1.Prediction of Pulmonary Nodule Progression Based on Multi-modal Data Fusion of CCNet-DGNN Model
Lehua YU ; Yehui PENG ; Wei YANG ; Xinghua XIANG ; Rui LIU ; Xiongjun ZHAO ; Maolan AYIDANA ; Yue LI ; Wenyuan XU ; Min JIN ; Shaoliang PENG ; Baojin HUA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):135-143
ObjectiveThis study aims to develop and validate a novel multimodal predictive model, termed criss-cross network(CCNet)-directed graph neural network(DGNN)(CGN), for accurate assessment of pulmonary nodule progression in high-risk individuals for lung cancer, by integrating longitudinal chest computed tomography(CT) imaging with both traditional Chinese and western clinical evaluation data. MethodsA cohort of 4 432 patients with pulmonary nodules was retrospectively analyzed. A twin CCNet was employed to extract spatiotemporal representations from paired sequential CT scans. Structured clinical assessment and imaging-derived features were encoded via a multilayer perceptron, and a similarity-based alignment strategy was adopted to harmonize multimodal imaging features across temporal dimensions. Subsequently, a DGNN was constructed to integrate heterogeneous features, where nodes represented modality-specific embeddings and edges denoted inter-modal information flow. Finally, model optimization was performed using a joint loss function combining cross-entropy and cosine similarity loss, facilitating robust classification of nodule progression status. ResultsThe proposed CGN model demonstrated superior predictive performance on the held-out test set, achieving an area under the receiver operating characteristic curve(AUC) of 0.830, accuracy of 0.843, sensitivity of 0.657, specificity of 0.712, Cohen's Kappa of 0.417, and F1 score of 0.544. Compared with unimodal baselines, the CGN model yielded a 36%-48% relative improvement in AUC. Ablation studies revealed a 2%-22% increase in AUC when compared to simplified architectures lacking key components, substantiating the efficacy of the proposed multimodal fusion strategy and modular design. Incorporation of traditional Chinese medicine (TCM)-specific symptomatology led to an additional 5% improvement in AUC, underscoring the complementary value of integrating TCM and western clinical data. Through gradient-weighted activation mapping visualization analysis, it was found that the model's attention predominantly focused on nodule regions and effectively captured dynamic associations between clinical data and imaging-derived features. ConclusionThe CGN model, by synergistically combining cross-attention encoding with directed graph-based feature integration, enables effective alignment and fusion of heterogeneous multimodal data. The incorporation of both TCM and western clinical information facilitates complementary feature enrichment, thereby enhancing predictive accuracy for pulmonary nodule progression. This approach holds significant potential for supporting intelligent risk stratification and personalized surveillance strategies in lung cancer prevention.
2.USP20 as a super-enhancer-regulated gene drives T-ALL progression via HIF1A deubiquitination.
Ling XU ; Zimu ZHANG ; Juanjuan YU ; Tongting JI ; Jia CHENG ; Xiaodong FEI ; Xinran CHU ; Yanfang TAO ; Yan XU ; Pengju YANG ; Wenyuan LIU ; Gen LI ; Yongping ZHANG ; Yan LI ; Fenli ZHANG ; Ying YANG ; Bi ZHOU ; Yumeng WU ; Zhongling WEI ; Yanling CHEN ; Jianwei WANG ; Di WU ; Xiaolu LI ; Yang YANG ; Guanghui QIAN ; Hongli YIN ; Shuiyan WU ; Shuqi ZHANG ; Dan LIU ; Jun-Jie FAN ; Lei SHI ; Xiaodong WANG ; Shaoyan HU ; Jun LU ; Jian PAN
Acta Pharmaceutica Sinica B 2025;15(9):4751-4771
T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.
3.Discovery of toad-derived peptide analogue targeting ARF6 to induce immunogenic cell death for immunotherapy of hepatocellular carcinoma.
Dihui XU ; Xiang LV ; Meng YU ; Ao TAN ; Jiaojiao WANG ; Xinyi TANG ; Mengyuan LI ; Wenyuan WU ; Yuyu ZHU ; Jing ZHOU ; Hongyue MA
Journal of Pharmaceutical Analysis 2025;15(3):101038-101038
Image 1.
4.Clinical Questions Construction in Clinical Practice Guidelines: Based on Case-guided Approach
Yicheng GAO ; Zijin YU ; Yaqi WANG ; Rui FANG ; Cheng WANG ; Yuanyuan LI ; Yingjie DENG ; Xue BAI ; Wenyuan XIANG ; Yutong FEI
Medical Journal of Peking Union Medical College Hospital 2024;16(1):198-203
Currently, there are practical and technical difficulties in the construction of clinical questions in the development of clinical practice guidelines. Clinicians or guideline developers seldom construct clinical questions based the actual case scenario, leading to some information loss between structured and actual clinical connotation. To overcome this challenge, we proposed a case-guided questions construction approach, and carried out case research and verification in the formulation of the guideline. We found that this method could more efficiently and scientifically assist the formulation of clinical questions, and provide reference for clinicians or guideline developers.
5.Effect of silencing Ras homolog family member C on proliferation,invasion,and migration of salivary adenoid cystic carcinoma
Wenyuan YU ; Peng ZHAO ; Yu SHAO ; Yong XU ; Jin XU ; Lei XIE ; Chenghao YU ; Qiuping HE ; Zhenggang CHEN
West China Journal of Stomatology 2024;42(6):723-734
Objective This study aimed to investigate the effects of silencing Ras homolog family member C(RhoC)on the proliferation,apoptosis,invasion,migration,and epithelial-mesenchymal transition(EMT)of salivary adenoid cystic carcinoma(SACC)and its molecular mechanisms.Methods A total of 27 SACC lesions and normal salivary gland tissues that were surgically resected at Qingdao Municipal Hospital from January 1,2019 to March 1,2024 were selected,and the expression levels of RhoC were detected by Western blot and immunohistochemistry.Three small interfering RNA(siRNAs)were designed to target the RhoC gene sequence,transfected into SACC-LM and SACC-83 cell lines,and evaluated for transfection efficiency.The protein expression levels of RhoC,Rho-asso-ciated protein kinase-1(ROCK1),p38 mitogen-activated protein kinase(p38MAPK),phosphorylated-p38MAPK(p-p38MAPK),twist family bHLH transcription factor 1(TWIST1),E-cadherin,N-cadherin,and Vimentin were com-pared using Western blot.CCK-8 assay,flow cytometry,transwell invasion assay,and wound healing assay were conducted to assess the differences in cell proliferation,apoptosis,invasion,and migration abilities among the groups.Bioinformatics methods were also used to predict possible upstream micro RNAs(miRNAs)of RhoC and their expression levels in SACC.Moreover,dual-luciferase reporter gene experiments were performed to verify the binding sites of miR-138-5p and RhoC.Results RhoC was highly expressed in SACC(P<0.05).After silencing RhoC,the test group showed a significant decrease in the expression level of ROCK1,p-p38MAPK,TWIST1,N-cadherin,and Vimentin,as well as a significant increase in the expression level of E-cadherin(P<0.05).No signifi-cant difference in the expression level of p38MAPK was observed(P>0.05).The cell proliferation,invasion,and mi-gration ability decreased in the test group,whereas the apoptosis rates significantly increased(P<0.05).miR-138-5p was lowly expressed in SACC,and miR-138-5p mimic can significantly downregulated the luciferase activity of 293T cells after transfection with a RhoC wild-type plasmid(P<0.05).Conclusion RhoC is highly expressed in SACC,and RhoC silencing may target the downstream ROCK1/p38MAPK/TWISTl signaling pathway,thereby in-hibiting the proliferation,invasion,migration,and EMT of SACC while promoting its apoptosis.On the contrary,miR-138-5p is lowly expressed in SACC and is a potential upstream gene of RhoC,and there may be binding sites between the two genes.
6.Comparison of Diagnostic Performance Between PI-RADS v2.1 and PI-RADS v2 for Prostate Cancer: A Meta-analysis
Guojie BAI ; Kexin LI ; Wenyuan LIU ; Guang LAN ; Hong GUO ; Yaping SUN ; Yu WANG ; Weiling TONG ; Keyu ZHANG
Cancer Research on Prevention and Treatment 2023;50(10):981-987
Objective To compare the diagnostic performance of PI-RADS v2.1 and PI-RADS v2 in the detection of clinically significant prostate cancer(csPCa) by Meta-analysis. Methods The major biomedical databases were searched (CNKI, CBM, Medline, and Embase) with the keywords "PIRADS v2.1" or "PI-RADS v2.1". The Quality Assessment of Diagnostic Accuracy Studies Tool v2 (QUADAS-2) was used to evaluate literature quality. Meta-analysis was performed using STATA17.0 and ReMan5.4 software. Forest plots were used to represent the sensitivity and specificity of PI-RADS v2.1 and PI-RADS v2 for each study. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were combined, and diagnostic performance was evaluated using asummary receiver operating characteristic curve (SROC). Subgroup analysis was performed on three covariables: tumor location, threshold, and the nationality of authors. Results A total of 12 studies were included, involving 3 158 patients and 3 243 lesions. Forall zones and the whole gland, PI-RADS v2.1 had a larger area under the SROC curve (AUC) for csPCa performance, compared with PI-RADS v2. Subgroup analysis: PI-RADS v2.1 also had a larger area under the SROC (AUC) to detect transitional zone csPCa. Different diagnostic thresholds: when a score of 4 was used for the threshold, PI-RADS v2.1 had the maximum area under SROC (AUC) for csPCa performance detection. Author nationality: Researches of PI-RADS v2.1 in Chinese authors had the largest area under the SROC (AUC) in detecting csPCa performance. Conclusion Compared with PI-RADS v2, the diagnostic performance of PI-RADS v2.1 in detecting csPCa is not obviously improved and overall specificity is still low.
7.Comparative chemical characters of Pseudostellaria heterophylla from geographical origins of China.
Miao SHA ; Xiaohuan LI ; Yu LIU ; Hongyue TIAN ; Xu LIANG ; Xia LI ; Wenyuan GAO
Chinese Herbal Medicines 2023;15(3):439-446
OBJECTIVE:
Pseudostellaria heterophylla has been paid more attention in recent years, mainly as a medicine food homology plant. The content determination of P. heterophylla is not specified in the Chinese Pharmacopoeia (version 2020). The environmental conditions in different production areas could exert an influence on the quality of P. heterophylla. The purpose of this study is to discriminate P. heterophylla collected from different geographical origins of China.
METHODS:
In this study, the content of polysaccharide in 28 batches of P. heterophylla was determined using phenol-sulfuric acid. HPLC fingerprints were established under optimised HPLC-PDA methods. Subsequently, the similarity analysis (SA) and the quantification of heterophyllin B were analyzed. The metabolites of P. heterophylla were identified and evaluated using UHPLC-Q Exactive HF orbitrap MS system. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), hierarchical cluster analysis (HCA) and orthogonal PLS-DA (OPLS-DA) were performed based on all peak areas.
RESULTS:
The polysaccharide content in Guizhou and Jiangsu was higher than that of other production areas, which varied significant from different origins. While the content of heterophyllin B in Anhui and Jiangsu was high. The correlation coefficients of HPLC fingerprints for 28 batches samples ranged from 0.877 to 0.990, and the characteristic map can be used to identify and evaluate the quality of P. heterophylla. The samples from Fujian, Guizhou, Jiangsu provinces can be relatively separated using multivariate statistical analysis including PCA, PLS-DA, HCA, OPLS-DA, indicating that their metabolic compositions were significantly different. Ultimately, a total of 15 metabolites which were filtrated by a VIP-value > 1 and a P-value < 0.05 associated with the separation of different origins were identified.
CONCLUSION
HPLC fingerprint was established to evaluate the quality and authenticity of P. heterophylla. The present work showed that the difference of geographic distributions had an influence on the internal chemical compositions. A sensitive and rapid untargeted metabolomics approach by UHPLC-Q Exactive HF orbitrap MS was utilized to evaluate P. heterophylla from different origins in China for the first time. Overall, this study provides insights to metabolomics of P. heterophylla and supplies important reference values for the development of functional foods.
8.Systematic Review of Chinese Medicine in Improving Sperm Quality in Animal Experiments Based on Structure and Function of Sertoli Cells
Yifeng SHEN ; Kun ZHU ; Wenyuan LI ; Liang DONG ; Yaodong YOU ; Degui CHANG ; Xujun YU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(21):201-211
ObjectiveTo systematically review the intervention effect of Chinese medicine on the structure and function of testicular Sertoli cells in animal models of impaired spermatogenesis. MethodThe databases, such as China National Knowledge Infrastructure (CNKI),VIP,Wanfang Data,EMbase,and Pubmed,were searched for experimental studies on the effect of Chinese medicine on the structure and function of testicular Sertoli cells in animal models with impaired spermatogenesis. The included studies were evaluated for risks of bias,and the outcome indicators were analyzed with RevMan and Stata software. ResultThirty studies were included,involving 37 randomized controlled trials (RCTs). As indicated by the Meta-analysis results, compared with the model group,Chinese medicine increased sperm density(SMD=2.42,95% confidence interval(CI)[1.47,3.37],P<0.000 01), promoted sperm motility(SMD=2.35,95%CI [1.70, 2.99],P<0.000 01), up-regulated the protein and mRNA levels of Vimentin (related to Sertoli cell cytoskeleton), elevated the levels of Occludin and Claudin-11 (related to tight junction of blood-testis barrier), boosted the levels of β-catenin and N-cadherin (related to adherens junction of blood-testis barrier), raised the level of connexin 43 (Cx43, related to gap junction of blood-testis barrier), improved the function of Sertoli cells, increased the serum content of Inhibin B (INHB), and up-regulated the levels of testicular follicle-stimulating hormone receptor (FSHR), INHB mRNA, androgen-binding protein (ABP) mRNA, transferrin(TF),stem cell factor(SCF),SCF mRNA,glial cell line-derived neurotrophic factor (GDNF),GDNF mRNA,bone morphogenetic protein 4(BMP4),and BMP4 mRNA (P<0.05). ConclusionChinese medicine can effectively increase sperm density and motility of animal models of impaired spermatogenesis,and improve the structure and function of testicular Sertoli cells. However,affected by the quality of the included studies,the above conclusion needs to be further verified by relevant high-quality studies.
9.Predictive value of preoperative left atrial diameter in the occurrence of postoperative atrial fibrillation after coronary artery bypass grafting
Mingxin GAO ; Kangjun FAN ; Wenyuan YU ; Hongli LIU ; Xiaohang DING ; Liang CHEN ; Haiyang LI ; Yang YU
Chinese Journal of Thoracic and Cardiovascular Surgery 2022;38(12):751-756
Objective:To investigate the predictive value of preoperative left atrial diameter in postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) in patients with coronary artery disease (CAD) and its influencing factors.Methods:This study was a prospective observational study. A total of 113 patients with CABG surgery were enrolled in Beijing Anzhen Hospital affiliated to Capital Medical University from January 2020 to December 2020. Preoperative coronary angiography, echocardiography and blood test were finished. The number of graft vessel was counted during the operation. The occurrence of POAF was confirmed by electrocardiogram or electrocardiograph monitoring after surgery. The preoperative baseline data, blood test, perioperative complications and other indicators of patients with or without POAF were compared.Results:According to the inclusion criteria and exclusion criteria, 90 patients undergoing CABG were enrolled in the study[71 males and 19 females, aged from 42 to 75, mean age (62±8)years old]. The incidence of POAF was 27.8%(25 cases). The left atrial diameter[40(36-43)mm vs. 35(33-37)mm, P=0.00]and troponin I[4.76(0.87-13.60)ng/ml vs. 1.48(0.56-4.52)ng/ml, P=0.04] in patients with POAF were significantly higher than that in patients without POAF. Compared to patients without POAF, POAF significantly increased the incidence of stroke[4(16%) vs. 0(0), P=0.01], ICU stay[67(24-96) days vs. 22(19-41) days, P=0.00] and hospital stay[21(19-24) days vs. 16(14-24) days, P=0.05]. Binary logistic regression showed that left atrial diameter was significantly correlated with the occurrence of POAF ( OR=1.9, 95% CI: 1.39-2.79, P<0.001). ROC curve analysis showed that 40 mm of left atrial diameter was a predictor of POAF( AUC=0.82, sensitivity 52%, specificity 100%, P<0.001). Linear regression analysis showed that left atrial diameter was significantly positively correlated with hypersensitive C-reactive protein ( Beta=0.24, 95% CI: 0.00-0.26, P=0.043). Conclusion:POAF significantly increased the incidence of stroke after CABG. Preoperative left atrial diameter is an independent predictor for POAF, which is closely related to the systemic inflammatory response.
10.Clinical guideline for spinal reconstruction of osteoporotic thoracolumbar fracture in elderly patients (version 2022)
Tao SUI ; Jian CHEN ; Zhenfei HUANG ; Zhiyi HU ; Weihua CAI ; Lipeng YU ; Xiaojian CAO ; Wei ZHOU ; Qingqing LI ; Jin FAN ; Qian WANG ; Pengyu TANG ; Shujie ZHAO ; Lin CHEN ; Zhiming CUI ; Wenyuan DING ; Shiqing FENG ; Xinmin FENG ; Yanzheng GAO ; Baorong HE ; Jianzhong HUO ; Haijun LI ; Jun LIU ; Fei LUO ; Chao MA ; Zhijun QIAO ; Qiang WANG ; Shouguo WANG ; Xiaotao WU ; Nanwei XU ; Jinglong YAN ; Zhaoming YE ; Feng YUAN ; Jishan YUAN ; Jie ZHAO ; Xiaozhong ZHOU ; Mengyuan WU ; Yongxin REN ; Guoyong YIN
Chinese Journal of Trauma 2022;38(12):1057-1066
Osteoporotic thoracolumbar fracture in the elderly will seriously reduce their quality of life and life expectancy. For osteoporotic thoracolumbar fracture in the elderly, spinal reconstruction is necessary, which should comprehensively consider factors such as the physical condition, fracture type, clinical characteristics and osteoporosis degree. While there lacks relevant clinical norms or guidelines on selection of spinal reconstruction strategies. In order to standardize the concept of spinal reconstruction for osteoporotic thoracolumbar fracture in the elderly, based on the principles of scientificity, practicality and progressiveness, the authors formulated the Clinical guideline for spinal reconstruction of osteoporotic thoracolumbar fracture in elderly patients ( version 2022), in which suggestions based on evidence of evidence-based medicine were put forward upon 10 important issues related to the fracture classification, non-operative treatment strategies and surgical treatment strategies in spinal reconstruction after osteoporosis thoracolumbar fracture in the elderly, hoping to provide a reference for clinical treatment.

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