1.Carthamus tinctorius L.extract ameliorates alcoholic liver disease by modulating PI3K/Akt/FoxO signaling pathway
Wen-Xuan WANG ; Xiang-Lei FU ; Man QI ; Fu-Rong FAN ; Fu-Rong ZHU ; Yuan-Chuang WANG ; Kai-Yue ZHANG ; Min LIU ; Sheng-Hui CHU
Chinese Pharmacological Bulletin 2024;40(6):1137-1145
		                        		
		                        			
		                        			Aim To investigate the effects of Cartham-us tinctorius L.extract(CTLE)on oxidative stress,lipid metabolism,and apoptosis levels of mice with al-cohol-induced liver injury and its mechanism of action.Methods The mouse model of alcohol-associated liver disease was established by chronic alcohol feeding and acute alcohol gavage.Mice were randomly divided into four groups.During the modeling period,the state changes of mice were observed every day,and their weight was recorded.At the end of modeling,blood and liver tissues were collected from each group of mice.The blood of mice was analyzed biochemically,and HE staining and Oil Red O staining were used to evaluate further the degree of pathological damage in the liver of mice.Quantitative real-time PCR(qPCR)and Western blot were applied to detect the mRNA and protein expression levels of p-PI3K,PI3K,p-Akt,Akt,p-mTOR,mTOR,p-FoxO1,FoxO1,p-FoxO3a,FoxO3a,p-FoxO4,FoxO4,BCL and BAX factors.Results Compared to the model group,the CTLE administration group showed improved hepatic patho-logical injury and reduced lipid deposition.The bio-chemical indexes in serum and liver,such as ALT,AST,TG,TC,and MDA levels were reduced,while GSH and SOD levels increased.Regulating the PI3K/Akt/FoxO pathway resulted in increased production of SOD,which reduced damage and apoptosis caused by reactive oxygen species(ROS).Conclusions CTLE can exert anti-oxidative stress and anti-apoptotic effects through the PI3K/Akt/FoxO pathway and attenuates alcoholic liver injury in mice,providing new ideas for the treatment of alcoholic liver disease and the develop-ment of related drugs.
		                        		
		                        		
		                        		
		                        	
2.Study on improvement effect of Danggui Shaoyao San on edema in rats with nephrotic syndrome and its mechanism
Xiao-Wen MA ; Sheng-Nan FAN ; Zai-Ping XU ; Qing-Zhen XIANG ; Zi-Hua XUAN ; Yun-Lai WANG ; Fan XU
Chinese Pharmacological Bulletin 2024;40(6):1172-1178
		                        		
		                        			
		                        			Aim To explore the effect of Danggui Shaoyao San on edema in rats with nephrotic syndrome and the underlying mechanism.Methods Rats were randomly divided into control group,model group,Danggui Shaoyao San group(17.2 g·kg-1·d-1),losartan group(30 mg·kg-1·d-1)and tolvaptan group(3 mg·kg-1·d-1).The rat model of nephrot-ic syndrome was established by tail vein injection of adriamycin.After four weeks of treatment,the levels of renal function and 24 h urinary protein were detected.The distribution of aquaporin 2(AQP2)and pS256-AQP2 in renal tissue was detected by immunohisto-chemistry.The levels of plasma arginine vasopressin(AVP)and angiotensin Ⅱ(Ang Ⅱ)were measured by radioimmunoassay.The expressions of renal AQP2,pS256-AQP2,angiotensin type 1 receptor(AT1R),arginine vasopressin receptor 2(V2R)protein and mRNA were measured by Western blot and RT-PCR,respectively.Results The three drugs could improve renal function,reduce proteinuria,decrease plasma AVP and Ang Ⅱ levels,and down-regulate AQP2 and pS256-AQP2 protein and mRNA expression in model rats.Danggui Shaoyao San and tolvaptan were more ef-fective than losartan in reducing plasma AVP levels.Conclusions Danggui Shaoyao San may regulate the expression of AQP2 by reducing the levels of AVP and Ang Ⅱ,and improve the edema of nephrotic syndrome rats.
		                        		
		                        		
		                        		
		                        	
3.Construction and validation of risk prediction model for recurrence of contralateral hip fracture in elderly patients within 2 years after operation
Tao WEN ; Jie ZHAO ; Yanyun WANG ; Xuan YIN ; Wen FAN ; Yao HAO
Chinese Journal of Modern Nursing 2024;30(20):2751-2756
		                        		
		                        			
		                        			Objective:To explore the risk factors of recurrent contralateral hip fracture within 2 years after operation in elderly patients with hip fracture, construct a nomogram prediction model and validate the model.Methods:A total of 601 elderly patients with hip fracture who underwent surgical treatment in Department of Orthopedics in First Hospital of Shanxi Medical University from June 2018 to June 2020 were selected as research objects by the convenient sampling method. They were divided into the modeling set ( n=421) and the verification set ( n=180). According to the incidence of recurrent contralateral hip fracture within 2 years of follow-up, the modeling set was divided into the recurrent fracture group and the normal group, and the clinical data of the two groups were compared. Logistic regression was used to analyze the risk factors for recurrent contralateral hip fracture in elderly patients within 2 years after surgery. R 3.6 software was used to build a risk factor nomogram model for recurrent contralateral hip fracture. Receiver operating characteristic ( ROC) curve and calibration curve were used to evaluate the differentiation and consistency of the model. Results:In 601 elderly patients with hip fracture, the incidence of recurrent contralateral hip fracture within 2 years after surgery was 8.49% (51/601), among which the incidence of modeling set was 8.31% (35/421) and the incidence of verification set was 8.89% (16/180). In the modeling set, the age, female proportion, osteoporosis proportion, combined internal medical disease proportion and malnutrition proportion of patients in the recurrent fracture group were higher than those in the normal group ( P<0.05). Logistic regression analysis showed that gender, age, osteoporosis and combined internal medical diseases were the factors affecting the recurrence of contralateral hip fracture within 2 years after operation in elderly patients with hip fracture ( P<0.05). The equation for constructing a nomogram prediction model was Logit ( P) = -8.521+0.335×age+ 0.116×female +0.341× osteoporosis +0.280 ×combined internal medical diseases. The modeling set predicted the probability of recurrent contralaterial hip fracture according to the nomogram model, and plotted the ROC curve with sensitivity of 0.826, specificity of 0.804, and area under ROC curve ( AUC) of 0.876. The sensitivity of ROC curve of the validation set was 0.788, the specificity was 0.781, and the AUC was 0.830. After internal verification by Bootstrap method, the prediction model of the modeling set and the verification set were well distinguished, and the prediction probability and the actual incidence were well consistent (Hosmer-Lemeshow χ 2=0.462, P=0.674) . Conclusions:Advanced age, female, osteoporosis and combined internal medical diseases are independent risk factors for recurrent contralateral hip fractures in elderly patients with hip fractures within 2 years after surgery. The nomogram model constructed based on this has high predictive efficacy for recurrent hip fractures, which can be used to assess the risk of recurrent fractures and improve the prognosis of patients.
		                        		
		                        		
		                        		
		                        	
4.Robot-assisted gait training on walking rehabilitation in stroke patients:A scoping review
Xiao-Qing YAN ; Yu-Jing LI ; Yi-Xuan LI ; Fan YANG ; Wen-Yan TIAN
Chinese Medical Equipment Journal 2024;45(7):105-111
		                        		
		                        			
		                        			Literature related to robot-assisted gait training(RAGT)for stroke patients was summarized,and the results of the systematic search were analyzed using the method of scoping review.The positive effects of robot-assisted gait training(RAGT)on the recovery of walking function in stroke patients were described,and recommendations such as developing RAGT-based exoskeleton equipment and implementing a diversified gait rehabilitation training program were proposed to promote the application and development of RAGT and the recovery of walking function in stroke patients.[Chinese Medical Equipment Journal,2024,45(7):105-111]
		                        		
		                        		
		                        		
		                        	
5.Determination of purity of a new anti-fatty liver drug IMH by differential scanning calorimetry method and uncertainty evaluation
Hui-hui SHAO ; Kang-fan LEI ; Tong QIN ; Wen-xuan ZHANG ; Song WU ; Qing-yun YANG
Acta Pharmaceutica Sinica 2023;58(3):767-772
		                        		
		                        			
		                        			 The purity of 4,4′-dimethoxy-5,6,5′,6′-bis (methylenedioxy)-2′-morpholine methylenebiphenyl-2-methyl formate methanesulfonate (IMH), a new drug for fatty liver treatment, was determined through differential scanning calorimetry (DSC). Analysis of two-factor non repeatability method was performed in the investigation the effects of two factors (heating rate and sample weight) on purity determination. The DSC experimental parameters were optimized as follows: heating rate was 10 ℃·min-1, temperature range was 150-300 ℃, sample weight was 2.0-4.1 mg, and N2 flow rate was 80 mL·min-1. The linear correlation coefficient (
		                        		
		                        	
		                				6.Research progress of anti-Acinetobacter baumannii  drug
		                			
		                			Kang-fan LEI ; Song WU ; Wen-xuan ZHANG
Acta Pharmaceutica Sinica 2023;58(12):3583-3598
		                        		
		                        			
		                        			 Compared with other drug-resistant strains,
		                        		
		                        	
7.A decision tree model to predict successful endovascular recanalization of non-acute internal carotid artery occlusion
Shuxian HUO ; Chao HOU ; Xuan SHI ; Qin YIN ; Xianjun HUANG ; Wen SUN ; Guodong XIAO ; Yong YANG ; Hongbing CHEN ; Min LI ; Mingyang DU ; Yunfei HAN ; Xiaobing FAN ; Xinfeng LIU ; Ruidong YE
International Journal of Cerebrovascular Diseases 2023;31(7):481-489
		                        		
		                        			
		                        			Objective:To investigate predictive factors for successful endovascular recanalization in patients with non-acute symptomatic internal carotid artery occlusion (SICAO), to develop a decision tree model using the Classification and Regression Tree (CART) algorithm, and to evaluate the predictive performance of the model.Methods:Patients with non-acute SICAO received endovascular therapy at 8 comprehensive stroke centers in China were included retrospectively. They were randomly assigned to a training set and a validation set. In the training set, the least absolute shrinkage and selection operator (LASSO) algorithm was used to screen important variables, and a decision tree prediction model was constructed based on CART algorithm. The model was evaluated using the receiver operating characteristic (ROC) curve, Hosmer-Lemeshow goodness-of-fit test and confusion matrix in the validation set.Results:A total of 511 patients with non-acute SICAO were included. They were randomly divided into a training set ( n=357) and a validation set ( n=154) in a 7:3 ratio. The successful recanalization rates after endovascular therapy were 58.8% and 58.4%, respectively. There was no statistically significant difference ( χ2=0.007, P=0.936). A CART decision tree model consisting of 5 variables, 5 layers and 9 classification rules was constructed using the six non-zero-coefficient variables selected by LASSO regression. The predictive factors for successful recanalization included fewer occluded segments, proximal tapered stump, ASITN/SIR collateral grading of 1-2, ischemic stroke, and a recent event to endovascular therapy time of 1-30 d. ROC analysis showed that the area under curve of the decision tree model in the training set was 0.810 (95% confidence interval 0.764-0.857), and the optimal cut-off value for predicting successful recanalization was 0.71. The area under curve in the validation set was 0.763 (95% confidence interval 0.687-0.839). The accuracy was 70.1%, precision was 81.4%, sensitivity was 63.3%, and specificity was 79.7%. The Hosmer-Lemeshow test in both groups showed P>0.05. Conclusion:Based on the type of ischemic event, the time from the latest event to endovascular therapy, proximal stump morphology, the number of occluded segments, and the ASITN/SIR collateral grading constructed the decision tree model can effectively predict successful recanalization after non-acute SICAO endovascular therapy.
		                        		
		                        		
		                        		
		                        	
8.Attentional Bias and Time Course towards Emotional Faces in College Students with Different Rumination Type
Xi FAN ; Xiao-le LI ; Yu-xuan WEN ; Zi-yin YANG ; Hui WANG
Journal of Sun Yat-sen University(Medical Sciences) 2022;43(6):946-957
		                        		
		                        			
		                        			ObjectiveTo investigate the attentional bias and its time course towards emotional faces in three different rumination types of college students. MethodsThe positive and negative rumination scale was used to identify three rumination types among college students, and we selected 28 students from each type to explore attentional bias within a dot probe paradigm combined with eye-tracking techonology. The emotional stimuli included positive-neutral, negative-neutral and neutral-neutral emotional face pairs. ResultsThe reaction time indices showed that for negative-neutral face pairs, the effects of rumination type on bias index (BI) and disengaging index (DI) were statistically significant (F = 20.11,P < 0.001, η2 = 0.33), (F = 11.46,P < 0.001, η2 = 0.22]. But no statistical significance was found for positive-neutral face pairs. BI (t = 7.06, P < 0.001, d = 1.34) and DI (t = 5.92, P < 0.001, d = 1.12) in the negative ruminators towards negative faces and BI in the positive ruminators towards positive faces (t = 2.78, P < 0.01, d = 0.53) were all statistically different from 0. No statistical difference between orienting index (OI) and 0 was found in three types towards any emotional stimuli (P > 0.05). Eye movement indicators revealed that the probabilities of the first fixation were statistically different from 0.5 in all participants under all conditions and the deviation of first fixation latency was statistically different from 0 in normal ruminators tworards positive and negative faces. In all participants towards positive and negative faces, statistical differences were found between the deviation of first fixation duration and 0, the percentage of dwell time and 0.5; and the main effects of face pictures were observed (F = 8.24,P = 0.005, η2 = 0.033), (F = 9.31,P = 0.003, η2 = 0.036). ConclusionsReaction time indices showed that negative ruminators had attentional bias to negative stimuli, manifested as difficulty in disengaging attention, while positive ruminators had attentional bias to positive stimuli. Eye movement indicators showed that all types of ruminators had orienting bias of first fixation, initial and overall attention maintenance to emotional stimuli, and the attention maintenance effect towards negative stimuli was greater. 
		                        		
		                        		
		                        		
		                        	
9. Bioinformatics analysis on structure and function and expression vector construction of SARS-CoV-2 related protein TMPRSS2
Ben-Jin XU ; Hong-Rong YAN ; Miao DU ; Yan XUAN ; Yan-Xiang HOU ; Ya-Nan YANG ; Ling LIU ; Zhuo-Xi LI ; Lei FAN ; Jing LI ; Xiao-Cong CHEN ; Wen-Ting TANG ; Jun-Xiao YU ; Jie MEN ; Bin-Yu SONG ; Xiao-Liang LIU
Chinese Pharmacological Bulletin 2022;38(8):1218-1226
		                        		
		                        			
		                        			 Aim Human TMPRSS2 is a transmembrane serine protease.In this paper, the structure and func¬tion of the protein were systematically analyzed by bioinformatics, the codon was optimized and the pro- karvotie expression vector was constructed to explore the molecular mechanism of SARS-CoV-2 infecting host cells.Methods The recombinant expression vector pET-22b-TMPRSS2 was generated by molecular clo¬ning technology.The homology, functional sites, sub¬cellular localization, three-dimensional structure and evolutionary characteristics of TMPRSS2 protein were systematically analyzed by using analytical tools such as Protparam, NetPhos3.1, Blast, Clustal X2 and MEGA7.0.Results The prokarvotic expression plas- mid was constructed correctly; TMPRSS2 belongs to medium molecular weight protein, which is composed of 492 amino acid residues.The theoretical isoelectric point is 8.12, the molecular extinction coefficient is 118 145 L • mol~1 • cm"1 , and the half-life is 30 h; TMPRSS2 has 15 potential glycosylation sites and 49 possible phosphorylation sites.It is a transmembrane hydrophilie protein without signal sequenee.In addi¬tion, the protein has 13 potential B-cell epitopes and 7 T-eell epitopes.Seeondarv structure analysis showed that random coil accounted for the highest proportion of TMPRSS2 protein ( 0.453 3) , followed by extended strand (0.252 0).Sequence comparison and evolu¬tionary analysis showed that the highest sequence con¬sistency and closest genetic relationship with human TMPRSS2 was Pan troglodytes, followed by gorilla.Conclusions Human-derived TMPRSS2 protein is ev- olutionarilv conserved and functionally important.Hie results of this study can help to reveal the structure and mechanism of action of TMPRSS2 protein, provide ide¬as for the diagnosis and treatment of COYID-19, and accelerate the research and development process of new drugs targeting TMPRSS2 protein. 
		                        		
		                        		
		                        		
		                        	
10. Epithelial Cell Adhesion Molecules (EpCAMs) Promote Drug Resistance in Breast Cancer Cells by Enhancing Tight Junctions
Ya-Nan NIU ; Yu GAO ; Yi-Fan HE ; Ke-Min LI ; Xuan-Ping ZHANG ; Rui-Zan SHI ; Rui-Han LI ; Wen-Long ZHANG
Chinese Journal of Biochemistry and Molecular Biology 2022;38(6):809-815
		                        		
		                        			
		                        			 Breast cancer is a malignant tumor with high mortality, and multidrug resistance (MDR) mediated by ABCG2 (ATP-Binding cassette G2) is an important cause of chemotherapy failure. It is an urgent problem to explore the mechanism of ABCG2-mediated drug resistance and its key molecules. Epithelial cell adhesion molecule (EpCAM) is involved in multiple tumor drug resistance and is closely related to breast cancer MDR. However, its role in ABCG2-mediated breast cancer drug resistance has not been clarified. The purpose of this study was to explore the regulation of EpCAM on ABCG2-mediated MDR in breast cancer cells and its mechanism. CCK8 cytotoxicity assays confirmed that the drug resistance of MCF-7/MX cell line to mitoxantrone (MX) was significantly increased compared with MCF-7 drug-sensitive strain of human breast cancer. Western blotting results showed that ABCG2 was highly expressed and EpCAM was up-regulated in MCF-7/MX cells compared with MCF-7. SiRNA knockdown of EpCAM in MCF-7/MX cells down-regulated ABCG2 expression and restored sensitivity to MX. Cell morphology was observed under an inverted microscope, and it was found that knocking down EpCAM reduced cell-cell connections between MCF-7/MX cells. The co-localization of EpCAM and claudin 1 in MCF-7/MX cells was observed by immunofluorescence. Furthermore, Western blotting results showed that EpCAM knockdown reduced claudin 1 expression in MCF-7/MX cells. In conclusion, EpCAM may promote ABCG2-mediated mMDR in breast cancers by enhancing intercellular tight junctions through interaction with claudin 1. 
		                        		
		                        		
		                        		
		                        	
            
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