1.Untargeted Metabolomics Analysis of Demyelination in the Brain of Balb/c Mice Infected by Angiostrongylus cantonensis
Zhen NIU ; Xiaojie WU ; Liang YANG ; Zhixuan MA ; Junxiong YANG ; Ying FENG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(2):293-300
ObjectiveTo investigate the demyelination induced by Angiostrongylus cantonensis (AC) infection in the brain of Balb/c mice and analyze the untargeted metabolomic changes in the corpus callosum, aiming to elucidate the underlying mechanisms. MethodsBalb/c mice were randomly assigned to a control group (n=6) and an infection group (n=6). The infection group was orally administered 30 third-stage larvae of AC, while the control group received an equal volume of saline. Body weight, visual function, and behavioral scores were measured on post-infection 3, 6, 9, 12, 15, 18, and 21 days to assess neurological alterations. After 21 days, brain tissues were harvested for immunofluorescence staining, hematoxylin-eosin (HE) staining, and transmission electron microscopy to examine morphological changes in brain myelin and retina. Metabolomics analysis was performed, and differential metabolites were identified using volcano plots and heatmaps. The distribution of fold changes and bar charts were used to profile the key metabolites. These differential metabolites were then subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and regulatory network analysis. ResultsOn the 9th day after AC infection, Balb/c mice showed a decline in neurological behavioral scores (P<0.05). By day 15, visual scores decreased (P<0.05), and by day 21, significant weight loss (P<0.001) and mortality were observed. Concurrently, transmission electron microscopy and immunofluorescence staining revealed significant myelin damage in the corpus callosum and a marked reduction in oligodendrocytes (P<0.001). HE staining showed severe retinal ganglion cell damage. Metabolomic analysis revealed that glycerophospholipids were the most abundant differential metabolites, with steroids and sphingolipids being relatively less abundant. Cholesteryl ester CE (20:2) was significantly upregulated (P<0.001), while phosphatidylmethanol (18:0_18:1) was significantly downregulated (P<0.01). KEGG enrichment and regulatory network analyses demonstrated that the differential metabolites were mainly enriched in metabolic pathways like steroid biosynthesis, bile secretion, and cholesterol metabolism, and were involved in key metabolic pathways such as sphingolipid metabolism, neural signal regulation, and glycerophospholipid metabolism. ConclusionsAC infection affects the metabolic state of mice via multiple pathways, modifying the levels of metabolites crucial for myelination and myelin stability. Demyelination may be closely linked to the disruption of these key metabolic pathways, particularly the dysregulation of cholesterol and sphingolipid metabolism, potentially playing a central role in demyelination onset. Furthermore, alterations in phospholipid metabolism and abnormal nerve signaling regulation may exacerbate myelin damage.
2.Study on relationships of MS4A1 gene polymorphism with blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma
Feng SHI ; Tao LIU ; He HUANG ; Caifu FANG ; Shaoxing GUAN ; Zhang ZHANG ; Zhao WANG ; Xiaojie FANG ; Zhuojia CHEN ; Shu LIU
China Pharmacy 2025;36(13):1641-1647
OBJECTIVE To explore the effects of CD20 coding gene (MS4A1) polymorphism on the blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma. METHODS A prospective observational study was conducted on 160 newly diagnosed non-Hodgkin’s lymphoma patients who received the R-CHOP regimen at the Sun Yat Sen University Cancer Center from January 2016 to December 2020, with a minimum follow-up period of approximately 5 years. The blood concentration of rituximab was detected by enzyme-linked immunosorbent assay. MS4A1 tagSNPs were selected by Haploview4.2 software, including rs1051461, rs17155034, rs4939364, and rs10501385. The genotype of MS4A1 was detected by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Univariate linear regression analysis was employed to examine the correlation between various factors(demographic, clinical, and genotypic variables) in patients and the steady-state trough concentration of rituximab during the first course of treatment, followed by multivariate linear regression analysis. Kaplan-Meier curves were drawn to evaluate progression-free survival (PFS) and overall survival (OS). Using MS4A1 genotype and tumor stage as independent variables, Cox regression model was employed to evaluate the factors influencing patient prognosis. RESULTS The blood concentration of rituximab in MS4A1 rs10501385 CC carriers was 15.20 μg/mL,which was significantly lower than 21.95 μg/mL in AA+AC carriers (P<0.05). The multivariate linear regression model incorporating tumor stage and MS4A1 rs10501385 polymorphism explained 7.3% of the interindividual variability in rituximab concentrations. Compared with MS4A1 rs1051461 CC carriers, CT+TT carriers had significantly prolonged PFS and OS (P<0.05). The Cox proportional hazards regression model showed that the MS4A1 rs1051461 CC genotype (HR=4.406, 95%CI:1.743-11.137, P<0.05) and tumor Ⅲ&Ⅳ (HR=3.233, 95%CI: 1.413-7.399, P<0.05) were independent risk factors for PFS. CONCLUSIONS The tumor staging and MS4A1 rs10501385 polymorphism are key influencing factors for blood concentration of rituximab, and MS4A1 rs1051461 polymorphism significantly affects PFS in non-Hodgkin’s lymphoma patients.
3.Analysis of syncopal DRVR in blood donors: multicenter hemovigilance data (2020—2023)
Junhong YANG ; Qing XU ; Wenqin ZHU ; Fei TANG ; Ruru HE ; Zhenping LU ; Zhujiang YE ; Fade ZHONG ; Gang WU ; Guoqiang FENG ; Xiaojie GUO ; Jia ZENG ; Xia HUANG
Chinese Journal of Blood Transfusion 2025;38(8):1071-1076
Objective: Data on syncopal donation-related vasovagal reaction (DRVR) collected from 74 blood centers between 2020 and 2023 was statistically analyzed to provide a reference for developing preventive strategies against syncopal DRVR. Methods: Data on blood donation adverse reactions and basic information of donors from 2020 to 2023 were collected through the information management system at monitoring sentinel sites. Statistical analysis was performed on the following aspects of syncopal DRVR: characteristics of donors who experienced syncope, reported incidence, triggers, duration, presence and occurrence time of syncope-related trauma, clinical management including outpatient and inpatient treatment, and severity grading. Results: From 2020 to 2023, 45 966 donation-related adverse reactions were recorded. Of these, 1 665 (3.72%) cases were syncopal DRVR. The incidence of syncopal DRVR decreased with age, being the highest in the 18-22 age group. Incidence was significantly higher in female donors than male donors, in first-time donors than repeat donors, and in university and individual donors than group donors (all P<0.05). There was no statistically significant difference among different blood donation locations (P>0.05). The top three triggers were tension, fatigue, and needle phobia or fear of blood. Among syncopal DRVR cases, 60.36% occurred during blood collection, 87.63% lasted for less than 60 seconds, and 5.05% were accompanied by trauma. Notably, 57.14% of these traumas occurred after donor had left the blood collection site. Syncope severity was graded based on required treatment: grade 1 (fully recovered without treatment, 95.50%); grade 2 (recovered after outpatient treatment, 4.02%); and grade 3 (recovered after inpatient treatment, 0.48%). Conclusion: By analyzing the data of syncopal DRVR cases, it is possible to provide a reference for formulating blood donor safety policies.
4.Research Progress on Traditional Chinese Medicine in Treating Viral Hepatitis: A Review
Xiaojie FENG ; Junjie YU ; Yingying SUI ; Lina WANG ; Fangang MENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):289-298
Viral hepatitis is an important cause of liver cirrhosis and liver cancer, which has become a major public health problem in the world. Traditional Chinese medicine has unique advantages in treating viral hepatitis, which can inhibit virus replication and enhance immunity. It can effectively prevent liver fibrosis and canceration, improving liver function and symptoms significantly with definite clinical curative effects, a high level of safety, and seldom drug resistance. In addition, it reduces the side effects of western medicine, achieving the effect of synergy and attenuation while reducing the recurrence rate of patients after drug withdrawal. Attention has been paid to the research on the treatment of viral hepatitis with traditional Chinese medicine, and great progress has been made in experimental research and clinical practice. In this paper, the research progress of traditional Chinese medicine in the treatment of viral hepatitis at home and abroad in recent five years was systematically reviewed. Modern research has confirmed that traditional Chinese medicine can play a role in the treatment of viral hepatitis by directly or indirectly inhibiting the virus, anti-inflammatory, anti-fibrosis, anti-oxidation, regulating immunity, regulating autophagy, and other signal pathways. In clinics, traditional Chinese medicine compound or combined with western medicine is often adopted to ameliorate the clinical symptoms of patients such as fatigue and loss of appetite, improve the immune mechanism of the body, enhance the antiviral ability, shorten the treatment course of patients and improve their quality of life. The research provides a reference for pharmacological research, clinical research, and new drug development for viral hepatitis.
5.Exploring Efficacy and Mechanism of Saffron Floral Bio-residues for Treatment of Hyperuricemia Combined with Gouty Arthritis Based on Compound Compatibility Environment
Jiping WU ; Qingqing LI ; Lan WANG ; Xiaojie YIN ; Shuyi FENG ; Zhihao WANG ; Rixin LIANG ; Bin YANG ; Zhiyong LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):129-140
ObjectiveTo investigate the efficacy and mechanism of saffron floral bio-residues(SFB) in the treatment of hyperuricemia(HUA) combined with gouty arthritis(GA) in a compound compatibility setting. MethodScreening candidate control Chinese medicines for compound and SFB based on network target distance calculation and data analysis. After adaptive feeding of 80 SD rats for 7 days, 10 rats were randomly selected as the blank group, while the remaining 70 rats were intraperitoneally injected with 3% potassium oxonate and orally administered with 1% adenine for 14 consecutive days. On the 13th day, rats were injected with 2.5% sodium urate solution into the right ankle joint cavity to induce swelling of the joint capsule on the opposite side, inducing a HUA combined with GA model. At the same time, the modeling rats were randomly divided into 7 groups, including the model group, benzbromarone group(positive drug, 0.02 g·kg-1), Tongfengshu tablets group(9 g·kg-1), Tongfengshu granules group(9 g·kg-1), SFB granules group(3.6 g·kg-1), Plantaginis Semen granules group(3.6 g·kg-1), and new formula group(SFB replacing Plantaginis Semen in Tongfengshu granules, 9 g·kg-1), with 10 rats in each group. Each treatment group was orally administered with the corresponding drugs according to body weight, while the control and model groups were given equal volume of distilled water by gavage once a day for 14 consecutive days. After 14 days of synchronous administration and modeling, changes in gait, ankle joint swelling and mechanical pain threshold in rats were observed, and serum uric acid, creatinine, urea nitrogen and xanthine oxidase(XOD) were measured. Enzyme-linked immunosorbent assay(ELSIA) was used to detect the levels of tumor necrosis factor(TNF)-α, interleukin(IL)-1β and IL-6 in rat serum, hematoxylin-eosin(HE) staining was used to observe the pathological changes in the liver, kidney and ankle joints of rats, Western blot was used to detect the expression levels of uric acid transporter 1(URAT1), glucose transporter 9 (GLUT9), organic anion transporter 1(OAT1), adenosine triphosphate(ATP) binding cassette transporter G2(ABCG2), and liver XOD proteins. ResultThrough network pharmacology analysis, Plantaginis Semen was selected as a candidate control herb, and Tongfengshu tablets was used as a compound compatibility environment to explore the efficacy of SFB in reducing blood uric acid levels and treating GA. Animal experiments showed that compared with the blank group, the gait score and joint swelling degree of the model group were significantly increased, and the mechanical pain threshold was significantly decreased(P<0.01). Compared with the model group, the gait score, joint swelling degree and mechanical pain threshold of rats in each medication group were improved to varying degrees. Biochemical indicators showed that compared with the blank group, the serum uric acid, creatinine, urea nitrogen and XOD levels of the model group were significantly increased(P<0.01). Compared with the model group, the serum uric acid and XOD levels of rats in each treatment group were significantly decreased(P<0.01). ELISA results showed that compared with the blank group, the levels of serum TNF-α, IL-1β and IL-6 in the model group were significantly increased(P<0.01). Compared with the model group, the levels of TNF-α, IL-1β and IL-6 in the benzbromarone group, Tongfengshu tablets group, Tongfengshu granules group and new formula group were significantly reduced(P<0.05,P<0.01). Western blot results showed that compared with the blank group, the expression levels of URAT1 and GLUT9 proteins in renal tissue and OXD protein in liver tissue of the model group were significantly increased, while the expression levels of renal OAT1 and ABCG2 were significantly decreased(P<0.01). Compared with the model group, the expression levels of renal URAT1 and GLUT9 in the SFB granules group, Tongfengshu granules group and new formula group were significantly decreased, while the expression levels of renal OAT1 and ABCG2 were significantly increased, and the expression of XOD protein in liver tissue was significantly decreased(P<0.05, P<0.01). Pathological analysis showed that focal infiltration of neutrophils, cell necrosis and nuclear fragmentation were observed in the liver tissue of the model group, sodium urate deposition crystals and tubular dilation appeared in renal tissue, synovial hyperplasia and inflammatory cell infiltration appeared in ankle joint. Compared with the model group, the abnormal degrees of liver, kidney and ankle joint tissue of rats in each treatment group were alleviated. ConclusionThe new formula of SFB replacing Plantaginis Semen has the same effect in the treatment of HUA combined with GA. This study proposes a new strategy to investigate the efficacy of new resources of Chinese medicine in a compound compatibility environment, which can provide a new demonstration for the research and development of new resources of Chinese medicine.
6.Comparison of Risk Prediction Models for Atherosclerosis in Type 2 Diabetes Mellitus
Yifan WANG ; Chaojun SHI ; Xiaojie MA ; Wenjia FENG ; Hongqing AN ; Qianqian GAO ; Qi JING ; Weiqin CAI ; Anning MA
Journal of Medical Informatics 2024;45(7):74-80
Purpose/Significance To explore the application and predictive accuracy of various models in predicting the risk of ather-osclerosis in diabetic patients.Method/Process Based on the biochemical data table from the"Diabetes Complications Warning Dataset"provided by the National Population Health Science Data Center,MATLAB software is used to construct risk prediction models for diabe-tes-induced atherosclerosis.The models are built by using k-nearest neighbors(KNN),decision trees,backpropagation(BP)neural networks,and Naive Bayes algorithms,and which are subjected to comparative analysis.Result/Conclusion In terms of effectiveness,the predictive accuracy of Naive Bayes algorithm is the highest(61.6%),followed by the decision tree model(58.2%),the KNN mod-el(57.7%),and the BP neural network model(55.9%).The results of the confusion matrix and the receiver operating characteristic(ROC)curve indicate that the Naive Bayes model performs best.When comparing the models in terms of effectiveness,performance and stability,the Naive Bayes model is superior.
7.MR lymphangiography radiomics for evaluating central conducting lymphatic anomaly
Yimeng ZHANG ; Jixue FENG ; Xiaojie ZHANG ; Haoyue LIU ; Mengke LIU ; Xingpeng LI ; Mingxia ZHANG ; Rengui WANG
Chinese Journal of Medical Imaging Technology 2024;40(11):1677-1681
Objective To observe the value of MR lymphangiography(MRL)radiomics for evaluating central conducting lymphatic anomaly(CCLA).Methods Sixty-one patients with complex lymphatic anomaly,including 41 CCLA(group A),20 non-CCLA(generalized lymphatic anomaly and Gorham-Stout disease)and 20 subjects with normal thoracic duct(group B,n=38)were retrospectively enrolled.Cervical and thoracic(combined with abdominal if necessary)MRL was acquired using three-dimensional heavily T2W fast spin echo sequence.ROI was delineated along overall thoracic duct,and radiomics features were extracted.Data sets of group A and B were divided into K subsets using 5-fold cross-validation.The union of(K-1)subset was always used as training set,while the other subsets were used as validation set.Radiomics model was constructed based on support vector machine(SVM)algorithm.Receiver operating characteristic curve was drawn,the area under the curve(AUC)was calculated to evaluate the efficacy of SVM model for assessing CCLA.Results The proportions of bifurcation,cystoid change and extension of main thoracic duct,and extension of terminal thoracic duct in group A were all higher,while of normal main and terminal thoracic duct in group A were both lower than those in group B(all P<0.05).No significant difference of proportions of multiple thoracic ducts,dextral thoracic duct,part of thoracic duct invisible,multiple terminal thoracic ducts,cystoid change of terminal thoracic duct nor terminal thoracic duct pampiniform was found between groups(all P>0.05).The sensitivity,specificity,accuracy,positive predictive,negative predictive and AUC of SVM model for evaluating CCLA in training set was 78.95%,97.56%,88.61%,96.77%,83.33%and 0.920,respectively,which in validation set was 78.95%,83.57%,82.28%,83.33%,81.40%and 0.833,respectively.Conclusion MRL radiomics could be used to effectively evaluate CCLA.
8.Comparative study of CT measurement of adult kidney depth with estimation formula
Liu FENG ; Xiaojie LIU ; Zhigang ZHANG ; Hongzhi WANG
China Modern Doctor 2024;62(29):33-36
Objective To analyze the correlation and consistency between different kidney depth estimation formulas and computed tomography(CT)measurement of kidney depth,discussing the best kidney depth calculation formula for this region.Methods A total of 213 patients who underwent renal dynamic imaging in the First Hospital of Jiaxing from January 2019 to January 2024 were retrospectively included in this study.The abdominal CT image data of the same period were obtained,and the gender,age,height and weight were recorded.The patient's body thickness and kidney depth were measured by CT.Seven calculation formulas(Tonnesen formula,Li Qian formula,Taylor formula,Inoue formula,Xue JJ formula,Li's equation and Ma G's formula)were used to estimate the kidney depth.Paired sample t-test,Pearson correlation analysis and Bland-Altman consistency analysis were performed between the kidney depth calculated by the equation and the kidney depth measured by CT.Results There was a correlation between the estimated values calculated by the calculation formulas and actual CT measurements,and the kidney depth calculated by the seven formulas were lower than the CT measurements.The results of correlation analysis showed that the correlation coefficient between Ma G's formula and CT measurements was better than other formulas,and the correlation coefficients of Tonnesen formula and Inoue formula were consistent.The bias between the kidney depth calculated by Tonnesen formula and the CT measured value is the largest,and the bias between the kidney depth calculated by Ma G's formula and the CT measured value is the smallest.Conclusion The Ma G'S formula introduces body thickness as a key reference variable for calculating kidney depth.Compared to the other six calculation formulas,it has demonstrated higher accuracy and reliability in estimating kidney depth,thereby having a broader applicability in clinical practice.
9.Analysis of the unqualified HCV detection results of blood donors from the served area of 22 domestic blood institutions
Zhongsi YANG ; Shouguang XU ; Wei ZHANG ; Jian ZHANG ; Xiaojie LIU ; Feng YANG ; Qin WANG ; Yanqin HE ; Lin BAO ; Zhiqiang YU ; Zhenxing WANG ; Changwen QIU ; Xiaobo CAI ; Li LI ; Peng WANG ; Zhanfeng XU ; Furong YU ; Chao ZHAO ; Jiankang WANG ; Youhua SHEN ; Jingjing BAO ; Jun ZHOU ; Yan QIU
Chinese Journal of Experimental and Clinical Virology 2023;37(4):367-372
Objective:To investigate the unqualified hepatitis C virus (HCV) detection result of blood donors from the served area of blood institutions.Methods:The data related to HCV markers detected of the first and repeat blood donors were collected from the system of practice comparison for the Chinese mainland blood institutions from 2017 to 2021. The anti-HCV reactive rate and the rates of anti-HCV negative but HCV-RNA reaction and all the relationship between rates and the annual, regional and different blood donors were statistically analyzed.Results:During 2017-2021, the number of anti-HCV reactive per 100 000 blood donors decreased from 444.3 to 250.44 in the served area of 22 blood institutions ( χ2=49.677, P<0.05). The number of HCV RNA detected positive per 100 000 anti-HCV negative increased from 0.69 to 2.05 year by year, but there was no statistical significance ( χ2=0.643, P>0.05). The anti-HCV unqualified rate was significantly different among regions ( χ2=3 260.283, P<0.05). The anti-HCV unqualified rate of the first blood donors was significantly higher than that of the repeated blood donors ( F=130.993, P < 0.05). The annual number of HCV RNA detected positive per 100 000 anti-HCV negative blood samples from donors ranged from 0 to 17.28. Conclusions:The anti-HCV unqualified rate of blood donors in the served area of 22 blood institutions decreased year by year. Compared with repeated blood donors, HCV infection should be emphasized in first-time blood donors. The implementation of HCV RNA test can detect out much more HCV infections and reduce the risk of transfusion transmitted infectious HCV.
10.Study on Gene Polymorphism Distribution of Clopidogrel Absorption and Metabolism Related Gene CYP2C19, ABCB1 and PON1 in Patients with Coronary Heart Disease in Xinjiang Uygur Autonomous Region
Shuangli YUAN ; Yuan YUAN ; Xiaojie AN ; Yukun LI ; Mingzhi YAN ; Wenling FENG ; Jun ZHAO
China Pharmacy 2021;32(19):2388-2393
OBJECTIVE:To study the relationship of polymorphism of clopidogrel absorption and metabolism related genes CYP2C19(* 2,* 3,* 17),ABCB1 C3435T and PON1 Q192R in patients with coronary heart disease in Xinjiang Uygur Autonomous Region ,and to explore the characteristics of population and combined diseases. METHODS :A total of 1 126 patients with coronary heart disease who underwent clopidogrel absorption and metabolism related gene testing during hospitalization in the First Affiliated Hospital of Xinjiang Medical University from January 2016 to June 2020 were included as the study subjects. The gender,age,body mass index (BMI),nationality and the proportion of combined with hypertension and diabetes were compared among different CYP2C19 metabolic phenotypes and ABCB1 C3435T and PON1 Q192R genotypes. RESULTS :Among 1 126 patients,1 126 had CYP2C19 * 2,* 3 and * 17 genotypes,1 109 had ABCB1 C3435T genotype and 1 123 had PON1 Q192R genotype. The distribution of each genotype was in line with Hardy-Weinberg balance (P>0.05). There were 66(5.86%), com 459(40.76%),476(42.27%) and 125(11.10%)patients with CYP2C19 ultra-rapid metabolizer (UM), extensive metabolizer(EM),intermediate metabolizer (IM)and poor metabolizer(PM),respectively. The proportion of patients with UM metabolism phenotype with BMI >24 was significantly higher than those of patients with IM and PM metabolism phenotypes (P<0.05). The proportion of Han nationality patients with UM metabolic phenotype was significantly lower than those of patients with EM ,IM and PM metabolic phenotypes (P<0.05);the proportion of Uygur nationality was significantly higher than that of patients with EM ,IM and PM metabolic phenotypes (P< 0.05). There were 355,538 and 216 patients with ABCB1 C3435T wild-type(CC),heterozygous(CT)and mutant homozygous (TT)genotypes,respectively;the proportion of Han nationality in TT genotype patients was significantly lower than that in CC and CT genotype patients (P<0.05),and the proportion of Uygur nationality was significantly higher than that in CC and CT genotype patients (P<0.05);the proportion of TT genotype patients with diabetes was significantly higher than that of patients with CT genotype (P<0.05). There were 365,519 and 239 patients with PON1 Q192R wild-type(GG),heterozygous(GA)and mutant homozygous (AA),respectively;the proportion of Han nationality in AA genotype patients was significantly lower than that in GG and GA genotype patients (P<0.05),and the proportion of Uygur nationality was significantly higher than that of GG and GA genotype patients (P<0.05);the proportion of Han nationality and BMI ≤24 in patients with AA genotype were significantly lower than those with GA genotype (P<0.05),and the proportion of Uygur nationality ,BMI>24 and hypertension were significantly higher than those in GA genotype patients (P<0.05). CONCLUSIONS :There are significant nationality differences among patients with different CYP2C19 metabolic phenotypes and ABCB1 C3435T and PON1 Q192R genotypes. In addition,patients with BMI >24 account for high proportion among CYP2C19 UM metabolism genotype ;patients with diabetes account for high proportion among ABCB1 C3435T TT genotype ;patients with BMI >24 and hypertension account for high proportion among PON1 Q192R AA genotype.

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