1.TAZ WW Domain-Mediated Regulation of Gluconeogenesis and Tumorigenesis in Hepatocellular Carcinoma through Interaction with the Glucocorticoid Receptor
Hongxiang HUANG ; Jinhong CHEN ; Xingyu TAO ; Peiyuan ZHONG ; Yanqiu MENG ; Sujuan PENG ; Wanying LUO ; Zhiyong HE ; Shuai LUO ; Xie ZHU ; Zhihui LU ; Li CHEN ; Yangyang LIU
Endocrinology and Metabolism 2026;41(2):267-287
Background:
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by poor prognosis due to its high proliferative and invasive potential. Tumor metabolic reprogramming, particularly involving glucose metabolism, is essential for tumor survival. This study investigates the role of the Hippo pathway effector transcriptional co-activator with PDZ-binding motif (TAZ) in regulating gluconeogenesis and promoting tumorigenesis in HCC.
Methods:
TAZ expression in HCC was analyzed using The Cancer Genome Atlas data and validated in clinical samples and cell lines. TAZ was overexpressed or silenced in HCC cell lines to evaluate its effects on cell proliferation, apoptosis, migration, and invasion. The expression and prognostic relevance of the gluconeogenesis-related genes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) were examined, along with their correlation with TAZ expression. Tumor growth was assessed in nude mice. Interactions between TAZ and the glucocorticoid receptor (GR) were investigated using co-immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays.
Results:
TAZ was significantly upregulated in HCC tissues and cell lines. TAZ overexpression enhanced proliferation, reduced apoptosis, and promoted migration and invasion. In contrast, PCK1 and G6PC were downregulated in HCC and showed a negative correlation with TAZ expression.
Conclusion
TAZ modulates gluconeogenesis and accelerates tumor growth, whereas its knockdown attenuates tumor progression. TAZ interacts with GR, suppressing its transcriptional activity on gluconeogenic gene promoters.
2.An excerpt of APASL clinical practice guidelines on the management of chronic hepatitis B infection: A 2026 update
Shi LIU ; Wanying LIANG ; Jianlu WANG ; Yidan CHEN ; Jinghua CHEN ; Jian SUN
Journal of Clinical Hepatology 2026;42(7):1561-1567
On June 27, 2026, the Asian Pacific Association for the Study of the Liver (APASL) released updated management guidelines for chronic HBV infection, which systematically elaborates on screening, vaccination, antiviral treatment, and hepatocellular carcinoma surveillance and other aspects in 13 key areas, and provides comprehensive recommendations. This article summarizes and makes an excerpt of the key recommendations from the updated guidelines.
3.Discovery of novel butyrylcholinesterase inhibitors for treating Alzheimer's disease.
Zhipei SANG ; Shuheng HUANG ; Wanying TAN ; Yujuan BAN ; Keren WANG ; Yufan FAN ; Hongsong CHEN ; Qiyao ZHANG ; Chanchan LIANG ; Jing MI ; Yunqi GAO ; Ya ZHANG ; Wenmin LIU ; Jianta WANG ; Wu DONG ; Zhenghuai TAN ; Lei TANG ; Haibin LUO
Acta Pharmaceutica Sinica B 2025;15(4):2134-2155
Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC50 = 0.049 μmol/L, huBuChE IC50 = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.
4.Trace component fishing strategy based on offline two-dimensional liquid chromatography combined with PRDX3-surface plasmon resonance for Uncaria alkaloids.
Hui NI ; Zijia ZHANG ; Ye LU ; Yaowen LIU ; Yang ZHOU ; Wenyong WU ; Xinqin KONG ; Liling SHEN ; Sihan CHEN ; Huali LONG ; Cheng LUO ; Hao ZHANG ; Jinjun HOU ; Wanying WU
Journal of Pharmaceutical Analysis 2025;15(9):101244-101244
The rapid screening of bioactive constituents within traditional Chinese medicine (TCM) presents a significant challenge to researchers. Prevailing strategies for the screening of active components in TCM often overlook trace components owing to their concealment by more abundant constituents. To address this limitation, a fishing strategy based on offline two-dimensional liquid chromatography (2D-LC) combined with surface plasmon resonance (SPR) was utilized to screen bioactive trace components targeting peroxiredoxin 3 (PRDX3), using Uncaria alkaloids (UAs) as a case study. Initially, an orthogonal preparative offline 2D-LC system combining a positively charged C18 column and a conventional C18 column under disparate mobile phase conditions was constructed. To fully reveal the trace alkaloids, 13 2D fractions of UAs were prepared, and their components were characterized using mass spectrometry (MS). Subsequently, employing PRDX3 as the targeting protein, a SPR-based screening approach was established and rigorously validated with geissoschizine methyl ether (GSM) serving as a positive control for binding. Employing this refined strategy, 29 candidate binding alkaloids were fished from the 13 2D fractions. Notably, combining offline 2D-LC with SPR increased the yield of candidate binding components from 10 to 29 when compared to SPR-based screening alone. Subsequent binding affinity assays confirmed that PRDX3 was a direct binding target for the 12 fished alkaloids, with isovallesiachotamine (IV), corynoxeine N-oxide (CO-N), and cadambine (CAD) demonstrating the highest affinity for PRDX3. Their interactions were further validated through molecular docking analysis. Subsequent intracellular H2O2 measurement assays and transfection experiments confirmed that these three trace alkaloids enhanced PRDX3-mediated H2O2 clearance. In conclusion, this study introduced an innovative strategy for the identification of active trace components in TCM. This approach holds promise for accelerating research on medicinal components within this field.
5.Development and validation of the rapid health aging assessment scale for the Chinese population
Bingqi YE ; Jialu YANG ; Jianhua LI ; Wunong CHEN ; Jianhua YE ; Xiaotao ZHOU ; Yong WANG ; Siqi LI ; Qi ZHANG ; Wanying ZHAO ; Jiayi SONG ; Chun WANG ; Yan LIU ; Min XIA
Chinese Journal of Preventive Medicine 2025;59(7):1078-1083
Objective:To develop a rapid assessment scale for healthy aging suitable for the Chinese population.Methods:Based on existing healthy aging assessment scales, national standards, and expert consensus, an initial Healthy Aging Rapid Assessment Scale was drafted through two rounds of expert consultation. A pre-survey was conducted with 3 220 subjects recruited from Guangzhou between July 2023 and July 2024. Items were screened through item analysis and exploratory factor analysis to form the final scale. Reliability and validity of the final scale were validated across five cities: Guangzhou, Dongguan, Shenzhen, Baoding, and Chuxiong.Results:The initial version comprised 36 items, while the finalized scale contained 18 items across three dimensions: metabolic health, mental health, and cognitive health. Test-retest reliability ranged from 0.71 to 0.81 across all study sites. The Spearman-Brown coefficient varied between 0.91-0.96, Cronbach′s α between 0.77-0.83, comparative fit index (CFI) between 0.90-0.98, goodness-of-fit index (GFI) between 0.90-0.99, and root-mean-square error of approximation (RMSEA) between 0.03-0.09. For the three dimensions, reliability and validity metrics demonstrated consistency: Spearman-Brown coefficients 0.87-0.99, Cronbach′s α 0.77-0.83, CFI 0.90-0.98, GFI 0.90-0.99, and RMSEA 0.03-0.09 across four regions.Conclusion:The developed Healthy Aging Rapid Assessment Scale for the Chinese population exhibits robust reliability and validity.
6.Assessment of the predictive value of ultrasound imaging characteristics combined with clinical indicators for the prognosis of pancreatic ductal adenocarcinoma
Hua LIANG ; Ke LYU ; Yang GUI ; Xueqi CHEN ; Tianjiao CHEN ; Li TAN ; Menghua DAI ; Weibin WANG ; Junchao GUO ; Qiang XU ; Huanyu WANG ; Xiaoyi YAN ; Wanying JIA ; Yuming SHAO
Chinese Journal of Preventive Medicine 2025;59(10):1748-1755
Objective:To explore the value of ultrasound imaging characteristics combined with clinical indicators in assessing the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC).Methods:A retrospective analysis was conducted for patients who underwent pancreatic contrast-enhanced ultrasound (CEUS) from September 2017 to October 2023 at Peking Union Medical College Hospital and were diagnosed with PDAC based on pathological findings. Various parameters were recorded, including CA19-9 levels, tumor size, location, morphologic features, echogenicity, presence of internal cystic components, dilatation of the main pancreatic duct, peripheral vascular invasion, CEUS characteristics, presence or absence of liver metastasis, and treatment methods. In April 2024, patient survival information was obtained through telephone follow-up or review of medical records. Based on the results of the cox regression model analysis, a nomogram model of the risk of death was developed. The receiver operating characteristic (ROC) curves were applied to evaluate the predictive efficacy of the model. The calibration curves were plotted to evaluate the accuracy of the model, and clinical decision curves were used to evaluate the clinical benefit of the model.Results:This study included a total of 207 patients with PDAC. As of April 2024, 71 patients were alive and 136 died, with a median survival time of 14 months (95% CI: 12 -17). Multivariate analysis confirmed that the elevated CA19-9 ( HR=1.689, 95% CI: 1.102-2.588), tumor size >4 cm ( HR=1.641, 95% CI: 1.159-2.322), taller-than-wide shapes ( HR=1.450, 95% CI: 1.019-2.065), incomplete hypo-enhancement ( HR=1.618, 95% CI: 1.100-2.380), and liver metastasis ( HR=1.687, 95% CI: 1.175-2.423) were independent risk factors for survival in patients with PDAC. A nomogram model was further constructed for 6-month, 12-month and 3-year survival of patients with PDAC. The areas under the ROC curve were 0.679, 0.705 and 0.815, respectively. The calibration curves suggested that the model was more accurate, and the clinical decision curves showed that the model had a better clinical benefit. Conclusion:The combined use of ultrasound imaging characteristics and clinical indicators could effectively predict the prognosis of PDAC patients. Specifically, tumor size >4 cm, taller-than-wide shapes, incomplete hypo-enhancement, elevated CA19-9, and the presence of liver metastasis are correlated with poorer survival outcomes. The nomogram model constructed on the basis of these factors can be used to assess the survival of patients with PDAC.
7.Research and application of a new deep learning based strategy for platelet histogram review
Enming ZHANG ; Chao YANG ; Xianchun CHEN ; Yan LIN ; Taixue AN ; Haixia LI ; Yongjian HE ; Zhiwei LIU ; Limei FENG ; Wanying LIN ; Tie XIONG ; Kai QIU ; Ya GAO ; Lizhu HUANG ; Jing HE ; Chunyan WANG ; Dehua SUN ; Bo SITU ; Lei ZHENG
Chinese Journal of Laboratory Medicine 2025;48(9):1201-1206
Objective:To develop an artificial intelligence (AI)-based platelet review strategy to identify abnormal platelet histograms with no significant difference between initial impedance platelet count (PLT-I) and PLT-F results.Methods:This study included 5 119 routine blood analysis in Nanfang Hospital of Southern Medical University and its Ganzhou branch from July 2023 and March 2024. Specimens exhibiting abnormal platelet histograms and an initial platelet count >40×10?/L underwent review using the fluorescent platelet count (PLT-F) channel. Consistency of the results was defined as a difference between impedance platelet count (PLT-I) and PLT-F less than ±20% of the PLT-F results. A deep learning model was developed using platelet and red blood cell histogram data from a training set of 3 807 specimens. The model′s diagnostic performance was evaluated on an independent external validation set ( n=805) using receiver operating characteristic (ROC) curve analysis. Changes in the number of reviewed samples and sample turnaround time were analyzed to assess its clinical utility. Results:The deep learning model based on platelet and red blood cell histograms achieved an area under the ROC curve (AUC) of 0.854 in the training set. At a cutoff value of 0.1, the sensitivity was 0.954 and specificity was 0.358. The model could reduce review by 16.80% (190/1 131). In the validation set, the AUC was 0.805, with a sensitivity of 0.955 and specificity of 0.307, corresponding to a reduction of 17.41% (47/270) in reviewed specimens.Conclusion:The platelet review prediction model developed based on deep learning technology can efficiently identify samples with consistent results before and after review, reducing unnecessary reviews and shortening specimen testing time, thereby improving the efficiency of platelet test.
8.Treatment of allergic rhinitis based on the theory of"spleen and stomach deficiency and excess transformation"
Yuechun ZHAO ; Hong GUO ; Dian CHEN ; Wanying XIA ; Jingya HUANG ; Lu ZHANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(6):827-832
The theory of"spleen and stomach deficiency and excess transformation"originates from Huangdi Neijing,which is based on the five elements theory.It systematically elucidates the physiological interconnections and pathological transmission relationships among spleen,stomach,and the five zang and six fu viscera.This theory was continuously developed and refined by later physicians.It was first systematically summarized and deepened by LI Dongyuan in his work Piwei Lun,which elaborates on the pathological transmission relationships of other zang-fu viscera after spleen and stomach deficiency.From the perspective of LI Dongyuan's theory of"spleen and stomach deficiency and excess transformation",this paper discusses the pathological relationships between spleen-earth,lung-metal,and kidney-water,and proposes that spleen-earth deficiency is the pathological basis for the onset of allergic rhinitis.Based on the pathological evolution following spleen-earth deficiency,the traditional Chinese medicine syndromes of allergic rhinitis were categorized into three types:earth deficiency with metal weakness,earth dryness with metal desiccation,and water cold with metal excess and earth decline.The treatment of allergic rhinitis should prioritize the spleen-earth,employing acrid and dispersing herbs with light properties to elevate the spleen,sweet-warm and sour-astringent herbs to tonify the spleen,and diuretic and dampness-resolving herbs to activate the spleen,thereby restoring spleen-earth function.Simultaneously,treatment should regulate lung-metal and kidney-water according to different pathological evolutions,incorporating cold-cool or acrid-warm herbs as appropriate,combining cold and warm properties,and treating both the manifestation and root cause of the disease.
9.Prediction of EGFR mutation status in non-small cell lung cancer based on CT radiomic features combined with clinical characteristics
Taotao YANG ; Xianqi WANG ; Cancan CHEN ; Wanying YAN ; Dawei WANG ; Kunlin XIONG ; Zhiyuan SUN ; Wei CHEN
Journal of Army Medical University 2025;47(8):847-857
Objective To investigate the predictive value of combined radiomic features derived from chest CT scans with clinical characteristics for epidermal growth factor receptor(EGFR)gene mutations in non-small cell lung cancer(NSCLC).Methods A multi-center case-control study was conducted on the clinical data and CT images of 1 070 NSCLC patients from the radiology departments of the 3 medical institutions between January 2013 and October 2023.The 719 NSCLC patients from the First Affiliated Hospital of Army Medical University were randomly divided into a training set and an internal validation set in a ratio of 7∶3;The 173 patients in the Eastern Theatre General Hospital and the 178 patients in Army Medical Centre of PLA were assigned into the external validation set 1 and 2,respectively.Least absolute shrinkage and selection operator(LASSO)regression was employed to identify the optimal radiomic features,which were subsequently used to construct a radiomics model.Univariate and multivariate logistic regression analyses were applied to identify clinical features associated with EGFR mutation,thereby developing a clinical model.The radiomic and clinical features were subsequently combined to develop a comprehensive model.All the 3 classification models were built using random forest(RF)machine learning.The area under curve(AUC),accuracy,sensitivity and specificity were utilized to evaluate the predictive performance of the models.Calibration curve was plotted to assess the goodness of fit of the comprehensive model,while decision curve analysis was performed to assess the clinical utility of the model.Results The AUC value of the radiomics model was 0.762 4(95%CI:0.692 4~0.825 1),0.745 4(95%CI:0.671 1~0.814 3),and 0.724 7(95%CI:0.639 7~0.801 6),respectively,in the internal validation set,external validation set 1,and external validation set 2;The AUC value of the clinical prediction model was 0.691 7(95%CI:0.627 9~0.757 6),0.652 5(95%CI:0.576 7~0.729 1),and 0.779 2(95%CI:0.712 5~0.847 3),respectively in the above sets in turn;The comprehensive model constructed based on clinical features and radiomic features showed the best predictive efficacy,with an AUC value of 0.818 0(95%CI:0.757 7~0.874 3),0.782 4(95%CI:0.703 1~0.848 2),and 0.796 6(95%CI:0.718 1~0.868 6),respectively in the above sets.Calibration curve analysis indicated that the comprehensive model had a good fit,while decision curve analysis revealed that the model provided a favorable net benefit.Conclusion Our comprehensive model constructed based on chest CT radiomic features and clinical characteristics shows superior predictive performance for EGFR gene mutations in NSCLC across multiple center datasets,which may be helpful for clinical decision-making for treatment strategies.
10.Integrative model combining deep learning,clinical and radiomic features enhances EGFR mutation prediction in non-small cell lung cancer
Taotao YANG ; Wei CHEN ; Cancan CHEN ; Wanying YAN ; Dawei WANG ; Kunlin XIONG ; Zhiyuan SUN ; Xianqi WANG
Journal of Army Medical University 2025;47(23):2991-3001
Objective To evaluate the predictive value of deep learning features from chest CT images combined with clinical and radiomics features for epidermal growth factor receptor(EGFR)mutations in non-small cell lung cancer(NSCLC).Methods This case-control study retrospectively analyzed clinical and imaging data of 1 070 NSCLC patients from radiology departments at three hospitals(January 2013 to October 2023).Patients were divided into:a training set(n=502)and internal validation set(n=217)via 7∶3 randomization of 719 cases from the First Affiliated Hospital of Army Medical University;external validation set 1(n=173)from General Hospital of Eastern Theater Command;external validation set 2(n=178)from Daping Hospital of Army Medical University.Deep learning features were extracted using a 2.5D convolutional neural network(CNN)with ResNet101 backbone,radiomics features were derived from CT images,and clinical risk factors were identified to construct models.An integrated model combined deep learning,clinical,and radiomics features.All four models were developed using random forest(RF)classifiers.Calibration curves assessed goodness-of-fit,and decision curve analysis(DCA)evaluated clinical utility.Results The deep learning model achieved AUCs of 0.833 7(95%CI:0.770 6~0.884 7),0.815 1(0.741 6~0.882 8),and 0.810 1(0.745 2~0.873 6)in the internal and two external validation sets,respectively.Clinical models yielded AUCs of 0.731 0(0.660 2~0.802 1),0.746 0(0.666 4~0.824 9),and 0.813 4(0.743 1~0.883 6);radiomics models showed AUCs of 0.762 4(0.692 4~0.825 1),0.745 4(0.671 1~0.814 3),and 0.724 7(0.639 7~0.801 6).The integrated model demonstrated optimal performance with AUCs of 0.905 5(0.857 0~0.945 4),0.832 7(0.763 3~0.896 4),and 0.889 0(0.834 4~0.934 3).DCA indicated significant net benefit for EGFR prediction at threshold probabilities of 0.15~0.85 using the integrated model.Conclusion Deep learning features from CT images effectively predict EGFR mutation status in NSCLC.The integrated model combining deep learning,clinical,and radiomics features further enhances predictive performance.

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