1.Study on epidemiological prevalence and serological marker characteristics of hepatitis E infection
Chengrong BIAN ; Xin LIU ; Ruirui HAN ; Lili ZHAO ; Yeli HE ; Lihua YANG ; Weiwei LI ; Lijuan SONG ; Yingwei SONG ; Yongli LI ; Aixia LIU ; Jinli LOU ; Bo′an LI
Chinese Journal of Laboratory Medicine 2024;47(3):245-251
		                        		
		                        			
		                        			Objective:This study aims to explore the prevalence of hepatitis E virus (HEV) infection in patients and the screening value of serological indicators for HEV infection patients.Methods:Retrospective analysis was conducted on 97 440 cases of anti-HEV IgM and IgG simultaneously tested in two Beijing hospitals from January 1, 2018 to August 31, 2023. Among them, there were 61 005 males and 36 435 females, with an average age of 51.65±13.05 years old. According to the positivity of anti HEV specific antibodies, they were divided into anti-HEV IgM positive group (3 588 cases), anti-HEV IgG positive group (18 083 cases), and anti-HEV antibody negative group (78 892 cases). Results of HEV RNA, liver function, AFP, PIVKA-Ⅱ and PT were collected, and their basic clinical information were recorded. The prevalence of HEV infection in patients, as well as the relationship between the positivity of anti-HEV specific antibodies and the patient′s age group, HEV RNA, and clinical characteristics were analyzed.Results:Among 97 440 patients who tested anti-HEV IgM and IgG simultaneously, the positivity rate of anti-HEV IgM was 3.68% (3 588/97 440), and was 18.56% for anti-HEV IgG (18 083/97 440). The overall positivity rates of anti-HEV IgM in two Beijing hospitals from 2018 to 2023 were 2.51%, 2.53%, 3.02%, 4.59%, 5.72%, and 4.26% ( χ2=1 401.73, P<0.001), while the positivity rates of anti-HEV IgG were 12.56%, 12.32%, 12.85%, 22.65%, 27.42%, and 26.66% ( χ2=1 058.29, P<0.001). These rates showed a gradual increase until 2023 when a decline was observed. The positivity rates of anti-HEV IgM (2.28%, 3.60%, 4.47%) ( χ2=89.62, P<0.001) and IgG (4.71%, 17.86%, 25.94%) ( χ2=2 017.32, P<0.001) increased with age in patients who aged 1-30, >30-60, and over 60 years old. The age and ALB values of patients in the anti-HEV IgM positive group were lower than the IgG-positive group, while the proportion of males, TBIL, ALT, AFP and PT values were higher than the IgG-positive group, and the differences were statistically significance ( P<0.05). Furthermore, patients in both the anti-HEV IgM and IgG positive groups had higher age, male proportion, TBIL, ALT, AFP, PIVKA-Ⅱ, and PT values than the anti-HEV negative group. Additionally, both groups had lower ALB values than the anti-HEV negative group, all of which were statistically significant ( P<0.05). 2 162 HEV infected patients were grouped based on HEV RNA positivity. The proportion of anti-HEV IgM single positive, IgG single positive, IgM+IgG double positive, and antibody negative patients in the HEV RNA positive group were 5.42% (18/332), 3.62% (12/332), 90.36% (300/332), and 0.60% (2/332), respectively. Among them, the proportion of anti-HEV IgM+IgG double positive patients in the HEV RNA positive group was higher than that in the HEV RNA negative group ( χ2=302.87, P<0.001), while the proportion of anti-HEV IgG single positive ( χ2=174.36, P<0.001) and anti-HEV antibody negative patients ( χ2=59.28, P<0.001) were lower than that in the HEV RNA negative group, both of which were statistically significant ( P<0.001). In addition, the positive rates of HEV RNA in anti-HEV IgM positive, IgG positive, and antibody negative patients were 29.23% (318/1 088), 17.59% (312/1 774), and 0.65% (2/306), respectively. Conclusion:The HEV infection rate among patients declined in 2023. HEV infection is age-related, with older individuals being more susceptible. Abnormal liver function and jaundice were commonly observed during HEV infection. It is crucial to note that the absence of anti-HEV specific antibodies cannot rule out HEV infection; therefore, additional testing for HEV RNA and/or HEV Ag is necessary for accurate diagnosis.
		                        		
		                        		
		                        		
		                        	
2.A risk scoring model based on M2 macrophage-related genes for predicting prognosis of HBV-related hepatocellular carcinoma
Pengcheng LIU ; Lijuan LOU ; Xia LIU ; Jian WANG ; Ying JIANG
Journal of Southern Medical University 2024;44(5):827-840
		                        		
		                        			
		                        			Objective To investigate the prognostic value of M2 macrophage-related genes(MRG)in hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).Methods The transcriptome data of 73 patients with HBV-related HCC were obtained from TCGA database,and the MRG modules were identified by WGCNA.The MRG-based risk scoring model was constructed by LASSO regression analysis and validated using an external dataset.The correlation of the risk score with immune cell infiltration and drug sensitivity of HCC were analyzed with CIBERSORT and R.pRRophetic.The signaling pathways of the differential genes between the high-and low-risk groups were investigated using GSVA and GSEA enrichment analyses,and MRG expressions at the single cell level were validated using R.Seurat.The cell interaction intensity was analyzed by R.Cellchat to identify important cell types related to HCC progression.MRG expression levels were detected by RT-qPCR in THP-1 cells with HCC-conditioned medium-induced M2 polarization and in HBV-positive HCC cells.Results A high M2 macrophage infiltration level was significantly correlated with a poor prognosis of HCC,and 5 hub MRG(VTN,GCLC,PARVB,TRIM27,and GMPR)were identified.The overall survival of HCC patients was significantly lower in the high-risk than in the low-risk group.The high-and the low-risk groups showed significant enrichment of M2 macrophages and na?ve B cells,respectively,and were sensitive to BI.2536 and to AG.014699,AKT.inhibitor.Ⅷ,AZD.0530,AZD7762,and BMS.708163,respectively.The proliferation-related and metabolism-related pathways were enriched in the high-risk group,where monocytes showed the most active cell interactions during HCC progression.VTN was significantly upregulated in HCC cell lines,while GCLC,PARVB,TRIM27,and GMPR were upregulated in M2 THP-1 cells.Conclusion The MRG-based risk scoring model can accurately predict the prognosis of HBV-related HCC and reveal the differences in tumor microenvironment to guide precision treatment of the patients.
		                        		
		                        		
		                        		
		                        	
3.A risk scoring model based on M2 macrophage-related genes for predicting prognosis of HBV-related hepatocellular carcinoma
Pengcheng LIU ; Lijuan LOU ; Xia LIU ; Jian WANG ; Ying JIANG
Journal of Southern Medical University 2024;44(5):827-840
		                        		
		                        			
		                        			Objective To investigate the prognostic value of M2 macrophage-related genes(MRG)in hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).Methods The transcriptome data of 73 patients with HBV-related HCC were obtained from TCGA database,and the MRG modules were identified by WGCNA.The MRG-based risk scoring model was constructed by LASSO regression analysis and validated using an external dataset.The correlation of the risk score with immune cell infiltration and drug sensitivity of HCC were analyzed with CIBERSORT and R.pRRophetic.The signaling pathways of the differential genes between the high-and low-risk groups were investigated using GSVA and GSEA enrichment analyses,and MRG expressions at the single cell level were validated using R.Seurat.The cell interaction intensity was analyzed by R.Cellchat to identify important cell types related to HCC progression.MRG expression levels were detected by RT-qPCR in THP-1 cells with HCC-conditioned medium-induced M2 polarization and in HBV-positive HCC cells.Results A high M2 macrophage infiltration level was significantly correlated with a poor prognosis of HCC,and 5 hub MRG(VTN,GCLC,PARVB,TRIM27,and GMPR)were identified.The overall survival of HCC patients was significantly lower in the high-risk than in the low-risk group.The high-and the low-risk groups showed significant enrichment of M2 macrophages and na?ve B cells,respectively,and were sensitive to BI.2536 and to AG.014699,AKT.inhibitor.Ⅷ,AZD.0530,AZD7762,and BMS.708163,respectively.The proliferation-related and metabolism-related pathways were enriched in the high-risk group,where monocytes showed the most active cell interactions during HCC progression.VTN was significantly upregulated in HCC cell lines,while GCLC,PARVB,TRIM27,and GMPR were upregulated in M2 THP-1 cells.Conclusion The MRG-based risk scoring model can accurately predict the prognosis of HBV-related HCC and reveal the differences in tumor microenvironment to guide precision treatment of the patients.
		                        		
		                        		
		                        		
		                        	
4.Study on the characteristics of serological indicators of hepatitis B virus infection in three hospitals in Beijing city
Chengrong BIAN ; Xin LIU ; Juan LIU ; Yingwei SONG ; Lijuan SONG ; Jun ZHOU ; Ruifeng YANG ; Jinli LOU ; Bo′an LI
Chinese Journal of Experimental and Clinical Virology 2022;36(6):629-636
		                        		
		                        			
		                        			Objective:To understand the characteristics of serological detection indicators of patients with hepatitis B virus (HBV) infection in three hospitals in Beijing from 2018 to 2021.Methods:The five markers of hepatitis B, liver function tests, HBV DNA load, AFP and PT test results and basic clinical information of HBsAg positive HBV infected patients in three hospitals in Beijing from 2018 to 2021 were collected. Then the diagnosis of HBV infection, the positive patterns of serological indicators for five markers of hepatitis B and the clinical characteristics of hepatitis B patients were analyzed by SAS 9.4 statistical software.Results:Among the 1 026 604 patients who were tested for the five markers of hepatitis B or hepatitis B surface antigen quantification (HBsAg-QN) in three hospitals in Beijing from 2018 to 2021, the positive detection rate of HBsAg was 53.50%. The annual positive detection rate of HBsAg was 57.22%, 55.05%, 53.64% and 47.69% successively, showing a downward trend year by year. 111 709 hepatitis B patients were divided into 1-30, 31-60 and>60 years old groups according to their age. The main diseases of the three groups of HBV infected patients was chronic hepatitis B (CHB), and the proportion of patients with acute hepatitis B (AHB) and CHB decreased with age, while the proportion of patients with HBV-related liver cirrhosis, HBV-related liver cancer, liver cancer surgery and liver transplantation increased with age, the difference of which was statistically significant (all P<0.05). In this research, a total of 24 positive patterns of the five markers of hepatitis B were detected, including 7 common patterns (the main pattern was 145), 14 rare patterns (the main pattern was 1345), and 3 unusual patterns (the main pattern was 12345). The age, male ratio, HBeAg positive detection rate, HBV DNA positive detection rate and load, TBIL, ALT, AFP and PT results in the HBsAg positive group (90 011cases) were higher than those in the HBsAg negative group (21 698 cases), and the above results of the two groups of hepatitis B patients were higher than those of the healthy control group (20 623 cases). The albumin (ALB) results were the lowest in the HBsAg positive group and the highest in the healthy control group. And the differences were statistically significant (all P<0.05). Conclusions:From 2018 to 2021, the positive rate of HBsAg among the patients who received the five markers of hepatitis B or HBsAg-QN test in three hospitals in Beijing decreased year by year. Age was associated with disease progression in patients with hepatitis B. The positive patterns of five markers of hepatitis B in HBV infected people showed diversity.
		                        		
		                        		
		                        		
		                        	
5.Characteristics of clinical and laboratory indexes in patients with liver disease with positive anti-liver cytosol antibody
Haiping ZHANG ; Huiping YAN ; Jinli LOU ; Chunyang HUANG ; Yinxue MA ; Lijuan LI ; Ying HAN ; Yanmin LIU
Chinese Journal of Hepatology 2021;29(12):1182-1187
		                        		
		                        			
		                        			Objective:To analyze the characteristics of clinical and laboratory indexes in patients with liver disease with positive anti-liver cytosol antibody type 1 (anti-LC1), in order to provide references for clinical and differential diagnosis.Methods:The clinical data of 23 832 inpatients and outpatients with positive anti-LC1 autoantibodies detected in routine autoantibody test from January 2010 to January 2020 were retrospectively analyzed, and their clinical and laboratory indexes were compared. Western blotting was used to detect anti-LC1, anti-soluble liver antigen antibody (anti-SLA), anti-glycoprotein 210 antibodies and anti-nucleosome 100 antibodies. Indirect immunofluorescence assay was used to detect anti-nuclear antibody (ANA), anti-mitochondrial antibody, anti-Smooth muscle antibody (ASMA), anti-liver and kidney microsomal antibody (anti-LKM) and other autoantibodies. Normally distributed measurement data between the two groups were compared by independent-sample t-test, and the multiple groups comparison were compared by one-way analysis of variance. Non-normally distributed measurement data were compared by non-parametric rank sum test.Results:38 anti-LC1 positive patients were detected in 23832 autoantibody tests. The age of initial diagnosis ranged from 11.0 to 84.0 (50.6 ± 16.0) years. There were 8 males (21.1%) and 30 females (78.9%). A total of 31 cases (81.6%) were positive for anti-LC1 and ANA, and the dominant karyotype was speckled pattern, accounting for 54.8%. Five cases (13.2%) were positive for ASMA, and no simultaneous positive with anti-LKM or anti-SLA. Among the 38 anti-LC1 positive patients, 9 were diagnosed with autoimmune hepatitis (AIH), 6 with possible AIH, 6 with primary biliary cholangitis (PBC), 8 with hepatitis B, 2 with hepatitis C, 1 with alcoholic liver disease, 2 with non-alcoholic fatty liver disease, 1 with drug-induced liver injury, 1 with hepatolenticular degeneration, and 2 with tumor. Confirmed and probable AIH cases accounted for 39.5% (15/38) of anti-LC1 positive cases. Among anti-LC1 positive patients, 47.4% (18/38) had entered the stage of liver cirrhosis. AIH group globulin level was higher than HBV group ( P = 0.006) and other disease groups ( P = 0.001). AIH group IgG level was higher than PBC group ( P = 0.027), HBV group ( P = 0.009) and other disease groups ( P = 0.004). the of the PBC group IgM level was higher than AIH group ( P = 0.003), HBV group ( P = 0.003) and other disease groups ( P = 0.006). Conclusion:Anti-LC1 is not only detected in AIH, but also observed in patients with primary biliary cholangitis, hepatitis B and C, alcoholic and non-alcoholic liver disease, drug-induced liver injury, hereditary metabolic liver disease and tumor. In addition, it is mainly female gender dominance and nearly half of ANA-positive young, middle-aged and elderly patients develop liver cirrhosis. For the diagnosis of type 2 autoimmune hepatitis, whether anti-LC1 is a specific antibody needs further research, but if AIH is highly suspected, this antibody can be used as a substitute.
		                        		
		                        		
		                        		
		                        	
6. Analysis of the autoantibodies characteristics of 77 anti-soluble liver antigen positive patients with liver diseases
Haiping ZHANG ; Yinxue MA ; Lijuan LI ; Dantong ZHAO ; Xinxin CHEN ; Jinli LOU ; Huiping YAN
Chinese Journal of Laboratory Medicine 2019;42(11):927-932
		                        		
		                        			 Objective:
		                        			To understand the characteristics and clinical significance of anti-soluble liver antigen antibody (anti-SLA) in patients with liver diseases.
		                        		
		                        			Methods:
		                        			Serum samples from seventy-seven patients with anti-SLA were collected from Beijing You'An Hospital during the period between January 2010 and December 2018. Anti-SLA, anti-liver cytosol type 1 antibody (anti-LC1), anti-glycoprotein 210 antibody(anti-gp210) and anti-nuclear body protein sp100 antibody(anti-sp100) were detected by immunoblotting; indirect immunofluorescence assay used for detecting anti-nuclear antibody (ANA), anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (SMA), and anti-liver kidney microsome antibody (anti-LKM). One-way analysis of variance was used to compare the ages of different anti-SLA groups. The non-parametric rank sum test was used to compare the liver function indexes and immunoglobulins in different intensity groups of anti-SLA. 
		                        		
		                        	
7.Application of Pender health promotion model for diabetic patients
Chinese Journal of Modern Nursing 2019;25(20):2597-2600
		                        		
		                        			
		                        			ObjectiveTo explore the application effect of Pender health promotion model in patients with diabetes and provide evidence for clinical nursing intervention. MethodsA convenient sampling method was used to select 100 patients with diabetes mellitus admitted to Department of Endocrinology, the First Affiliated Hospital of Harbin Medical University from October 2017 to September 2018. According to the patient's hospitalization time, the patients admitted from October 2017 to March 2018 were set as the control group, and the patients admitted from April to September 2018 were set as the observation group. Patients in the control group were given routine health education for diabetic patients, and patients in the observation group were treated with interventions based on the health promotion model. The effect of the intervention was evaluated using the Self-Management Behavior Scale for Type 2 Diabetes and the MOS 36-Item Short-From Health Survey (SF-36). ResultsThe total score of the Self-Management Behavior Scale and scores of each dimensions in the observation group were higher than those in the control group at 1 month after discharge, and the differences were statistically significant (P<0.05). There was no statistical differences in the physical health and mental health scores in SF-36 between the two groups after intervention (P> 0.05). ConclusionsPender health promotion model can improve the self-management behavior of diabetic patients and it is worthy of promotion and application.
		                        		
		                        		
		                        		
		                        	
8.The comparison of different immunoassays for the detection on autoantibodies specific to primary biliary cholangitis
Haiping ZHANG ; Huiping YAN ; Xiaosan CHEN ; Le LIU ; Qingchun LI ; Yingxue MA ; Lijuan LI ; Jiyang LI ; Jinli LOU
Chinese Journal of Laboratory Medicine 2018;41(3):203-207
		                        		
		                        			
		                        			Objective To compare the test performance of different immunoassays for the detection on autoantibodies specific to primary biliary cholangitis,including anti-mitochondrial type 2 antibody(AMA-M2),anti-glycoprotein 210(anti-gp210)and anti-nuclear body protein sp100(anti-sp100).Methods Serum samples from Primary Biliary Cholangitis(PBC, n=91), liver disease control(including viral hepatitis,autoimmune hepatitis and liver cirrhosis,n=67)and healthy individual(n=40)were collected from Beijing Youan Hospital during the period between April 2014 and April 2017.All samples were tested with chemiluminescent immunoassay(CLIA)and enzyme linked immunosorbent assay(ELISA)for AMA-M2, meanwhile the detection on anti-gp210 and anti-sp100 were compared between CLIA and Line Immunoassay(LIA).The Kappa coefficient were used to measure the level of qualitative agreement between different assays.The diagnostic accuracy of AMA-M2 detected with CLIA and ELISA were compared by receiver operating characteristic curve(ROC).Results The overall qualitative agreement between CLIA and ELISA for the detection to AMA-M2 is 88.4%(Kappa =0.765, P<0.01).Excellent qualitative agreement between CLIA and LIA for the detection to anti-gp210 and anti-sp100 was also found with overall agreement as 96.5%(Kappa=0.852,P<0.01)and 98%(Kappa=0.884,P<0.01), respectively.The ROC analysis also showed similar area under the curve(AUC)for CLIA(0.965, P<0.01)and ELISA (0.928,P<0.01)on detection to AMA-M2.Conclusions CLIA and ELISA showed excellent agreement for the detection to AMA-M2.High qualitative agreement between CLIA and LIA was also found when testing anti-gp210 and anti-sp100.
		                        		
		                        		
		                        		
		                        	
9.Study on the intervention of caffeine citrate in the treatment of neonatal apnea
Jingjing FU ; Lijuan YE ; Qiaoyan JIN ; Yanfang LOU
Chinese Journal of Biochemical Pharmaceutics 2017;37(9):256-257,259
		                        		
		                        			
		                        			Objective To investigate the effect of caffeine citrate in the treatment of neonatal apnea and the corresponding intervention measures. Methods A total of 88 children with apnea were enrolled in this study from December 2015 to February 2017, and were randomly divided into control group and study group, 44 cases in each group.The study group on the basis of conventional therapy plus caffeine citrate, the control group on the basis of conventional therapy plus aminophylline group, two newborns with apnea were duration of treatment should be 7 for 7 days, record the treatment effect and the incidence of adverse reactions. Results The total effective rate was 88.64% in the study group and 72.73% in the control group (P<0.05). The incidence of adverse reactions was 11.36% in the study group and 40.91% in the control group (P<0.05). Conclusion The application of caffeine citrate treatment of apnea with clinical efficacy and safety of the ideal of the newborn, in the course of treatment given targeted clinical nursing intervention is conducive to the protection of newborns with apnea of quality of life and life safety.
		                        		
		                        		
		                        		
		                        	
10.Exploration of the interconnection working mechanism for secondary management organization of the interns in medical universities
Fushou YANG ; Aiyun ZHANG ; Lijuan JI ; Yuan XU ; Yuan LI ; Yang LOU ; Bo LI ; Lin LU
Chinese Journal of Medical Education Research 2016;15(2):209-212
		                        		
		                        			
		                        			As the medical college students are scattered to each practice hospital, the status of the secondary clinical medical colleges' education management to interns is weakened, and the problems and contradictions are becoming increasingly prominent. In the process of internship education management, through the establishment of the secondary medical colleges' interconnection management working mecha-nism, we can effectively solve the outstanding problems in the current internship edu-cation management, to achieve mutual trust between the secondary clinical medical college and the training hospital, and en-hance the effectiveness of the management of interns.
		                        		
		                        		
		                        		
		                        	
            
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