1.Textual Analysis of Classical Prescription Yangweitang Based on Ancient Literature
Lyuyuan LIANG ; Jialei CAO ; Yiping WANG ; Mengmeng GENG ; Lujun ZHU ; Wenxin WEI ; Bingqi WEI ; Wenli SHI ; Bingxiang MA
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):147-157
		                        		
		                        			
		                        			The classical prescription Yangweitang, derived from Zhengzhi Zhunsheng, is specialized in treating syndromes of chill and fever due to exogenous pathogens, inner-cooling, and malaria, and it has been included in the Catalogue of Ancient Classical Formulas (the First Batch) published by the National Administration of Traditional Chinese Medicine (TCM) in 2018. Through bibliographical research, the relevant ancient books and modern documents were systematically sorted out, and it was found that there were many prescriptions related to the Yangweitang from Zhengzhi Zhunsheng. They were interwoven with Yangweitang from Zhengzhi Zhunsheng and widely used in clinical practice. In order to clarify their history and evolution, this paper combed the historical origin of Yangweitang and its related prescriptions and conducted textual analysis on key information such as semantic composition, herb origin, processing method, and efficacy. A total of 896 pieces of data on Yangweitang from Zhengzhi Zhunsheng were collected. 26 pieces of effective data were included after the screening, involving 17 ancient TCM books. Then, a total of 28 pieces of data on prescriptions related to the Yangweitang from Zhengzhi Zhunsheng were included, involving 23 ancient TCM books for reference. The textual analysis showed that Yangweitang originated from the Renshen Yangweitang recorded in Taiping Huimin Heji Jufang in the Song dynasty. Based on the original formula, medical experts from later generations have modified it into many different versions. A comparative analysis showed that Yangweitang from different generations had similar compositions, and the herb origin and processing method were basically clear. The recommended prescriptions are as follows: 37.3 g of Pinelliae Rhizoma Praeparatum Cum Alumine, Magnoliae Officinalis Cortex(fried with ginger juice), and frying with rice water Atractlodis Rhizoma, 27.98 g of Citri Exocarpium Rubrum, 18.65 g of Pogostemon cablin leaf, Tsaoko Fructus, Poria, and Ginseng Radix et Rhizoma, and 9.33 g of Glycyrrhizae Radix et Rhizoma. They could be ground into a coarse powder, with 14.92 g for every dose, and they could be orally taken after being decocted with 450 mL of water, 7 g of fresh ginger, and 2 g of Mume Fructus to 270 mL in warm conditions. Yangweitang from Zhengzhi Zhunsheng has the effect of warming the middle and releasing the external, and it can treat many syndromes including spleen and stomach disharmony caused by chill and fever due to exogenous pathogens and inner-cooling, as well as all kinds of malaria. Modern clinical applications mainly focus on chronic atrophic gastritis and other digestive system diseases. 
		                        		
		                        		
		                        		
		                        	
2.Radiation dose and fractionation regimen for limited stage small cell lung cancer: a survey of current practice patterns of Chinese radiation oncologists
Chang XU ; Meng LI ; Ming CHEN ; Shuchai ZHU ; Nan BI ; Xuwei CAI ; Shuanghu YUAN ; Jianzhong CAO ; Xiao HU ; Jiancheng LI ; Wei ZHOU ; Ping WANG ; Jun WANG ; Lujun ZHAO ; Ningbo LIU
Chinese Journal of Radiation Oncology 2023;32(2):93-98
		                        		
		                        			
		                        			Objective:To investigate the radiation dose and fractionation regimens for limited stage small cell lung cancer (LS-SCLC) in Chinese radiation oncologists.Methods:Over 500 radiation oncologists were surveyed through questionnaire for radiation dose and fractionation regimens for LS-SCLC and 216 valid samples were collected for further analysis. All data were collected by online questionnaire designed by WJX software. Data collection and statistical analysis were performed by SPSS 25.0 statistical software. The differences in categorical variables among different groups were analyzed by Chi-square test and Fisher's exact test. Results:Among 216 participants, 94.9% preferred early concurrent chemoradiotherapy, 69.4% recommended conventional fractionation, 70.8% preferred a total dose of 60 Gy when delivering conventional radiotherapy and 78.7% recommended 45 Gy when administering hyperfractionated radiotherapy.Conclusions:Despite differences in LS-SCLC treatment plans, most of Chinese radiation oncologists prefer to choose 60 Gy conventional fractionated radiotherapy as the main treatment strategy for LS-SCLC patients. Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN) and Chinese Medical Association guidelines or expert consensus play a critical role in guiding treatment decision-making.
		                        		
		                        		
		                        		
		                        	
3.Dosiomics-based prediction of incidence of radiation pneumonitis in lung cancer patients
Meng YAN ; Zhen ZHANG ; Jiaqi YU ; Wei WANG ; Qingxin WANG ; Lujun ZHAO
Chinese Journal of Radiation Oncology 2022;31(8):698-703
		                        		
		                        			
		                        			Objective:To explore the potential of dosiomics in predicting the incidence of radiation pneumonitis by extracting dosiomic features of definitive radiotherapy for lung cancer, and building a machine learning model.Methods:The clinical data, dose files of radiotherapy, planning CT and follow-up CT of 314 patients with lung cancer undergoing definitive radiotherapy were collected retrospectively. According to the clinical data and follow-up CT, the radiation pneumonia was graded, and the dosiomic features of the whole lung were extracted to establish a machine learning model. Dosiomic features associated with radiation pneumonia by LASSO-LR with 1000 bootstrap and AIC backward method with 1000 bootstraps were selected. Training cohort and validation cohort were randomly divided on the basis of 7:3.Logistic regression was used to establish the prediction model, and ROC curve and calibration curve were adopted to evaluate the performance of the model.Results:A total of 120 dosiomic features were extracted. After LASSO-LR dimensionality reduction, 12 features were selected into the "feature pool".After AIC, 6 dosiomic features were finally selected for model construction. The AUC of training cohort was 0.77(95% CI: 0.65 to 0.87), and the AUC of validation cohort was 0.72 (95% CI: 0.64 to 0.81). Conclusion:The dosiomics prediction model has the potential to predict the incidence of radiation pneumonia, but it still needs to include multicenter data and prospective data.
		                        		
		                        		
		                        		
		                        	
4.Meta-analysis of the incidence of radiation pneumonitis between European, American and Asian populations
Jia WEI ; Zhen ZHANG ; Jiaqi YU ; Huijun JIA ; Jia TIAN ; Chunliu MENG ; Kai REN ; Lujun ZHAO
Chinese Journal of Radiation Oncology 2021;30(6):556-562
		                        		
		                        			
		                        			Objective:To compare the incidence of radiation pneumonitis (RP) between lung cancer patients from the European, American and Asian regions.Methods:The studies related to lung cancer and RP were searched from PubMed, Embase, and Cochrane library. According to the different places where the studies were conducted, the searched studies were divided into two types: Asian studies and European, American and Australian studies. The incidence of RP between two regions was summarized. Studies related to dosimetry parameters were searched from PubMed database.Results:A total of 3, 190 patients from 14studies were included. Meta-analysis results showed that the incidence of ≥ grade 3 RP was similar in patients from Asia and Europe, America and Australia (4.9% vs. 4.6%, P=0.895), whereas the incidence of grade 5 RP in Asia was significantly higher than that in Europe, America and Australia (1.5% vs. 0.2%, P=0.002). Moreover, the lung irradiation dose received by the patients in the Asian group was relatively low. Lung V 20Gy dose limitation standard was reported in 21studies. Further analysis found no statistical significance in lung V 20Gy dose limitation standard between two regions ( P=0.440), and the standard in Asian studies is likely to be even stricter. Conclusions:The incidence of RP after chemoradiotherapy in lung cancer patients in Asia is relatively higher compared with those in Europe, America and Australia. The differences in dose limitation standard should be noted when the thoracic radiation regimen based solely on the data from foreign studies is applied to the patients in Asia.
		                        		
		                        		
		                        		
		                        	
5.Study of application of radiomics model in predicting radiation pneumontis in patients with lung cancer and esophageal cancer
Jiaqi YU ; Zhen ZHANG ; Kai REN ; Wei WANG ; Ying LIU ; Qian LI ; Zhaoxiang YE ; Lujun ZHAO
Chinese Journal of Radiation Oncology 2021;30(11):1111-1116
		                        		
		                        			
		                        			Objective:To analyze and explore the common radiomics features of radiation pneumonitis (RP) in patients with lung cancer and esophageal cancer, and then establish a prediction model that can predict the occurrence of RP in two types of cancer after radiotherapy.Methods:Clinical data of 100 patients with stage Ⅲ lung cancer and 100 patients with stage Ⅲ esophageal cancer who received radical radiotherapy were retrospectively analyzed. The RP was graded by imaging data and clinical information during follow-up, and the planning CT images were collected. The whole lung was used as the volume of interest to extract radiomics features. The radiomics features, clinical and dosimetric parameters related to RP were analyzed, and the model was constructed by machine learning.Results:A total of 1691 radiomics features were extracted from CT images. After ANOVA and LASSO dimensionality reduction in lung cancer and esophageal cancer patients, 8 and 6 radiomics features associated with RP were identified, and 5 of them were the same. Using the random forest to construct the prediction model, lung cancer and esophageal cancer were alternately used as the training and validation sets. The AUC values of esophageal cancer and lung cancer as the independent validation set were 0.662 and 0.645.Conclusions:It is feasible to construct a common prediction model of RP in patients with lung cancer and esophageal cancer. Nevertheless, it is necessary to further expand the sample size and include clinical and dosimetric parameters to increase its accuracy, stability and generalization ability.
		                        		
		                        		
		                        		
		                        	
6.Preliminary study of predicting radiation pneumonitis based on radiomics technology
Zhen ZHANG ; Lujun ZHAO ; Wei WANG ; Jingjing CUI ; Qi WANG ; Ying LIU ; Qingxin WANG ; Daguang ZHANG
Chinese Journal of Radiation Oncology 2020;29(6):427-431
		                        		
		                        			
		                        			Objective:To identify the radiomics features related to the occurrence of radiation pneumonitis based on localized CT images of the chest in lung cancer patients, establish a machine learning model and investigate the value of radiomics technology in predicting the incidence of radiation pneumonitis.Methods:Clinical data of 86 patients with stage Ⅲ non-small cell lung cancer who received radical intensity-modulated radiation therapy (IMRT) were retrospectively analyzed. The radiation pneumonitis was graded by follow-up imaging data and clinical information. The planning CT images were collected. The lung was used as the volume of interest for extraction of radiomics features. The radiomics features, clinical and dosimetric parameters associated with the incidence of radiation pneumonitis were analyzed. Using the support vector machine to construct the model, the prediction performance of the model was evaluated by the five-fold verification method.Results:A total of 1029 radiomics features were extracted from CT images and 5 features were selected by ANOVA and LASSO. Two validation sets showed differences between adopting radiomics features alone and incorporating clinical and dosimetric parameters and radiomics features (AUC=0.67 and 0.71, respectively).Conclusions:The radiomics model constructed by planning CT images of lung cancer patients has the potential to predict the occurrence of radiation pneumonitis. Addition of clinical and dosimetric parameters can further improve the prediction performance of the model.
		                        		
		                        		
		                        		
		                        	
7.Effects of Na+-H+ exchanger 1 knockdown on protein expression levels of ATP binding cassette transporter A1 and cholesterol efflux in hypoxic RAW264.7 cells
Xiangang MO ; Li ZHANG ; Luochao ZHANG ; Wei HONG ; Lan WANG ; Lujun DAI ; Qianjun WEN
Chinese Journal of Geriatrics 2017;36(8):909-914
		                        		
		                        			
		                        			Objective To explore the effects of Na+ H-exchanger 1(NHE1) knockdown on ATP binding cassette transporter A1 (ABCA1) protein expression levels and cholesterol efflux in the hypoxic RAW264.7 cells.Methods The RAW264.7 cells were infected with lentiviral vectors expressing shRNA specific for NHE1(siNHE1) or scramble RNA (siNC).The expression of NHE1 at mRNA or protein level was detected by qRT-PCR and Western blotting respectively in the infected cells after 24 h in a hypoxia condition.In the meantime,the methods of SNARF-1,Fluo-4 NW andSuc-LLVY-aminoluciferin were employed to determine NHE1 activity,intracellular Ca2+ ([Ca2+]i) and calpain activity,respectively.Furthermore,ABCA1 protein levels were detected by Western blotting in the 24 h hypoxic cells.In parallel,the intracellular cholesterol content and cholesterol efflux were analyzed by the methods of combined enzymatic HLPC and 3 H-cholesterol.Results The hypoxia condition versus the normoxia condition up-regulated NHE1 mRNA and protein expression level and activity by 2.48 folds,1.28 folds and 61.96% (all P<0.05),and increased[Ca2+]i and calpain activity by 4.51 folds and 2.41 folds(all P<0.05).Whereas the NHE1 mRNA and protein expression and activity at the presence of hypoxia were inhibited by siNHE1 with the inhibition ratio of 84.95%,60.75% and 66.44%,respectively (all P<0.05)and[Ca2+]i and calpain activity were reduced by 59.23% and 54.66% (P<0.05).Furthermore,the ABCA1 protein level was 61.67% lower in the hypoxic cells than in the normoxic cells (P<0.05),and siNHE1 was increased by 56.52% after treatment of Hypoxia.Hypoxia elevated intracellular total cholesterol and cholesterol ester by 74.57 % and 101.81% (all P<0.05).Treatment with siNHE1 in the hypoxia condition can reduce total cholesterol and cholesterol ester by 34.24 % 及 49.66 % (all P<0.05).Hypoxia reduced the cholesterol efflux by 34.79%(P<0.05),which were partially reversed by siNHE1.Conclusions NHE1 might play an important role in hypoxia-induced ABCA1 protein attenuation and reverse cholesterol transport dysfunction through[Ca2+]i/calpain pathway.
		                        		
		                        		
		                        		
		                        	
8.Screening of High-Affinity α-Glucosidase Inhibitors fromCichorium Glandulosum Boiss.et Hout Seed Based on UltrafiltrationLiquid Chromatography-Mass Spectrometry and Molecular Docking
Haijun CHEN ; Huiyu QIN ; Fei LONG ; Wei YU ; Yinghui WANG ; Lujun CHEN ; Quankai LI ; Wen CHEN ; Dongmei QIN ; Bo HAN
Chinese Journal of Analytical Chemistry 2017;45(6):889-897
		                        		
		                        			
		                        			High-affinity α-glucosidase inhibitors were screened from Cichorium glundulosum Boiss.et Hout seed (CGS) extract by ultra-filtration affinity-liquid chromatography-mass spectrometry (UF-LC-MS) and molecular docking.By taking 4-nitrobenzene-α-D-glucopyranoside (PNPG) as substrate and acarbose as positive control to evaluate the inhibitory activity of CGS extract, IC50 of acarbose and CGS extract were 0.003 mg/mL and 0.447 mg/mL, respectively.Meanwhile, 4 compounds from CGS extract by UF-LC-MS were screened and identified.Then by using autodock software, the compounds that combined with α-glucosidase were well screened out, including chlorogenic acid and isochlorogenic acid A.The inhibitory activity of chlorogenic acid and chlorogenic acid A against α-glucosidase was verified in vitro.The results showed that the inhibitory activity of the compounds toward α-glucosidase presented the sequence of acarbose>isochlorogenic acid A>chlorogenic acid.The inhibition rate of isochlorogenic acid A was close to acarbose.The experimental results illustrated that UF-LC-MS and molecular docking could be used to screen high affinity enzyme inhibitors from CGS.
		                        		
		                        		
		                        		
		                        	
9.Radiochemotherapy combined with adoptive immunotherapy with cytokine-induced killer cells for locally advanced non-small cell lung cancer:a preliminary study
Shuai WANG ; Xiubao REN ; Feng WEI ; Yang CHEN ; Jing LUO ; Lujun ZHAO
Chinese Journal of Radiation Oncology 2016;25(4):345-350
		                        		
		                        			
		                        			Objective To investigate and compare the clinical effects of radiochemotherapy alone or in combination with adoptive immunotherapy with cytokine-induced killer ( CIK) cells in patients with locally advanced non-small cell lung cancer (NSCLC).Methods The clinical data of 125 patients with locally advanced NSCLC who were admitted from 2011 to 2012 and did not undergo surgery were analyzed retrospectively, and among these patients, 102 received radiochemotherapy alone ( control group) , and 23 received radiochemotherapy combined with adoptive immunotherapy with CIK cells ( multimodality therapy group) .The two groups were matched at a ratio of 1:2 using propensity score matching, and the factors considered included tumor stage, radiochemotherapy regimen, and outcome after radiochemotherapy.Then 59 patients ( 22 from the multimodality therapy group and 37 from the control group) were enrolled, and survival and tumor control were compared between the two groups.The Kaplan-Meier method was used to calculate survival rates and the log-rank test was used for survival difference analysis and univariate prognostic analysis.Results The 1-, 2-, and 3-year overall survival ( OS) rates were 73%, 32%, and 16%, respectively, in the control group, and 91%, 59%, and 41%, respectively, in the multimodality therapy group ( P=0.030) .The 1-, 2-, and 3-year progression-free survival rates were 61%, 21%, and 17%, respectively, in the control group, and 45%, 10%, and 10%, respectively, in the multimodality therapy group ( P=0.538) .As for the patients with stage ⅢB NSCLC, those in the multimodality therapy group had a significantly higher 3-year OS rate than those in the control group (47%vs.11%, P=0.026). In the patients receiving sequential chemoradiotherapy, those in the multimodality therapy group had a significantly higher 3-year OS rate than those in the control group ( 46%vs.11%, P=0.003) .As for the 
 patients with squamous cell carcinoma, those in the multimodality therapy group had a significantly higher 3-year distant metastasis-free survival rate than those in the control group ( 73%vs.22%, P=0.029) .The two groups showed similar incidence rates of adverse events, and compared with the control group, the multimodality therapy group had a lower incidence rate of radiation pneumonitis (9%vs.15%, P=0.889) and a higher incidence rate of radiation esophagitis (12%vs.7%, P=0.097).Conclusions Some patients with locally advanced NSCLC can benefit from radiochemotherapy combined with adoptive immunotherapy with CIK cells, but the intended population, timing, and dose safety still need further investigation.
		                        		
		                        		
		                        		
		                        	
10.A study of finite discontinuity-volumetric modulated arc therapy for mid-and distal-Esophageal Carcinoma
Qingxin WANG ; Bo JIANG ; Jiana SUN ; Lujun ZHAO ; Zhiyong YUAN ; Liming XU ; Wei WANG
Chinese Journal of Radiation Oncology 2016;25(11):1238-1243
		                        		
		                        			
		                        			Objective To implement the finite discontinuity?volumetric modulated arc therapy ( FD?VMAT) in the Pinnacle planning system, and to investigate its clinical significance. Methods Eight patients with thoracic esophageal cancer in our hospital were enrolled as subjects. FD?VMAT was fulfilled in the Pinnacle planning system using a developed program. FD?VMAT, VMAT, and fixed?field intensity?modulated radiotherapy ( IMRT ) plans were designed for each patient. The conformity index ( CI ) and homogeneity index ( HI) of the planning target volume ( PTV) ,doses to organs at risk,passing rate for plan verification,number of monitor units,and treatment time were used to evaluate the plans. Comparison between different plans was made by paired t test. Results For the PTV,there was no significant difference in CI between FD?VMAT and VAMT ( P=0?186 );FD?VMAT had a significantly worse HI than VMAT ( P=0?001);however,both the CI and HI were significantly improved in FD?VMAT than in IMRT ( P=0?006, 0?002) . Compared with IMRT, FD?VMAT, retaining the advantage of VMAT, had pulmonary V20 and V30 significantly reduced by 19?79% and 20?32%,respectively (P=0?000,0?000).For the pulmonary low?dose regions (≤V5 ) ,FD?VMAT retained the advantage of IMRT and had lower doses than VMAT. Particularly, pulmonary V2 was significantly reduced by 16?79%(P=0?000).The mean lung dose was significantly lower in FD?VMAT than in VMAT or IMRT (P=0?001,0?000).There were no significant differences in D1cc to spinal cord PRV,heart V30,or passing rate for plan verification between the three therapies. The heart V40 and mean heart dose in FD?VMAT were similar to those in VMAT (P=0?175,0?468),but significantly lower than those in IMRT ( P=0?021,0?002) . FD?VMAT had a larger number of monitor units and longer treatment time than VMAT. Compared with IMRT, the number of monitor units and treatment time were reduced by 13?6% and 49?6% in FD?VMAT,respectively. Conclusions Compared with VMAT and IMRT, the application of the developed FD?VMAT in the treatment of thoracic esophageal cancer can further reduce the lung dose while keeping the PTV coverage,protection of the heart and spinal cord,and high efficacy. FD?VMAT is a new therapy available for thoracic esophageal cancer.
		                        		
		                        		
		                        		
		                        	
            
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