1.Mechanism of nephrotoxicity induced by chronic exposure of bisphenol A in mice based on oxidative stress and cell apoptosis.
Zhongwei TANG ; Huimin WANG ; Zhuo ZHANG ; Yanbiao KONG ; Xuepei LEI ; Jianqin YUAN
Chinese Journal of Biotechnology 2023;39(1):372-385
Bisphenol A (BPA) is widely used to produce epoxy resin and polycarbonate plastic products. In severe cases, these plastics may release BPA, which then infiltrates into the environment. Various concentrations of BPA have been found in most biological fluid. Its presence has been well shown to be closely related to many chronic diseases, including chronic kidney disease (CKD). However, little is known regarding the adverse effects of BPA exposure and its succedent cellular events on CKD. Hence, in the current in vivo study, we aimed to assess the effects of chronic exposure to BPA on animal nephrotoxicity through investigating oxidative stress and apoptosis. Upon exposure to BPA at 0.01, 0.1, and 1 mg/L via drinking water for four weeks, the mated and pregnant females were continuously exposed to BPA until weaning. Subsequently, three weeks old F1-male neonates were also orally challenged with the same three doses of BPA for ten weeks. The results showed that the kidneys of 0.1 and 1 mg/L BPA-treated mice were seriously damaged; the contents of serum renal function indexes and lipid peroxidation products were significantly increased, including urea nitrogen, creatinine, uric acid, and thiobarbituric acid reactive substances; the morphological structure of mouse kidneys was impaired; the expressions of antioxidant-related genes at mRNA and protein levels from mouse kidneys were markedly diminished, including glutathione-S-transferase, superoxide dismutase, and catalase; the expressions of genes and proteins related to apoptosis index (ratio of Bax/Bcl-1 and Caspase-3) were significantly enhanced. The data manifested that cumulative oxidative stress and apoptosis might play an essential role in the animal nephrotoxicity induced by chronic exposure to BPA.
Female
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Male
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Mice
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Animals
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Oxidative Stress
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Antioxidants
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Apoptosis
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Renal Insufficiency, Chronic
2.Radiomics based on multimodal MRI for the differential diagnosis of benign and malignant lung nodule/mass
Jia LIU ; Jianqin JIANG ; Jianbing YIN ; Yanan ZHANG ; Ying XUE ; Lei CUI
Chinese Journal of Radiology 2022;56(5):542-548
Objective:To develop a multimodal MRI-based radiomics model for the differential diagnosis of benign and malignant lung lesions, and to compare the discriminative abilities of different models.Methods:Totally 114 patients with 115 lesions (44 benign and 71 malignant) in Nantong First Peoples′s Hospital from January 2014 to October 2019 were included in the study. All patients underwent non-enhanced MR examination, and textural features from T 1WI,T 2WI and apparent diffusion coefficient (ADC) imaging were extracted. The feature selection methods included L1 based, mutual information, tree based, recursive feature elimination and F-test. Then we constructed a prediction model by using logistic regression (LR), support vector machine (SVM), random forest (RF) and k-nearest neighbor (KNN) respectively. In order to control the number of modeling features and reduce the ininterpretability of the model, the new model was obtained by manually modifying some parameters of the hyperparameter model. One hundred and fourteen cases were rotated as training and validation sets. The performance of each model was evaluated by confounding matrix and receiver operating characteristic (ROC) curve. Results:The area under the curve (AUC) of T 2WI based LR model for the differential diagnosis of benign and malignant pulmonary nodules/masses was 0.71 and the F1 score was 0.57. Based on T 1WI images, LR and SVM model could be used to identify benign and malignant pulmonary nodules, the AUC before parameter adjustment were 0.77 and 0.78, the accuracy after parameter adjustment (LR a,SVM a) was 0.67, 0.70, and both the AUC were 0.72. However, no matter which feature or classifier was selected, both the AUC and accuracy of ADC-based model were less than 0.70. Conclusion:Multimodal MRI-based radiomics model is valuable for the differential diagnosis of benign and malignant pulmonary nodules/masses, and T 1WI-based model shows the best discrimination.
3.Skin microecology in patients with severe atopic dermatitis at acute and remission phases
Suling HE ; Xin TIAN ; Jingyao LIANG ; Lei SHAO ; Junlong LI ; Qiongxiao HUANG ; Yumei LIU ; Jianqin WANG
Chinese Journal of Dermatology 2022;55(4):329-336
Objective:To investigate changes in skin microecological structures and functions between acute and remission phases in adult patients with severe atopic dermatitis (AD) .Methods:From October 2019 to November 2020, skin scale specimens were collected from 5 body sites (cheeks, cubital fossa, back of the hand, abdomen, lower limbs) of 4 adult patients with severe AD in the acute and remission phases, who visited the outpatient clinic of Guangzhou Institute of Dermatology. The next-generation high-throughput sequencing was performed for metagenomic sequencing to construct the microbial gene catalogue of these specimens, followed by gene annotation and bioinformatics analysis for each sample.Results:A total of 18 phyla, 37 classes, 73 orders, 142 families, 237 genera, and 331 species were identified in the skin specimens from the 4 patients with severe AD. The patients with AD in the remission phase showed significantly increased diversity of skin microbiota and markedly different relative abundance of skin microorganisms compared with those in the acute phase (both P < 0.05). At the microbial species level, Staphylococcus aureus showed the highest impact on the acute phase of AD, while Staphylococcus epidermidis, Moraxella osloensis, Francisella sp., Staphylococcus cohnii, Staphylococcus warneri, Malassezia globosa and Malassezia restricta were enriched in the remission phase of AD with the absolute value of the common logarithm of the linear discriminant analysis score > 2 (Kruksal-Wallis test, all P < 0.05). As KEGG pathway enrichment analysis showed, the differentially abundant genes were annotated into a total of 355 functional pathways, of which 38 pathways were significantly enriched (all P < 0.05), mainly involving Staphylococcus aureus infection, tryptophan metabolism, histidine metabolism, nitrogen metabolism, metabolism of arginine and proline, biosynthesis and degradation of valine, leucine and isoleucine, fatty acid degradation, peroxisome proliferator-activated receptor signaling pathway, etc. Conclusion:The skin microecological structure significantly differed between the acute and remission phases among the patients with severe AD, which may be related to multiple functional pathways, such as Staphylococcus aureus infection, tryptophan metabolism, histidine metabolism and nitrogen metabolism.
4.Practice and exploration of discipline construction in tertiary specialized hospital with a view of high quality development
Xiuhua WANG ; Songyan ZHANG ; Weijing YIN ; Bo LEI ; Jianqin GU
Chinese Journal of Medical Science Research Management 2021;34(2):144-147
Objective:This paper analyzes the factors influencing the development of discipline construction in a tertiary specialized hospital, explores discipline improvement measures, so as to provide possible references for other medical institutions.Methods:Taking Henan Eye Hospital as an example, we analyze the current status of discipline construction, review the managing practice for the development in recent years, find out the factors influencing the development of disciplines and new challenges, and puts forward improvement measures.Results:The managing practice showed that the affecting factors of discipline construction included discipline orientation, talent teams, original innovation, medical level, academic exchanges and research platforms. Facing to the new problems under the further goal, to figure out the novel way is a guarantee for the smooth development of the medical institute.Conclusions:These measures may foster the development of discipline construction, which include focusing on discipline direction, strengthening the construction of talents, encouraging scientific and technological innovation, developing medical services, deepening the domestic and international cooperation and exchange and constructing platforms. It is important to achieve high-quality development of high-level specialized medical institutions for reaching the goal of health for all citizens.
5.The Wolfiporia cocos Genome and Transcriptome Shed Light on the Formation of Its Edible and Medicinal Sclerotium
Luo HONGMEI ; Qian JUN ; Xu ZHICHAO ; Liu WANJING ; Xu LEI ; Li YING ; Xu JIANG ; Zhang JIANHONG ; Xu XIAOLAN ; Liu CHANG ; He LIU ; Li JIANQIN ; Sun CHAO ; Martin FRANCIS ; Song JINGYUAN ; Chen SHILIN
Genomics, Proteomics & Bioinformatics 2020;18(4):455-467
Wolfiporia cocos (F. A. Wolf) has been praised as a food delicacy and medicine for cen-turies in China. Here, we present the genome and transcriptome of the Chinese strain CGMCC5.78 of W. cocos. High-confidence functional prediction was made for 9277 genes among the 10,908 total predicted gene models in the W. cocos genome. Up to 2838 differentially expressed genes (DEGs) were identified to be related to sclerotial development by comparing the transcriptomes of mycelial and sclerotial tissues. These DEGs are involved in mating processes, differentiation of fruiting body tissues, and metabolic pathways. A number of genes encoding enzymes and regulatory factors related to polysaccharide and triterpenoid production were strikingly regulated. A potential triter-penoid gene cluster including the signature lanosterol synthase (LSS) gene and its modified compo-nents were annotated. In addition, five nonribosomal peptide synthase (NRPS)-like gene clusters, eight polyketide synthase (PKS) gene clusters, and 15 terpene gene clusters were discovered in the genome. The differential expression of the velevt family proteins, transcription factors,carbohydrate-active enzymes, and signaling components indicated their essential roles in the regu-lation of fungal development and secondary metabolism in W. cocos. These genomic and transcrip-tomic resources will be valuable for further investigations of the molecular mechanisms controlling sclerotial formation and for its improved medicinal applications.
6. Identification of differentially expressed genes in lesional versus nonlesional skin of patients with atopic dermatitis by using high-throughput transcriptome-wide RNA sequencing
Lijie CHEN ; Jingyao LIANG ; Xibao ZHANG ; Lei SHAO ; Qingli PAN ; Suling HE ; Yumei LIU ; Jianqin WANG
Chinese Journal of Dermatology 2019;52(10):729-735
Objective:
To identify differentially expressed genes in the transcriptome of the lesional versus nonlesional skin tissues of patients with moderate and severe atopic dermatitis (AD) , and to elucidate their roles in the pathogenesis of AD.
Methods:
From July to October in 2016, lesional and nonlesional skin tissues were obtained from 5 outpatients of Han nationality with AD in Guangzhou Institute of Dermatology, Institute of Dermatology, Guangzhou Medical University. The next-generation high-throughput transcriptome-wide RNA sequencing (RNA-seq) was performed to identify differentially expressed genes, which were subjected to GO function annotation and KEGG pathway analysis. Real-time fluorescence-based quantitative PCR (qRT-PCR) was conducted to verify differences in candidate gene expression between lesional and nonlesional skin tissues.
Results:
An average of 10.96 GBs sequence reads were acquired among 10 samples. A total of 21 729 genes were detected, including 19 268 known genes and 2 545 predicted novel genes. A total of 23 153 new transcripts were detected, of which 18 889 were new alternative splicing subtypes of known protein-coding genes, 2 545 were transcripts belonging to new protein-coding genes, and the remaining 1 719 belonged to long-stranded non-coding RNA. Totally, 78 differentially expressed genes were identified between the lesional and nonlesional skin tissues, including 69 upregulated and 11 downregulated genes in the lesional skin tissues. Among them, there were several genes known to be associated with AD inflammation (CXCL1/2/8, IL6/IL1β, MMP1, SERPINB4, S100A2, GZMB, OASL, OSM) and barrier (KRT16, FABP5, CYP1A1) and keratinocyte differentiation (IL-20) . GO analysis revealed that functions of 72 differentially expressed genes could be annotated. KEGG pathway analysis showed that the differentially expressed genes were grouped into 132 signaling pathways, of which 13 were significantly enriched, including the interleukin (IL) -17 pathway, NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, etc. qRT-PCR showed that the mRNA expression levels of candidate genes CXCL1, KRT6A, IL36A, SERPINB4 and PSAPL1 was consistent with the transcriptome sequencing results.
Conclusions
Differentially expressed genes and related important regulatory signaling pathways were identified between the lesional and nonlesional skin tissues of patients with AD at the transcriptional level, and the IL-17 pathway was found to be mostly enriched in AD lesions in patients of Han nationality. These findings provide an important basis for further study on the pathogenesis of AD..
7.Short-term reproducibility and impact factors of intravoxel incoherent motion parameters for lung cancer
Jianqin JIANG ; Rongfang CAI ; Lei CUI ; Jianbing YIN ; Yiming XU ; Hang MA ; Haiyan HE
Chinese Journal of Medical Imaging Technology 2018;34(4):543-547
Objective To prospectively evaluate the short-term test-retest reproducibility of intravoxel incoherent motion (IVIM) parameters for lung cancer,and to investigate its impact factors.Methods Thirty-eight lung cancer patients underwent twice free breathing IVIM scanning (0.5-1.0 h interval).Two radiologists independently analyzed IVIM images to obtain true diffusion coefficient (D),pseudo-diffusion coefficient (D*) and perfusion fraction (f).All the parameters were compared between repeated measurements and scans.Intra-and inter-observer,test-retest reproducibility was assessed with interclass correlation coefficients (ICCs).The impact of lung cancer type (peripheral and central),size (the largest diameter ≥2 cm and <2 cm) and location (upper,mid,and lower lung field) on short-term reproducibility were compared by using coefficient of variations (WCVs).Results There was no significant difference between repeated measurements for all parameters (all P> 0.05).All the parameters showed good intra-and inter-observer agreement.WCVsof D* and f (19.88%-36.83%) were higher than those of D (2.97%-4.62%).WCVs of D were higher for central lung cancer and the largest diameter <2 cm,and increasing from apical to lower zone.WCV of f was larger in the central lung cancer and the largest diameter ≥2 cm,while D* was greatly influenced by type,size and location of lung cancer.Conclusion The test retest reproducibility of D is good,while of D* and f are poor in lung cancer.The type,size and location of lung cancers are the impact factors of IVIM parameters.
8.The value of diffusion-weighted imaging based on monoexponential and biexponential model in predicting the response of chemotherapy in non-small cell lung cancer patients
Jianqin JIANG ; Lei CUI ; Rongfang CAI ; Jia LIU ; Jianbing YIN ; Liang ZHANG ; Hang MA ; Sumei YAO
Chinese Journal of Radiology 2018;52(11):829-835
Objective To investigate the ADC value and intravoxel incoherent motion (IVIM) parameters to predict the early response to chemotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). Methods Twenty-six patients with pathologically confirmed NSCLC in our hospital from June 2015 to January 2017 were prospectively studied. MR routine scan, DWI and IVIM scans were performed before and at the end of the first cycle of chemotherapy. The ADC value, pure diffusion parameter (D), perfusion parameter (D*) and perfusion fraction (f) before and after chemotherapy were recorded respectively, and the maximum diameter of tumor (MDMRI) was measured on T2WI. The effective group and the ineffective group were divided according to RECIST 1.1. Intra- and interobserver reproducibility were assessed with intraclass correlation coefficient (ICC). The differences of the parameters and their change rate were compared pre-and posttreatment, in the effective and the ineffective groups by using t test. Receiver operating characteristic (ROC) curves were generated to explore the optimal parameters and thresholds for early prediction of the efficacy of chemotherapy. Z test was used to compare the differences in the areas under the ROC curves. Results The repeatability of D*was relatively poor (ICC 0.507-0.716). The ADC and D values of the effective group before chemotherapy were (1.28±0.21)×10-3 and (1.05±0.14)×10-3mm2/s, respectively, and those of the ineffective group were (1.55 ± 0.25) × 10-3 and (1.29 ± 0.18) × 10-3mm2/s, respectively. The differences between two groups were statistically significant (t=-2.989, -3.755, respectively, P all<0.05). While there was no significant difference in f between the effective and ineffective groups before chemotherapy (t=-1.034, P=0.312). The ADC, D and f values of the effective group before chemotherapy were lower than those after chemotherapy, and the differences were statistically significant (t=-3.969,-5.617 and-2.876, respectively, P all<0.05). While there was no significant difference in ADC and D values in ineffective group (t=-0.737, -0.866, P>0.05, respectively). The difference of f was statistically significant (t=-2.731, P<0.05).ΔADC%,ΔD%andΔMDMRI%in effective group were (23.90 ± 22.28)%, (32.58 ± 20.63)% and (18.77 ± 10.36)%, respectively, and those in ineffective group were (1.19 ± 11.35)%, (6.22 ± 21.63)% and (9.35 ± 8.26)%, respectively. The differences between two groups were statistically significant (t=3.393, 3.154 and 2.487, respectively, P all<0.05). There was no significant difference inΔf%between two groups (t=1.346, P=0.191). ROC curve analysis showed that the area under curve (AUC) of preADC, preD, ΔADC%, ΔD% and ΔMDMRI% was 0.788, 0.848, 0.800, 0.830 and 0.727, respectively. When setting the preD=1.20×10-3 mm2/s as the boundary under the largest AUC, however, there was no significant differences in AUC compared with preADC, ΔADC%, ΔD% and ΔMDMRI% (Z=1.336, 0.363, 0.136, 1.395, P>0.05). Conclusion The ADC value, D value before chemotherapy and the early change rate after chemotherapy can better predict the early response of chemotherapy in NSCLC patients.
9.Changes of cytokines in aqueous humor of patients with proliferative diabetic retinopathy after intravitreal bevacizumab and their correlation analysis
Guolong DING ; Anming XIE ; Jianqin LEI ; Guopeng DING ; Yaguang HU
Recent Advances in Ophthalmology 2017;37(4):358-361
Objective To study the changes of cytokines in aqueous humor of patients with proliferative diabetic retinopathy (PDR)after intravitreal bevacizumab (IVB) and the correlation of these cytokines.Methods Fifty-six patients(63 eyes) with severe PDR underwent pars piana vitrectomy (PPV) with IVB pretreatment in our hospital from April,2014 to February,2015 were collected.All the patients received IVB therapy from 3 days to 7 days before PPV.Aqueous humor samples were collected at the time of IVB and PPV treatment.The concentrations of vascular endothelial growth factor (VEGF),interleukin-6 (IL-6),interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) were measured by cytoinetric bead array (CBA).The changes of these cyto-kines after IVB were analyzed by using Wilcoxon rank sum test for paired data.The correlation between these cytokines was analyzed by using Spearman rank test.Results From 3 days to 7 days after IVB,the concentration of VEGF in aqueous humor was (6.57 ± 12.29)pg · mL-1,lower than the pre-operation of (278.71 ±340.20)pg · mL-1,the difference was statistically significant (P < 0.05).The concentration of IL-8 was (385.60 ± 1099.47) pg · mL-1,higher than pre-operation of(298.87 ± 1005.79) pg ·mL-1,the difference was statistically significant (P < 0.05).IL-6 and MCP-1 were increased after IVB,but the difference was not statistically significant (all P > 0.05).VEGF,IL-6,IL-8 and MCP-1 had an obviously relationship between each two factors(all P < 0.05).Conclusion Angiogenesis in patients with PDR are regulated by a variety of cytokines,and targeted reduction of VEGF may compensatory increase the concentration of other inflammatory cytokines.
10.Progresses of intravoxel incoherent motion DWI in evaluation of treatment response of tumors
Jianqin JIANG ; Lei CUI ; Xiaowen GU ; Rongfang CAI
Chinese Journal of Medical Imaging Technology 2017;33(6):949-953
Intravoxel incoherent motion (IVIM) can distinguish the molecular diffusion from the pseudo-diffusion of microcircular perfusion to obtain true diffusion coefficient (D),pseudo-diffusion coefficient (D*) and perfusion fraction (f),which are sensitive to detect alterations in cellularity and microcirculation perfusion.IVIM can also evaluate early therapeutic effects,optimize treatment plan,predict prognoses,and provide information for choosing appropriate treatment methods.In this paper,the principle of IVIM and its application in tumor response evaluation were reviewed.

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