1.Methodology of drug screening and target identification for new necroptosis inhibitors
Pengchao PAN ; Zhenyu CAI ; Chunlin ZHUANG ; Xiaofei CHEN ; Yifeng CHAI
Journal of Pharmaceutical Analysis 2019;9(2):71-76
Apoptosis has been considered as the only form of regulated cell death for a long time. However, a novel form of programmed cell death called necroptosis was recently reported. The process of necroptosis is regulated and plays a critical role in the occurrence and development of multiple human diseases. Thus, the study on the molecular mechanism of necroptosis and its effective inhibitors has been an attractive field for researchers. Herein, we introduce the molecular mechanism of necroptosis and focus on the literature about necroptosis drug screening in recent years. In addition, the identification of the critical drug targets of the necroptosis is also discussed.
2.Optimization of the compound herba lysimachiae extraction prosess based on orthogonal experiment and response surface method
Pengchao PAN ; Xiaofei CHEN ; Wei CHEN ; Zhiyong GUO ; Yifeng CHAI
Journal of Pharmaceutical Practice 2020;38(1):27-34
Objective To optimize the extraction process of the compound herba lysimachiae by orthogonal experiment and response surface method. Methods The sum of the peak areas of multiple representative components in the compound herba lysimachiae was used as the evaluation index. The ultrasonic extraction time, ultrasonic temperature and ethanol ratio were analyzed to optimize the extraction process conditions by orthogonal experiment and Box-Behnken response surface analysis method. Results Ultrasonic extraction time and ethanol ratio are important factors in the extraction process of the compound herba lysimachiae. The effect of ultrasonic temperature in the extraction process is not significant. The optimal extraction condition for compound herba lysimachiaeare is 10 min ultrasonic extraction time at 55 ℃ with 55% ethanol. Conclusion The optimal extraction process parameters obtained by combining orthogonal experiment and Box-Behnken response surface method can be used for the extraction of representative components from the compound herba lysimachiae and pharmaceutical research in the future.
3.Clinical and CT radiomics features for predicting microsatellite instability-high status of gastric cancer
Pengchao ZHAN ; Liming LI ; Dongbo LYU ; Chenglong LUO ; Zhiwei HU ; Pan LIANG ; Jianbo GAO
Chinese Journal of Medical Imaging Technology 2024;40(1):77-82
Objective To observe the value of clinical and CT radiomics features for predicting microsatellite instability-high(MSI-H)status of gastric cancer.Methods Totally 150 gastric cancer patients including 30 cases of MSI-H positive and 120 cases of MSI-H negative were enrolled and divided into training set(n=105)or validation set(n=45)at the ratio of 7∶3.Based on abdominal vein phase enhanced CT images,lesions radiomics features were extracted and screened,and radiomics scores(Radscore)was calculated.Clinical data and Radscores were compared between MSI-H positive and negative patients in training set and validation set.Based on clinical factors and Radscores being significant different between MSI-H positive and negative ones,clinical model,CT radiomics model and clinical-CT radiomics combination model were constructed,and their predictive value for MSI-H status of gastric cancer were observed.Results Significant differences of tumor location and Radscore were found between MSI-H positive and negative patients in both training and validation sets(all P<0.05).The area under the curve(AUC)of clinical model,CT radiomics model and combination model for evaluating MSI-H status of gastric cancer in training set was 0.760,0.799 and 0.864,respectively,of that in validation set was 0.735,0.812 and 0.849,respectively.AUC of clinical-CT radiomics combination model was greater than that of the other 2 single models(all P<0.05).Conclusion Clinical-CT radiomics combination model based on tumor location and Radscore could effectively predict MSI-H status of gastric cancer.
4.Reproducibility of virtual monoenergetic CT image-derived radiomics features:Experimental study
Pengchao ZHAN ; Xing LIU ; Yahua LI ; Kunpeng WU ; Zhen LI ; Peijie LYU ; Pan LIANG ; Jianbo GAO
Chinese Journal of Medical Imaging Technology 2024;40(5):712-717
Objective To observe the reproducibility of radiomics feature(RF)extracted from virtual monoenergetic image(VMI)of rabbit VX2 hepatoma models obtained with 3 different dual-energy CT(DECT)systems,and to explore relationship of reproducibility and diagnostic performance of RF.Methods Fifteen rabbits with VX2 hepatoma were randomly divided into 3 groups(each n=5).Contrast-enhanced abdominal CT scanning under volume CT dose index(CTDIvol)levels of 6,9 and 12 mGy were performed with dual-source DECT(dsDECT),rapid kV switching DECT(rsDECT)and dual-layer detector DECT(dlDECT),respectively.VMI were reconstructed at 10 keV increments from 40 to 140 keV.RF were extracted from VMI,the reproducibility was assessed using intra-class correlation coefficient(ICC),and those with ICC≥0.8 were considered as reproducible RF.The percentage of reproducible features(denoted by R)were compared among different scanner pairings and different CTDIvol levels.Within each CTDIvol group,the reconstruction energy levels yielding the maximum number(denoted by N)of common RF across different scanner pairings were identified.The receiver operating characteristic(ROC)curve was drawn,the area under the curve(AUC)was calculated,and the diagnostic efficacies of reproducible RF and other RF were compared under optimal reproducible conditions.Spearman correlation coefficient between ICC and the corresponding AUC of RF were calculated.Results RrsDECT-dsDECT(6.45%,95%CI[2.36%,8.87%])was higher than RdlDECT-dsDECT(0.72%,95%CI[0.15%,1.79%])and RrsDECT-dlDECT(1.43%,95%CI[0.60%,4.06%])(all adjusted P<0.05),R9mGy(3.70%,95%CI[1.31%,5.73%])and R12mGy(2.63%,95%CI[0.60%,6.69%])were higher than R6mGy(1.31%,95%CI[0.12%,1.55%])(all adjusted P<0.05).The optimal reproducible reconstruction energy levels of RF under CTDIvol of 6,9 and 12 mGy concentrated at 50-70 keV.AUC of reproducible RFs were higher than of other RF(all adjusted P<0.05)and had certain correlation with the reproducibility(rs=0.102-0.516,P<0.05).Conclusion The reproducibility of RF extracted from contrast-enhanced VMI CT images of rabbit VX2 hepatoma models associated with DECT scanner,CTDIvol level and reconstruction energy level.RF with higher reproducibility might have better diagnostic performance.
5.Clinical data combined with CT radiomics features for evaluating programmed cell death-ligand 1 status in gastric cancer
Qinglong LI ; Pengchao ZHAN ; Jingjing XING ; Xing LIU ; Pan LIANG ; Yonggao ZHANG ; Jianbo GAO
Chinese Journal of Medical Imaging Technology 2024;40(9):1371-1376
Objective To observe the value of clinical data combined with CT radiomics features for evaluating programmed cell death-ligand 1(PD-L1)status in gastric cancer.Methods Totally 277 gastric cancer patients were retrospectively enrolled and randomly divided into training set(n=195)and validation set(n=82)at the ratio of 7:3.There were 88 cases in PD-L1 positive subgroup and 107 cases in negative subgroup of training set,while 37 and 45 cases of validation set,respectively.The clinical and conventional CT features were compared between subgroups in both sets,the independent influencing factors of PD-L1 status in gastric cancer were analyzed,and radiomic features were screened based on CT data.Then clinical model,radiomics model and clinical-radiomics model were established,and the efficacy of each model for evaluating PD-L1 status in gastric cancer was observed.Results In training set,Borrmann type,cN stage,cM stage,clinical stage,maximum diameter and thickness were significant difference between subgroups(all P<0.05).Borrmann type,clinical stage and the thickness were all independent influencing factors of PD-L1 positivity(all P<0.05).The area under the curve(AUC)of clinical model,radiomic model and clinical-radiomics model for evaluating PD-L1 status in gastric cancer in training set was 0.748,0.832 and 0.841,respectively,and was 0.657,0.801 and 0.789 in validation set,respectively.AUC of clinical model was lower than the other models(all P<0.05).Conclusion Clinical data combined with CT radiomics features was helpful for evaluating PD-L1 status in gastric cancer.
6.Preliminary study of quantitative parameters from gastric tumor and spleen CT to predict the clinical stage of gastric cancer
Dongbo LYU ; Pan LIANG ; Mengru LIU ; Pengchao ZHAN ; Zhiwei HU ; Bingbing ZHU ; Songwei YUE ; Jianbo GAO
Chinese Journal of Radiology 2024;58(9):923-928
Objective:To investigate the value of CT quantitative parameters of tumor and spleen in predicting the clinical stage of gastric cancer (Ⅰ/Ⅱ stage and Ⅲ/Ⅳ stage).Methods:This study was a case-control study. The data of 145 patients with gastric cancer confirmed by pathology in the First Affiliated Hospital of Zhengzhou University from February 2019 to June 2021 were retrospectively collected, including 70 cases of Ⅰ/Ⅱ stage and 75 cases of Ⅲ/Ⅳ stage. On the baseline CT images, the tumor related parameters, including tumor thickness, length of tumor, CT attenuation of tumor unenhanced phase, CT attenuation of tumor arterial phase, CT attenuation of tumor venous phase were measured. The spleen related parameters, including splenic thickness, CT attenuation of splenic unenhanced phase, CT attenuation of splenic arterial phase, CT attenuation of splenic venous phase, and standard deviation of CT attenuation (CTsd) in splenic unenhanced phase were also measured. The independent sample t test or Mann-Whitney U test was used to compare the parameters between the Ⅰ/Ⅱ stage and Ⅲ/Ⅳ stage patients. The multi-factor logistic regression analysis was used to find the independent predictors of gastric cancer clinical stage, and establish the combined parameters. The efficiency to the diagnosis of gastric cancer stage of single and combined parameters was evaluated using the operating characteristic curve, and the DeLong test was used to compare the differences of area under the curve (AUC). Results:There were significant differences in tumor thickness, length of tumor, CT attenuation of tumor venous phase, CT attenuation of splenic unenhanced phase, CT attenuation of splenic venous phase, CTsd in splenic unenhanced phase between the Ⅰ/Ⅱ stage and Ⅲ/Ⅳ stage of gastric cancer ( P<0.05). Multivariate analysis showed that tumor thickness ( OR=1.073, 95% CI 1.026-1.123, P=0.002), CT attenuation of splenic venous phase ( OR=1.040, 95% CI 1.011-1.070, P=0.006) and CTsd in splenic unenhanced phase ( OR=1.625, 95% CI 1.330-1.987, P<0.001) were independent risk factors for the clinical stage of gastric cancer and the combined parameters were established. The AUC values of tumor thickness, CT attenuation of splenic venous phase, CTsd in splenic unenhanced phase and combined parameters were 0.655, 0.614, 0.749 and 0.806, respectively. The AUC of combined parameters was higher than those of tumor thickness and CT attenuation of splenic venous phase, and the differences were statistically significant ( Z=3.37, 3.82, both P<0.001). Conclusion:Tumor thickness, CT attenuation of splenic venous phase and CTsd in splenic unenhanced phase are independent risk factors for the clinical stage of gastric cancer, and combined parameters can improve the diagnostic efficiency.
7.UHPLC-Q-TOF/MS analysis of chemical constituents in compound Jinqiancao granules
Zhe ZHANG ; Zhuoran SUN ; Pengchao PAN ; Xiaofei CHEN ; Yifeng CHAI
Journal of Pharmaceutical Practice 2022;40(2):146-151
Objective To qualitatively analyze the main chemical components in compound Jinqiancao granules by ultra high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Methods XBridge BEH C18 column (2.1 mm×100 mm, 2.5 µm) was used for chromatographic separation. The mobile phase was composed of 0.1% formic acid water and 0.1% formic acid-acetonitrile, gradient elution, and the flow rate was 0.4 ml/min. Mass spectrometry was characterized by Quadrupole time-of-flight mass spectrometry (Q-TOF/MS) and positive ion mode scanning. Results Under the optimized LC/MS condition, 47 components in compound Jinqiancao granules were identified. The isomers were distinguished by software calculation. The source of medicinal materials was assigned. Conclusion A rapid and efficient analytical method was established for the identification of chemical components in compound Jinqiancao granules by UHPLC-Q-TOF/MS.