1.MiR-142-3p enhances chemosensitivity of breast cancer cells and inhibits autophagy by targeting HMGB1.
Lu LIANG ; Jijun FU ; Siran WANG ; Huiyu CEN ; Lingmin ZHANG ; Safur Rehman MANDUKHAIL ; Lingran DU ; Qianni WU ; Peiquan ZHANG ; Xiyong YU
Acta Pharmaceutica Sinica B 2020;10(6):1036-1046
		                        		
		                        			
		                        			MiR-142-3p has been reported to act as a tumor suppressor in breast cancer. However, the regulatory effect of miR-142-3p on drug resistance of breast cancer cells and its underlying mechanism remain unknown. Here, we found that miR-142-3p was significantly downregulated in the doxorubicin (DOX)-resistant MCF-7 cell line (MCF-7/DOX). MiR-142-3p overexpression increased DOX sensitivity and enhanced DOX-induced apoptosis in breast cancer cells. High-mobility group box 1 (HMGB1) is a direct functional target of miR-142-3p in breast cancer cells and miR-142-3p negatively regulated HMGB1 expression. Moreover, overexpression of HMGB1 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by miR-142-3p up-regulation. In conclusion, miR-142-3p overexpression may inhibit autophagy and promote the drug sensitivity of breast cancer cells to DOX by targeting HMGB1. The miR-142-3p/HMGB1 axis might be a novel target to regulate the drug resistance of breast cancer patients.
		                        		
		                        		
		                        		
		                        	
2.Lineage reprogramming of fibroblasts into induced cardiac progenitor cells by CRISPR/Cas9-based transcriptional activators.
Jianglin WANG ; Xueyan JIANG ; Lixin ZHAO ; Shengjia ZUO ; Xiantong CHEN ; Lingmin ZHANG ; Zhongxiao LIN ; Xiaoya ZHAO ; Yuyan QIN ; Xinke ZHOU ; Xi-Yong YU
Acta Pharmaceutica Sinica B 2020;10(2):313-326
		                        		
		                        			
		                        			Overexpression of exogenous lineage-determining factors succeeds in directly reprogramming fibroblasts to various cell types. Several studies have reported reprogramming of fibroblasts into induced cardiac progenitor cells (iCPCs). CRISPR/Cas9-mediated gene activation is a potential approach for cellular reprogramming due to its high precision and multiplexing capacity. Here we show lineage reprogramming to iCPCs through a dead Cas9 (dCas9)-based transcription activation system. Targeted and robust activation of endogenous cardiac factors, including GATA4, HAND2, MEF2C and TBX5 (G, H, M and T; GHMT), can reprogram human fibroblasts toward iCPCs. The iCPCs show potentials to differentiate into cardiomyocytes, smooth muscle cells and endothelial cells . Addition of MEIS1 to GHMT induces cell cycle arrest in G2/M and facilitates cardiac reprogramming. Lineage reprogramming of human fibroblasts into iCPCs provides a promising cellular resource for disease modeling, drug discovery and individualized cardiac cell therapy.
		                        		
		                        		
		                        		
		                        	
3. Mental health status in railway female workers and its occupational influencing factors
Fuling JI ; Zhenmei LIU ; Zhisheng LIU ; Jianfan ZOU ; Wenlan YU ; Hongmei LI ; Juan LI ; Lingmin KONG ; Qian JIANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2018;36(2):102-105
		                        		
		                        			 Objective:
		                        			To investigate the mental health status of railway female workers and related influencing factors, and to provide a scientific strategy for labor protection regulations in railway female workers.
		                        		
		                        			Methods:
		                        			Cluster sampling was used to select 5033 female workers from Jinan, Nanning, Qinghai-Tibet, and Wuhan railway systems in China from January to August, 2016. A uniform reproductive health questionnaire, as well as the Symptom Checklist-90 (SCL-90) , was used to investigate their general information (age, marital status, education level, and family income) , work type (day shift, night shift, or work on shift) , work position, and the presence or absence of exposure to occupational hazardous factors. The score on each factor of SCL-90 and the positive rate of mental health status were calculated.
		                        		
		                        			Results:
		                        			The positive rate of mental health status was 10.6% in railway female workers. The workers exposed to occupational hazardous factors had a significantly higher positive rate of mental health status than those not exposed to occupational hazardous factors (14.20% 
		                        		
		                        	
4.An association of ulcerative colitis with tumor necrosis factor superfamily member 15 gene polymorphisms in Chinese patients
Wei YANG ; Shouxing YANG ; Changlong XU ; Lingmin YU ; Hao LIN ; Yi JIANG
Chinese Journal of Internal Medicine 2018;57(7):476-482
		                        		
		                        			
		                        			Objective To explore the relationship between ulcerative colitis (UC) susceptibility and tumor necrosis factor superfamily member (TNFSF) 15 gene polymorphisms and haplotypes in Han nationality in Zhejiang province of China. Methods A total of 408 UC patients and 574 healthy controls were recruited in this study. Three single nucleotide polymorphisms of TNFSF15 (rs3810936, rs4263839, rs4979462) were examined by improved multiple ligase detection reaction (iMLDR) technique. Analyses of linkage disequilibrium (LD) and haplotype were performed by Haploview 4.2 software in all study subjects. Results The variant allele A and genotype (GA+AA) of rs4263839 were less frequent in UC patients than in controls (45.34% vs. 50.17%, P=0.035; 68.38% vs. 76.66%, P=0.004). According to the severity and location of disease, UC patients were divided into different subgroups. After multiple comparison correction (α=0.012 5), the frequencies of variant allele A and genotype (GA+AA) of rs4263839 were lower in patients with severe UC than in the controls (37.69% vs. 50.17%, P=0.007;60.00% vs. 76.66%, P=0.004). Similar findings were also drawn for patients with extensive colitis in contrast with the controls (42.22% vs. 50.17%, P=0.009; 63.33% vs. 76.66%, P<0.001). Furthermore, the haplotype analysis indicated that three SNPs above were in a strong LD. The frequency of haplotype TAC was lower in UC patients than in the controls (40.83% vs. 46.04%, P=0.023). Also it was less prevalent in patients with severe UC and patients with extensive colitis when compared with controls respectively (33.38% vs. 46.04%, P=0.005;37.22% vs. 46.04%, P=0.003). Conclusions TNFSF15 (rs4263839) variation might not only reduce the risk of UC, but also affect the severity and lesion location of UC. The haplotype TAC formed by rs3810936, rs4263839 and rs4979462 might be related to a lower risk of UC, especially in patients with severe colitis or patients with extensive colitis.
		                        		
		                        		
		                        		
		                        	
5.Left Atrial Appendage Occlusion Under the Guidance of Local Anesthesia and Modified Transseptal Puncture Technology
Lihui ZHENG ; Lingmin WU ; Wei SUN ; Jinyue GUO ; Yu QIAO ; Ligang DING ; Gang CHEN ; Yan YAO
Chinese Circulation Journal 2017;32(7):646-649
		                        		
		                        			
		                        			To explore the safety and efficacy of left atrial appendage (LAA) occlusion under the guidance of local anesthesia and modified transseptal puncture technology by coronary sinus assisted positioning in patients with nonvavular atrial fibrillation (NVAF). Methods: A total of 16 NVAF patients received local anesthesia and percutaneous LAmbre or Amplatzer cardiac plug occluder implantation. There were 12 males and the patients mean age was at (71.0±6.0) years with CHA2DS2-VASc score at (4.1±1.5); all patients had walfarin contradiction or with walfarin related side effect. Transseptal puncture was conducted by coronary sinus catheter as the anatomic location marker. Results: All 16 patients finished transseptal puncture and no relevant complication occurred. 15/16 (93.8%) patients had successful LAA occlusion, 1 patient was abandoned because of LAA anatomic structure variation. The mean operative time was (65.0±23.0) min and the mean X-ray exposure time was (12.0±3.0) min. The mean diameter of occluder was (32.5±6.0)mm. Conclusion: LAA occlusion was safe and effective with local anesthesia and modified transseptal puncture technology by coronary sinus assisted positioning in relevant patients.
		                        		
		                        		
		                        		
		                        	
6.Safety and Efficacy of Left Atrial Endocardial Vagal Denervation Catheter Ablation for Treating the Patients With Refractory Vasovagal Syncope
Wei SUN ; Lihui ZHENG ; Yan YAO ; Yu QIAO ; Bingbo HOU ; Lingmin WU ; Jinrui GUO ; Shu ZHANG
Chinese Circulation Journal 2016;31(3):254-258
		                        		
		                        			
		                        			Objective: To explore the safety and efficacy of left atrial (LA) endocardial vagal denervation catheter ablation for treating the patients with refractory vasovagal syncope (VVS). 
 Methods: A total of 57 consecutive refractory VVS patients with severe symptom and positive response to head-up tilt test (HUT) were enrolled. There were 22 male at the mean age of (43 ± 13) years. The patients had no response or couldn’t tolerate routine treatment. LA model was re-established by three-dimensional mapping system, 10 patients received high-frequency stimulation technique for ganglionated plexi (GP) ablation and 47 received regional catheter ablation at 5 anatomic sites of GP for LA endocardial vagal denervation treatment. In-operative vagal response including hypotension, sinus bradycardia or asystole were observed, the endpoint of ablation was abolition of evoked vagal relfexes. Periodical follow-up was conducted to record the syncope recurrence and to re-examine ECG and HUT in all patients. 
 Results: There were 52/57(91.2%) patients had positive vagal response by radiofrequency application and reached the endpoint of ablation; 4 patients couldn’t receive obvious evoked vagal relfexes. During (36 ± 22) months follow-up period, there were 52 (91.2%) cases without syncope recurrence, 11 cases still having palpitation, amaurosis and dizziness as the precursors of syncope while the symptoms were much better then they were before. No complication occurred. 
 Conclusion: LA endocardial vagal denervation catheter ablation is a safe and effective method for treating the patients with refractory VVS, it may also effectively prevent VVS recurrence.
		                        		
		                        		
		                        		
		                        	
7.Characteristics of Deceleration Capacity and Heart Rate Variability in Patients With Vasovagal Syncope
Wei SUN ; Lihui ZHENG ; Yan YAO ; Zhiyuan WENG ; Yu QIAO ; Bingbo HOU ; Lingmin WU ; Jinrui GUO ; Shu ZHANG
Chinese Circulation Journal 2015;(11):1067-1070
		                        		
		                        			
		                        			Objective: To quantitatively evaluate the abnormal tense of parasympathetic nerve via measuring the heart rate deceleration capacity (DC) and heart rate variability (HRV) in patients with vasovagal syncope (VVS). 
 Methods: Our research included 2 groups: VVS group,n=28 patients with positive head-up tilt test treated in our hospital from 2013-06 to 2014-08 and Control group,n=30 patients without cardiovascular disorders. The DC and HRV were examined and compared between 2 groups. 
 Results:① The overall deceleration capacity (ODC) (9.4 ± 2.9) ms and daytime deceleration capacity (DDC) (8.9 ± 2.9) ms in VVS group were higher than those in Control group (7.5 ± 2.5) ms and (7.5 ± 2.5) ms respectively,P<0.05.② More patients in VVS group presented daytime-to-nighttime deceleration capacity ratio (DNratio) >1 than those in Control group (9/28, 32.1% vs 2/30, 6.7%),P=0.019.③ The SDNN (139.8 ± 34.0) ms, SDSD (29.9 ± 15.7) ms and rMSSD (40.9 ± 18.8) ms in VVS group were higher than those in Control group, (115.5 ± 29.4) ms, (21.8 ± 6.6) ms and (28.9 ± 8.4) ms respectively,P<0.05.④ Multivariate Logistic regression analysis indicated that ODC was positively related to vasovagal syncope occurrence (OR=2.045, 95% CI: 1.100-3.801,P=0.024). 
 Conclusion: VVS patients have abnormally increased indexes of DC and HRV, HDC is the predictor for vasovagal syncope occurrence.
		                        		
		                        		
		                        		
		                        	
8.Clinical features and impact factors of simple renal cysts
Yi YUAN ; Lingmin MENG ; Shouling WU ; Xiaoxu LAN ; Yao YU
Clinical Medicine of China 2015;31(12):1138-1143
		                        		
		                        			
		                        			Objective To analyze the main clinical features and impact factors of simple renal cyst (SRC), and to provide evidence for the future prevation and cure of simple renal cysts.Methods In this crosssectional study,a total number of 91 433 participants(aged 18-98 years old) were included who underwent health examinations during 2012-2014.The main life styles and clinical features of each participants were recored,and blood biochemistry test, urinanalysis and renal ultrasonography were performed.Results The prevalence of SRC was 2.70% (2 465 subjects were diagnosed by ultrasonography).It was higher in men than women(2.95% vs.1.68%, P =0.00), which was increased with the increasing of age (respectively 0.37%, 0.57%, 1.30% ,2.69% ,4.46% and 6.91% in the group of ≤29year,30-39 year,40-49 year,50-59 year,60 -69 year and ≥70 year,P<0.01).The maximum diameter of simple renal cysts were (2.6±1.7) cm.Age,rate of men, body mass index, glucose, total cholesterol, creatinine, urea nitrogen, and urinary protein positive rate, kidney stone prevalence were higher in SRC group(respectively (61.11±11.24)year vs.(51.37±13.72) year, 87.59% vs.79.88%, (25.27 ± 3.19) kg/m2 vs.(24.97 ± 3.35) kg/m2, (6.09 ± 2.08) mmol/L vs.(5.70 ± 1.85) mmol/L, (5.11 ± 1.54) mmol/L vs.(5.02 ± 1.37) mmol/L, (90.71 ± 34.84) μmol/L vs.(80.72 ±28.04) μmol/L, (6.03±3.60) mmol/L vs.(5.55±5.15) mmol/L,7.46% vs.4.25% ,7.06% vs.1.28% ,P <0.01) ,but glomerular filtration rate, triglycerides, rate of like salty, drink, smoke was lower than the group withoutSRC((79.01±19.89) ml/(min· 1.73 m2) vs.91.74±21.8 ml/(min · 1.73 m2),(1.57±1.48) mmol/L vs.(1.69± 1.82) mmol/L, 4.38% vs.7.94%, 22.68% vs.30.75%, 24.91% vs.30.97%;P< 0.01).But,there was no difference between these two groups in serum uric acid ((309.16± 85.79) μmol/L vs.(312.38±91.22) μmol/L,P>0.05).SRC as a dependent variable of multivariate log regression analysis.The result showed the OR of age, gender, fasting blood glucose, urea nitrogen, glomerular filtration rate, positive urine protein,kidney stone were respectively 1.040, 1.862, 1.035, 1.005,0.982, 1.254, 4.526, 95% CI =1.037 -1.045,1.643-2.110,1.017-1.053,1.000-1.010, 0.980-0.984, 1.068-1.473,3.812-5.374;P <0.01).While the OR of multiple SRC was 0.43,95% CI: 0.210-0.867 (P<0.05) , when kidney stone as a dependent variable.Conclusion Old-age males are high risk population of catching SRC.Kidney stone and positive urine protein are important risk factors of SRC.Meanwhile kidney stone more easily induce single and small SRC.SRC is a key risk factor to induce renal function decrease.Therefore, GFR is a sensitive index of renal disfunction that induced by SRC.
		                        		
		                        		
		                        		
		                        	
9.Application of quality control circle on reducing incidence of chemotherapy related oral mucositis in children with acute lymphoblastic leukemia
Si CHEN ; Xiaoqin QI ; Pengshuang SHI ; Yanping ZHAO ; Yuhuan CHEN ; Lingmin DONG ; Litao ZHOU ; Liang YU
Chinese Journal of Modern Nursing 2015;(14):1621-1624
		                        		
		                        			
		                        			Objective To investigate the effect of quality control circle ( QCC ) application in reducing incidence of oral mucositis in children with acute lymphoblastic leukemia ( ALL ) during chemotherapy. Methods We founded QCC team and established “Reducing incidence of oral mucositis in children with ALL” as the subject, conducted survey, analyzed the reasons for the occurrence of oral mucositis, set goals, developed countermeasures, and conducted effect evaluation. Results The incidence of oral mucositis in children with ALL was 14. 86% in the experimental group compared 39. 19% of the control group (χ2 =22. 20,P<0. 01), both were lower than the goals and achieved our aims. The severity in the experimental group was significantly lower than that the control group in oral mucositis incidence ( P<0. 05). Conclusions QCC application can not only reduces incidence of oral mucositis in children with ALL, but also improves the responsibilities and quality management capabilities of QCC members, and promotes the continuous improvement of the quality of nursing in Department of Hematology.
		                        		
		                        		
		                        		
		                        	
10.Preparation and cytocompatibility of novel porous calcium metaphosphate composite membranes
Yueheng WU ; Peng CHEN ; Liping MAI ; Lingmin ZHANG ; Shunqing TANG ; Xiyong YU
Chinese Journal of Tissue Engineering Research 2013;(34):6123-6130
		                        		
		                        			
		                        			BACKGROUND:Porous poly(3-hydroxybutyrate-co-4-hydroxybutyrate)/calcium metaphosphate composite membranes prepared previously is too thick and uneven in holes. 
OBJECTIVE:To prepare the thin even porous poly(3-hydroxybutyrate-co-4-hydroxybutyrate)/calcium metaphosphate composite membrane, and to evaluate the cytocompatibility and differentiation capacity. 
METHODS:Porous and nonporous, thin and even poly(3-hydroxybutyrate-co-4-hydroxybutyrate)/calcium metaphosphate composite membranes were prepared by phase separation method. Its thickness and weight loss rate were determined. Human bone marrow mesenchymal stem cel s were cocultured with porous and nonporous poly(3-hydroxybutyrate-co-4-hydroxybutyrate)/calcium metaphosphate composite membranes for 7 days. Ultrastructure of composite membranes was observed under the scanning electron microscopy. Surface markers of the bone marrow mesenchymal stem cel s on the composite membranes were analyzed using flow cytometry. 
RESULTS AND CONCLUSION:The thickness of the porous and nonporous composite membranes was (0.041 ± 0.005) mm and (0.058±0.004) mm. Weight loss rates of porous and nonporous composite membranes were respectively 19.93%and 7.64%at 24 hours. Calcium metaphosphate particles were evenly distributed in porous and nonporous composite membrane. Cel s spread entirely, showing spindle shape. Calcium metaphosphate particles were evenly distributed in porous composite membrane. Pore in porous composite membranes was also uniformly distributed, and pore size was about 2-8μm. Cel s spread entirely, showing polygonal shape with multiple tentacles. The tentacles of some cel s entered into the scaffold. CD105, CD90, CD44, CD29 and CD73 expression was detected in porous and nonporous composite membranes. There was no significant difference in cel-positive rate. Poly(3-hydroxybutyrate-co-4-hydroxybutyrate)/calcium metaphosphate composite membranes prepared in this study has good biocompatibility and could not promote cel differentiation.
		                        		
		                        		
		                        		
		                        	
            
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