1.Discovery of a first-in-class ANXA3 degrader for the treatment of triple-negative breast cancer.
Yongxi LIANG ; Delin MIN ; Hulin FAN ; Kunlin LIU ; Juchuanli TU ; Xueyan HE ; Bingjie LIU ; Lu ZHOU ; Suling LIU ; Xun SUN
Acta Pharmaceutica Sinica B 2023;13(4):1686-1698
		                        		
		                        			
		                        			Triple-negative breast cancer (TNBC) is a nasty disease with extremely high malignancy and poor prognosis. Annexin A3 (ANXA3) is a potential prognosis biomarker, displaying an excellent correlation of ANXA3 overexpression with patients' poor prognosis. Silencing the expression of ANXA3 effectively inhibits the proliferation and metastasis of TNBC, suggesting that ANXA3 can be a promising therapeutic target to treat TNBC. Herein, we report a first-in-class ANXA3-targeted small molecule (R)-SL18, which demonstrated excellent anti-proliferative and anti-invasive activities to TNBC cells. (R)-SL18 directly bound to ANXA3 and increased its ubiquitination, thereby inducing ANXA3 degradation with moderate family selectivity. Importantly, (R)-SL18 showed a safe and effective therapeutic potency in a high ANXA3-expressing TNBC patient-derived xenograft model. Furthermore, (R)-SL18 could reduce the β-catenin level, and accordingly inhibit the Wnt/β-catenin signaling pathway in TNBC cells. Collectively, our data suggested that targeting degradation of ANXA3 by (R)-SL18 possesses the potential to treat TNBC.
		                        		
		                        		
		                        		
		                        	
2.LncRNA Prognostic Risk Scoring Model for Gastrointestinal Tumors Based on TCGA Database
Menghan LI ; Qiong XIAO ; Peng GAO ; Yu FU ; Chenrui SUN ; Yongxi SONG
Cancer Research on Prevention and Treatment 2022;49(6):606-611
		                        		
		                        			
		                        			Objective To establish a lncRNA prognostic risk model for gastrointestinal tumors based on the TCGA database and evaluate the prognosis of patients. Methods We collected the data of patients with esophageal cancer, gastric cancer, colon cancer and rectal cancer in the TCGA database. Univariate Cox analysis, Lasso and multivariate Cox analysis were performed to construct the prognostic risk scoring model. The model was validated and tested for independence. Time-dependent ROC curve analysis was performed to evaluate the clinical application value of the model. Results We established a prognostic risk model based on 13 lncRNAs. The three-year AUC of the training set and the validation set were 0.746 and 0.704, respectively. The pan-cancer data set was divided into high- and low-risk groups for survival analysis. The 5-year survival rate of the low-risk group was significantly higher than that of the high-risk group; among all cancer types, the five-year survival rates of the low-risk group were higher than those of the high-risk group. Multivariate Cox analysis showed that the risk score could be an independent indicator of prognosis. Conclusion The 13-gene prognostic risk score model is constructed successfully. The risk score obtained by this model can be used as an independent prognostic predictor of the patients with gastrointestinal cancer.
		                        		
		                        		
		                        		
		                        	
3.Screening of Potential Biomarkers for Gastric Cancer with Diagnostic Value Using Label-free Global Proteome Analysis
Song YONGXI ; Wang JUN ; Sun JINGXU ; Chen XIAOWAN ; Shi JINXIN ; Wu ZHONGHUA ; Yu DEHAO ; Zhang FEI ; Wang ZHENNING
Genomics, Proteomics & Bioinformatics 2020;18(6):679-695
		                        		
		                        			
		                        			Gastric cancer (GC) is known as a top malignant type of tumors worldwide. Despite the recent decrease in mortality rates, the prognosis remains poor. Therefore, it is necessary to find novel biomarkers with early diagnostic value for GC. In this study, we present a large-scale proteomic analysis of 30 GC tissues and 30 matched healthy tissues using label-free global proteome profiling. Our results identified 537 differentially expressed proteins, including 280 upregulated and 257 downregulated pro-teins. The ingenuity pathway analysis (IPA) results indicated that the sirtuin signaling pathway was the most activated pathway in GC tissues whereas oxidative phosphorylation was the most inhibited. More-over, the most activated molecular function was cellular movement, including tissue invasion by tumor cell lines. Based on IPA results, 15 hub proteins were screened. Using the receiver operating character-istic curve, most of hub proteins showed a high diagnostic power in distinguishing between tumors and healthy controls. A four-protein (ATP5B-ATP5O-NDUFB4-NDUFB8) diagnostic signature was built using a random forest model. The area under the curve (AUC) values of this model were 0.996 and 0.886 for the training and testing sets, respectively, suggesting that the four-protein signature has a high diag-nostic power. This signature was further tested with independent datasets using plasma enzyme-linked immune sorbent assays, resulting in an AUC value of 0.778 for distinguishing GC tissues from healthy controls, and using immunohistochemical tissue microarray analysis, resulting in an AUC value of 0.805. In conclusion, this study identifies potential biomarkers and improves our understanding of the pathogenesis, providing novel therapeutic targets for GC.
		                        		
		                        		
		                        		
		                        	
4. Lower respiratory tract of infection patients with coal worker's pneumoconiosis on isolation characteristics and drug resistance in HACEK bacteria
Yongxi SUN ; Guihua SUN ; Peiyue LIU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2019;37(7):535-538
		                        		
		                        			 Objective:
		                        			To summarize the isolation characteristics and drug resistance of HACEK bacteria in lower respiratory tract infection of coal worker's pneumoconiosis.
		                        		
		                        			Methods:
		                        			From 2016 to 2018, K-B method and MIC method were used to test the susceptibility of 10 commonly used antimicrobial agents to isolated 46 strains of HACEK bacteria, and the drug resistance of lactamase and non-enzyme producing haemophilus was compared.
		                        		
		                        			Results:
		                        			Haemophilus influenza (Hi) accounted for 71.74% (33/46) of the HACEK bacteria in the lower respiratory tract infection patients of coal workers' pneumoconiosis in our hospital, Haemophilus parainfluenzae (HPi) accounted for 23.91% (11/46) , which corroded one strain of Eikenella and one strain of actinomycetes. HACEK bacteria were isolated most in winter and spring, and less in summer and autumn. Cefuroxime, ceftriaxone, amoxicillin/clavulanic acid and levofloxacin have good antimicrobial activity against HACEK bacteria. The sensitivity of non-enzyme-producing strains Tetracycline (TE) , Compound trimethoprim (SXT) , Azithromycin (AZI) and Ampicillin (AMP) was stronger than that of enzyme-producing strains (
		                        		
		                        	
5. Clinicpathological features and survival of patients with AIDS related non-Hodgkin’s lymphoma
Kaiyu SUN ; Xien GUI ; Di DENG ; Yong XIONG ; Liping DENG ; Shicheng GAO ; Yongxi ZHANG
Chinese Journal of Hematology 2017;38(2):97-101
		                        		
		                        			 Objective:
		                        			To analyze the clinical characteristics, pathological features and survival of patients with AIDS related non-Hodgkin’s lymphoma (ARL) .
		                        		
		                        			Methods:
		                        			The clinical data of 53 ARL cases diagnosed and received care at Zhongnan hospital of Wuhan University were retrospectively studied, and 106 controls were enrolled as control group according to 1∶2 for paired cases and control. SPSS 13.0 package was used for statistical analysis. Kaplan-Meier was applied to assess the survival probability.
		                        		
		                        			Results:
		                        			The mean age of patients with ARL was 43 (11-67) years. Male versus female was approximately 4∶1. The median CD4+ T cell count was (146±20) /ml. The Ann Arbor clinical classification showed that 52.8% of the cases were of stage Ⅲ and Ⅳ. Approximately 54.7% of the patients had elevated serum lactate dehydrogenase (LDH) . According to international prognosis index score, 64.2% of the patients were in high risk group. Diffuse large B-cell lymphoma (DLBCL) was the predominant histological subtype. Among 53 cases, 33 cases (62.3%) received combination of anti-HIV therapy and anti-NHL (CHOP) chemotherapy regimen, 8 cases (15.1%) only received anti-HIV therapy, and 12 cases (22.6%) asked for alleviative treatment. Median survival time was (6.0±1.3) months for ARL cases versus (48.0±10.0) months for controls (
		                        		
		                        	
6.The clinical effect of the platelet rich plasma in treatment of chronic painless wound
Yongxi YANG ; Jiaxiong FENG ; Xiaotao HUANG ; Yanran XU ; Zeguang SUN ; Chuzheng YAO
Chinese Journal of Primary Medicine and Pharmacy 2016;23(11):1637-1640
		                        		
		                        			
		                        			Objective To observe and analyze the clinical curative effect of the platelet rich plasma (PRP) in treatment of chronic difficult to heal the wound.Methods We selected 60 patients with chronic difficult healing wounds and they were divide into two groups at random,30 patients of A group,B group of 30 patients.All patients were given routine debridement,drainage and decompression treatment,B group was given autologous PRP wound injection and follow-up on the basis of conventional treatment.After injection of PRP,platelet count,platelet recovery and application of PRP granulation tissue growth and wound healing were observed.Results The wound healing effect at the 7th,14th,21 st day between the two groups,and compared with the 1 st day,the differences were statistically significant (A group:10.28%,22.16%,43.25%,65.78%;B group:18.75%,37.58%,61.84%,80.26%;X2:7.895,8.934,10.231,9.076,all P < 0.05).Two groups of patients had obvious difference in healing time,in B group the average healing time was (12.6 ± 5.2) d,which in was (17.3 ± 7.4) d,the difference was statistically significant (t =1.932,P < 0.05).Conclusion The PRP can effectively promote the wound repair of soft tissue,to promote healing of chronic difficult wound healing,the curative effect is distinct,it is worthy of clinical popularization and application.
		                        		
		                        		
		                        		
		                        	
7.Therapeutic effect of early scab-cutting combined with axis-like abdomen skin flap implanting in patients with wrist deep electrical burns
Yongxi YANG ; Jiaxiong FENG ; Xiaotao HUANG ; Zeguang SUN ; Yanran XU
Chinese Journal of Primary Medicine and Pharmacy 2015;(7):1032-1034
		                        		
		                        			
		                        			Objective To observe therapeutic effects of early scab-cutting combined with axis-like abdo-men skin flap implanting in patients with wrist deep electrical burns.Methods Retrospective study was employed to analyze 70 patients received axis -like abdomen skin flap implanting for wrist deep electrical burns.All the cases were separated with early scab-cutting group(35 cases)and delayed scab-cutting group(35 cases),according to types of skin flap implanting.The therapeutic effect for the two groups were evaluated with rate of infection,duration of healing,living rate of skin flap,grade of skin burning,and rate of amputate.Results In the early scab -cutting group,the rate of infection was 11%,the duration of healing was(24.0 ±6.0)days,the rate of amputate was 3%,the living rate of skin flap was 97.0%,the wound healing of class A was 94.3%.In the delayed scab-cutting group,the data were respectively 31%,(35.0 ±7.4)days,17.0%,31% and 28.6%.Compared with the data of the two groups,the difference had statistical significance(the chi-square value or T value were respectively 4.151,6.831,3. 968,31.895,3.968.All the P values was less than 0.05).Conclusion Early scab-cutting combined with varied sorts of skin flap implanting shown great benefits for treatment of wounded and facilitate rehabilitation in function of wrist,which suggest decrease rate of complications and minimized hospitalized duration.
		                        		
		                        		
		                        		
		                        	
8.The curative effect of anterolateral thigh flap in repairing defect caused by resection of malignant melanoma in the heel region
Yanran XU ; Zeguang SUN ; Yongxi YANG ; Xiaotao HUANG ; Jiaxiong FENG
Chinese Journal of Primary Medicine and Pharmacy 2015;(20):3054-3056,3057
		                        		
		                        			
		                        			Objective To observe the clinical effect of the anterolateral thigh flap in repairing defect caused by resection of malignant melanoma in the heel region.Methods 8 patients with heel malignant melanoma were trea-ted by surgery.The malignant melanoma was further diagnosed by histopathological examination.Their heel defects caused by large resection of malignant melanoma were treated by anterolateral thigh flap.Results All skin flaps sur-vived and all the patients could walk normally 1 month after operation.The recovery of the function and sense was well 6 months after operation.Compared with the another well heel,the flaps had normal texture,color and appearance of heel.8 patients had complete follow -up,ranged form 6 months to 3 years.All cases survived with neither local recur-rence nor distant metastasis.Conclusion The anterolateral thigh flap can achieve good clinical effect in treating heel defect caused by the resection of malignant melamoma.And especially apply in large skin and tissue defect of heel area.The flap can weight,wear -resisting and reduce overheating and over cold damage.The range of resection can not be restricted by local skin flap.The clinical effect is satisfied.
		                        		
		                        		
		                        		
		                        	
9.Application of ultrasound-guided Mammotome in the diagnosis and treatment of breast neoplasms
Jian SUN ; Ang DING ; Taiming SUN ; Maoli WANG ; Yuchun JIN ; Hongliang CHEN ; Yongxi YUAN
Clinical Medicine of China 2010;26(11):1219-1221
		                        		
		                        			
		                        			Objective To summarize and explore the clinical value of Mammotome technology in the diagnosis and treatment of breast neoplasms. Methods Nine hundred and eighty-seven breast neoplasms of 710patients were biopsied and excised with the aid of ultrasound-guided Mammotome system. The malignant neoplasms,according to the histological report,were radically removed during the operation without delay. All patients enrolled into the study were followed up closely on the complcations and satisfaction degree. Results All the operations except one were successful and got the sufficient specimen to perform the pathological examination,the biopsy achievement rate was 99. 8% . Both the sensitivity and specificity of the diagnosis were 100% in 16 breast tumors. Complete resection rate was 99%. The incision length was about 3 mm,showing good cosmetic outcome. Complcations were mild,mainly composed of haematoma and ecchymosis. The patients' general satisfactory rate was 93%. Conclusions This technique can help achieve biopsy of breast neplasm and excision of benign lesions at the same time with cosmetic result Further attention should be paid to reduce the lesion residue and hemorrhagic complications.
		                        		
		                        		
		                        		
		                        	
10.Method used in analyzing and controlling dosage of HIFU for tumor therapy
Jianhui JIANG ; Xiaoping QIAN ; Fucheng SUN ; Yikang WANG ; Yongxi YUAN
Chinese Medical Equipment Journal 2004;0(07):-
		                        		
		                        			
		                        			As an emerging tumor therapy, high intensity focused ultrasound (HIFU) therapy has difficulty in controlling its dosage due to the complex human tissues. The dosage is related to the tumor such as its depth, size, characteristics and the tissue performances of its growth site. The existing cases are applied to establishing a repository with the above-mentioned parameters of the tumor analyzed. Then reasoning and self-learning are performed. So, the therapeutic dosage can be provided to the clinician when a new case occurs.
		                        		
		                        		
		                        		
		                        	
            
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