1.The Association of Intestinal Flora Metabolite TMAO with Non-alcoholic Fatty Liver Disease
Yuanyuan LI ; Yaxian SONG ; Yushan XU ; Xiaofu ZENG ; Hui YUAN ; Zhao XU ; Yan JIANG
Journal of Kunming Medical University 2024;45(2):77-84
		                        		
		                        			
		                        			Objective To explore the role of TMAO from gut microbiota in non-alcoholic fatty liver disease(NAFLD),we detected the serum level of TMAO and its precursor metabolites in NAFLD,as well as the expression level of Eubacterium rectum,Bacteroidetes multiforme,Lactobacillus and bifidobacterium in the intestinal flora.Methods We collected 118 subjects and divided into NAFLD group(86 cases)and healthy control group(32 cases)randomly.We also detected the serum level of TMAO and its precursor metabolites in subjects by high performance liquid chromatography tandem mass spectrometry detection(LC-MS),and the expression of target bacterial DNA was detected by qRT-PCR.Results Serum TMAO,TMA and choline levels were significantly increased in NAFLD(P<0.05),and liver fat content was positively correlated with TMAO(P<0.05).The expression level of Lactobacillus and Eubacterium rectum in NAFLD group were increased(P<0.05);the expression level of Bifidobacterium and Bacteroides multiform were decreased(P<0.05).The serum TMAO level was positively correlated with Eubacterium rectum(r=0.280,P<0.05),and negatively correlated with Bifidobacterium(r=-0.332,P<0.05).Conclusion The level of TMAO in serum shows a positive correlation with NAFLD.The structure of intestinal flora in individuals with NAFLD is altered and linked to TMAO.This suggests that the intestinal flora may have a significant impact on the development of NAFLD through TMAO.
		                        		
		                        		
		                        		
		                        	
2.Progress in role of silent information regulator 3 in improving idiopathic pulmonary fibrosis by regulating mitochondrial dysfunction
Shusen YANG ; Yushan LIU ; Yilin ZHANG ; Yi HUI ; Jingtao LI ; Shuguang YAN
Chinese Journal of Pathophysiology 2024;40(2):358-364
		                        		
		                        			
		                        			Idiopathic pulmonary fibrosis(IPF)is a chronic progressive interstitial lung disease of unknown etiology,with a rapid disease course,poor prognosis,and the absence of effective therapeutic drugs.Mitochondrial dys-function is one of the crucial causes of inducing IPF.Silent information regulator 3(SIRT3)can restore mitochondrial ho-meostasis by inhibiting mitochondrial oxidative stress,repairing mitochondrial DNA damage,and ameliorating abnormal mitochondrial lipid metabolism.This paper summarizes the role and mechanism of SIRT3 in attenuating mitochondrial dys-function based on delineating the relationship between mitochondrial dysfunction and IPF,aiming to provide references for finding effective treatment methods for IPF.
		                        		
		                        		
		                        		
		                        	
3.Clinical study on the combination of the Danzhi Jiangtang Capsule and dapagliflozin for type 2 diabetes mellitus with peripheral vascular disease
Jian LIU ; Zhaohui FANG ; Yingqun NI ; Jindong ZHAO ; Ruimin LU ; Ben WANG ; Yushan YAN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(8):1119-1125
		                        		
		                        			
		                        			Objective This study aimed to explore the effect of the combined Danzhi Jiangtang Capsule with dapagliflozin on the blood lipid profile and related inflammatory markers in patients with type 2 diabetes mellitus with peripheral vascular disease. Methods 72 patients with type 2 diabetes mellitus with peripheral vascular disease who met the inclusion criteria were admitted to the Department of Endocrinology,The First Affiliated Hospital of Anhui University of Chinese Medicine,from April 2021 to April 2023. The patients were assigned to the experimental group and the control group using the random number table method (36 cases in each group). The control group was treated with dapagliflozin in addition to standard treatment,while the experimental group received the Danzhi Jiangtang Capsule for 12 weeks. Clinical efficacy,glucose and lipid metabolism indicators,hypersensitive C-reactive protein (hs-CRP),body mass index (BMI) levels,and traditional Chinese medicine (TCM) syndrome scores were observed pre-and post-treatment.Results In post-treatment,the clinical efficacy was higher in the experimental group than in the control group. Significant reductions in fasting blood glucose (FPG),2 h postprandial glucose (2 hPG),triglycerides (TG),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),hs-CRP,BMI,and increased high-density lipoprotein cholesterol (HDL-C) were observed. Scores for TCM syndrome and individual items also decreased (P<0.05). Comparisons within the groups for pre-and post-treatment showed reductions in FPG,2 hPG,TG,TC,LDL-C,hs-CRP,and an increase in HDL-C,along with a decrease in total scores of TCM syndrome (P<0.05). Conclusion The Danzhi Jiangtang Capsule combined with dapagliflozin in the treatment of type 2 diabetes mellitus with peripheral vascular disease can regulate the blood lipid profile,reduce inflammatory factors,and improve patient's symptoms. Integrated traditional Chinese and Western medicine treatment are more conducive to controlling the disease,and TCM can be used in clinical practice as a combination treatment.
		                        		
		                        		
		                        		
		                        	
4.Prognostic nutritional index application value for acute-on-chronic liver failure co-infection
Yamin WANG ; Yushan LIU ; Juan LI ; Qiao ZHANG ; Taotao YAN ; Danfeng REN ; Li ZHU ; Guoyu ZHANG ; Yuan YANG ; Jinfeng LIU ; Tianyan CHEN ; Yingren ZHAO ; Yingli HE
Chinese Journal of Hepatology 2024;32(3):235-241
		                        		
		                        			
		                        			Objective:To explore the predictive value of the prognostic nutritional index (PNI) in concurrently infected patients with acute-on-chronic liver failure (ACLF).Methods:220 cases with ACLF diagnosed and treated at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2016 were selected. Patients were divided into an infection and non-infection group according to whether they had co-infections during the course of the disease. Clinical data differences were compared between the two groups of patients. Binary logistic regression analysis was used to screen out influencing factors related to co-infection. The receiver operating characteristic curve was used to evaluate the predictive value of PNI for ACLF co-infection. The measurement data between groups were compared using the independent sample t-test and the Mann-Whitney U rank sum test. The enumeration data were analyzed using the Fisher exact probability test or the Pearson χ2 test. The Pearson method was performed for correlation analysis. The independent risk factors for liver failure associated with co-infection were analyzed by multivariate logistic analysis. Results:There were statistically significant differences in ascites, hepatorenal syndrome, PNI score, and albumin between the infection and the non-infection group ( P ?0.05). Among the 220 ACLF cases, 158 (71.82%) were infected with the hepatitis B virus (HBV). The incidence rate of infection during hospitalization was 69.09% (152/220). The common sites of infection were intraabdominal (57.07%) and pulmonary infection (29.29%). Pearson correlation analysis showed that PNI and MELD-Na were negatively correlated ( r ?=?-0.150, P ?0.05). Multivariate logistic analysis results showed that low PNI score ( OR=0.916, 95% CI: 0.865~0.970), ascites ( OR=4.243, 95% CI: 2.237~8.047), and hepatorenal syndrome ( OR=4.082, 95% CI : 1.106~15.067) were risk factors for ACLF co-infection ( P ?0.05). The ROC results showed that the PNI curve area (0.648) was higher than the MELD-Na score curve area (0.610, P ?0.05). The effectiveness of predicting infection risk when PNI was combined with ascites and hepatorenal syndrome complications was raised. Patients with co-infections had a good predictive effect when PNI ≤ 40.625. The sensitivity and specificity were 84.2% and 41.2%, respectively. Conclusion:Low PNI score and ACLF co-infection have a close correlation. Therefore, PNI has a certain appraisal value for ACLF co-infection.
		                        		
		                        		
		                        		
		                        	
5.Epidemiological investigation and risk factors of diabetic retinopathy in Yunnan Province
Li SHI ; Xuemei XIA ; Xuhong HOU ; Jianfang LIU ; Xin NIAN ; Yan JIANG ; Yaxian SONG ; Yushan XU
Chinese Journal of Internal Medicine 2024;63(6):613-617
		                        		
		                        			
		                        			To investigate the prevalence and epidemiological characteristics of diabetic retinopathy (DR) in Yunnan Province, explore its risk factors, and provide a basis for the prevention and treatment of chronic complications of diabetes mellitus (DM). This is a large cross-sectional study, in all, 1 524 DM patients in 16 communities and villages of Yunnan Province who were registered in health service centers were included in this study from August to November 2019. All patients completed a uniform questionnaire, anthropometric measurements, biochemical measurements, and auxiliary examinations. Logistic regression analysis was used to screen the risk factors of DR. The prevalence rates of DR, mild non-proliferative DR (mild-NPDR), and referable DR (RDR) were 16.0% (244/1 524), 4.5% (69/1 524), and 11.5% (175/1 524), respectively. Glycated hemoglobin A 1c (HbA 1c)≥7.0% was the risk factor of mild-NPDR ( OR=1.872, 95% CI 1.055-3.323) and RDR ( OR=4.821, 95% CI 2.917-7.969). Blood pressure≥130/80 mmHg (1 mmHg=0.133 kPa) was the risk factor of mild-NPDR ( OR=1.933, 95% CI 1.112-3.358) and RDR ( OR=1.505, 95% CI 1.063-2.130). In Yunnan Province, 16.0% DM patients had accompanying DR, wherein about 71.7% of them required an ophthalmology referral, and the high incidence of RDR in DM patients was associated with poor control of blood glucose and blood pressure.
		                        		
		                        		
		                        		
		                        	
6.Mechanism of Nrf2 in the treatment of ulcerative colitis via regulating macrophage polarization
Yilin ZHANG ; Yushan LIU ; Shusen YANG ; Shuguang YAN
Journal of Central South University(Medical Sciences) 2023;48(11):1746-1752
		                        		
		                        			
		                        			Ulcerative colitis(UC)is an inflammatory bowel disease induced by multiple factors,which causes abnormal activation of intestinal immune cells and excessive release of antibodies and inflammatory factors,repeatedly damaging the intestinal mucosa.Macrophages,as innate intestinal immune cells,often maintain the balance of M1/M2 macrophages polarization to normalize the regression inflammation,and the imbalance of their polarization will cause repeated damage of intestinal mucosa and persistent inflammation,which is a main cause of UC.Nuclear factor E2-related factor 2(Nrf2),as an important regulator of antioxidant and anti-inflammatory,is often used as a target for the treatment of autoimmune diseases.Nrf2 alleviates intestinal high oxidative stress and inflammatory factors by balancing macrophage polarization,which may be of great significance for the prevention and treatment of UC.Summarizing the mechanism of macrophage polarization imbalance on the course of UC and the possible regulatory mechanism of Nrf2 may provide basis for the development of UC targeted therapeutic drugs.
		                        		
		                        		
		                        		
		                        	
7.Value of peripheral blood lymphocyte count in evaluating the short-term prognosis of patients with acute-on-chronic liver failure
Xiaohua LIU ; Shujuan YANG ; Yushan LIU ; Juan LI ; Qiao ZHANG ; Yamin WANG ; Taotao YAN ; Yuan YANG ; Yingren ZHAO ; Yingli HE
Journal of Clinical Hepatology 2023;39(10):2383-2389
		                        		
		                        			
		                        			ObjectiveTo investigate the influencing factors for the prognosis of patients with acute-on-chronic liver failure (ACLF), and to establish a short-term prognostic model. MethodsA retrospective analysis was performed for the baseline clinical data of 247 patients with ACLF who were hospitalized in Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, from January 2011 to December 2016, and the patients were divided into survival group and death group. The two groups were compared to identify the influencing factors for prognosis; a prognostic model was established, and the receiver operating characteristic (ROC) curve was used to assess its predictive efficacy and determine the optimal cut-off value. The independent-samples t test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between groups; the Fisher’s exact test or the Pearson’s chi-square test was used for comparison of categorical data between groups. The univariate and multivariate logistic regression analyses were used to investigate the independent risk factors for 28- and 90-day prognosis, and the Kaplan-Meier method was used to plot the 28-day survival curves. ResultsA total of 220 patients with ACLF were included based on the inclusion and exclusion criteria; there were 148 patients in the 28-day survival group and 72 patients in the 28-day death group, with a 28-day transplantation-free survival rate of 67.27%; there were 115 patients in the 90-day survival group and 105 patients in the 90-day death group, with a 90-day transplantation-free survival rate of 52.27%. The logistic regression analysis showed that female sex (odds ratio [OR]=2.149, P=0.030), high Model for End-Stage Liver Disease (MELD) score (OR=1.120, P<0.001), and low lymphocyte count (OR=0.411, P=0.002) were independent risk factors for 28-day prognosis, and an LS-MELD model for 28-day prognosis was established as Logit (28-day prognosis)=-3.432+0.765×sex-0.890×lymphocyte count×10-9+0.113×MELD(1 for male sex and 2 for female sex). The ROC curve analysis showed that this model had an optimal cut-off value of 0.35, and then the patients were divided into low LS-MELD group (≤0.35) and high LS-MELD group (>0.35); the low LS-MELD group had a significantly higher 28-day survival rate than the high LS-MELD group (P<0.001). ConclusionPeripheral blood lymphocyte count combined with sex and MELD score has a certain value in predicting the short-term prognosis of ALCF patients. 
		                        		
		                        		
		                        		
		                        	
8.Changes of volatile components and their content determination of Olibanum after processing
Ying WANG ; Yushan ZHANG ; Liping SUN ; Haoyuan CHEN ; Qing WANG ; Kaili YAN ; Bin QI ; Li LIU
China Pharmacy 2022;33(10):1172-1176
		                        		
		                        			
		                        			OBJECTIVE To analyze the changes of volatile co mponents in Olibanum and its processed products ,and to determine the contents of 4 components as octyl acetate. METHODS The volatile oil of Olibanum ,fried Olibanum and Olibanum stir-baked with vinegar were extracted. The components of volatile components were identified by GC-MS. The structure identification and data analysis of the chemical components with similarity ≥80% were performed by using Xcalibur 4.0 software and NIST 2.0 mass spectrum database. The peak area normalization method was used to calculate the relative content of each component. GC method was adopted to simultaneously determine and compare the contents of limonene ,octyl acetate ,linalool and n-octanol in volatile components of Olibanum and its processed products. RESULTS Thirteen components were identified from volatile components of Olibanum ,fried Olibanum and Olibanum stir-baked with vinegar ,mainly including alcohols ,olefins and esters;among them ,relative contents of octyl acetate in Olibanum ,fried Olibanum and Olibanum stir-baked with vinegar were higher,which were 23.86% ,37.80% and 53.86% respectively. The linear ranges of limonene ,octyl acetate ,linalool and n-octanol were 0.006 6-0.066 4,0.179 2 -1.792 0,0.003 7-0.037 0 and 0.032 8-0.328 0(r>0.999 5)respectively;RSDs of precision,repeatability and stability (24 h)tests were all less than 2%;average recoveries were 98.56%,100.02%,99.13% and 98.66%,respectively(RSD≤2.16,n=6). Average contents of 4 components in Olibanum were 0.15%,16.27%,0.36% and 2.26%,while those of fried Olibanum were 0.85%,17.58%,0.66% and 3.47%,respectively;those of Olibanum stir-baked with vinegar were 0.50%,19.75%,0.58% and 3.34%,respectively. Compared with Olibanum ,average contents of octyl acetate , linalool,n-octanol and limonene in volatile components of fried Olibanum and Olibanum stir-baked with vinegar were increased significantly(P<0.05 or P<0.01). Compared with fried Olibanum ,average contents of limonene ,linalool and n-octanol were decreased significantly ,while those of octyl acetate were increased significantly (P<0.05 or P<0.01). CONCLUSIONS After fried and stir-baked with vinegar ,the volatile components in Olibanum are similar ,but the relative contents are different ,and the contents of octyl acetate and other components are increased.
		                        		
		                        		
		                        		
		                        	
9.Preclinical characterization and comparison between CD3/CD19 bispecific and novel CD3/CD19/CD20 trispecific antibodies against B-cell acute lymphoblastic leukemia: targeted immunotherapy for acute lymphoblastic leukemia.
Sisi WANG ; Lijun PENG ; Wenqian XU ; Yuebo ZHOU ; Ziyan ZHU ; Yushan KONG ; Stewart LEUNG ; Jin WANG ; Xiaoqiang YAN ; Jian-Qing MI
Frontiers of Medicine 2022;16(1):139-149
		                        		
		                        			
		                        			The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. However, several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight, and thus its clinical use is limited. Furthermore, multiple trials have shown that approximately 30% of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells. Here, we design and characterize two novel antibodies, A-319 and A-2019. Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures, and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function. Our in vitro, ex vivo, and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells, enhancing T-cell function, mediating B-cell depletion, and eventually inhibiting tumor growth in Raji xenograft models. The two molecules are complementary in terms of efficacy and specificity profile. The activity of A-319 demonstrated superior to that of A-2019, whereas A-2019 has an additional capability to target CD20 in cells missing CD19, suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.
		                        		
		                        		
		                        		
		                        			Antigens, CD19/therapeutic use*
		                        			;
		                        		
		                        			Antineoplastic Agents/pharmacology*
		                        			;
		                        		
		                        			Humans
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		                        			Immunotherapy
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		                        			Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
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		                        			T-Lymphocytes
		                        			
		                        		
		                        	
10.Analysis of treatment for 360 critically ill pregnant and parturient women in intensive care unit
Jinxi YUE ; Qingqing HUANG ; Zongfang REN ; Yang YANG ; Yushan DUAN ; Yan CHEN ; Linjun WAN
Chinese Critical Care Medicine 2022;34(8):853-857
		                        		
		                        			
		                        			Objective:To analyze the clinical characteristics and outcomes of critically ill pregnant and parturient women in intensive care unit (ICU), and to provide clinical experience for the subspecialty construction of critical obstetrics.Methods:The clinical data of critically ill pregnant and parturient women admitted to the department of critical care medicine, the Second Affiliated Hospital of Kunming Medical University from January 2011 to December 2019 were collected. The main reasons for maternal transfer to ICU, the causes of maternal death, and organ support measures, etc. were summarized.Results:A total of 39 567 critically ill pregnant and parturient women were admitted to the department of obstetrics in our hospital, and 360 were transferred to ICU, with an average ICU transfer rate of 0.91%. Since 2016, the number of obstetric admissions, the number of ICU transfers and the ICU transfer rate had increased significantly. The average age of severe maternals admitted to ICU was (30.9±5.7) years old. The average acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score was 7 (4, 10). The average length of ICU stay was 1 (1, 2) day. The average ventilator duration was 9.0 (3.0, 17.5) hours. The main delivery mode of pregnant women in ICU was cesarean section (84.72%). Forty-eight patients (13.33%) underwent hysterectomy, of which 42 (87.5%) due to postpartum hemorrhage. The top 3 causes of ICU admission were severe postpartum hemorrhage [36.94% (133/360)], hypertensive disorders of pregnancy [21.67% (78/360)], pregnancy with cardiac disease [15.00% (54/360)]. The leading cause of postpartum hemorrhage in women transferred to ICU was placental abnormality [63.98% (103/161)], followed by uterine atony [28.57% (46/161)]. The average blood loss was (4 019±2 327) mL within 24 hours after delivery, and the number of women who underwent hysterectomy due to postpartum hemorrhage decreased year by year. During the study period, there were 2 maternal deaths, which were indirect obstetric deaths, 3 cases were discharged against-advice (expected death), including 1 indirect death and 2 direct obstetric death; the mortality in ICU was 1.39% (5/360).Conclusions:The most common reasons for pregnant and parturient women to be admitted to ICU were severe postpartum hemorrhage and hypertensive disorders of pregnancy. The leading cause of postpartum hemorrhage was placental problem. Indirect obstetric deaths exceeded direct obstetric deaths, mainly due to pregnancy complicated with cardiac disease and severe pneumonia. ICU has become an important battlefield for rescuing critically ill maternal and an important guarantee for reducing the maternal mortality.
		                        		
		                        		
		                        		
		                        	
            
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