1.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.
2.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.
3.LIU Shenlin's Experience in Treating Gastric Cancer with the Thinking of "Prescription According to Tendency"
Qingmin SUN ; Cancan ZHANG ; Xiaoxia ZHENG ; Yujia LU ; Xiang ZHANG ; Shanshan ZHENG ; Jian WU ;
Journal of Traditional Chinese Medicine 2024;65(20):2075-2080
This paper summarized the clinical experience of Professor LIU Shenlin in diagnosing and treating gastric cancer with the thinking of "prescription according to tendency". In this paper, the thinking of diagnosis and treatment for gastric cancer and medication skills were summarized into four dimensions: power, energy, chronology and situation. The diagnosis emphasizes the tendency of qi power, considering that the onset of gastric cancer primarily stems from the disorder of qi movement in zang-fu organs, and emphasizing the importance of regulating the liver and spleen qi to intercept the tendency of disease. It points out that dampness-phlegm-stasis-toxin is a crucial link leading to the metabolic imbalance of body energy, and Professor LIU adepts at using methods such as breaking up blood and expelling stasis, and clearing heat and resolving toxins to block the pathological chain reaction caused by energy imbalance and to restore the homeostasis of the organism. In the treatment process, according to the characteristics of gastric cancer staging and chronological evolution, we will explore the changes of the exuberance and weakness of healthy qi and pathogenic qi in the context of the chronologic tendency, and adjust the dosage of attacking and tonic medicines in different stages of the disease in order to balance and restore the body. The "situation" is in line with the state of consumptive disease in advanced gastric cancer, Professor LIU skillfully uses large doses of Huangqi (Astragalus mongholicus) with flexible combination of medicinals to replenish deficiencies, invigorate qi, and regulate blood vessels.
4.Application of magnetic resonance imaging in patients with type 2 diabetic painful neuropathy
Shuqian WANG ; Cancan HUI ; Yuwei CHENG ; Xiujuan HU ; Xiaorong YIN ; Mengjie CUI ; Qinyi HUANG ; Yangliu YIN ; Yan SUN
Journal of Clinical Medicine in Practice 2024;28(8):16-21
Objective To observe the application effect of magnetic resonance imaging technology in evaluating the brain structure and function of patients with type 2 diabetic painful neuropathy (PDN). Methods Forty patients with type 2 diabetes mellitus hospitalized in our hospital were selected as the study objects, and were divided into diabetes mellitus (DM) group (
5.Association of time in range and glucose management indicator with the risk of type 2 diabetic nephropathy
Shuqian Wang ; Xiujuan Hu ; Xiaorong Yin ; Mengjie Cui ; qinyi Huang ; Yangliu Yin ; Cancan Hui ; Yuwei Cheng ; Ya Zhang ; Yan Sun
Acta Universitatis Medicinalis Anhui 2023;58(10):1782-1786
Objective :
To explore the association of time in range(TIR) and glucose management indicator ( GMI) with the risk of type 2 diabetic nephropathy (DN) .
Methods :
The clinical data of 215 patients with type 2 diabetes mellitus (T2DM) were collected and analyzed.According to the results of estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio( UACR) ,they were divided into 117 patients with T2DM and 98 patients with DN.The clinical data,biochemical indicators and continuous glucose monitoring ( CGM) indicators of the two groups were compared.Logistic regression was used to analyze the influencing factors of DN risk.The predictive value of TIR and GMI on the risk of DN was evaluated by receiver operating characteristic (ROC) curve.
Results:
There were significant differences in age,duration of diabetes,systolic blood pressure,glycosylated hemoglobin ( HbA1c) ,fasting plasma glucose (FPG) ,2 hour postprandial plasma glucose (2hPG) ,creatinine( Cr) ,UACR, eGFR between the two groups(P<0. 05) .There were statistically significant differences between the two groups in the CGM indexes of GMI,mean absolute difference of mean of daily differences ( MODD) ,glucose above target range time(TAR) and TIR(P<0. 05) .The results of logistic regression analysis showed that TIR was a protective factor of DN.In the ROC curve analysis of TIR prediction DN,the area under the ROC curve was 0. 718 (95% CI = 0. 648 ~0. 789,P<0. 001) ,and the Yoden index was 0. 38.At this time,the sensitivity was 66. 7% ,and the specificity was 71. 3%.In the ROC curve analysis of GMI prediction DN,the area under the ROC curve was 0. 701 (95% CI = 0. 629 ~0. 774,P<0. 001) ,and the Yoden index was 0. 368.At this time,the sensitivity was 63. 3% , and the specificity was 73. 5%.
Conclusion
Specifically,lower TIR and higher GMI increase the risk of DN.
6.Study on the intestinal absorption characteristics of saikosaponins
Yazhi WANG ; Qiyi WANG ; Wenzhong FENG ; Shuangshuang CHEN ; Xinguang SUN ; Lijuan ZHOU ; Yan ZHANG ; Jianyong ZHANG ; Cancan DUAN
China Pharmacy 2023;34(14):1681-1685
OBJECTIVE To explore the intestinal absorption characteristics of saikosaponins. METHODS Based on everted intestinal sac model, using accumulative absorption amount (Q) and absorption rate constant (Ka) as indexes, UHPLC-MS/MS technique as a method, the absorption of saikosaponin A, B2, C, D and F from total saponins of Bupleurum chinense (8 g/mL, by crude drug) in the duodenum, jejunum and ileum was detected. RESULTS The correlation coefficients (r) of the regression equations for the absorption of saikosaponins A, B2, C and F in the duodenum, jejunum and ileum were all higher than 0.95, while the r of saikosaponin D in the above intestinal segments was lower than 0.95; compared with the absorption of the same composition in the duodenum, the Q and Ka of saikosaponin A and C circulating in jejunum and ileum for 120 min, as well as the Q and Ka of saikosaponin F circulating in the ileum for 120 min were significantly decreased (P<0.05). CONCLUSIONS Saikosaponin A and the other 4 saikosaponins are all absorbed in the duodenum, jejunum and ileum; among them, saikosaponin A, B2, C and F are linearly absorbed, which conforms to the zero-order absorption characteristics, but saikosaponin D shows non- linear absorption.
7.KCTD4 interacts with CLIC1 to disrupt calcium homeostasis and promote metastasis in esophageal cancer.
Cancan ZHENG ; Xiaomei YU ; Taoyang XU ; Zhichao LIU ; Zhili JIANG ; Jiaojiao XU ; Jing YANG ; Guogeng ZHANG ; Yan HE ; Han YANG ; Xingyuan SHI ; Zhigang LI ; Jinbao LIU ; Wen Wen XU
Acta Pharmaceutica Sinica B 2023;13(10):4217-4233
Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca2+ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca2+-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.
8.Establishment of the fingerprint of Temurin- 5 powder and content determination of 4 components
Cancan SUN ; Jing ZHOU ; Tuerhong SUBIYINUER ; Guizhi MA
China Pharmacy 2022;33(4):452-457
OBJECTIVE To establish the fing erprint of Temurin- 5 powder,conduct chemical pattern recognition analysis ,and determine the contents of 4 components simultaneously. METHODS The fingerprints of 10 batches of Temurin- 5 powder were established and similarity evaluation was performed by using high performance liquid chromatography (HPLC)combined with the Similarity Evaluation System of Chromatographic Fingerprints of Traditional Chinese Medicine (2012 edition);common peaks were identified by comparing with mixed substance control. The common peaks were analyzed by systematic cluster analysis and principal component analysis with SPSS 26.0 software. The HPLC method was used to determine the contents of gallic acid , geniposide,chlorogenic acid and ellagic acid in 10 batches of samples. RESULTS A total of 15 common peaks were identified from the fingerprints of 10 batches of Temurin-5 powder,and the similarity was 0.997-0.999. It was identified that peak 1 was gallic acid ,peak 3 was geniposide ,peak 5 was chlorogenic acid and peak 12 was ellagic acid. Among the 10 batches of samples , S4 and S 9 were grouped into one category ,S6-S8 were grouped into one category ,and the other batches of samples were grouped into one category. The accumulative variance contribution rate of first three principal components was 89.245%. The linear ranges of gallic acid ,geniposide,chlorogenic acid and ellagic acid were 5.55-177.5,15.98-511.5,2.56-82.0 and 13.48-431.5 μg/mL, respectively. RSDs of precision ,stability(24 h)and repeatability tests were all less than 2%(n=6 or n=7). The average recoveries were 101.56%,102.21%,98.60% and 96.62%,respectively,RSDs were 1.90%,1.61%,1.58% and 1.73%(n=6). Average contents of above components were 5.03-5.64,10.38-12.16,1.40-1.69,6.47-7.11 mg/g,respectively. CONCLUSIONS The established fingerprint is stable and feasible ,and the content determination method meets the relevant regulations. Combined with chemical pattern recognition analysis ,it can be used for the quality control of Temurin- 5 powder.
9.One-step multiplex nested real-time RT-PCR assay for 2019-nCoV and Influenza A/B viruses detection
Kui ZHENG ; Fangfang SUN ; Cancan YAO ; Jun DAI ; Yongxia SHI ; Xiaobo LI ; Jicheng HUANG
Chinese Journal of Laboratory Medicine 2022;45(11):1144-1149
Objective:To develop a single-tube one-step multiplex nested real-time reverse transcription polymerase chain reaction (RT-PCR) assay for the simultaneous detection of 2019-nCoV, influenza A virus, influenza B virus and internal-control with human-derived gene.Methods:This study included 30 positive specimens for 2019-nCoV nucleic acid detection and 336 screening specimens collected from the arrivals at Guangzhou Baiyun Airport between February 2020 and February 2022. Sixty-four positive specimens of other respiratory pathogens were also collected from the arrivals at Guangzhou Baiyun Airport during the three-year period before the occurrence of COVID19 outbreak in 2020, and 7 positive viral strains of respiratory pathogens were provided by collaborative laboratories. In order to establish a set of multiplex nested real-time RT-PCR assay, a group of primers and probe combinations for a multiplex nested real-time RT-PCR was designed and screened according to a selection of nucleotide conserved regions of the ORF and N genes of 2019-nCoV and the M gene of influenza A and B viruses, while nested amplification primers and probe for the internal-control with human-derived gene were introduced. Then the prepared pseudovirus-positive quality control and sample discs were applied to evaluate the sensitivity and specificity. Clinical specimens were performed to validate the applicability of the method.Results:The results show that the established one-step multiplex nested real-time RT-PCR assay can specifically detect 2019-nCoV and influenza A and B viruses, with the limit-of-detection of about 125 copies/ml for 2019-nCoV and about 250 copies/ml for influenza A and B viruses. Totally 101 positive samples of various respiratory pathogens were detected, showing that the detection sensitivities of 2019-nCoV and influenza A and B viruses were 96.67%, 92.86% and 96.15%, respectively, with the specificity of 100%. No false-positive detection was found in the applied detection of more than 300 clinical samples.Conclusions:A one-step multiplex nested real-time RT-PCR assay for 2019-nCoV, influenza A and B viruses and human-derived gene internal-control was developed. The assay has good sensitivity and specificity and can be used for rapid screening of 2019-nCoV and influenza A and B viruses in high-volume samples.
10.Identification of Medium-Length Antineurofilament Autoantibodies in Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis
Shisi WANG ; Cancan XU ; Xiaobo SUN ; Yifan ZHOU ; Yaqing SHU ; Shangzhou XIA ; Zhengqi LU ; Wei QIU ; Xiaofen ZHONG ; Lisheng PENG
Journal of Clinical Neurology 2020;16(3):470-479
Background:
and Purpose: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe central nervous system disorder mediated by NMDAR antibodies that damages neurons. We investigated the correlation between cytoskeletal autoantibodies and the clinical severity in patients with anti-NMDAR encephalitis.
Methods:
Non-NMDAR autoantibodies were identified by screening matched cerebrospinal fluid (CSF) and the serum samples of 45 consecutive patients with anti-NMDAR encephalitis and 60 healthy individuals against N-methyl-D-aspartate receptor 1-transfected and nontransfected human embryonic kidney 293T cells. Immunocytochemistry was performed to assess antibody binding in rat brain sections and primary cortical neurons. Cell-based assays and Western blotting were applied to identify autoantibodies targeting medium neurofilaments (NFMs). We compared clinical characteristics between patients with NMDAR encephalitis who were positive and negative for anti-NFM-autoantibodies.
Results:
Anti-NFM autoantibodies were detected in both the serum and CSF in one patient (2%) and in the serum only in six patients (13%). No antibodies were detected in the serum of healthy controls (7/45 vs. 0/60, p=0.0016). Four of the seven patients with anti-NFM autoantibodies in serum were children (57%), and three (43%) had abnormalities in brain magnetic resonance imaging. These patients responded well to immunotherapy, and either no significant or only mild disability was observed at the last follow-up. Anti-NMDAR encephalitis did not differ with the presence of anti-NFM autoantibodies.
Conclusions
Anti-NFM autoantibodies may be present in patients with anti-NMDAR encephalitis, indicating underlying neuronal damage. A large cohort study is warranted to investigate the clinical differences between patients with NMDAR encephalitis according to their antiNFM antibody status.


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