ; Xiuyan LI ; Xiaojie YOU ; Shengjie WU ; Haibo YIN ; Wenping LIU ; Qiao LI ; Jie MU
Journal of Clinical Hepatology 2026;42(9):2075-2085
ObjectiveTo screen for and validate key differentially expressed proteins in serum of patients with metabolic dysfunction‑associated fatty liver disease (MAFLD), and to provide a basis for identifying diagnostic biomarkers and developing intervention strategies for this disease. MethodsA total of 20 patients who were diagnosed with MAFLD in the third affiliated hospital of Chengdu University of Traditional Chinese Medicine from December 2024 to January 2025 were enrolled as MAFLD group, and 20 healthy controls were enrolled as HC group. Demographic data and serum biochemical parameters were collected from both groups. Data-independent acquisition (DIA) quantitative proteomics was used to measure the relative expression levels of serum proteins, and related methods were used to obtain significantly differentially expressed proteins, including the gene ontology functional enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, protein-protein interaction (PPI) network, Hub node interaction, and weighted gene co-expression network analysis (WGCNA). Rats were given a high-fat diet to establish a model of MAFLD, and randomly assigned to the control group and model group. Serum biochemical parameters and inflammatory factors were measured, liver histopathological changes were observed, and the protein expression levels of MER proto-oncogene tyrosine kinase (MERTK) and matrix metalloproteinase-9 (MMP-9) in liver tissue were verified. The independent-samples t test was used for comparison of normally distributed continuous data between groups, while the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or data with heterogeneity of variance between groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsCompared with the HC group, the MAFLD group had significant increases in the serum levels of aspartate aminotransferase (t=-7.348, P<0.05), alanine aminotransferase (Z=5.088, P<0.05), alkaline phosphatase (t=-3.943, P<0.05), triglyceride (Z=2.070, P<0.05), and high-density lipoprotein cholesterol (t=3.867, P<0.05). A total of 3 559 proteins were identified by DIA serum proteomics, among which 160 differentially expressed proteins were mainly enriched in pathways including metabolic disorders, immune inflammatory response, and extracellular matrix remodeling. The PPI network and the Hub node analysis showed that serpin family E member 1, MMP-9, and intercellular cell adhesion molecule-1 were core regulatory proteins. WGCNA showed that the MEyellow module was significantly positively correlated with MAFLD phenotype (cor=0.55, P<0.001), which was functionally enriched in the efferocytosis pathway. MERTK (P<0.001) and MMP-9 (P<0.001) showed the most significant differential expression in this module. A rat model of MAFLD was successfully established using a high-fat diet, and compared with the control group, the model group had enlarged, yellowish, and greasy liver and disordered structure of hepatic lobules, hepatocyte fatty degeneration, and inflammatory cell infiltration based on HE staining, as well as massive lipid droplet deposition based on oil red O staining, while no obvious fibrous cords were observed in Masson staining. Compared with the control group, the model group had significant increases in the serum levels of aspartate aminotransferase (t=-5.148, P<0.05), alanine aminotransferase (t=-5.663, P<0.05), total bilirubin (t=-13.061, P<0.05), triglyceride (Z=-2.722, P<0.05), total cholesterol (t=3.588, P<0.05), and tumor necrosis factor-α (t=-16.741, P<0.05), as well as significant increases in the protein expression levels of MERTK (t=-11.448, P<0.001) and MMP-9 (t=-10.875, P<0.001) in liver tissue. ConclusionMMP-9 and MERTK are abnormally expressed in MAFLD and may be used as potential diagnostic biomarkers for this disease.
2.Clinical Efficacy of Fuyuan Tongluo Prescription in Prevention and Treatment of Restenosis with Collateral Obstruction Syndrome After Interventional Operation of Lower Limb Arteriosclerosis Obliterans
Fangfang WU ; Xiaoyu LI ; Guobin LIU ; Hongfei WANG ; Weijing FAN ; Renyan HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):134-140
ObjectiveTo observe the effects of the Fuyuan Tongluo prescription (composed of Astragali Radix, Carthami Flos, Spatholobi Caulis, Liquidambaris Fructus, Lycopodii Herba, Centellae Herba, etc.) in the treatment of restenosis with collateral obstruction syndrome after interventional operation of lower limb arteriosclerosis obliterans, and its impact on the primary patency rate. MethodsA total of 88 patients with collateral obstruction syndrome after interventional surgery for lower limb arteriosclerosis obliterans were randomly divided into two groups. The control group (n1=44) received dual antiplatelet therapy with aspirin and clopidogrel. The observation group (n2=44) was treated with Fuyuan Tongluo prescription non-decocted granules in addition to aspirin and clopidogrel. Both groups received treatment for 24 weeks and were followed up for 36 weeks. The changes in primary patency rate, symptom scores, ankle-brachial index (ABI), coagulation function, and inflammatory markers before and after treatment were compared between the two groups. ResultsFor primary patency rate, after 36 weeks of treatment, the observation group had a significantly better primary patency rate than the control group (χ2=4.14,P<0.05). After 24 weeks of treatment, there was no significant difference in primary patency rate between the two groups. Clinical efficacy comparison: Based on symptom quantification scores, and using the Nimodipine method as a reference, the overall efficacy of the observation group was superior to that of the control group after 24 weeks of treatment (χ2=2.24,P<0.05). ABI levels: The observation group had a higher ABI than the control group after 24 and 36 weeks of treatment (P<0.05). Coagulation function indicators: After 24 and 36 weeks of treatment, D-dimer and fibrinogen levels in both groups were lower than before treatment (P<0.05). Inflammatory markers: After 24 and 36 weeks of treatment, CRP levels in the observation group were lower than those in the control group (P<0.05). There were no significant differences in white blood cell (WBC) and erythrocyte sedimentation rate (ESR) levels before and after treatment between the two groups. ConclusionAdding Fuyuan Tongluo prescription non-decocted granules to dual antiplatelet therapy can improve the primary patency rate of the affected vessels in patients with lower limb arteriosclerosis obliterans after interventional surgery. Longer use of Fuyuan Tongluo prescription can significantly improve clinical symptoms, demonstrating clinical application value.
3.Clinical Efficacy of Fuyuan Tongluo Prescription in Prevention and Treatment of Restenosis with Collateral Obstruction Syndrome After Interventional Operation of Lower Limb Arteriosclerosis Obliterans
Fangfang WU ; Xiaoyu LI ; Guobin LIU ; Hongfei WANG ; Weijing FAN ; Renyan HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):134-140
ObjectiveTo observe the effects of the Fuyuan Tongluo prescription (composed of Astragali Radix, Carthami Flos, Spatholobi Caulis, Liquidambaris Fructus, Lycopodii Herba, Centellae Herba, etc.) in the treatment of restenosis with collateral obstruction syndrome after interventional operation of lower limb arteriosclerosis obliterans, and its impact on the primary patency rate. MethodsA total of 88 patients with collateral obstruction syndrome after interventional surgery for lower limb arteriosclerosis obliterans were randomly divided into two groups. The control group (n1=44) received dual antiplatelet therapy with aspirin and clopidogrel. The observation group (n2=44) was treated with Fuyuan Tongluo prescription non-decocted granules in addition to aspirin and clopidogrel. Both groups received treatment for 24 weeks and were followed up for 36 weeks. The changes in primary patency rate, symptom scores, ankle-brachial index (ABI), coagulation function, and inflammatory markers before and after treatment were compared between the two groups. ResultsFor primary patency rate, after 36 weeks of treatment, the observation group had a significantly better primary patency rate than the control group (χ2=4.14,P<0.05). After 24 weeks of treatment, there was no significant difference in primary patency rate between the two groups. Clinical efficacy comparison: Based on symptom quantification scores, and using the Nimodipine method as a reference, the overall efficacy of the observation group was superior to that of the control group after 24 weeks of treatment (χ2=2.24,P<0.05). ABI levels: The observation group had a higher ABI than the control group after 24 and 36 weeks of treatment (P<0.05). Coagulation function indicators: After 24 and 36 weeks of treatment, D-dimer and fibrinogen levels in both groups were lower than before treatment (P<0.05). Inflammatory markers: After 24 and 36 weeks of treatment, CRP levels in the observation group were lower than those in the control group (P<0.05). There were no significant differences in white blood cell (WBC) and erythrocyte sedimentation rate (ESR) levels before and after treatment between the two groups. ConclusionAdding Fuyuan Tongluo prescription non-decocted granules to dual antiplatelet therapy can improve the primary patency rate of the affected vessels in patients with lower limb arteriosclerosis obliterans after interventional surgery. Longer use of Fuyuan Tongluo prescription can significantly improve clinical symptoms, demonstrating clinical application value.
4.Association of school climate and suicidal behavior of primary and secondary school students
LIU Chang, YANG Le, QU Hongfei, LIU Yuejia
Chinese Journal of School Health 2025;46(12):1754-1759
Objective:
To explore the association between school climate and suicide behavior among primary and secondary school students, so as to provide recommendations for preventing student suicide in schools.
Methods:
From June to July 2024, a stratified cluster random sampling method was employed to conduct a questionnaire survey on suicidal behavior and school climate among 8 722 students from 36 schools in Lüliang, Linfen, and Datong cities, Shanxi Province. The relationship between school climate and suicidal behavior was analyzed using Chi square test and binary Logistic regression, supplemented by gender heterogeneity and interaction analyses.
Results:
The prevalence of suicidal behavior among students in Shanxi Province was 11.1%. After adjusting for age, gender, educational stage, parents educational level, residential status, family economic condition, parents marital status and depressive symptoms, binary Logistic regression analysis revealed that peer relationships ( OR=0.72, 95%CI =0.57- 0.91 ), peer trust ( OR=0.73, 95%CI =0.58-0.92), teacher support ( OR=0.66, 95%CI =0.53-0.82), school safety ( OR=0.61, 95%CI =0.48-0.78), having more than six friends ( OR=0.64, 95%CI =0.43-0.98), and school belongingness ( OR=0.70, 95%CI =0.56-0.88) among primary and secondary school students were associated with a lower risk of suicidal behavior (all P <0.05). Students who experienced school bullying showed a higher risk of suicidal behavior ( OR=2.95, 95%CI =1.80-4.82, P <0.05). Gender specific analysis revealed that peer relationships ( OR=0.67, 95%CI =0.48-0.92), peer trust ( OR=0.66, 95%CI =0.49-0.90), and school belongingness ( OR=0.62, 95%CI =0.45-0.84) were associated with a lower risk of suicidal behavior suicide behavior in girls; teacher support ( OR=0.50, 95%CI =0.36-0.70) and having more than six friends ( OR=0.51, 95%CI =0.27- 0.96 ) were associated with a lower risk of suicidal behavior in boys, who experienced school bullying showed a higher risk of suicidal behavior ( OR=4.19, 95%CI =2.18-8.03) (all P <0.05). Interactive analysis revealed that the dual interaction between peer support and school safety could reduced the risk of suicide behavior among primary and secondary school students safety ( OR= 0.83 , 95%CI=0.70-0.99, P <0.05).
Conclusions
School climate is closely associated with suicidal behavior among primary and secondary school students in Shanxi Province, with gender differences present. Schools should foster a positive school environment to prevent student suicide behaviors.
5.Combined detection of p16 and Rb with high-risk human papilloma virus infection in non-oropharyngeal squamous cell carcinoma of the head and neck
Sisi LIU ; Hong ZHANG ; Donglin MA ; Hongfei WAN ; Yahui LI ; Rui LI ; Honggang LIU ; Yingshi PIAO
Chinese Journal of Pathology 2025;54(6):612-617
Objective:To investigate the correlation of combined detection of p16 and Rb with high-risk human papilloma virus (HR-HPV) infection in non-oropharyngeal squamous cell carcinoma (NOPSCC) of the head and neck.Methods:A total of 68 NOPSCC cases of the head and neck (23 cases of the nasal cavity and paranasal sinuses and 45 cases of larynx) with complete clinical and pathological data, diagnosed at the Beijing Tongren Hospital, Capital Medical University, Beijing, China from November 2013 to December 2023, were collected. The expression of p16 and Rb was detected using immunohistochemistry of the EnVision two-step method, while the HR-HPV mRNA expression was detected using in situ hybridization. The concordance, sensitivity, and specificity of p16 alone and the combined detection of p16 and Rb for detecting HR-HPV infection were analyzed.Results:Among the 68 patients with NOPSCC, 53 were male and 15 were female, with a median age of 63.5 (range, 57.3 to 66.8) years. 41 patients had a smoking history and 27 did not. 33 patients had an early T stage (T1/T2) and 35 had advanced T stage (T3/T4). 14 patients had lymph node metastasis and 2 had distant metastasis. Histological types included 62 cases of keratinized squamous cell carcinoma, 5 cases of non-keratinized squamous cell carcinoma, and 1 case of basal-like squamous cell carcinoma. 25 cases were positive for p16. Among the 25 cases, 16 cases were positive for Rb, and 6 cases were positive for HR-HPV mRNA. 43 cases were negative for p16, including 38 cases positive for Rb and no cases positive for HR-HPV mRNA. The concordance between p16 and HR-HPV mRNA expression was poor ( Kappa=0.285, P=0.001), with a sensitivity of 100.0% and specificity of 69.4%. In contrast, the combined detection of p16+/Rb- showed high concordance with HR-HPV mRNA expression ( Kappa=0.719, P<0.001), with a sensitivity of 100.0% and specificity of 95.2%. Conclusions:In NOPSCC of the head and neck, the combined detection of p16 and Rb may be used as a marker for assessing HR-HPV infection. Recognizing the p16+/Rb- expression pattern in NOPSCC can improve the specificity of HR-HPV detection.
6.Safety, pharmacokinetics, and dosimetry of 177Lu-AB-3PRGD2 in patients with advanced integrin α v β 3-positive tumors: A first-in-human study.
Huimin SUI ; Feng GUO ; Hongfei LIU ; Rongxi WANG ; Linlin LI ; Jiarou WANG ; Chenhao JIA ; Jialin XIANG ; Yingkui LIANG ; Xiaohong CHEN ; Zhaohui ZHU ; Fan WANG
Acta Pharmaceutica Sinica B 2025;15(2):669-680
Integrin α v β 3 is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of 177Lu-AB-3PRGD2, a novel integrin α v β 3-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α v β 3-avid tumors were recruited to accept 177Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. 177Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of 177Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α v β 3-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.
7.Differention and Treatment of Brain Metastasis from Lung Cancer Based on Theory of "Yang Qi Depletion and Latent Pathogens Transmitting to the Brain"
Huiying ZHAO ; Yanxia LIANG ; Guangsen LI ; Wenwen WANG ; Wenwen SU ; Fenggu LIU ; Hongfei XING ; Maorong FAN
Journal of Traditional Chinese Medicine 2025;66(9):968-972
8.CT Skull Image Reconstruction Using Deep Learning Method Based on Magnetic Resonance Dixon Images:A Comparative Study
Hongfei ZHAO ; Haipeng DONG ; Qiong HUANG ; Yuan QU ; Keming LIU ; Xiaomeng WU ; Yurong SHANG ; Xiping CHEN
Chinese Journal of Medical Imaging 2025;33(4):428-432,438
Purpose Based on a variety of combinations of cranial MR Dixon images,the deep learning method is used to generate CT images,and the reconstruction efficiency is evaluated by comparing with the corresponding CT images.Materials and Methods A total of 77 cranial CT and MR images were collected retrospectively in Ruijin Hospital,Shanghai Jiaotong University School of Medicine from June to December 2021.The U-Net neural network was used for network training,with 62 cases in the training set and 15 cases in the test set.CT image reconstruction was performed using four kinds of Dixon images and a total of seven models among the various combinations.Mean absolute error,mean squared error,Pearson correlation coefficient and skull area Dice similarity coefficient were used to evaluate the image reconstruction efficiency.Results The generated CT images of the various Dixon image combination models showed strong correlation with the corresponding CT images(R>0.75,P<0.05),and the CT images reconstructed by the four-channel model had the closest value to the actual CT images[mean absolute error=147.516±30.802,mean squared error=(8.648±3.403)×104],the highest correlation coefficient(R=0.796±0.055),and the highest similarity coefficient in the cranial region(Dice similarity coefficient=0.800±0.036).Conclusion Deep learning training through Dixon images can be used to generate CT images,and the combination of four kinds of Dixon contrast images can improve the CT image reconstruction efficiency.
9.Analgesic effect of fire needle on rats with postherpetic neuralgia and its effect on IL-10/β-EP signaling pathway
Han LI ; Hongfei ZHOU ; Jun LIU ; Wei GU
Chinese Journal of Immunology 2025;41(3):561-565
Objective:To investigate analgesic effect of fire needle on postherpetic neuralgia(PHN)rats and its effect on IL-10/β-endorphin(β-EP)signaling pathway.Methods:Forty rats were randomly divided into 4 groups:control group,model group,fire needle group and drug group,with 10 rats in each group.PHN model was constructed by intraperitoneal injection of resin toxin.Af-ter successful modeling,fire needle group was intervened by fire needle at L4~6 Jiaji points,and drug group was intervened by intra-peritoneal injection of gabapentin.Von Frey electronic pain meter was used to measure paw withdrawal mechanical threshold(PW-MT)of rats in each group.Thermal latency of paw withdrawal(PWTL)of rats was measured by thermal radiation stimulator.Prosta-glandin E2(PGE2)and substance P(SP)in dorsal root ganglion tissues,serum IL-6,TNF-α and IL-1β levels were detected by ELI-SA.IL-10 and β-EP protein expressions in spinal cord of rats were detected by Western blot.Results:Compared with control group,PWMT of model group was decreased significantly(P<0.05),PWTL,levels of PGE2 and SP in spinal cord tissue and levels of IL-6,TNF-α and IL-1β in serum were increased significantly(P<0.05),IL-10 and β-EP protein expressions in spinal dorsal horn were decreased significantly(P<0.05).Compared with model group,PWMT of fire needle group and drug group was significantly increased(P<0.05),PWTL,PGE2 and SP in spinal cord tissue and serum IL-6,TNF-α and IL-1β levels were significantly decreased(P<0.05),IL-10 and β-EP protein expressions in spinal dorsal horn were significantly increased(P<0.05).Conclusion:Fire needle can improve pain response of PHN rats and reduce peripheral blood inflammation level,which may be related to activation of IL-10/β-EP signaling pathway.
10.Pinoresinol diglucoside activates the Wnt/beta-catenin signaling pathway to protect osteoblasts
Peng YU ; Dongfang MENG ; Huiying LI ; Hongfei LIU ; Zike HE
Chinese Journal of Tissue Engineering Research 2025;29(2):339-346
BACKGROUND:Pinoresinol diglucoside promotes bone formation and bone matrix synthesis and accelerates bone tissue repair.However,the mechanism of action and effects of this compound in osteoblasts need to be further explored. OBJECTIVE:To investigate the effect and mechanism of action of pinoresinol diglucoside on dexamethasone-treated osteoblasts based on the Wnt/β-catenin signaling pathway. METHODS:Different concentrations of dexamethasone groups and pinoresinol diglucoside groups were set to treat osteoblasts for 24 hours,and the optimal intervention concentrations were screened.Osteoblasts were treated with dexamethasone,pinoresinol diglucoside and inhibitor XAV-939.Then,control group,dexamethasone group,XVA-939 group,pinoresinol diglucoside group,pinoresinol diglucoside+XVA-939 group were set up.Cell counting kit-8 assay was used to detect cell activity.Alkaline phosphatase activity and caspase3/7 enzyme activity in cells were detected.Annexin V/PI staining and EdU assay were used to detect cell apoptosis and proliferation.Real-time qPCR and western blot were used to detect the mRNA and protein expression levels of Wnt3a,β-catenin,c-myc,osteocalcin,and type I collagen,respectively. RESULTS AND CONCLUSION:After dexamethasone and pinoresinol diglucoside intervened in osteoblasts for 24 hours,10 μmol/L dexamethasone was found to be the optimal intervention concentration for cell inhibition,and cell proliferation was most pronounced at a concentration of pinoresinol diglucoside of 100 μmol/L.Compared with the dexamethasone group,alkaline phosphatase activity was significantly enhanced(P<0.05)and caspase3/7 enzyme activity was significantly reduced(P<0.05)in the pinoresinol diglucoside group.Annexin V/PI staining and cell proliferation assay by EdU method showed that pinoresinol diglucoside inhibited apoptosis and promoted proliferation of osteoblasts after dexamethasone intervention.The mRNA and protein expression levels of Wnt3a,β-catenin,c-myc,osteocalcin,and type I collagen were significantly higher in the pinoresinol diglucoside group and pinoresinol diglucoside+XVA-939 group compared with the dexamethasone and XVA-939 groups(P<0.05).To conclude,pinoresinol diglucoside can inhibit osteoblast apoptosis after dexamethasone intervention,protect osteoblast activity and promote osteoblast proliferation by activating the Wnt/β-catenin signaling pathway,which may play a role in delaying steroid-induced osteonecrosis of the femoral head.


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