1.Identification and in vitro validation of causative proteins in metabolic dysfunction-associated fatty liver disease: A study based on proteome-wide Mendelian randomization
Jianyi CHEN ; Wentao HUANG ; Yang LI ; Zewei ZHUO ; Qinming LI ; Yu LONG ; Weihong SHA ; Hao CHEN
Journal of Clinical Hepatology 2026;42(9):2067-2074
ObjectiveTo identify protein biomarkers and potential therapeutic targets associated with metabolic dysfunction-associated fatty liver disease (MAFLD) through an integrative multi-omics analysis. MethodsLarge-scale plasma protein quantitative trait locus data were integrated with MAFLD genome-wide association study data, and a proteome-wide Mendelian randomization analysis was performed. Summary data-based Mendelian Randomization (SMR)/heterogeneity in dependent instruments (HEIDI) test and colocalization analysis were used to assess significant proteins. The independent samples t-test was used for comparison of continuous data with homogeneity of variance between two groups, and the Welch-corrected t-test was used for comparison of continuous data with heterogeneity of variance. The transcriptomic validation results were compared with the Mendelian randomization results to evaluate the changing trends of gene expression, and boxplots were used to display the expression distribution of candidate genes between groups. ResultsAmong 7 130 proteins analyzed, 40 showed a causal relationship with MAFLD, among which 26 increased the risk of MAFLD and 14 exerted a protective effect against MAFLD (FDR<0.05). Nine proteins were supported by SMR/HEIDI (PSMR<0.05, PHEIDI>0.05), and 14 showed a strong colocalization signal (PPH4>0.9). The transcriptomic analysis identified 5 differentially expressed proteins (all P<0.05), i.e., adenosine diphosphate-ribosylation factor-like GTPase 2, insulin-like growth factor binding protein 2, casein kinase 1 delta (CSNK1D), leucine-rich repeat neuronal 1, and moesin (MSN). In vitro validation showed upregulated expression levels of MSN (1.612±0.346 vs 0.569±0.077, P<0.05), 14-3-3 protein theta (YWHAQ) (1.267±0.126 vs 0.313±0.029, P<0.05), and CSNK1D (0.871±0.025 vs 0.431±0.080, P<0.05) and a downregulated expression level of histone deacetylase 8 (0.637±0.059 vs 1.097±0.260, P<0.05) in the MAFLD cell model. Functional annotation showed that CSNK1D participated in circadian and metabolic regulation, YWHAQ modulated the Hippo pathway and lipid signal transduction, and MSN was associated with cytoskeletal remodeling and fibrogenic responses. ConclusionThe integrative proteogenomic analysis in this study shows that CSNK1D, YWHAQ, and MSN may be key mediators in the pathogenesis of MAFLD. These proteins have the potential to serve as novel biomarkers and therapeutic targets, providing new directions for research on disease mechanisms and the development of intervention strategies.
2.Potential value of 18F-DPA-714 PET/MR in the diagnosis of autoimmune encephalitis
Xinyi SUN ; Xiaoyu CHEN ; Hangxing CHUNYU ; Yu ZHANG ; Wangxi HAI ; Huanyu MENG ; Qinming ZHOU ; Lu HE ; Sheng CHEN ; Biao LI ; Min ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(4):218-223
Objective:To evaluate the potential value of 18×10 3 translocator protein (TSPO) radioligand ( N, N-diethy1-2-(2-(4-(2- 18F-fluoroethoxy) phenyl)-5, 7-dimethylpyrazolo[1, 5-A]pyrimidin-3-yl)acetamide, 18F-DPA-714) PET compared with conventional MR in the detection of autoimmune encephalitis (AE), the correlation with clinical symptoms, and the monitoring of immunotherapy efficacy in patients with AE. Methods:From December 2021 to June 2024, 45 AE patients (17 males, 28 females, age (38.3±17.0) years) diagnosed at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine and 10 healthy volunteers (7 males, 3 females, age (28.7±5.1) years) were enrolled in this prospective study. All participants underwent baseline 18F-DPA-714 PET/MR scans, and 23 of these AE patients underwent further follow-up 18F-DPA-714 PET/MR scans. 18F-DPA-714 PET positivity was defined as having an uptake intensity threshold higher than the mean SUV ratio (SUVR)+ 2 s of the corresponding brain region in healthy controls. MR positivity was defined as abnormal hyperintensity in a specific brain region or multiple brain regions on the T 2 fluid attenuated inversion recovery (FLAIR). The positive detection rates of 18F-DPA-714 PET and MR was analyzed using McNemar χ2 test, and the differences in the uptake intensity (SUVR) of 18F-DPA-714 between symptomatic and non-symptomatic groups, and between remission and non-remission groups after immunotherapy were compared using independent-sample t test or Wilcoxon rank sum test. Spearman rank correlation analysis was used to analyze the correlation between the changing rate of SUVR and the changing of the modified Rankin Scale (mRS) score before and after treatment. Results:The positive detecting rate of 18F-DPA-714 PET for AE was significantly higher than that of MR (73.3%(33/45) vs 35.6%(16/45); χ2=11.56, P=0.001). The cerebellar SUVR of ataxia patients was significantly higher than that of asymptomatic patients (1.22(1.06, 1.33) vs 1.08(0.99, 1.20); Z=-2.14, P=0.034). Follow-up imaging showed that the SUVR of patients in the remission group after immunotherapy was significantly lower than that in the non-remission group ((-15.19±10.17)% vs (14.26±13.36)%; t=5.81, P<0.001). There was a significant correlation between the changing rate of SUVR and the changing of the mRS score before and after treatment ( rs=0.65, P<0.001). Conclusion:Compared with conventional MR, 18F-DPA-714 PET has a higher positive detecting rate for AE, and has the potential to reflect the clinical symptoms of AE and monitor the efficacy of immunotherapy.
3.Potential value of 18F-DPA-714 PET/MR in the diagnosis of autoimmune encephalitis
Xinyi SUN ; Xiaoyu CHEN ; Hangxing CHUNYU ; Yu ZHANG ; Wangxi HAI ; Huanyu MENG ; Qinming ZHOU ; Lu HE ; Sheng CHEN ; Biao LI ; Min ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(4):218-223
Objective:To evaluate the potential value of 18×10 3 translocator protein (TSPO) radioligand ( N, N-diethy1-2-(2-(4-(2- 18F-fluoroethoxy) phenyl)-5, 7-dimethylpyrazolo[1, 5-A]pyrimidin-3-yl)acetamide, 18F-DPA-714) PET compared with conventional MR in the detection of autoimmune encephalitis (AE), the correlation with clinical symptoms, and the monitoring of immunotherapy efficacy in patients with AE. Methods:From December 2021 to June 2024, 45 AE patients (17 males, 28 females, age (38.3±17.0) years) diagnosed at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine and 10 healthy volunteers (7 males, 3 females, age (28.7±5.1) years) were enrolled in this prospective study. All participants underwent baseline 18F-DPA-714 PET/MR scans, and 23 of these AE patients underwent further follow-up 18F-DPA-714 PET/MR scans. 18F-DPA-714 PET positivity was defined as having an uptake intensity threshold higher than the mean SUV ratio (SUVR)+ 2 s of the corresponding brain region in healthy controls. MR positivity was defined as abnormal hyperintensity in a specific brain region or multiple brain regions on the T 2 fluid attenuated inversion recovery (FLAIR). The positive detection rates of 18F-DPA-714 PET and MR was analyzed using McNemar χ2 test, and the differences in the uptake intensity (SUVR) of 18F-DPA-714 between symptomatic and non-symptomatic groups, and between remission and non-remission groups after immunotherapy were compared using independent-sample t test or Wilcoxon rank sum test. Spearman rank correlation analysis was used to analyze the correlation between the changing rate of SUVR and the changing of the modified Rankin Scale (mRS) score before and after treatment. Results:The positive detecting rate of 18F-DPA-714 PET for AE was significantly higher than that of MR (73.3%(33/45) vs 35.6%(16/45); χ2=11.56, P=0.001). The cerebellar SUVR of ataxia patients was significantly higher than that of asymptomatic patients (1.22(1.06, 1.33) vs 1.08(0.99, 1.20); Z=-2.14, P=0.034). Follow-up imaging showed that the SUVR of patients in the remission group after immunotherapy was significantly lower than that in the non-remission group ((-15.19±10.17)% vs (14.26±13.36)%; t=5.81, P<0.001). There was a significant correlation between the changing rate of SUVR and the changing of the mRS score before and after treatment ( rs=0.65, P<0.001). Conclusion:Compared with conventional MR, 18F-DPA-714 PET has a higher positive detecting rate for AE, and has the potential to reflect the clinical symptoms of AE and monitor the efficacy of immunotherapy.
4.Performing the socialist core values in the cultural inheritance and innovation of traditional Chinese medicine
Gang YUAN ; Nan ZHENG ; Qinming YU ; Rongxing ZHANG ; Hewei LI
International Journal of Traditional Chinese Medicine 2015;(7):580-582
System combing the internal unity of traditional Chinese medicine culture and socialist core values is the demands of both contemporary TCM culture intrinsic appeal and also the practice of socialist core values. Based on exploring the inner link between the core value of traditional Chinese medicine culture and socialist core values, this article discuss the specific path of promoting socialist core values in the process of TCM culture inheritance and innovation.
5.Practice of integrating moral education into outstanding traditional culture of traditional Chi-nese medicine and its reflection
Gang YUAN ; Hewei LI ; Rongxing ZHANG ; Qinming YU
Chinese Journal of Medical Education Research 2013;(10):1078-1080
Outstanding traditional culture of traditional Chinese medicine contains rich hu-manistic knowledge and is the precious spiritual resource and important education material for moral education. Heilongjiang University of Chinese Medicine gave full play of outstanding traditional cul-ture of traditional Chinese medicine in moral education and integrated it into moral education thus to innovate teaching methods and expand development room of moral education.
6.Study of dynamic pressure to promote the angiogenesis of bone matrix
Jun YANG ; Zhendong ZHOU ; Jianjun LI ; Qinming ZHANG
Chinese Journal of Orthopaedics 2011;31(4):372-378
Objective To observe the effects of dynamic pressure for the ability of endothelial progenitor cells (EPCs) to form blood vessels, when EPCs seeded into DBM with load. Methods Use the Ficoll density gradient centrifuge combined with difference-speed adherence screening method to separate MNCs from rat bone marrow. Identify the induced EPCs by means of immunohistochemistry and immunofluorescence. Through the organization of fixed, defatted, decalcified and other steps use of spine vertebral body,demineralized bone matrix (DBM) samples of pig were prepared in vitro. Divided scaffolds into two groups A and groups B. Induced EPCs were seeded into DBM. The cell-seeded scaffolds of groups A were dynamically loaded in compression using a sine wave at 1 Hz, 5% strain in the media-filled chamber for 4 h on days 5 of culture. and cell-seeded scaffolds of groups B were cultured directly without any load. Both of two groups were cultured two weeks. Then the ability of EPCs to form blood vessels was observed. Primer desig;Extract total RNA from cells with Trlzol; Reverse transcription reaction; PCR. Results Two groups of cells in HE staining and fluorescent staining showed the formation of vascular bundles. There were formation of blood vessels. It was obvious that the formation in group A was more than that in group B. Test the mRNA expression of vWF and Flk-1 during the EPCs differentiationby RT-PCR. Group A was significantly stronger than that of group B. Conclusion When DBM combines together with EPC, it has become organization engineering bone, then with press on it, the bone graft has been vascularized, so it has clinical application on the direction of repair bone defect.
7.Characteristics of insulin resistance in patients with ketosis-prone diabetes
Qinming YAN ; Lingyan RUAN ; Zuhua GAO ; Chaoli YU ; Jun LI
Chinese Journal of Endocrinology and Metabolism 2008;24(2):182-183
Thirty-five patients with ketosis-prone diabetes (KPD) and 38 patients with newly-diagonosed common type 2 diabetes mellitus (DM) were treated with insulin for 3 months.The results showed that the existing insulin resistance in patients with KPD was mild as compared with common type 2 DM, and the recovery of insulin sensitivity was less marked in patients with KPD after blood glucose was well controlled.

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