1.Effect of Chronic Unpredictable Mild Stress and Sertraline on Vitamin D Metabolism in Rat Prefrontal Cortex
Xiaoxue GONG ; Ruili DANG ; Yujin GUO ; Hualin CAI ; Pei JIANG
Herald of Medicine 2017;36(6):606-609
Objective To explore the relationship between vitamin D and depression and the effects of chronic unpredictable mild stress (CUMS) plus sertraline on vitamin D metabolism in rat brain.Methods Male SD rats were randomly divided into normal control group,normal control + sertraline group,CUMS group and CUMS+sertraline group.CUMS was used to build the animal model of depression.After chronic exposure to CUMS or sertraline (8 mg·kg-1·d-1) for 6 weeks,behavioral response (sucrose preference test) and vitamin D metabolism in the prefrontal cortex were analyzed.Results Compared with normal control group,6 weeks of CUMS procedure induced the rats to a depression-like state,decreased weight and sucrose preference,and increased the expression of enzymes involved in vitamin D activation and catabolism (CYP27B1 and CYP24A1,respectively) and vitamin D receptor (VDR) in rat prefrontal cortex.As compared with CUMS group,CYP27B1,CYP24A1 and VDR were significantly decreased in CUMS+sertraline group (P<0.01 or P<0.05).Conclusion CUMS activates vitamin D signaling in the brain of the animal models of depression,while sertraline alleviates depressive behavior and relieves stress-induced activation of vitamin D signaling,indicating that vitamin D signaling may be involved in the stress-induced depression.
2.Effect of exposure to chrysotile on ribosomal DNA copy number variation and DNA damage response
Jiaqi LIU ; Lingfang FENG ; Junfei CHEN ; Hailing XIA ; Zhaoqiang JIANG ; Fan WU ; Xiaoxue GONG ; Jianlin LOU
Journal of Preventive Medicine 2022;34(6):547-554
Objective:
To investigate the effect of chrysotile exposure on ribosomal DNA (rDNA) copy number and DNA damage response, so as to provide insights into the mechanism of asbestos-induced carcinogenesis.
Methods:
Human pleural mesothelial MeT-5A cells were treated with chrysotile suspensions at doses of 1.25, 2.5 and 5 μg/cm2 (low-, medium-, high-dose group), while PBS served as controls. MeT-5A cells were harvested 6, 24, 48 and 72 h post-treatment, and the rDNA copy numbers and the BIRC5, HRAS, GINS4 and RRM2 mRNA expression were determined using a quantitative real-time PCR (qPCR) assay. The apoptosis of MeT-5A cells and DNA damage were detected using Muse cell analyzer. The rDNA copy numbers, DNA damage responses and BIRC5, HRAS, GINS4 and RRM2 mRNA expression were compared in MeT-5A cells treated with different doses of chrysotile suspensions.
Results:
There were significant differences in 45S rDNA copy numbers among low-, medium-, high-dose groups and the control groups 6, 48 and 72 h post-treatment with chrysotile suspensions, and significantly lower 45S rDNA copy numbers were measured in low-, medium- and high-dose groups than in the control group 6 h post-treatment, while significantly higher 45S rDNA copy numbers were found in the high-dose group than in low- and medium-dose groups 48 and 72 h post-treatment (all P<0.05). There were significant differences in 5S rDNA copy numbers among low-, medium-, high-dose groups and the control groups 24, 48 and 72 h post-treatment with chrysotile suspensions, and significantly lower 5S rDNA copy numbers were measured in medium- and high-dose groups than in the control group 24 and 48 h post-treatment, while significantly lower 5S rDNA copy numbers were found in medium- and high-dose groups than in the low-dose group 24, 72 h post-treatment (all P<0.05). There were significant differences in the overall apoptotic rate of MeT-5A cells among groups at different time points, and the overall apoptotic rate of MeT-5A cells were significantly higher in medium- and high-dose groups than in the control group (all P<0.05), with late-stage apoptosis predominantly detected. There were significant differences in the rates of ATM activation and DNA double-strand break in MeT-5A cells among groups 72 h post-treatment, and higher rates of ATM activation and DNA double-strand break were measured in medium- and high-dose groups than in the control group (all P<0.05). In addition, there were significant differences in the relative mRNA expression of BIRC5, HRAS, GINS4 and RRM2 genes among groups 24 and 48 h post-treatment, and significantly lower BIRC5, HRAS, GINS4 and RRM2 mRNA expression was quantified in medium- and high-dose groups than in the control group (all P<0.05).
Conclusion
Exposure to chrysotile may induce rDNA copy number variations and altered expression of nucleolar proteins in human pleural mesothelial cells, which may be involved in the regulation of DNA damage responses.
3.Short-term Therapeutic Effect of Recombinant Human Endostatin Combined with Cis-platinum on Malignant Pleural Effusions: A Meta-analysis
Chuanfeng LYU ; Shan WANG ; Fang YUAN ; Jia YAO ; Xiaoxue GONG ; Donglou LIANG ; Yujin GUO
Herald of Medicine 2017;36(5):558-563
Objective To evaluate the efficacy and safety of recombinant human endostatin (rh-endostatin) combined with cis-platinum for patients with malignant pleural effusions.Methods A computer-based online search was performed through Elsevier, PubMed, Medline, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database and Wanfang Database.According to the inclusion and exclusion criteria, the randomized controlled trials about short-term therapeutic effect of rh-endostatin combined with cis-platinum on malignant pleural effusions published until December 2015 were selected.Quality of the studies was assessed using modified Jadad scale.After data extraction, a Meta-analysis was performed by RevMan 5.3 software.Relative risk (RR) and its 95% confidence interval (CI) were calculated.The Egger test was performed by Stata 12.0 software.Results Fourteen eligible randomized controlled trials were included in this Meta-analysis involving 1 330 patients,665 in cis-platinum alone group(control group), and 665 in rh-endostatin combined with cis-platinum group(treatment group).The results showed that there were significant improvements in overall response rate (ORR) [73.53% vs 45.41%,RR=1.62,95%CI(1.47,1.78),P<0.000 01] and the rate of quality of life improvement [71.65% vs 46.94%,RR=1.52,95%CI(1.38,1.68),P<0.000 01] in the treatment group, as compared with those of the control group.Meanwhile, there were no statistically significant differences in the rate of cardio toxicity [10.38% vs 5.77%,RR=1.73,95%CI(0.99,3.03),P=0.06].Conclusion This Meta-analysis indicated that in comparison with cis-platinum alone, rh-endostatin combined with cis-platinum has a better therapeutic effect on malignant pleural effusions.
4.Effect of hexavalent chromium-induced ribosomal DNA copy number variation on DNA damage response in various cell lines
WU Fan ; FENG Lingfang ; CHEN Junfei ; JIANG Zhaoqiang ; GONG Xiaoxue ; QIN Yao ; LOU Jianlin
Journal of Preventive Medicine 2023;35(5):374-379
Objective:
To investigate the effect of ribosomal DNA (rDNA) copy number variation caused by hexavalent chromium exposure on DNA damage response in different cell lines, so as to provide insights into the involvement of hexavalent chromium-induced rDNA copy number variation in DNA damage responses.
:
Methods Human lung epithelial BEAS-2B cells and human embryonic lung MRC-5 cells were treated with 2 μmol/L potassium dichromate for 24 hours, and then cells were transferred to fresh media for further incubation, while cells treated with the same volume of phosphate buffer solution served as controls. Cells treated with potassium dichromate for 24 hours, and 3 and 7 days post-detoxification, were harvested, and rDNA copy number was quantified in cells using a quantitative fluorescent real-time PCR assay. Cell cycle, apoptosis and DNA damage were detected using a Muse cell analyzer, and the DNA damage was evaluated with the proportion of ataxia telangiectasia-mutated (ATM) gene activation, proportion of double-strand DNA breaks and the percentage of the H2A.X variant histone phosphorylatio.
:
Results The 45S and 5S rDNA copy numbers of were significantly higher in MRC-5 cells than in BEAS-2B cells [(1.54±0.26) vs. (1.02±0.18), P<0.05; (6.97±1.07) vs. (3.00±0.15), P<0.05]. The 45S rDNA copy number was lower in MRC-5 cells 3 days post-detoxification (0.80±0.04) than in controls (P<0.05), and was higher in BEAS-2B cells 3 days post-detoxification (1.43±0.07) than in controls (P<0.05) . G0/G1 phase arrest was found in MRC-5 cells 24 hours post-treatment, and the apoptotic rates were significantly higher in MRC-5 cells 3 and 7 days post-detoxification than in controls [(11.53±1.53)%, (18.33±0.70)% vs. (3.53±0.93)%, P<0.05]. The overall apoptotic rates 24 hours post-treatment and 3 days post-detoxification [(2.80±0.17)%, (3.33±0.57)% vs. (1.53±0.61)%, P<0.05], proportion of ATM gene activation 3 days post-detoxification [(3.37±0.67%) vs. (1.18±0.22)%, P<0.05], proportion of double-strand DNA breaks 3 days post-detoxification [(4.45±0.85)% vs. (0.97±0.21)%, P<0.05] and percentage of the H2A.X variant histone phosphorylation 3 days post-detoxification [(1.68±0.56)% vs. (0.29±0.06)%, P<0.05] in BEAS-2B cells were higher than in controls.
Conclusions
Hexavalent chromium-induced rDNA copy number variation affects DNA damage response in different cell lines. A stronger DNA damage response is found in BEAS-2B cells with a low rDNA copy number, and a relative stable response is observed in MRC-5 cells with a high rDNA copy number.
5.Ribosomal DNA copy number variation in peripheral blood and its influencing factors among patients with pneumoconiosis
GONG Xiaoxue ; FENG Lingfang ; CHEN Junfei ; FU Hao ; JIANG Zhaoqiang ; LIU Shuang ; DONG Xiaowen ; WU Fan ; LOU Jianlin
Journal of Preventive Medicine 2024;36(2):101-104
Objective:
To explore the changes in ribosomal DNA copy number in peripheral blood among patients with pneumoconiosis and its influencing factors, so as to provide insights into prevention and treatment of pneumoconiosis.
Methods:
Eighty-eight patients with pneumoconiosis who visited a designated hospital and 71 community residents with no history of pneumoconiosis or dust exposure were selected as the pneumoconiosis group and control group, and age, smoking history, drinking history and cumulative years of exposure to dust were collected through questionnaire surveys. The copy number of 45S rDNA and 5S rDNA was detected using real-time fluorescence quantitative PCR, and the differences between the two groups were compared. Factors affecting the copy number of 45S rDNA and 5S rDNA were identified by a multiple linear regression model.
Results:
The pneumoconiosis group had a median age of 56.00 (interquartile range, 15.25) and a mean cumulative dust exposure duration of (12.40±8.08) years, with 56.82% smoking and 62.50% drinking. The control group had a median age of 64.00 (interquartile range, 37.00) years, with 32.39% smoking and 26.76% drinking. The median copy number of 45S rDNA in the pneumoconiosis group was 1.29 (interquartile range, 0.59), which was lower than 2.10 (interquartile range, 1.88) in the control group; the median copy number of 5S rDNA in the pneumoconiosis group was 5.33 (interquartile range, 0.85), which was higher than 4.66 (1.34) in the control group (both P<0.05). Multiple linear regression analysis identified age (β=-0.034) and pneumoconiosis (β=-1.595) as factors affecting 45S rDNA copy number, age (β=-0.013) as a factor affecting 5S rDNA copy number, and age (β=0.018) as a factor affecting 5S rDNA copy number in the pneumoconiosis group (all P<0.05).
Conclusions
Compared with community residents with no history of pneumoconiosis or dust exposure, the copy number of 45S rDNA in peripheral blood among patients with pneumoconiosis is reduced and the copy number of 5S rDNA is increased.
6.Establishment of mouse silicosis fibrosis model by non-exposed tracheal perfusion
Xiaoxue GONG ; Lingfang FENG ; Yongxin LI ; Junfei CHEN ; Xiaowen DONG ; Jiaohui YAO ; Jianlin LOU
China Occupational Medicine 2023;50(1):17-22
7. Prognostic significance of combined TERT and IDH gene mutation analysis in diffusely infiltrating gliomas
Qianqi LIU ; Xiaoxue YIN ; Yan ZOU ; Tianping YU ; Jing GONG ; Xueqin CHEN ; Ling NIE ; Miao XU ; Mengni ZHANG ; Qiao ZHOU ; Ni CHEN
Chinese Journal of Pathology 2018;47(9):658-663
Objective:
To investigate the status and prognostic significance of TERT and IDH1/2 genes mutations in diffusely infiltrating gliomas.
Methods:
Hot spot mutations of TERT and IDH1/2 genes were detected by DNA sequencing in 236 cases of gliomas at West China Hospital from 2012 to 2016, including pilocytic astrocytoma (WHO grade Ⅰ, 16 cases), diffuse astrocytoma and oligodendroglioma (WHO grade Ⅱ, 89 cases), anaplastic astrocytoma and oligodendroglioma (WHO grade Ⅲ, 72 cases) and glioblastoma (WHO grade Ⅳ, 59 cases). The prognostic significance of TERT and IDH1/2 hot spot mutations was evaluated.
Results:
No IDH or TERT mutations were detected in pilocytic gliomas. TERT promoter mutation frequency was higher in patients aged ≥40 years(60.8%, 93/153) than in patients aged <40 years (32.8%, 22/67;
8.Interleukin-6 induces epithelial mesenchymal transition of human peritoneal mesothelial cells by STAT3
Jing XIAO ; Cong WANG ; Ya'nan GONG ; Xiaoxiao LI ; Jie MENG ; Xiaoyang WANG ; Xiaoxue ZHANG ; Yijun DONG ; Genyang CHENG
Chinese Journal of Nephrology 2017;33(9):711-717
Objective To investigate the role of STAT3 transcription factor in IL-6 inducing epithelial mesenchymal transition (EMT) of human peritoneal mesothelial cells (HPMCs).Methods HPMCs were cultured in vitro and grouped.(1) According to the stimulation time with 50 μg/L IL-6,HPMCs were divided into 24,48,72 h groups.(2) HPMCs were grouped 50,100 μg/L according to IL-6 concentration.(3) HPMCs were respectively divided into control group,IL-6 group,empty vector group,empty vector+IL-6 group,virus infecting group and virus infecting+IL-6 group,as lenti-virus vector mediating RNA interference targeting STAT3 was applied.The mRNA expressions of E-cadherin,α-smooth muscle actin (α-SMA) and vascular endothelial growth factor (VEGF) were detected by real time PCR;their protein expressions and the phosphorylation of JAK2 and STAT3 were detected by Western blotting;the expressions and distribution of E-cadherin and α-SMA were observed by immunofluorescence.Results Compared with those in control group,the expression of E-cadherin decreased remarkably (P < 0.05),while the expressions of VEGF and α-SMA and the ratio of phosphorylated (p)-JAK2/JAK2 and p-STAT3/STAT3 increased significantly in IL-6 concentration groups and stimulation time groups (all P < 0.05),which had been dose and time dependent.Compared with empty vector+IL-6 group,virus infecting+IL-6 group had decreased expressions of VEGF and α-SMA,while increased expressions of E-cadherin (all P < 0.05).Conclusions IL-6 can promote VEGF and α-SMA gene expression and prevent E-cadherin gene expression by STAT3,which involves in EMT of peritoneum fibrosis.While STAT3 gene is knocked-down,EMT is inhibited in HPMCs.
9.Multicenter retrospective investigation and analysis of the rationality of the application of human albumin in cardiac surgery during the perioperative period
Wenfei PAN ; Huan YU ; Dasheng DANG ; Lijuan CHEN ; Te LI ; Tianlu SHI ; Banghua HUANG ; Boxia LI ; Xiaoxue GONG ; Ying WANG
Chinese Journal of Pharmacoepidemiology 2024;33(2):176-183
Objective To investigate the clinical application of perioperative human serum albumin(HSA)in cardiac surgery in multiple regions in China,and to evaluate the rationality of its clinical application in conjunction with the clinical guidelines,in order to provide a reference for promoting the rational application of HSA.Methods The medical records of patients who underwent cardiac surgery from April to June 2019 in eight hospitals across the country were retrospectively collected.The statistical information on patients'general information,the dosage,course of treatment,and cost of HSA,and the serum albumin level before and after medication was analyzed to evaluate the use of HSA.Relevant evaluation criteria were established,and the rationality of its medication was evaluated.Results Data from a total of 449 patients were included for analysis,the appropriate rate of medication was 81.1%.The course of medication was mostly>2-5 days and the total amount of HSA was mostly 50-99 g.The main purpose of medicaiton were improving colloid osmotic pressure,reducing exudation to improve interstitial edema,postoperative volume expansion.Conclusion Clinical attention should be paid to ensure the rational application of HSA in cardiac surgery during the perioperative period and prevent the abuse of blood products.
10.Association between red cell distribution width and mortality in patients undergoing continuous ambulatory peritoneal dialysis
Jie MENG ; Xiaoyang WANG ; Xiaoxiao LI ; Cong WANG ; Ya'nan GONG ; Shuang MA ; Yijun DONG ; Xiaoxue ZHANG ; Genyang CHENG ; Dong LIU ; Yanna DOU ; Yansheng LI ; Jing XIAO ; Zhanzheng ZHAO
Chinese Journal of Nephrology 2018;34(2):87-93
Objective To investigate the association of red cell distribution width (RDW) with all-cause and cardiovascular disease (CVD)-related mortality in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).Methods A retrospective analysis was performed on 207 patients who initiated CAPD for more than 3 months between July 2005 and March 2016 in the First Hospital Affiliated to Zhengzhou University.Baseline data on demographic,clinical and biochemical variables as well as comorbidities were obtained;medications and clinic outcomes were recorded.According to receiver operator characteristic curve (ROC) analysis,patients were divided into high RDW (RDW > 15.1%) and low RDW (RDW≤ 15.1%) groups.The data of two groups were compared and Spearman's correlation analysis was used to explore the association of RDW with clinical and biochemical parameters.Survival curves were calculated using Kaplan-Meier method.Cox regression model was employed to analyze risk factors of all-cause and CVD-related mortality.Results In this study,207 CAPD patients were enrolled.The overall median survival time was 80 months.And the median survival time of high RDW group (68 patients) and low RDW group (139 patients) were 59 months and 96 months,respectively.There were statistical differences in diastole pressure,hemoglobin,hematocrit,serum albumin,intact parathyroid hormone (iPTH),eGFR,cholesterol,lipoprotein a,4-hour dialysate-to-plasma ratio for creatinine (4hD/Pcr),total Ccr (P < 0.05,respectively);the two groups also varied in the proportion of chronic obstructive pulmonary disease,cardiovascular disease and hyperlipidemia,as well as in the use of iron supplements,angiotensin-converting enzyme (ACE) inhibitors or angiotensin Ⅱ receptor blockers (ARB),and beta-receptor blockers (P<0.05,respectively).Cardiovascular event was a leading cause of mortality.Kaplan-Meier survival curves showed that the high RDW group had higher all-cause and CVD-related mortality compared with the low RDW group (P < 0.01).The 1-year,3-year,and 5-year patient survivals of the high RDW and low RDW group were 87.97% vs 97.01%,58.02% vs 81.53%,and 41.62% vs 67.96%,respectively,demonstrating significant differences (P=0.001).Multivariate Cox regression analysis showed that high RDW was independent risk factor for all-cause mortality (HR=1.212,95%CI:1.007-1.458,P=0.042) and CVD-related mortality (HR=1.697,95% CI:1.030-2.795,P=0.038).Conclusion RDW is associated with mortality risks in CAPD patients and can be stratified as a valuable indicator for the risk of death.