1.Long-term efficacy analysis of salvage re-irradiation therapy for patients with locally recurrent esophageal cancer after definitive chemoradiotherapy
Guangbin GAO ; Chen ZHENG ; Qihui LI ; Qing LIU ; Wenpeng JIAO ; Yajing WU ; Yunjie CHENG ; Chang ZHAI ; Yueping LIU ; Jun WANG
Chinese Journal of Radiation Oncology 2024;33(8):711-718
		                        		
		                        			
		                        			Objective:To analyze clinical features, short-term efficacy and side effects of salvage re-irradiation therapy for patients with locally recurrent esophageal cancer after definitive chemoradiotherapy, to investigate the prognostic factors of re-irradiation with precise radiotherapy techniques.Methods:A retrospective analysis was performed on patients with locally recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy treated in the Fourth Hospital of Hebei Medical University from January 2008 to December 2016. The patients underwent re-irradiation therapy (re-RT) or re-irradiation therapy concurrent chemotherapy (re-CCRT). The main observation index was after-recurrence survival (ARS), which was calculated by Kaplan-Meier method for survival analysis. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox regression model.Results:A total of 109 patients were included, with a median age of 66 years (43-89 years), and a median follow-up time of 120.8 months (79.0-176.5 months). The objective response rates (ORR) and dysphagia improvement rates (DIR) in all patients were 64.2% and 63.0%, respectively. The median ARS and 1-, 3-, 5-, 8-year survival rates in all patients were 7.8 months and 32.1%, 9.2%, 7.3% and 2.3%, respectively. The median ARS and 1-, 3-, 5-years survival rates were 10.8 months and 45.9%, 13.5%, 10.8% for patients with time to recurrence (TTR) ≥24 months, significantly longer than those of 5.7 months and 25.0%, 6.9%, 5.6% for patients with TTR<24 months ( χ2=7.99, P=0.005). The median ARS in groups with re-irradiation dose of ≤50 Gy,>50-54 Gy, and>54 Gy groups were 5.7, 10.0 and 8.1 months, respectively ( χ2=6.94, P=0.031). The 1-, 3- and 5-year survival rates were 30.4%, 5.1%, and 3.8% for re-RT versus 36.7%, 20.0%, and 16.7% for re-CCRT ( χ2=2.12, P=0.145). Multivariate analysis showed that TTR ( HR=0.607, 95% CI=0.372-0.991, P=0.046) and lesion length ( HR=0.603, 95% CI=0.371-0.982, P=0.042) were the independent factors for ARS. There was no significant difference in ≥2 grade pneumonitis and 2-3 grade radiation esophagitis between the re-RT and re-CCRT groups ( χ2=0.25, P=0.619; χ2=0.51, P=0.808). The morbidity of ≥2 grade myelosuppression in the re-RT group was significantly lower than that in the re-CCRT group (3.7% vs. 36.7%, χ2=18.15, P<0.001). Conclusions:Precise re-irradiation therapy for patients with locally recurrent esophageal cancer after definitive chemoradiotherapy can alleviate dysphagia, but ARS remains poor. Re-irradiation dose range from>50-54 Gy may be suitable for locally relapse patients as salvage treatment. Patients with TTR≥24 months and lesion length ≤5 cm obtain favorable prognosis.
		                        		
		                        		
		                        		
		                        	
2.Research progress of artemisinin and its derivatives in prevention and treatment of cardiovascular diseases
Wenkuan LUO ; Jianqi LU ; Wenpeng CHEN ; Yan PANG ; Chaoxin PAN ; Zhihao WEN
China Pharmacy 2023;34(2):246-250
		                        		
		                        			
		                        			Artemisinin is a sesquiterpene lactone containing a peroxide group isolated from the plant Artemisia annua. It has antimalarial activity and is effective for the treatment of malaria. With the deepening of research on artemisinin, the pharmacological effects of artemisinin and its derivatives in other systems have gradually become a research hotspot. This article reviews the research progress of artemisinin and its derivatives in the prevention and treatment of cardiovascular diseases. Artemisinin and its derivatives in the prevention and treatment of cardiovascular disease have shown anti-atherosclerosis, lipid- lowering, inhibition of vascular remodeling, reducing vascular pressure, improving ventricular remodeling, anti-arrhythmia, protection of vascular endothelium, prevention and treatment of diabetic cardiovascular complications and protection of myocardial cells and other pharmacological effects. It provides a new treatment strategy for common cardiovascular diseases such as hypertension, arrhythmia, coronary heart disease complications after stent implantation, hyperlipidemia, etc. However, there are few studies on the antiplatelet aggregation and antithrombotic effects of artemisinin and its derivatives, the molecular mechanisms behind many pharmacological effects have not yet been clarified, and there is little clinical application. A large number of basic studies and clinical trials are still needed to answer these questions.
		                        		
		                        		
		                        		
		                        	
3.Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapy.
Xiaoshuang NIU ; Menghan WU ; Guodong LI ; Xiuman ZHOU ; Wenpeng CAO ; Wenjie ZHAI ; Aijun WU ; Xiaowen ZHOU ; Shengzhe JIN ; Guanyu CHEN ; Yanying LI ; Jiangfeng DU ; Yahong WU ; Lu QIU ; Wenshan ZHAO ; Yanfeng GAO
Acta Pharmaceutica Sinica B 2023;13(11):4511-4522
		                        		
		                        			
		                        			Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8+ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8+ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.
		                        		
		                        		
		                        		
		                        	
4.Identification of Microscopic Characteristics of Amomum villosum from Different Habitats and Its Adulterants
Xinhua HU ; Wenpeng YUAN ; Jie WANG ; Wanshan CHEN ; Shuhong WANG ; Yanming WANG
China Pharmacy 2021;32(5):590-594
		                        		
		                        			
		                        			OBJECTIVE:To identify Amomum villosum from different habitats and its adulterants. METHODS :Through the identification methods of microscopic characteristics ,microscopic characteristics maps of 9 batches of A. villosum from genuine producing areas ,domestic commercially available A. villosum and its adulterants were obtained. The feature maps were extracted digitally and analyzed by SPSS 21.0 software. RESULTS :Commercially available A. villosum was mainly from Guangdong , Guangxi,Yunnan and Fujian ;the collected adulterants of A. villosum included A. villosum Lour. var. xanthioides T.L.Wu et Senjen , A. aurantiacum H. T. Tsai et S. W. Zhao and other A. species from Yunnan Xishuangbanna , Laos and Myanmar. Under the microscope,it was observed that microscopic characteristics of surface (such as exocarp color ,prickle,non-glandular hairs , endocarp color ,endocarp oil chamber ) of A. villosum from different habitats and its adulterants were different. There was statistically significant difference in fruit width values and endocarp oil point diameter among all samples (P<0.05). CONCLUSIONS:The microscopic characteristics maps of A. villosum from different habitats and its adulterants by the microscopic characteristics identification methods will make up for the deficiency of traditional experience identification. The quantitative analysis of micro-property and the establishment of micro-property database of A. villosum can provide reference for the property identification and quality control of this medicinal material.
		                        		
		                        		
		                        		
		                        	
5.Interpretation of group standard for Clostridioides difficile infection diagnosis
Yuan WU ; Jinxing LU ; Zhongqiang YAN ; Yunxi LIU ; Wenpeng GU ; Xiaoqing FU ; Yingchun XU ; Anhua WU ; Haihui HUANG ; Zhiyong ZONG ; Dazhi JIN ; Jianhong ZHAO ; Ye CHEN ; Weiping LIU ; Weiguang LI
Chinese Journal of Epidemiology 2021;42(1):64-67
		                        		
		                        			
		                        			Clostridioides difficile is a key pathogen of antibiotic related diarrhea and hospital associated infection, causing several outbreaks in Europe and North Americans and resulting in severe disease burden. However, the standardized diagnostic principle and detection specifications in C. difficile infection (CDI) survey are limited in China, and the infection rate and disease burden of CDI in China are unclear. Therefore, National Institute for Communicable Disease Control and Prevention,National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, together with another 11 institutions, draft the group standard entitled "Diagnosis of Clostridium difficile infection (T/CPMA 008-2020)" of Chinese Preventive Medicine Association. Based on the principle of "legality, scientificity, advancement, and feasibility", this standard clarifies risk factors, diagnosis principles, diagnoses and differential diagnoses in order to improve the accuracy of CDI diagnosis in clinical practice, guide the surveillance for CDI, and understand the infection rate and disease burden of CDI in China .
		                        		
		                        		
		                        		
		                        	
6.Identification of serum peptide biomarker for ovarian cancer diagnosis by Clin-TOF-II-MS combined with magnetic beads technology
Lin XIU ; Ning LI ; Wenpeng WANG ; Feng CHEN ; Guangwen YUAN ; Yangchun SUN ; Rong ZHANG ; Xiaoguang LI ; Jing ZUO ; Nan LI ; Wei CUI ; Lingying WU
Chinese Journal of Oncology 2021;43(11):1188-1195
		                        		
		                        			
		                        			Objective:To explore the serum cyclic polypeptide biomarkers for ovarian cancer diagnosis.Methods:A total of 54 patients with epithelial ovarian cancer confirmed by pathology in Cancer Hospital, Chinese Academy of Medical Sciences from March 2018 to September 2018 were selected as the study subjects, and 40 healthy women with normal examination results in the cancer screening center were selected as the control. All of the samples were randomly divided into training set and validation set at the ratio of 1∶1 with a random number. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead technology was used for detecting peptide profiling in serum samples to screen significantly differently expressed peptides between ovarian cancer group and control group of the training set (score>5). Receiver operating characteristic (ROC) curve analysis was used to screen differential peptide peaks with area under curve (AUC) ≥0.8, sensitivity and specificity>90% in the training set and validation set. Liquid chromatography-mass spectrometry (LC-MS/MS) was further used to determine the composition of differentially expressed peptides.Results:By comparing the peptide profiles of the two groups, 102 differential peptide peaks were initially detected in the mass-to-charge ratio range of 1 000 to 10 000. ROC curve analysis showed that there were 42 differential peptide peaks with AUC ≥0.8 in both training set and validation set, 19 of which were highly expressed in ovarian cancer group, and 23 were lowly expressed. There were 15 different peptide peaks in highly expressed ovarian cancer group with sensitivity and specificity over 90%. The mass-to-charge ratios were 7 744.27, 5 913.41, 5 329.87, 4 634.21, 4 202.02, 3 879.26, 3 273.35, 3 253.79, 3 234.34, 2 950.33, 2 664.51, 2 018.38, 1 893.37, 1 498.69 and 1 287.55. There were 15 different peptide peaks in lowly expressed ovarian cancer group with sensitivity and specificity over 90%, the mass-to-charge ratios were 9 288.46, 7 759.77, 5 925.24, 4 652.77, 4 210.42, 3 887.02, 3 279.90, 3 240.82, 2 962.15, 2 932.70, 2 022.42, 1 897.16, 1 501.69, 1 337.38 and 1 290.13. No protein composition was identified in 15 different peptide peaks in lowly expressed ovarian cancer group. The two protein compositions identified in 15 different peptide peaks in highly expressed ovarian cancer group were recombinant serglycin (SRGN) and fibinogen alpha chain (FGA), the mass-to-charge ratios of which were 1 498.696 and 5 913.417, respectively. The sensitivity and specificity of the two proteins for ovarian cancer diagnosis were 100%, 100% and 90.9%, 100%, respectively.Conclusion:SRGN and FGA are highly expressed in the serum of ovarian cancer patients, which may be potential diagnostic markers for ovarian cancer.
		                        		
		                        		
		                        		
		                        	
7.Identification of serum peptide biomarker for ovarian cancer diagnosis by Clin-TOF-II-MS combined with magnetic beads technology
Lin XIU ; Ning LI ; Wenpeng WANG ; Feng CHEN ; Guangwen YUAN ; Yangchun SUN ; Rong ZHANG ; Xiaoguang LI ; Jing ZUO ; Nan LI ; Wei CUI ; Lingying WU
Chinese Journal of Oncology 2021;43(11):1188-1195
		                        		
		                        			
		                        			Objective:To explore the serum cyclic polypeptide biomarkers for ovarian cancer diagnosis.Methods:A total of 54 patients with epithelial ovarian cancer confirmed by pathology in Cancer Hospital, Chinese Academy of Medical Sciences from March 2018 to September 2018 were selected as the study subjects, and 40 healthy women with normal examination results in the cancer screening center were selected as the control. All of the samples were randomly divided into training set and validation set at the ratio of 1∶1 with a random number. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead technology was used for detecting peptide profiling in serum samples to screen significantly differently expressed peptides between ovarian cancer group and control group of the training set (score>5). Receiver operating characteristic (ROC) curve analysis was used to screen differential peptide peaks with area under curve (AUC) ≥0.8, sensitivity and specificity>90% in the training set and validation set. Liquid chromatography-mass spectrometry (LC-MS/MS) was further used to determine the composition of differentially expressed peptides.Results:By comparing the peptide profiles of the two groups, 102 differential peptide peaks were initially detected in the mass-to-charge ratio range of 1 000 to 10 000. ROC curve analysis showed that there were 42 differential peptide peaks with AUC ≥0.8 in both training set and validation set, 19 of which were highly expressed in ovarian cancer group, and 23 were lowly expressed. There were 15 different peptide peaks in highly expressed ovarian cancer group with sensitivity and specificity over 90%. The mass-to-charge ratios were 7 744.27, 5 913.41, 5 329.87, 4 634.21, 4 202.02, 3 879.26, 3 273.35, 3 253.79, 3 234.34, 2 950.33, 2 664.51, 2 018.38, 1 893.37, 1 498.69 and 1 287.55. There were 15 different peptide peaks in lowly expressed ovarian cancer group with sensitivity and specificity over 90%, the mass-to-charge ratios were 9 288.46, 7 759.77, 5 925.24, 4 652.77, 4 210.42, 3 887.02, 3 279.90, 3 240.82, 2 962.15, 2 932.70, 2 022.42, 1 897.16, 1 501.69, 1 337.38 and 1 290.13. No protein composition was identified in 15 different peptide peaks in lowly expressed ovarian cancer group. The two protein compositions identified in 15 different peptide peaks in highly expressed ovarian cancer group were recombinant serglycin (SRGN) and fibinogen alpha chain (FGA), the mass-to-charge ratios of which were 1 498.696 and 5 913.417, respectively. The sensitivity and specificity of the two proteins for ovarian cancer diagnosis were 100%, 100% and 90.9%, 100%, respectively.Conclusion:SRGN and FGA are highly expressed in the serum of ovarian cancer patients, which may be potential diagnostic markers for ovarian cancer.
		                        		
		                        		
		                        		
		                        	
8.Clinical characteristics and treatment outcomes of relapsing, recurrent and repeat peritoneal dialysis-associated peritonitis: a multicenter study
Qiao ZHAO ; Liming YANG ; Xueyan ZHU ; Xiaoxuan ZHANG ; Yangyang CHEN ; Xiaohua ZHUANG ; Ping LUO ; Wenpeng CUI
Chinese Journal of Nephrology 2020;36(9):696-702
		                        		
		                        			
		                        			Objective:To explore the clinical characteristics and treatment outcomes of different types of peritoneal dialysis-associated peritonitis (PDAP).Methods:The clinical data of PDAP patients admitted to the Second Hospital of Jilin University, Second Part of the First Hospital of Jilin University, Jilin Central Hospital and Jilin First Automobile Work General Hospital in Jilin province from 2013 to 2019 were reviewed. According to the type of PDAP, the patients were divided into relapsing group, recurrent group, repeat group and control group, and the baseline data, pathogens culture and treatment outcomes among the four groups were compared.Results:A total of 542 patients with PDAP were enrolled in the study, including 43 cases in relapsing group, 32 cases in recurrent group, 27 cases in repeat group and 440 cases in control group. The median follow-up time was 30.5 (16.0, 50.0) months. The rate of Gram-positive bacteria in repeat group was higher than that of control group (70.37% vs 42.95%, P=0.030); the rate of fungi in recurrence group was higher than that of control group (21.88% vs 3.86%, P=0.006). Compared with control group, relapsing group had a lower cure rate (67.44% vs 83.64%, P=0.048) and a higher relapse rate (23.26% vs 2.27%, P=0.002), and recurrent group had a higher catheter removal rate (28.13% vs 8.18%, P=0.012). Multivariate logistic regression showed that recurrence was an independent risk factor for catheter removal ( OR=5.137, 95% CI 2.105-12.539, P<0.001). The technical failure rates in relapsing group and recurrent group were both higher than those in control group (41.86% vs 17.05%, P=0.002; 46.88% vs 17.05%, P=0.002). Multivariate Cox regression showed that relapse and recurrence were both independent risk factors for technical failure ( HR=2.587, 95% CI 1.525-4.389, P<0.001; HR=3.571, 95% CI 2.022-6.306, P<0.001), and also were independent risk factors for composite endpoint ( HR=1.565, 95% CI 1.045-2.344, P=0.030; HR=2.004, 95% CI 1.269-3.164, P=0.003). Conclusion:Compared with common PDAP, the therapeutic effects and prognosis of relapsing and recurrent PDAP are worse.
		                        		
		                        		
		                        		
		                        	
9.Expression and significance of Nek2B and β-catenin in triple negative breast cancer
Wenpeng YAN ; Honghong SHEN ; Wenxia MA ; Ziyue WANG ; Lifang SHANG ; Ningning SHEN ; Guoye QI ; Rong WEI ; Xiaoqin ZHANG ; Chen WANG
Chinese Journal of Pathology 2020;49(5):424-429
		                        		
		                        			
		                        			Objective:To investigate the expression and significance of Nek2B and β-catenin expression in triple negative breast cancer (TNBC) at molecule levels.Methods:By using the methods of bioinformatics [GEO2R online tool, gene ontology (GO) function analysis, KEGG biological pathway enrichment analysis], the differentially expressed genes were screened from TNBC microarray data.Expression levels of Nek2B and β-catenin TNBC cell lines were detected by Western blot and qRT-PCR.From January 1, 2007 to December 31, 2012, eighty cases of TNBC were collected from the Second Hospital of Shanxi Medical University. The expression of Nek2B in TNBC tumor tissue was detected by immunohistochemistry and tissue microarray, and the relationship between Nek2B and clinical pathological characteristics of TNBC was analyzed.Results:Through bioinformatics analysis of the cDNA chip sets of 2 TNBC tumors(GSE38959,GSE27447), 998 differentially expressed genes were obtained in the initial screening, and 13 differentially expressed genes were revealed after intersection. The results of biological pathway analysis showed that the common differential expression genes were closely related to Wnt/β-catenin pathway, among which Nek2 expression showed the greatest difference and was associated with poor prognosis. Expression intensity of Nek2B and repeated β-catenin in the same TNBC cell line was consistent.The results of immunohistochemistry showed that the high expression of Nek2B was related to the high histological stage (G3;84.3% vs.37.9%, P<0.001), lymph node metastasis group (76.7% vs.54.1%, P=0.032), high Ki-67 positive index group (78.6% vs.52.6%, P=0.007) and β-catenin positive expression group (72.5% vs.27.3%, P=0.018). Conclusions:The high level of Nek2B expression is related to a poor prognosis in TNBC patients. In TNBC tissues and cells, the expression of Nek2B is correlated with β-catenin, suggesting that Nek2B may affect the occurrence and development of TNBC by regulating the Wnt/β-catenin patients signaling pathway.
		                        		
		                        		
		                        		
		                        	
10.Efficient lung cancer-targeted drug delivery a nanoparticle/MSC system.
Xusheng WANG ; Haiyan CHEN ; Xiaowei ZENG ; Wenpeng GUO ; Yu JIN ; Shan WANG ; Ruiyun TIAN ; Yanjiang HAN ; Ling GUO ; Jimin HAN ; Yaojiong WU ; Lin MEI
Acta Pharmaceutica Sinica B 2019;9(1):167-176
		                        		
		                        			
		                        			Low targeting efficiency limits the applications of nanoparticles in cancer therapy. The fact that mesenchymal stem cells (MSC) trapped in the lung after systemic infusion is a disadvantage for cell therapy purposes. Here, we utilized MSC as lung cancer-targeted drug delivery vehicles by loading nanoparticles (NP) with anti-cancer drug. MSC showed a higher drug intake capacity than fibroblasts. In addition, MSC showed predominant lung trapping in both rabbit and monkey. IR-780 dye, a fluorescent probe used to represent docetaxel (DTX) in NP, delivered MSC accumulated in the lung. Both MSC/A549 cell experiments and MSC/lung cancer experiments validated the intercellular transportation of NP between MSC and cancer cells. assays showed that the MSC/NP/DTX drug delivery system exerted primary tumor inhibition efficiency similar to that of a NP/DTX drug system. Collectively, the MSC/NP drug delivery system is promising for lung-targeted drug delivery for the treatment of lung cancer and other lung-related diseases.
		                        		
		                        		
		                        		
		                        	
            
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