1.Metal-organic Framework Immobilized Enzyme and Its Application in Screening of Enzyme Inhibitors of Traditional Chinese Medicine:A Review
Haipeng LIU ; Yong ZHANG ; Jing WANG ; Tianci LYU ; Ruixin DING ; Guihua GAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):256-264
		                        		
		                        			
		                        			Enzymes are widely used in chemical and pharmaceutical industries because of their advantages of high efficiency and specificity. However, the shortcomings of the free enzymes, such as poor stability and difficulty in recycling, limit their application. Therefore, the immobilization and application of enzymes have become one of the research hotspots. The selection of the immobilization carriers is a critical step in the process of enzyme immobilization. Metal-organic frameworks(MOFs), a kind of porous materials, are formed by the coordination of metal ions or metal clusters with organic ligands. As an emerging immobilization carrier, its advantages such as high porosity, strong stability, and surface modifiability make it ideal for immobilized enzyme carriers. By immobilizing the free enzyme on MOFs, the above mentioned deficiencies of the free enzymes can be effectively solved, which greatly broaden the applicable condition. Ligand fishing is a method to find receptor-specific ligands from complex components, which has the advantages of high efficiency, simple sample pretreatment and high specificity. The MOF-enzyme complex formed by enzyme immobilization can act as a "fishing rod" for ligand fishing, which can screen out the targets from the complex system of components. The complex chemical composition and various active ingredients of traditional Chinese medicine(TCM) make the ligand fishing technology to play a big role in the screening of enzyme inhibitors from TCM. And the screened enzyme inhibitors are expected to be further developed into the lead compounds with good efficacy and low adverse effects, so the immobilized enzymes of MOFs have a wide application in the screening of active ingredients from TCM. Based on this, this paper summarized the methods of immobilized enzymes of MOFs in recent years, analyzed the characteristics, advantages and disadvantages of each method, and summarized the laws of preparation conditions and mechanisms. Meanwhile, the application and future development of immobilized enzymes of MOFs in the field of enzyme inhibitor screening from TCM were also summarized and prospected, with a view to providing a reference for the development of natural ingredients and the modernization of TCM. 
		                        		
		                        		
		                        		
		                        	
2.Serological index PAI-1 as risk factor of complications of femoral head necrosis after internal fixation of femoral neck fracture
Yang GAO ; Feng LIU ; Haipeng DONG ; Yaqian WANG ; Chao LIU
International Journal of Laboratory Medicine 2024;45(1):17-21,28
		                        		
		                        			
		                        			Objective To investigate the risk factors of femoral head necrosis after internal fixation of fem-oral neck fracture,and to clarify the predictive role of serological index plasminogen activator inhibitors-1(PAI-1)on femoral head necrosis.Methods A total of 95 patients undergoing internal fixation for femoral neck fracture were included in the study.Relevant clinical information of patients was obtained and the serum PAI-1 levels of the patients before surgery,1,2,and 3 days after surgery were detected.After 1-year follow-up,patients were divided into necrosis group and non-necrosis group according to the occurrence of femoral head necrosis.Visual Analog Scale(VAS),Western Ontario McMaster University Osteoarthritis Index(WOMAC),and Harris Hip Score(HHS)were conducted in all patients one year after the surgery.The differences of basic clinical information and serum PAI-1 levels before and after the surgery between necrosis group and non-necrosis group were compared,and Logistic regression analysis was performed to identify the relevant risk factors for femoral head necrosis.The relationships between the PAI-1 level after operation and the VAS,WOMAC,and HHS scores of patients were figured out.The receiver operating characteristic(ROC)curve of serum PAI-1 as a predictive indicator for femoral head necrosis was drawn to clarify its predictive val-ue.Results Garden classification and reduction quality between the necrosis group and the non-necrosis group were risk factors for femoral head necrosis(P<0.05).The serum PAI-1 at 1 day and 2 days after surgery in the necrosis group were significantly higher than that in the non-necrosis group(P<0.05).The level of PAI-1 at 1 day and 2 days after surgery was positively correlated with VAS and WOMAC(P<0.05),and negative-ly correlated with HHS(P<0.05).Logistic regression analysis showed that the increase of serum PAI-1 level at 1 day and 2 days after surgery were risk factors for femoral head necrosis(P<0.05).The ROC curve showed that serum PAI-1 level at 2 days after surgery had higher predictive value than that at 1 day after sur-gery,and the cut-off value was 44.8 ng/L,the sensitivity was 68.49%,the specificity was 86.36%,and the ar-ea under the curve(AUC)was 0.807.Conclusion The serum PAI-1 level at 1 day and 2 days after internal fixation of femoral neck fracture could be used to predict the occurrence of femoral head necrosis,especially the serum PAI-1 levels at 2 days after surgery.
		                        		
		                        		
		                        		
		                        	
3.Retrospective study on the influence of smoking,overweight and alcoholism on femoral head necrosis after internal fixation of femoral neck fracture
Yang GAO ; Haipeng DONG ; Feng LIU ; Wenjuan WANG ; Chao LIU
Journal of Clinical Surgery 2024;32(5):525-528
		                        		
		                        			
		                        			Objective Investigating the relationship between smoking,overweight,and bibulosity with plasma PAI-1 and osteonecrosis of the femoral head after internal fixation by retrospective study,and providing reference for clinical treatment.Methods A total of 95 patients with femoral neck fracture treated with internal fixation from January 2021 to January 2022 were retrospectively studied.The data of smoking,overweight,alcohol abuse,preoperative and postoperative plasma PAI-1 levels were collected.The patients were divided into necrosis group and non-necrosis group according to the occurrence of femoral head necrosis at the last follow-up.Univariate analysis was performed on smoking,overweight,alcohol abuse,plasma PAI-1 level before and 2 days after operation,and the presence of smoking,overweight and bibulosity factors was analyzed.The association of smoking,overweight and bibulosity with plasma PAI-1 level was analyzed.Figure out the relationship between smoking,overweight,bibulosity and plasma PAI-1 and femoral head necrosis after internal fixation.Results Femoral head necrosis occurred in 22 of 95 patients.Age,gender,smoking,overweight and bibulosity were not independent risk factors for postoperative femoral head necrosis(P>0.05).The plasma PAI-1 level at 2 days after operation in necrosis group was(46.95±2.35)ng/ml,which was significantly higher than that in non-necrosis group[(41.94±4.73)ng/ml,P<0.05].The level of plasma PAI-1 at 2 days after operation was(48.29± 1.78)ng/ml in patients with smoking,overweight and alcohol abuse at the same time,which was significantly higher than that in other patients[(42.40±4.60 ng/ml,P<0.05].In addition,when the smoking,overweight,and bibulosity were concurrent,it was a risk factor for femoral head necrosis(P<0.05).Conclusion When the smoking,overweight,and bibulosity were concurrent,it can increases the risk of osteonecrosis of the femoral head after internal fixation,which may be related to the significant increase of plasma PAI-1 level,especially at 2 days after surgery.
		                        		
		                        		
		                        		
		                        	
4.Hippo pathway-manipulating neutrophil-mimic hybrid nanoparticles for cardiac ischemic injury via modulation of local immunity and cardiac regeneration.
Qiaozi WANG ; Yanan SONG ; Jinfeng GAO ; Qiyu LI ; Jing CHEN ; Yifang XIE ; Zhengmin WANG ; Haipeng TAN ; Hongbo YANG ; Ning ZHANG ; Juying QIAN ; Zhiqing PANG ; Zheyong HUANG ; Junbo GE
Acta Pharmaceutica Sinica B 2023;13(12):4999-5015
		                        		
		                        			
		                        			The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.
		                        		
		                        		
		                        		
		                        	
5.A comparative study of three primary screening methods for gastric cancer among healthy people
Yuexing LAI ; Xiaolan XIE ; Ping XU ; Jing WANG ; Xiuzhen SHI ; Haipeng YUAN ; Jie WU ; Wei GAO
Chinese Journal of Digestive Endoscopy 2023;40(11):875-880
		                        		
		                        			
		                        			Objective:To compare the role and efficacy of serum Helicobacter pylori ( HP) antibody combined with pepsinogen (PG) (ABC method), serum PG combined with gastrin-17 (G-17) (new ABC method) and a new gastric cancer screening scoring system for early gastric cancer screening in healthy people. Methods:Serological examinations were performed on healthy people who underwent physical examination and gastroscopy at the Physical Examination Center of Shanghai Songjiang District Central Hospital from January 2019 to December 2021. The population were divided into low-risk population, medium-risk population and high-risk population based on the above three primary screening methods for gastric cancer. Using gastroscopy and biopsy pathology as the gold standard, the ratio of each risk stratification and the detection rate of gastric cancer of the three screening methods were calculated. Advantages and disadvantages of the three methods were evaluated.Results:A total of 3 199 people who completed physical examination and gastroscopy were included in the study. Ten cases (0.31%) of esophageal cancer were detected by endoscopy, all of whom were early esophageal cancer. Thirty-seven cases (1.16%) of gastric cancer were detected,and the detection rate of early gastric cancer was 86.49%(32/37). The three gastric cancer screening methods were used to evaluate the risk of gastric cancer. According to ABC method, there were 1 853 cases (7.92%) in the low-risk group, 1 339 cases (41.86%) in the medium-risk group, and 7 cases (0.22%) in the high-risk group. The detection rates of gastric cancer were 0.97% (18/1 853), 1.42% (19/1 339), and 0.00%, respectively. According to the new ABC method, there were 2 362 cases (73.84%) in the low-risk group, 804 cases (25.13%) in the medium-risk group, and 33 cases (1.03%) in the high-risk group. The detection rates of gastric cancer were 1.14% (27/2 362), 1.24% (10/804), and 0.00%, respectively. According to the new gastric cancer screening scoring system, there were 1 448 cases (45.26%) in the low-risk group, 1 213 cases (37.92%) in the medium-risk group and 538 cases (16.82%) in the high-risk group. The detection rates of gastric cancer were 0.28% (4/1 448), 1.32% (16/1 213) and 3.16% (17/538), respectively. The detection rate of gastric cancer in the medium- and high-risk groups in total was significantly higher than that in the low-risk group with significant difference ( χ 2=17.935, P<0.001). The ROC curve showed that the AUC of the ABC method, the new ABC method and the new gastric cancer screening scoring system were 0.546, 0.503 and 0.760, respectively. The AUC of the new gastric cancer screening scoring system was significantly higher than those of the ABC method and the new ABC method, and the differences were statistically significant ( P<0.001). Conclusion:The detection rate of gastric cancer in the medium- and high-risk groups of the new gastric cancer screening scoring system is higher than that of the low-risk group, and the missed diagnosis rate of the new gastric cancer screening scoring system is lower than those of the ABC method and the new ABC method. The screening score is of high value for early gastric cancer screening in the healthy population.
		                        		
		                        		
		                        		
		                        	
6.Risk factors of pancreatitis after percutaneous transhepatic biliary drainage in patients with pancreatic cancer and obstructive jaundice
Mei LI ; Haisong WANG ; Chengli WANG ; Lei ZHANG ; Xueling YANG ; Yan XU ; Wei GAO ; Zhi GUO ; Haipeng YU
Chinese Journal of Internal Medicine 2022;61(1):82-85
		                        		
		                        			
		                        			Objective:To explore the risk factors and preventive strategies of pancreatitis after percutaneous transhepatic biliary drainage (PTBD) in patients with pancreatic cancer and obstructive jaundice.Methods:A total of 241 patients were retrospectively analyzed from May 2001 to October 2014 in Tianjin Medical University Cancer Institute and Hospital. The possibly correlated 9 factors were analyzed, including gender, age, hemoglobin level, total bilirubin level, degree of pancreatic duct dilatation, degree of pancreatic atrophy, degree of biliary stenosis, the pancreatic duct visualization, and drainage mode.Results:Univariate analysis suggested that pancreatic duct dilatation, pancreatic atrophy, visualized pancreatic duct and drainage mode were associated with the incidence of pancreatitis after PTBD ( P<0.05). Logistic regression analysis showed that visualization of pancreatic duct ( OR=6.33) was a risk factor for pancreatitis, while pancreatic duct dilatation ( OR=0.14), pancreatic atrophy ( OR=0.12) and external drainage ( OR=0.11) were protective factors for pancreatitis. Conclusion:In pateints with pancreatic cancer and obstructive jaundice, pancreatic duct dilatation and pancreatic atrophy predict low risk of pancreatitis after PTBD,while intraoperative pancreatic duct visualization and internal or external drainage may increase the incidence of postoperative pancreatitis.
		                        		
		                        		
		                        		
		                        	
7. Updates on extended criteria donor for liver transplantation
Haipeng MENG ; Jingjing GAO ; Hanguang DONG ; Qun WANG
Chinese Journal of Hepatobiliary Surgery 2019;25(10):789-794
		                        		
		                        			
		                        			 Though achieved great success as the only curative treatment for end-stage liver diseases, liver transplantation has been severely restricted by the shortage of donors. The adoption of extended criteria donor (ECD) tackles the donor shortage problem to some extent, thus became an issue we must face in China at present stage. As the transplantation effect and recipient safety is largely decided by the quality of liver graft, ECD graft should be cautiously selected and adopted because of its inherent defects. This relies on individualized decisions made for recipients by transplant surgeons who have a good understanding of the risk factors and evaluation criteria of ECD. In this article, we investigate the risk factors, evaluation criteriaand allocation of ECD liver grafts as well as the application of mechanic perfusion, and we discuss the fundamental issues and prospects of ECD study. 
		                        		
		                        		
		                        		
		                        	
9.Effect of Early Mother-to-child Isolation on Neuronal Cell Apoptosis in Neonatal Mice
Haipeng YANG ; Liwei WANG ; Qingliang SHAO ; Yue GAO ; Xuan ZHAO ; Xuehua QU
Progress in Modern Biomedicine 2017;17(26):5034-5037
		                        		
		                        			
		                        			Objective:To explore the effect of early mother to child separation on neonatal nervous system and its related mechanism.Methods:Randomly selected during January 2015 to September 2015,was born in 120 cases of newborn mice as the research object,the newborn mice was born after the implemented of mother-to-child separation as observation group (60),not the implemented of separation of mother and baby after birth as the control group (60),in view of the two groups of newborn mice of the nervous system,the change of the nerve cells were compared and researched.Results:The apoptotic rate of neurons in the neonatal mice was significantly higher than that in the control group (P <0.05).The neurons of caspase-3 protein expression was significantly higher than the control group (P <0.05).The expression of Caveo-1 protein in the glial cells of 14 days and 21 days was observed in the neonatal mice.The expression of Caveo-1 protein in the glial cells of the control group For comparison,(P <0.05),which were statistically significant.Conclusion:The early implementation of matemal and infant birth separation of neonatal nervous system will produce great influence,and influence the expression of the nervous system in the development of newborn,which affect the behavior of the neonatal adult dysplasia.
		                        		
		                        		
		                        		
		                        	
10.Effect of olanzapine and quetiapine on swallowing function in patients with Alzheimer's disease
Haipeng QIU ; Xiaoxuan ZHANG ; Yanjun GAO
Chinese Journal of Biochemical Pharmaceutics 2015;(9):130-132
		                        		
		                        			
		                        			Objective To investigate the olanzapine and quetiapine quetiapine in the treatment of Alzheimer's disease patients of different clinical effects and influence on the swallowing function of patient.Methods According to the order of visits to the author departments were 73 cases of Alzheimer's patients were divided into group A(37 cases) and group B(36 cases).Patients in group A were treated with olanzapine in the treatment of, and group B with quetiapine in the treatment, the time of the two groups of patients are 12 weeks, to observe the differences of the two groups during the treatment of swallowing function indexes and clinical efficacy.Results After treatment, the MMSE scores of two groups of patients compared with pre-treatment, there was no statistical significance and BEHAVE-AD score before treatment significantly decreased ( P <0.05 ).Post-treatment, the patients in two groups of MMSE, BEHAVE-AD score difference does not have statistical significance.The difference of clinical efficacy between two groups post-treatment was not statistically significant.Watian drinking water test score of two groups Post-treatment, SaO2 decreased value compared with those pre-treatment significantly increased (P<0.05).After treatment of two groups of patients Watian drinking water test score difference does not have statistical significance, and post-treatment, patients in group B of SaO2 decreased value lower than that in group A ( P <0.05 ).Mild dysphagia, two cases of moderate swallowing dysfunction occurred in twenty-six patients in group A, group B with mild swallowing dysfunction occurred in twenty-one patients, A group of swallowing dysfunction more serious than group B serious ( P <0.05 ) .Conclusion Olanzapine and quetiapine quetiapine in the treatment of patients with Alzheimer's disease clinical effect quite, patient's swallowing function cause some adverse effects, effects of olanzapine is more serious.
		                        		
		                        		
		                        		
		                        	
            
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