1.Network pharmacology-based study of the mechanism of Ginkgo biloba extract (GBE) in the treatment of atherosclerosis by activating PPARγ
Ziyuan WANG ; Hui TAO ; Yingxue XIAO ; Zhiqi YIN
Journal of China Pharmaceutical University 2025;56(2):225-235
To investigate the effect of Ginkgo biloba extract (GBE) on lipids accumulation and the progression of atherosclerosis(AS), ApoE-/- mice fed with HFD were injected i.g. with two different doses of GBE (GBE-L 50 mg/(kg·d) or GBE-H 150 mg/(kg·d)) for 9 weeks. The core targets and potential mechanisms of GBE therapy for AS were investigated using network pharmacological target prediction. Subsequently, oxidized low-density lipoprotein (ox-LDL)-induced THP-1 was used to investigate the effect of GBE on foam cell formation through oil red staining and Dil-oxLDL fluorescent staining. The mRNA alterations in cholesterol uptake and efflux receptors were detected by real-time quantitative PCR. Finally, the impact of GBE on the expression of PPARγ as the core target was assessed through Western blot and immunofluorescence. It was found that GBE improved serum lipid profile, reduced necrotic cores and lipid deposition in aortic root plaques, and decreased the level of inflammatory factors in serum of ApoE-/- mice. Moreover, GBE treatment reduced the level of intracellular lipid accumulation and inhibited cholesterol uptake and efflux to alleviate foam cell formation. GBE activated PPARγ to enhance ABCA1/ABCG1-induced cholesterol efflux in THP-1. These results suggest that GBE can suppress lipid accumulation and alleviate foam cell formation by activating PPARγ pathway.
2.Multi-level ranking classification algorithm for nuclear cataract based on AS-OCT image
Lixin FANG ; Yu ZHOU ; Yuanyuan GU ; Ziyuan JIANG ; Lei MOU ; Yang WANG ; Fang LIU ; Yitian ZHAO
Chinese Journal of Experimental Ophthalmology 2024;42(3):264-270
Objective:To investigate the diagnostic value of an intelligent assisted grading algorithm for nuclear cataract using anterior segment optical coherence tomography (AS-OCT) images.Methods:A diagnostic test study was conducted.AS-OCT image data were collected from 939 cases of 1 608 eyes of nuclear cataract patients at the Shanghai Tenth People's Hospital of Tongji University from November 2020 to September 2021.The data were obtained from the electronic case system and met the requirements for clinical reading clarity.Among them, there were 398 cases of 664 male eyes and 541 cases of 944 female eyes.The ages of the patients ranged from 18 to 94 years, with a mean age of (65.7±18.6) years.The AS-OCT images were labelled manually from one to six levels according to the Lens Opacities Classification System Ⅲ (LOCS Ⅲ grading system) by three experienced clinicians.This study proposed a global-local cataract grading algorithm based on multi-level ranking, which contains five basic binary classification global local network (GL-Net).Each GL-Net aggregates multi-scale information, including the cataract nucleus region and original image, for nuclear cataract grading.Based on ablation test and model comparison test, the model's performance was evaluated using accuracy, precision, sensitivity, F1 and Kappa, and all results were cross-validated by five-fold.This study adhered to the Declaration of Helsinjki and was approrved by Shanghai Tenth People's Hospital of Tongji University (No.21K216).Results:The model achieved the results with an accuracy of 87.81%, precision of 88.88%, sensitivity of 88.33%, F1 of 88.51%, and Kappa of 85.22% on the cataract dataset.The ablation experiments demonstrated that ResNet18 combining local and global features for multi-level ranking classification improved the accuracy, recall, specificity, F1, and Kappa metrics.Compared with ResNet34, VGG16, Ranking-CNN, MRF-Net models, the performance index of this model were improved.Conclusions:The deep learning-based AS-OCT nuclear cataract image multi-level ranking classification algorithm demonstrates high accuracy in grading cataracts.This algorithm may help ophthalmologists in improving the diagnostic accuracy and efficiency of nuclear cataract.
3.A Rapid PCR-RFLP Method for Assessing Heterozygosity of Murraya paniculata Germplasm
Bocheng WANG ; Ziyuan CHEN ; Zhongyi HUA ; Hui TIAN ; Wenbo XIE ; Yuan YUAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(4):29-34
ObjectiveTo establish a rapid method for evaluating the heterozygosity of Murraya paniculata germplasm materials and provide as a foundation for developing germplasm breeding and innovation measures for M. paniculata. MethodSingle nucleotide polymorphisms (SNPs) were screened from the genome resequencing data of 65 plants of M. paniculata. A self-written script was used to transform 20 SNPs into restriction fragment length polymorphism (RFLP) markers. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was employed to detect the 20 RFLP markers in 12 M. paniculata germplasm accessions, and the heterozygosity of M. paniculata germplasm accessions was calculated based on the number of enzyme-cutting bands at the 20 RFLP marker sites. Plink was used to calculate the whole genome heterozygosity of 12 M. paniculata germplasm accessions, and the results obtained with different methods were compared. ResultThere was no significant difference in the heterozygosity calculated by the PCR-RFLP method and the genome resequencing method. The PCR-RFLP and genome resequencing methods identified 8 and 9 germplasm accessions, respectively, with a heterozygosity level less than 30%. Seven germplasm accessions with heterozygosity less than 30.00% were calculated by both methods. ConclusionThe PCR-RFLP method established in this study for evaluating the heterozygosity of M. paniculata germplasm demonstrates the precision of 87.5% and the accuracy of 77.8%. This method serves as a reference for developing heterozygosity evaluation methods in other medicinal plant germplasm resources.
4.Optimization of 18F-FDG PET/CT semi-quantitative diagnostic model for children with autoimmune encephalitis with epilepsy and negative MRI
Ziyuan LI ; Jing WU ; Shuqi WU ; Mingming CAO ; Suyun CHEN ; Ling LI ; Hui WANG ; Yafu YIN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(4):213-219
Objective:To investigate the value of 18F-FDG PET/CT imaging in the diagnosis of suspected autoimmune encephalitis (AE) in children with epilepsy and negative MRI. Methods:From May 2019 to August 2022, 94 suspected AE children (49 males, 45 females; age 1-15 years) with epilepsy and negative MRI who underwent brain 18F-FDG PET/CT imaging at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. All patients were divided into AE and non-AE groups based on clinical final diagnosis. The effectiveness of visual diagnosis was evaluated. The cortical lesion extent score (S), and SUV max, SUV mean and minimum of SUV (SUV min) of cortical lesions (L), basal ganglia (B) and thalamus (T) were measured and SUV ratios (SUVR) of L/B or L/T were obtained. Independent-sample t test or Mann-Whitney U test was used to analyze data. Binary logistic regression analysis was used to screen the diagnostic factors of AE, and a diagnostic model was established. The diagnostic efficiency was evaluated by ROC curve analysis and Delong test. Results:There were 53 cases in AE group and 41 cases in non-AE group. Based on visual analysis, the sensitivity, specificity and accuracy of 18F-FDG PET/CT for AE were 100%(53/53), 43.9%(18/41) and 75.5%(71/94), respectively. Differences of LSUV max, LSUV mean, LSUV min, L/BSUVR max, L/BSUVR mean, L/BSUVR min, L/TSUVR max, L/TSUVR mean, L/TSUVR min and S between AE and non-AE groups were statistically significant ( z=-6.74, t values: from -8.51 to -3.97, all P<0.001). ROC curve analysis showed that the AUC of L/BSUVR max was the highest (0.914) among visual analysis and semi-quantitative parameters. Logistic regression analysis showed that S (odds ratio ( OR)=11.40, 95% CI: 2.18-59.52, P=0.004), L/BSUVR max( OR=13.19, 95% CI: 2.11-82.51, P=0.006) and L/TSUVR max( OR=9.66, 95% CI: 1.57-59.55, P=0.015) were independent diagnostic factors for AE. Regression model was established: P=1/(1+ e - x), x=2.433×S+ 2.580×L/BSUVR max+ 2.267×L/TSUVR max-3.802. The AUC of this model was 0.948, with the sensitivity, specificity and accuracy of 98.1%(52/53), 90.2%(37/41) and 94.7%(89/94), respectively. The diagnostic efficacy of the optimized scoring system was consistent with the pre-optimization model, and were both superior to L/BSUVR max(both z=2.01, both P=0.040). Conclusion:The diagnostic model and scoring system based on the semi-quantitative analysis of 18F-FDG PET/CT have better diagnostic efficacy for AE and are superior to semi-quantitative parameters alone.
5.Association of individual and area level socioeconomic status with depressive symptoms for older adults—evidence from China Health and Retirement Longitudinal Study
Xu ZHANG ; Ziyuan WANG ; Shuduo ZHOU
Chinese Journal of Health Management 2024;18(2):114-119
Objective:To analyze the impact of individual and regional level socioeconomic characteristics on the mental health of middle-aged and older adults based on data from the China Health and Retirement Longitudinal Study.Methods:This study was a cohort study. Using the data from the China Health and Retirement Longitudinal Study, subjects without depression were screened in the baseline survey, the depression status of the selected subjects was tracked and observed for seven years. Descriptive statistical analysis, multivariate logistic analysis, joint analysis were used to analyze the influence of factors such as gender, personal annual income, education level, urban and rural areas, and eastern, central, and western regions on the risk of depression among middle-aged and elderly people.Results:The 7-year follow-up results showed that the prevalence of depression symptoms in the study subjects was 42.24%; compared with men, women′s risk of developing depression symptoms was significantly increased ( OR=1.782); compared with junior college education and above, middle school (including technical secondary school), primary and lower education levels had a significantly increased risk of developing depression symptoms ( OR=1.476, 2.134); compared with annual income of more than 10 000 yuan, subjects with an annual income of 10 000 yuan or below had significantly increased risk of developing depression symptoms ( OR=1.251). At the same time, compared with the urban area, the risk of developing depression symptoms was significantly increased in the rural areas ( OR=1.389). Compared with the eastern area, the risk of developing depression symptoms was significantly higher in the central and western areas ( OR=1.342, 1.730). The joint analysis results showed that compared with high-income and high-education men, low-income low-education women, high-income low-education women, low-income middle-education women, and high-income middle-education women were at the top four odd ratios for developing depression symptoms ( OR=5.050, 3.662, 3.047, 2.641); compared with men in eastern cities, rural women in the west, rural women in the middle, women in the western cities, and rural women in the east ranked the first four odd ratios for developing depression symptoms ( OR=4.286, 3.216, 2.642, 2.158). Conclusion:Socioeconomic factors at the individual and regional levels have a significant impact on the risk of developing depressive symptoms in middle-aged and older adults, and mental health management of middle-aged and older adults with low socioeconomic status should be strengthened.
6.Efficacy of modified electroconvulsive therapy combined with medication in inpatient schizophrenia patients and urban-rural differences
Hongcheng XIE ; Shuangshuang FENG ; Tingting WANG ; Junfan LIANG ; Jiajun REN ; Hongli ZHANG ; Ziyuan LIN ; Siru WANG ; Bo XIANG ; Kezhi LIU
Sichuan Mental Health 2024;37(6):497-501
BackgroundCombination of antipsychotic drugs and modified electroconvulsive therapy (MECT) is currently a commonly used method for treating schizophrenia, but its efficacy varies among different patient groups. ObjectiveTo explore the therapeutic effects of MECT on schizophrenia patients living in different urban versus rural environments, so as to provide references for the selection of treatment plans based on patients' residence. MethodsA total of 587 patients hospitalized at Luzhou Mental Health Center, Zigong Mental Health Center and Yibin Fourth People's Hospital from May 2018 to August 2022, who met the diagnostic criteria for schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) ,were included in the study. Patients were divided into two groups: medication-only group (n=106) and MECT combined with medication group (n=481). In MECT combined with medication group, 24 rural patients residing in urban areas were excluded, leaving the remaining patients divided into urban group (n=103) and rural group (n=354) based on their place of residence. Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of symptoms. Clinical efficacy was evaluated using PANSS score reduction rate, and covariance analysis was used to compare the therapeutic effects of different patients. ResultsThe differences of reduction rate of PANSS total score, positive symptom scale score and negative symptom scale score as well as treatment effectiveness rate between MECT combined with medication group and medication-only group were statistically significant (F=11.149, 12.111, 31.725, χ2=14.010, P<0.01). Statistically significant differences were also observed in reduction rate of PANSS total score and positive symptom subscale score as well as treatment effectiveness rate between urban and rural patients in MECT combined with medication group (F=3.946, 4.523, χ2=4.033, P<0.05). ConclusionThe efficacy of MECT combined with medication may be superior to medication alone in the treatment of schizophrenia, and the combined therapy may be more effective in urban patients than that in rural patients, with potentially more pronounced improvements in positive symptoms.
7.Predictive value of controlling nutritional status score in the prognosis of patients with advanced diffuse large B-cell lymphoma
Huirong SHAN ; Xicheng CHEN ; Hao ZHANG ; Yuqing MIAO ; Fei WANG ; Yuye SHI ; Ling WANG ; Jingjing YE ; Ziyuan SHEN ; Wei SANG ; Hongfeng GE
Journal of Leukemia & Lymphoma 2024;33(2):104-109
Objective:To investigate the predictive value of controlling nutritional status (CONUT) score in the prognosis of patients with advanced diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 654 patients newly diagnosed with advanced DLBCL diagnosed in 7 medical centers in Huaihai Lymphoma Working Group from October 2009 to January 2022 were retrospectively collected. All the patients received rituximab-based immune chemotherapy regimens. The patients were randomly assigned to the training set (458 cases) and the validation set (196 cases) in a 7:3 ratio. The clinicopathological data of patients were collected, and the CONUT score was calculated based on albumin, lymphocyte count, and total cholesterol. The optimal critical value of CONUT scote was determined by using MaxStat method. Kaplan-Meier method was used to draw survival curves; Cox proportional hazards model was used to make univariate analysis and multivariate analysis on the factors influencing overall survival (OS). The efficacy of CONUT score in combination with the International prognostic index (IPI) and an enhanced IPI (NCCN-IPI) in predicting OS was evaluated by using receiver operating characteristic (ROC) curves.Results:The median follow-up time of 654 patients was 38.1 months (95% CI: 35.3 months- 40.9 months), and the 5-year OS rate was 49.2%. According to the MaxStat method, the optimal critical value for CONUT score was determined to be 6 points. All the patients were classified into the normal nutritional status group (CONUT score ≤ 6 points, 489 cases) and the poor nutritional status group (CONUT score > 6 points, 165 cases). The results of the multivariate analysis showed that CONUT score > 6 points, male, lactate dehydrogenase >240 U/L, high white blood cell count, low hemoglobin level and age > 60 years were independent risk factors for OS of patients with advanced DLBCL (all P < 0.05). Patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group in the overall cohort of advanced DLBCL. Subgroup analysis revealed that among patients with Eastern Cooperative Oncology Group-performance status (ECOG PS) score < 2 points, IPI low-intermediate risk, IPI intermediate-high risk, NCCN-IPI low-intermediate risk, and NCCN-IPI intermediate-high risk, the patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group (CONUT score ≤ 6 points) (all P < 0.05). Conclusions:CONUT score has a certain value in the assessment of the prognosis of patients with advanced DLBCL, and its predictive efficacy is further improved when combined with IPI and NCCN-IPI.
8.Efficacy and safety of modified VIALE-A regimen for treatment of elderly patients with intermediate or high risk myelodysplastic syndromes
Qixin SUN ; Zhenzhen WEN ; Xiaoyan CHEN ; Ahui WANG ; Guiping CHEN ; Ziyuan ZHAO ; Zhigang ZHU
Journal of Leukemia & Lymphoma 2024;33(8):462-465
Objective:To explore the efficacy and safety of the modified VIALE-A regimen in the treatment of elderly (>75 years old) patients with intermediate or high risk myelodysplastic syndromes (MDS).Methods:A retrospective case series analysis was conducted. Clinical data were collected from 7 MDS patients aged >75 years who were continuously treated with the modified VIALE-A regimen (azacytidine 75 mg/m 2 per day from day 1 to day 7 + venetoclax 200 mg per day from day 8 to day 28) from May 2021 to August 2023, and the patients were diagnosed according to the World Health Organization 2016 staging criteria and were determined to be at intermediate or high risk according to the revised International Prognostic Scoring System. The patients' efficacy and common adverse reactions were analyzed, and the Kaplan-Meier method was used for survival analysis. Results:Of the 7 patients, 5 were female and 2 were male; the median age [ M ( Q1, Q3)] was 84 years old (80 years old, 90 years old). One patient failed the initial treatment, and the remaining 6 achieved complete remission or complete remission in bone marrow after induction therapy with the modified VIALE-A regimen in 1-2 courses. By the follow-up cut-off date of December 31st, 2023, the median follow-up was 10 months (5 months, 18 months) and the median overall survival time was 18 months (95% CI: 0-39 months). Grade 3-4 myelosuppression occurred in all 7 patients during the induction phase, with granulocytopenia lasting 7-10 d; Of the 64 courses of maintenance treatment, 54 (84%) had grade 1-3 myelosuppression; non-hematologic adverse reactions were mild; no treatment interruptions occurred in the cumulative 73 courses. Conclusions:The modified VIALE-A regimen is moderately efficacious in elderly patients with intermediate or high risk MDS, with controllable adverse reactions.
9.Correlation between physical exercise and semen quality in 1 059 men of childbearing age in Jinan City
Wenyu WANG ; Song LIU ; Zhida SHI ; Huijun YANG ; Jingchao REN ; Huidong JIN ; Guanghui ZHANG ; Ziyuan ZHOU ; Guanghong YANG
Journal of Army Medical University 2024;46(10):1164-1171
Objective To explore the effect of physical exercise on semen quality in order to provide basic data and theoretical basis for the improvement of male reproductive health.Methods A cross-sectional study was conducted on 1 059 males who visited the Reproductive Medicine Center of Shandong Maternal and Child Health Hospital for medical treatment and physical examination during July 2022 and April 2023.Their demographic data and physical exercise data were surveyed with questionnaires.Total sperm count,sperm concentration,total sperm motility,forward movement and normal sperm morphology were analyzed with computer aided analysis.Logistic regression model and multiple linear regression model were applied to analyze the effects of physical exercise on semen quality.Results After adjustment for confounding factors such as age,body mass index,alcohol consumption and smoking,logistic regression analysis showed that the risk of abnormal semen quality was increased in patients with moderate and heavy exercise intensity(OR=2.103,OR=2.229).Compared with the participants with physical exercise ≤10 min per session,those with>20 min per session had a lower risk of abnormal semen quality(OR=0.357,0.256,0.289 for exercise time for>20~30,>30~60,>60 min,respectively).There was no statistical significance between physical exercise frequency and semen quality(P>0.05).The participants having exercise well were at a lower risk for abnormal semen quality(OR=0.711).Multiple linear regression analysis revealed that the frequency of physical exercise was an influencing factor of sperm concentration(β=7.474,95%CI:4.800~10.149,P<0.05);the time of physical exercise per session was an influencing factor for total sperm count(β=20.632,95%CI:7.634~33.629);the intensity of physical exercise(β=-1.461,95%CI:-2.392~-0.530)and time of physical exercise per session(β=2.608,95%CI:1.404~3.812,P<0.05)were influencing factors for percentage of forward motility sperm(P<0.05);and physical exercise intensity(β=-1.934,95%CI:-3.238~-0.630),time of physical exercise per session(β=4.211,95%CI:2.525~5.897)and frequency of physical exercise(β=-2.008,95%CI:-3.480~-0.536)were influencing factors of total sperm motility(P<0.05).Conclusion Physical exercise may affect semen quality,greater intensity of physical exercise may be a risk factor for abnormal semen quality,and longer physical exercise time may be related to improving semen quality.Therefore,proper physical exercise can help improve semen quality.
10.Recombinant expression and immunological characterization of Burkholderia pseudomallei type Ⅲ secretion system protein BipD
Dongqi NAN ; Yuan WEN ; Jiangao CHEN ; Chenglong RAO ; Pan WU ; Ziyuan ZHANG ; Shiwei WANG ; Jingmin YAN ; Qian LI ; Xuhu MAO
Journal of Army Medical University 2024;46(15):1713-1720
Objective To express recombinant Burkholderia pseudomallei(B.pseudomallei)type Ⅲ secretion system BipD protein,prepare its polyclonal antibodies and verify their immunological traits.Methods The recombinant pET-28a-BipD plasmid was generated,and the pET-28a-BipD-carried E.coli BL21(DE3)bacteria were induced with isopropyl-β-d-thiogalactoside(IPTG)to express recombinant BipD(rBipD)protein.The rBipD was obtained by affinity chromatography using His Trap column,then mixed with Fredrick's adjuvant to immunize BALB/c mice by intraperitoneal injection in order to obtain anti-rBipD polyclonal antibodies.The immunoreactivity of rBipD was detected by Western blot assay using rabbit anti-melioidosis serum and the serum from melioidosis patients.The immunogenicity of rBipD was evaluated using Western blotting and immunofluorescence staining.Finally,rBipD was used to establish an indirect ELISA to detect serum antibodies of clinical melioidosis patients.Results The recombinant plasmid pET-28a-BipD was successfully constructed and transformed into E.coli BL21(DE3)to induce rBipD expression with IPTG treatment.The obtained rBipD had a relative molecular weight of 36×103 and a purity of 95.4%,and had good immunogenicity and immunoreactivity.It could induce the production of specific antibodies after immunizing mice,and mouse polyclonal antibodies against rBipD were prepared with the titer of 1∶512 000.rBipD of 5.0 μg/mL produced specific immune response with the serum of melioidosis patients,but had no specific reaction with the serum of tuberculosis patients,with statistical difference(P<0.01).Conclusion rBipD with immunological activity is successfully prepared and purified,and its polyclonal antibodies are also developed,which provide a good tool for clinical immunological diagnosis and study of immune mechanism of B.pseudomallei infection.

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