1.Oral submucosal fibrosis induced by active components in areca nut:a network pharmacology-based analysis and validation of the mechanism
Ruibo LI ; Ge GAO ; Xi XIE ; Haibin LUO
Journal of Southern Medical University 2024;44(5):930-940
		                        		
		                        			
		                        			Objective To explore the pharmacologically active components in areca nut that induce oral submucosal fibrosis(OSF)and the possible mechanism.Methods The chemical components in areca nut were analyzed using Thermo QE plus liquid chromatography tandem high-resolution mass spectrometer and Compound discover 3.2 data processing software.The chemical activity of the top 20 compounds was analyzed based on Chinese Pharmacopoeia(2015),PubChem,Chemical book,and SciFinder databases.The potential active components,core targets,biological functions and signaling pathways affecting OSF were analyzed by network pharmacology.The targets of OSF were obtained by integrating Genecards and KEGG databases.The compounds acting on the targets were selected from the Systematic Pharmacology Technology Platform of Traditional Chinese Medicine(TCMSP),and the target-compound,compound-TCM,target-compound-TCM network was constructed.Molecular docking was used to analyze the component-target binding.Immunohistochemistry was used to examine the expressions of key proteins in the PI3K-Akt and MAPK pathways in clinical samples of OSF.Results The core intersection target genes between the top 10 active ingredients in areca nut extract and OSF involved mainly the PI3K-Akt and MAPK pathways.In the clinical samples,the expressions of PI3K protein decreased and the expressions p-PI3K,AKT1 and P-Akt all increased significantly in OSF tissue,where increased JNK protein expression and enhanced activity of c-Jun and c-Fos transcriptional factors were also detected.The OSF patients had significantly elevated plasma levels of IL-6 and IL-8 compared with healthy individuals.Conclusion The main active ingredients including arecoline,arecaine,and guvacine are capable of activating the PI3K-Akt and MAPK pathways to promote the expressions of inflammatory mediators IL-6 and IL-8 and induce collagen hyperplasia,thus leading to the occurrence of oral submucosal fibrosis.
		                        		
		                        		
		                        		
		                        	
2.Oral submucosal fibrosis induced by active components in areca nut:a network pharmacology-based analysis and validation of the mechanism
Ruibo LI ; Ge GAO ; Xi XIE ; Haibin LUO
Journal of Southern Medical University 2024;44(5):930-940
		                        		
		                        			
		                        			Objective To explore the pharmacologically active components in areca nut that induce oral submucosal fibrosis(OSF)and the possible mechanism.Methods The chemical components in areca nut were analyzed using Thermo QE plus liquid chromatography tandem high-resolution mass spectrometer and Compound discover 3.2 data processing software.The chemical activity of the top 20 compounds was analyzed based on Chinese Pharmacopoeia(2015),PubChem,Chemical book,and SciFinder databases.The potential active components,core targets,biological functions and signaling pathways affecting OSF were analyzed by network pharmacology.The targets of OSF were obtained by integrating Genecards and KEGG databases.The compounds acting on the targets were selected from the Systematic Pharmacology Technology Platform of Traditional Chinese Medicine(TCMSP),and the target-compound,compound-TCM,target-compound-TCM network was constructed.Molecular docking was used to analyze the component-target binding.Immunohistochemistry was used to examine the expressions of key proteins in the PI3K-Akt and MAPK pathways in clinical samples of OSF.Results The core intersection target genes between the top 10 active ingredients in areca nut extract and OSF involved mainly the PI3K-Akt and MAPK pathways.In the clinical samples,the expressions of PI3K protein decreased and the expressions p-PI3K,AKT1 and P-Akt all increased significantly in OSF tissue,where increased JNK protein expression and enhanced activity of c-Jun and c-Fos transcriptional factors were also detected.The OSF patients had significantly elevated plasma levels of IL-6 and IL-8 compared with healthy individuals.Conclusion The main active ingredients including arecoline,arecaine,and guvacine are capable of activating the PI3K-Akt and MAPK pathways to promote the expressions of inflammatory mediators IL-6 and IL-8 and induce collagen hyperplasia,thus leading to the occurrence of oral submucosal fibrosis.
		                        		
		                        		
		                        		
		                        	
3.Polymyxin resistance caused by large-scale genomic inversion due to IS26 intramolecular translocation in Klebsiella pneumoniae.
Haibin LI ; Lang SUN ; Han QIAO ; Zongti SUN ; Penghe WANG ; Chunyang XIE ; Xinxin HU ; Tongying NIE ; Xinyi YANG ; Guoqing LI ; Youwen ZHANG ; Xiukun WANG ; Zhuorong LI ; Jiandong JIANG ; Congran LI ; Xuefu YOU
Acta Pharmaceutica Sinica B 2023;13(9):3678-3693
		                        		
		                        			
		                        			Polymyxin B and polymyxin E (colistin) are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae. Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing. Polymyxin S2 (S2) is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin. To predict the possible resistant mechanism of S2 for wide clinical application, we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms. Mut-S, a resistant mutant of K. pneumoniae ATCC BAA-2146 (Kpn2146) induced by S2, was analyzed by whole genome sequencing, transcriptomics, mass spectrometry and complementation experiment. Surprisingly, large-scale genomic inversion (LSGI) of approximately 1.1 Mbp in the chromosome caused by IS26 mediated intramolecular transposition was found in Mut-S, which led to mgrB truncation, lipid A modification and hence S2 resistance. The resistance can be complemented by plasmid carrying intact mgrB. The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146 (Mut-B and Mut-E, respectively). This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K. pneumoniae. The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.
		                        		
		                        		
		                        		
		                        	
4.Status of HVPG clinical application in China in 2021
Wen ZHANG ; Fuquan LIU ; Linpeng ZHANG ; Huiguo DING ; Yuzheng ZHUGE ; Jitao WANG ; Lei LI ; Guangchuan WANG ; Hao WU ; Hui LI ; Guohong CAO ; Xuefeng LU ; Derun KONG ; Lin SUN ; Wei WU ; Junhui SUN ; Jiangtao LIU ; He ZHU ; Dongliang LI ; Wuhua GUO ; Hui XUE ; Yu WANG ; Jiancuo GENGZANG ; Tian ZHAO ; Min YUAN ; Shirong LIU ; Hui HUAN ; Meng NIU ; Xin LI ; Jun MA ; Qingliang ZHU ; Wenbo GUO ; Kunpeng ZHANG ; Xiaoliang ZHU ; Birun HUANG ; Jianan LI ; Weidong WANG ; Hongfeng YI ; Qi ZHANG ; Long GAO ; Guo ZHANG ; Zhongwei ZHAO ; Kai XIONG ; Zexin WANG ; Hong SHAN ; Mingsheng LI ; Xueqiang ZHANG ; Haibin SHI ; Xiaogang HU ; Kangshun ZHU ; Zhanguo ZHANG ; Hong JIANG ; Jianbo ZHAO ; Mingsheng HUANG ; Wenyong SHEN ; Lin ZHANG ; Feng XIE ; Zhiwei LI ; Changlong HOU ; Shengjuan HU ; Jianwei LU ; Xudong CUI ; Ting LU ; Shaoqi YANG ; Wei LIU ; Junping SHI ; Yanming LEI ; Jinlun BAO ; Tao WANG ; Weixin REN ; Xiaoli ZHU ; Yong WANG ; Lei YU ; Qiang YU ; Huiling XIANG ; Wenqiang LUO ; Xiaolong QI
Chinese Journal of Hepatology 2022;30(6):637-643
		                        		
		                        			
		                        			Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.
		                        		
		                        		
		                        		
		                        	
5.Regulation and mechanism of Myosin X on radiosensitivity of non-small cell lung cancer cell line H1975 in vitro
Hui SHEN ; Haibin OU ; Jin SHAO ; Yaofei JIANG ; Yu LIU ; Junhong ZHANG ; Conghua XIE
Chinese Journal of Radiation Oncology 2021;30(9):949-955
		                        		
		                        			
		                        			Objective:To investigate the effect and mechanism of Myosin X on the radiosensitivity of non-small cell lung cancer (NSCLC) cell line H1975 in vitro. Methods:Western blot was applied to detect the expression level of Myosin X expression. The H1975 cell line with stable knockout of Myosin X (KO group) and infected with control virus (NC group) were constucted by using CRISPR/Cas9 technique. The knockout efficiency was validated. The radiosensitivity of two cell lines was measured by colony formation assay and single-hit multi-target model. γ-H 2AX focus formation test and RNA sequencing (RNAseq) analysis were employed to identify the regulatory mechanism of the radiosensitivity of lung cancer cell lines mediated by Myosin X. Results:The expression level of Myosin X in the H1975 cells was significantly up-regulated than those in other NSCLC cell lines (all P<0.01). The lentiviral vector of Myosin X sgRNA-Lenti-CRISPR v2 was successfully constructed. After the puromycin screening, H1975 cell lines with complete knockout of Myosin X and control cell lines (NC group) were obtained. Colony formation assay demonstrated that compared with the NC group, the radiosensitivity in the KO group was significantly higher (The D 0 value was decreased from 1.28 Gy to 1.03 Gy, SF 2 decreased from 0.29 to 0.21, and the sensitization ratio was 1.24). The γ-H 2AX focus formation test showed that the number of damage focus formed at 1 h and 6 h after irradiation in the KO group was significantly larger than that in the NC group ( P<0.05. RNAseq analysis indicated that the expression level of ISLR in the KO group was significantly down-regulated than that IN the NC group ( P<0.05). Conclusion:Knockout of Myosin X can increase the radiosensitivity of H1975 cells probably by interfering the repair of DNA double-strand damage and down-regulating the expression level of ISLR.
		                        		
		                        		
		                        		
		                        	
6.The Effect of Trunk Motion Control on Biomechanical Parameters of Knee During Landing
Bin MA ; Di XIE ; Huifang CHEN ; Tiantian ZHANG ; Yudong JIA ; Pengsong GU ; Jingyi SUN ; Haimei WANG ; Haibin LIU ; Xiaoming LI
Journal of Medical Biomechanics 2021;36(6):E963-E969
		                        		
		                        			
		                        			 Objective To determine the effect of trunk motion control on knee biomechanics during single-leg landing. Methods Twenty male healthy basketball players were recruited. The kinematics, kinetics parameters and surface electromyogram (EMG) of knee joints under trunk motion control during single-leg landing were studied by using Vicon motion Analysis system, Kistler force platform and Noraxon surface EMG system. Results Compared with natural landing, there were significant differences in flexion angle at initial contact moment, peak flexion angle and peak flexion moment during deeply inspiratory landing and landing with a stick, and a significantly larger flexion angle at initial contact moment, a larger peak flexion angle and smaller peak flexion moment were also found. Compared with natural landing, there was no statistical difference in peak valgus angle and peak valgus moment, as well as EMG activity of hamstrings, quadriceps muscles of the knee during deeply inspiratory landing and landing with a stick. Conclusions Deeply inspiratory landing or landing with a stick reduce the risk of anterior cruciate ligament (ACL) injury, and the results provide the theoretical basis for prevention of ACL injuries in basketball players during landing. 
		                        		
		                        		
		                        		
		                        	
7.Effects of Ankle Taping on Knee Biomechanics during Dominant-Legged Drop Landing
Haimei WANG ; Di XIE ; Xu MA ; Huifang CHEN ; Xiao SHI ; Bin MA ; Haibin LIU ; Xiaoming LI
Journal of Medical Biomechanics 2020;35(6):E679-E684
		                        		
		                        			
		                        			Objective To study the effect of ankle taping (restriction of ankle varus and plantar flexion) on biomechanical characteristics of the knee during drop landing on the dominant leg. Methods Eighteen amateur athletes performed the dominant-legged drop landing under two different ankle conditions (with or without taping). Vicon three-dimensional (3D) motion capture system,  Kistler force plate and Noraxon surface electromyography (sEMG) system were used to collect kinetic, kinematic and sEMG data for statistical analysis. Results Compared with control group, ankle taping significantly increased flexion angle at initial contact and maximum flexion angle, while significantly decreased the maximum valgus angle. Conclusions The restriction of varus and plantar flexion might reduce the risk of anterior cruciate ligament (ACL) injury. The intervention with ankle taping could modify biomechanical parameters of the knee during drop landing. The ankle taping by restriction of ankle varus and plantar flexion may be an effective measure to prevent ACL injury for collegiate athletes.
		                        		
		                        		
		                        		
		                        	
8.Reconstruction of digestive tract with Roux-en-Y anastomosis in 4K laparoscopic distal radical gastrectomy
Qian WANG ; Jiaju CHEN ; Hongxin YANG ; Lei ZHANG ; Haibin WANG ; Zhiqiang YAN ; Haitao XIE
Chinese Journal of Digestive Surgery 2020;19(S1):85-87
		                        		
		                        			
		                        			The laparoscopic vision platform developed from the prototype of candlelight reflector device to HD, 3D and 4K ultra HD, which revolutionized surgery from open surgery to minimally invasive surgery. With the continuous application in gastric cancer surgery, the importance of laparoscopy in radical gastrectomy is gradually recognized. Radical gastrectomy mainly includes lymph node dissection and digestive tract reconstruction. The reconstruction of digestive tract after radical gastrectomy for distal gastric cancer has been a hot topic of discussion and research, which is directly related to the incidence of postoperative complications, nutritional status and quality of life. This paper mainly discusses the Roux-en-Y digestive tract reconstruction of radical gastrectomy for distal gastric cancer with 4K laparoscopic.
		                        		
		                        		
		                        		
		                        	
9. Replication of 3D laparoscopic membrane anatomic radical gastrectomy for gastric cancer
Qian WANG ; Hongxin YANG ; Lei ZHANG ; Haibin WANG ; Zhiqiang YAN ; Haitao XIE ; Jiaju CHEN
Chinese Journal of Gastrointestinal Surgery 2019;22(5):423-426
		                        		
		                        			
		                        			 According to the current evidence-based medicine researches, the eastern and western countries have reached a consensus that D2 operation is a standardized procedure for advanced gastric cancer.However, the postoperative five-year survival rate is still not satisfactory. Professor Gong Jianping of Tongji Hospital, Tongji Medical Gollege of Huazhong University of Science and Technology proposed a theory of membrane anatomy (the third element of surgical anatomy) and the concept of cancer leakage—an epoch-making concept in surgical anatomy. The Department of Gastrointestinal Surgery, The Affiliated Hospital of Guizhou Medical University was honored to be selected as one of the first domestic replication units of 3D laparoscopic radical gastrectomy under membrane anatomy. Professor Gong Jianping has visited our hospital several times for surgical demonstration, explanation of membrane anatomy theory and replication training. Through the understanding of membrane anatomy theory, we found that 3D laparoscopic radical gastrectomy guided by membrane anatomy can achieve good results, e.g less bleeding, complete resection, complete lymph node dissection and avoidance of side damage, meanwhile the operation is simple and safe. At the same time, it can avoid the shedding of cancer cells, so as to reduce the iatrogenic leakage of cancer and improve the efficacy of radical gastrectomy. In addition, the standardized procedure of laparoscopic radical gastrectomy makes it scientific, reproducible and easy to be popularized. 
		                        		
		                        		
		                        		
		                        	
10. Exploring on occupational health risk assessment of 2-butoxyethanol in a printing house
Xue TAO ; Haibin LI ; Shuang SONG ; Tiandi LI ; Zihuang XIE
Chinese Journal of Industrial Hygiene and Occupational Diseases 2019;37(7):554-557
		                        		
		                        			 Objective:
		                        			To apply GBZ/T298-2017 "Guidelines for occupational health risk assessment of chemicals in the workplace" to conduct an occupational health risk assessment of 2-butoxyethanol exposure in a printing enterprise, in order to protect the laborers' health.
		                        		
		                        			Methods:
		                        			Conducted a worksite survey of occupational health include data collection, site investigation, determination 2-butoxyethanol in workplace air and raw and auxiliary material, determination 2-butoxyacetic acid in urine after shift from May 17 to 24, 2017, using the above results, conducting 2-butoxyethanol occupational health risk assessment.
		                        		
		                        			Results:
		                        			Concentrations of 2-butoxyethanol in the workplace air ranged from 1.2-30.8 mg/m3. Concentrations of 2-butoxyaceticacid in urine ranged from 35.5 mg/L to 563.3 mg/L. The printing shop with the highest concentration of air in the workplace in the enterprise was a medium risk for 2-butoxyethanol occupational health risks, and the binding workshop printer was a low risk for 2-butoxyethanol occupational health risks. The occupational health risk of 2-butoxyethanol in the print shop was medium.
		                        		
		                        			Conclusion
		                        			Occupational health risks of 2-butoxyethanol for companies is medium, which should be included in the evaluation of routine occupational hazards and provide more targeted recommendations based on the action levels. 
		                        		
		                        		
		                        		
		                        	
            
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