1.Long non-coding RNA MALAT1 regulates astrocyte proliferation and apoptosis and affects MAPK/ERK1,2 signaling pathway
Hui HU ; Xue WANG ; Yuhan WU ; Huafeng DONG ; Ling ZHANG ; Aijun WEI ; Fang XIE ; Yun ZHAO ; Zhaowei SUN ; Lingjia QIAN
Military Medical Sciences 2024;48(5):347-354
Objective To investigate the effect of MALAT1 expressions on cell proliferation and apoptosis in astrocytes by regulating mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase(ERK1,2)pathway.Methods The MALAT1 gene was knocked down and over-expressed in C8-D1A cells by lentiviral and plasmid vectors,respectively.The expressions of MALAT1,cell proliferation-related markers(Ki67,MCM2,PCNA)and apoptosis-related proteins(Caspase-3,Bax,Bcl-2)were detected by quantitative real-time polymerase chain reaction(qPCR).CCK-8 assay and flow cytometry were used for cell proliferation and apoptosis in C8-D1A cells.Immunofluorescence was adopted to detect the protein expressions of Caspase-3 and Ki67.Western blotting was used to detect the protein expressions of Caspase-3,Bax,Bcl-2,ERK1/2,p-ERK1/2,p38MAPK and p-p38MAPK.Results Compared with the control group,over-expressed MALAT1 inhibited cell proliferation and induced cell apoptosis in C8-D1A cells while the knockdown of MALAT1 significantly enhanced cell proliferation and anti-apoptotic ability in C8-D1A cells.The proportion of C8-D1A cells in G0/G1-phase and G2/M-phase was higher than in the control group as evidenced by flow cytometry,but was lower in S-phase.Meanwhile,data showed that Caspase-3 was increased while p-ERK1/2 was decreased in terms of protein levels.The mRNA expressions of Ki67 and PCNA were decreased.After knockdown of MALAT1,the proportion of C8-D1A cells in S-phase was higher,but was lower in G2/M-phase.The protein expressions of Caspase-3 and Bax decreased while those of p-ERK1/2 and p-p38MAPK increased.The mRNA expressions of Ki67,MCM2 and PCNA were increased.The differences were all statistically significant(P<0.05).Conclusion MALAT1 promotes astrocyte apoptosis and inhibits proliferation by regulating the MAPK/ERK1,2 signaling pathway.
2.Sampling inspection results of disinfection products in Shaanxi Province in 2020 - 2023
Yongbing CHENG ; Baobao CHEN ; Xiaoling ZHANG ; Jianfeng XUE ; Xiaofeng DONG ; Zhaowei MENG
Journal of Public Health and Preventive Medicine 2024;35(6):93-96
Objectives To understand the quality status of disinfection products in the market in Shaanxi Province, and to provide a basis for taking targeted management measures. Methods From 2020 to 2023, in accordance with the national disinfection product management regulations and standards, the physicochemical and microbial tests of disinfection products in Shaanxi Province were carried out through supervised sampling, and the test results were analyzed according to the active ingredients, illegal addition, stability, and bactericidal or bacteriostatic performance. Results The overall qualification rate of the active ingredient content of disinfectants sampled in Shaanxi Province was 90.48%, with the lowest qualification rate in 2023 (84.38%). The overall qualification rate of quantitative sterilization test of disinfectants was 90.12%, showing a decreasing trend year by year (P=0.272). The overall qualification rate of anti-bacterial products was 88.59%, and the bactericidal test results of 20 antibacterial products were all qualified. The overall qualification rate of bacteriostatic performance testing for bacteriostatic products was 86.17%, with the pass rate of bacteriostatic product germicidal efficacy testing of different components in descending order being quaternary ammonium salt/silver ion > guanidine > others > lysozyme, and there was statistically significant difference (P=0.004). The detection rate of illegal additives in antimicrobial products was 7.07%, with the main detection indicators being miconazole nitrate, clobetasol propionate, and dexamethasone acetate. Conclusion The qualified rate of disinfection products in Shaanxi Province is relatively high, but there is a downward trend. It is necessary to continue to strengthen the daily supervision and product testing of disinfection product manufacturers, and promote the continuous improvement of disinfection product quality.
3.Comparison of robot-assisted and open surgery in the treatment of renal carcinoma with Mayo Ⅰ-Ⅲ inferior vena cava tumor thrombus
Ali ZHU ; Jin TAO ; Jinshan CUI ; Shengzheng WANG ; Shuanbao YU ; Yafeng FAN ; Zhaowei ZHU ; Biao DONG ; Xuepei ZHANG
Journal of Modern Urology 2023;28(5):382-386
【Objective】 To compare the clinical efficacy of robot-assisted and open surgery in the treatment of renal carcinoma with inferior vena cava cancer thrombus, and to analyze the safety and feasibility of robot-assisted radical nephrectomy. 【Methods】 Clinical data of 55 patients surgically treated for renal carcinoma with Mayo Ⅰ-Ⅲ inferior vena cava tumor thrombus during Dec.2015 and Dec.2021 were retrospectively analyzed. Based on the operation methods, the patients were divided into the robotic surgery group (n=36) and open surgery group (n=19). The perioperative data, oncological results and survival of the two groups were compared. 【Results】 All operations were successful. The median operation time was 176 (IQR:137-234) min, and grade Ⅲ and above complications occurred in 9(16.4%) cases. The robotic surgery group had lower intraoperative blood loss [300 (IQR:200-625) mL vs.1 000 (IQR:600-1 184) mL] and blood transfusion ratio [(20/36) vs. (18/19)] than the open surgery group, but higher postoperative hemoglobin level[109(98-120) g/L vs. 90(84-100) g/L]. During a median follow-up of 26 (IQR:19-39) months, 19(34.5%) patients developed new metastases and 12(21.8%) patients died. The postoperative tumor-specific survival (HR=0.39, 95%CI:0.13-1.16, P=0.090) and overall survival (HR=0.71, 95%CI:0.22-2.23,P=0.554) were not significantly different between the two groups. 【Conclusion】 There are no significant differences in the incidence of postoperative complications, tumor-specific survival and overall survival between robot-assisted and open surgery for Mayo Ⅰ-Ⅲ inferior vena cava tumor thrombus, but the intraoperative blood loss in robotic group is lower than that in the open surgery group.
4.Comparison between robot-assisted and open radical nephrectomy in the treatment of complex kidney neoplasm >8 cm in diameter
Jinshan CUI ; Shuanbao YU ; Guodong HONG ; Jin TAO ; Yafeng FAN ; Biao DONG ; Zhaowei ZHU ; Xuepei ZHANG
Journal of Modern Urology 2023;28(2):111-114
【Objective】 To compare the feasibility, safety, and efficacy of robot-assisted and open radical nephrectomy for complex kidney neoplasm >8 cm in diameter. 【Methods】 Clinical data of 24 patients with large kidney neoplasm undergoing robot-assisted radical nephrectomy (9 cases, 37.5%) and open radical nephrectomy (15 cases, 62.5%) during Nov.2015 and Aug.2019 were retrospectively analyzed. The surgical parameters, perioperative complications and follow-up outcomes were compared between the two groups. 【Results】 All operations were successful. Compared with the robot group, the open group had a higher incidence of clinical symptoms (93.3% vs.44.4%, P=0.015) and larger maximum tumor diameter (124 mm vs.95 mm, P=0.021). There were no significant differences in other preoperative characteristics between the two groups. The robot group had less intraoperative blood loss (100 mL vs.800 mL, P=0.006) and lower blood transfusion rate (0% vs. 60.0%, P=0.007) than the open group. During the median follow-up of 50 (range: 25-67) months, 4 patients in the open group and 1 in the robot group developed new metastases, and 4 patients in the open group died due to advanced tumor stage. 【Conclusion】 Robot-assisted radical nephrectomy is safe in the treatment of complex and large renal tumors, and causes less intraoperative blood loss than open surgery.
5.Synergistic mechanisms of ferroptosis in anaplastic thyroid cancer induced by dihydroartemisinin and sorafenib
Jiayue DONG ; Shujie LI ; Yan WANG ; Lei YANG ; Dihua LI ; Zhaowei MENG
Chinese Journal of Endocrinology and Metabolism 2023;39(7):596-604
Objective:To investigate the synergistic effects and molecular mechanisms of dihydroartemisinin(DHA) and sorafenib(SOR) in inducing ferroptosis in anaplastic thyroid cancer(ATC) cells.Methods:CCK-8 and flow cytometry assays were performed to detect the effects of DHA and SOR on the proliferation and ferroptosis of ATC cells(CAL-62). Real-time fluorescence quantitative PCR and Western blotting assays were performed to detect the expressions of ferroptosis-related genes glutathione peroxidase 4(GPX4), solute carrier family 7 member 11 gene(SCL7A11), lipoxygenase-15(LOX-15), and p53. The levels of iron death intermediate metabolites including lactate dehydrogenase(LDH), glutathione(GSH), malondialdehyde(MDA), ferrous ion(Fe 2+ ), nitric oxide(NO), and reactive oxygen species(ROS)were measured by corresponding assay kits. The corresponding inhibition of DHA and SOR on ATC in vivo was analyzed in a tumor model in nude mice. Results:Compared with the control group, DHA, SOR, and DHA+ SOR treatment significantly inhibited cell proliferation and apoptosis in a dose-dependent manner( P<0.001), with increased LDH, Fe 2+, MDA, and ROS contents and reduced GSH activity( P<0.001), which were promoted by ferrous sulfate(FeSO 4)and reversed by ferroptosis inhibitor-1. Compared with the control group and the drug monotherapy group, 15-LOX-2 and p53 expressions were upregulated in DHA+ SOR group while GPX4 and SCL7A11 expressions were decreased( P<0.001), without significant difference in 15-LOX-1 protein content. In addition, NO level was significantly increased in DHA+ SOR group( P<0.001). DHA and SOR inhibited tumor growth of ATC in vivo. Conclusion:DHA and SOR synergistically induced ferroptosis via upregulating the expression of 15-LOX-2 gene and inhibiting NO synthesis in ATC cells.
6.Exploration of Material Basis of "Clearing Excessive Fire of Liver-gallbladder" of Bile-processed Coptidis Rhizoma Based on UPLC-Q-TOF/MS Metabolomics and Molecular Docking Technology
Zhaowei DONG ; Maoying TIAN ; Yu YANG ; Jin WANG ; Qinwan HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(23):140-149
ObjectiveTo explore the material basis of bile-processed Coptidis Rhizoma clearing excessive fire of liver-gallbladder based on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF/MS) metabolomics and molecular docking. MethodUPLC-Q-TOF/MS metabolomics was used to analyze the chemical constituents of Coptidis Rhizoma, water-processed Coptidis Rhizoma and bile-processed Coptidis Rhizoma. Chromatographic separation was achieved with 0.1% formic acid aqueous solution(A)-acetonitrile(B) as the mobile phase in gradient elution(0-2 min, 5%B; 2-20 min, 5%-65%B; 20-40 min, 65%-10%B; 40-45 min, 10%B; 45-46 min, 10%-95%B; 46-49 min, 95%B), and electrospray ionization(ESI) was applied and operated in positive and negative ion modes, the acquisition range was m/z 80-1 200. Based on this, partial least squares-discriminant analysis(PLS-DA) and variance analysis were used to screen the differential compounds among the three products of Coptidis Rhizoma. Network pharmacology and molecular docking were used to verify the degree of association between differential compounds and excessive fire of liver-gallbladder syndrome. ResultA total of 33 chemical constituents were identified, including 2 phenolic acids, 5 binding bile acids and 26 alkaloids. And 16 differential compounds were identified by multivariate statistical analysis, including 11 alkaloids and 5 binding bile acids. Pathway enrichment analysis in the Kyoto Encyclopedia of Genes and Genomes(KEGG) database yielded 8 pathways related to excessive fire of liver-gallbladder, and the key protein phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform(PIK3CA) was obtained according to the "component-target-pathway" network analysis. Molecular docking results showed that 11 alkaloids had good binding ability with PIK3CA. ConclusionPorcine bile is unique in the processing of bile-processed Coptidis Rhizoma, which can promote the production and dissolution of 11 alkaloids, including berberine and dihydrochelerythrine. Based on the results of molecular docking and reported pharmacological experiments, it can be concluded that 16 different compounds such as berberine, dihydrochelerythrine and taurohyodeoxycholic acid are the material basis of bile-processed Coptidis Rhizoma.
7.Role of CD5 molecular-like on hepatocellular carcinoma
Zhaowei GAO ; Xianan WU ; Lan YANG ; Chong LIU ; Xi WANG ; Huiping WANG ; Ke DONG
Chinese Medical Journal 2023;136(5):556-564
Background::CD5L (CD5 molecular-like) plays an important role in lipid metabolism and immune regulation. This study aimed to investigate the roles of CD5L on liver hepatocellular carcinoma (LIHC).Methods::We analyzed the CD5L mRNA expression and its potential prognostic value based on The Cancer Genome Atlas and Gene Expression Omnibus databases. Immunohistochemical analysis was used to investigate the CD5L levels in LIHC tissues. Serum CD5L levels in LIHC were detected by enzyme-linked immunosorbent assay. Cell Counting Kit-8 (CCK-8) assay was used to investigate the effect of CD5L treatment on HepG2 and QSG-7701 cell proliferation. CD5L expression correlated genes were exhumed based on the LinkedOmics. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses for CD5L associated genes were performed. The correlation between CD5L and tumor immune infiltration was analyzed by using Tumor Immune Estimation Resource (TIMER) 2.0.Results::CD5L mRNA and protein levels were significantly decreased in LIHC tumor tissue compared with non-tumor control tissues. Moreover, serum CD5L levels were significantly lower in LIHC patients than that in healthy subjects. Gene Expression Profiling Interactive Analysis 2 and Kaplan-Meier plotter analysis showed that a high-CD5L expression was correlated with favorable overall survival in LIHC patients, except the LIHC patients with hepatitis virus. CCK-8 results showed that CD5L treatment significantly decreased HepG2 cell proliferation in a concentration-dependent manner, and CD5L treatment had no effect on the proliferation of non-tumor hepatocyte line QSG-7701. CD5L associated genes were enriched in the immune response biological process, and CD5L expression levels were positively correlated with the immune infiltrates of CD8 + T cell and M1 macrophage cells but negatively correlated with CD4 + T cells and M0 macrophage cell infiltration. Conclusions::Exogenous CD5L inhibits cell proliferation of hepatocellular carcinoma. CD5L may act as a role of prognostic marker.
8.Interfering with B7-H4 expression can inhibit proliferation of breast cancer cells by down-regulating E2F family related transcription factors
CHEN Haochuan ; GAO Zhaowei ; LONG Min ; LIU Chong ; DONG Ke ; ZHANG Huizhong
Chinese Journal of Cancer Biotherapy 2022;29(3):195-201
[摘 要] 目的:探讨干扰B7-H4表达对乳腺癌细胞增殖、凋亡、周期以及相关下游分子表达的影响。方法:利用脂质体转染技术分别将特异性靶向B7-H4的siRNA(siB7-H4)及其阴性对照(siNC)转染至对数生长期的乳腺癌T47D和MCF-7细胞,分别命名为T47D-siB7-H4、T47D-siNC、MCF-7-siB7-H4和MCF-7-siNC组。用qPCR法和WB法验证siRNA干扰效果及其对细胞周期分子cyclin D1表达的影响,CCK-8法和FCM分别检测干扰B7-H4表达对T47D和MCF-7细胞增殖、周期和凋亡的影响,qPCR法检测B7-H4干扰对E2F家族相关转录因子表达的影响。结果:成功构建干扰B7-H4表达的乳腺癌T47D和MCF-7细胞。与T47D-siNC和MCF-7-siNC组相比,T47D-siB7-H4和MCF-7-siB7-H4组细胞中B7-H4 mRNA和蛋白表达水平均显著降低、细胞增殖能力显著降低(均P<0.01),并伴有G1/S期细胞周期阻滞以及cyclin D1表达下调(均P<0.01),但细胞凋亡率差异无统计学意义(均P>0.05)。与T47D-siNC相比,干扰B7-H4后T47D细胞中E2F1、E2F2、E2F7和E2F8 mRNA水平有不同程度的降低(均P<0.01);与MCF-7-siNC相比,干扰B7-H4后MCF-7细胞中E2F1、E2F2、E2F3、E2F7和E2F8 mRNA水平均有不同程度的降低(P<0.05或P<0.01)。结论:干扰乳腺癌细胞B7-H4表达可下调cyclin D1和E2F家族相关转录因子的表达,导致细胞周期阻滞并抑制细胞增殖。
9.A survey on the scientific research competitiveness of newly-established medical universities — taking four medical colleges in Shanghai, Shaanxi, Zhejiang and Fujian of China as examples
Zongzhong WANG ; Zhaowei LI ; Xin SHU ; Enhong DONG
Chinese Journal of Medical Education Research 2022;21(10):1421-1426
Objective:To provide reference for the construction and development of medical colleges and universities by comparing the scientific research competitiveness of four newly-established medical universities in Shanghai, Shaanxi, Zhejiang and Fujian of China.Methods:Four young state-owned medical universities, founded successively from 2015 in Shanghai, Shaanxi, Zhejiang and Fujian provinces, were selected as the research samples. Both CNKI and WoS databases were used to conduct comparative bibliometric analysis of high-quality literature published in core Chinese and foreign journals during 2016 to 2020 from such perspectives as number of papers, discipline distribution, source titles and funding, etc.Results:All four universities have displayed an increasing trend of publishing literature in core Chinese and foreign journals, but there are relatively fewer literature published in top international journals. The university from Shaanxi leads the other three with most indexes, and the two universities from Shanghai and Zhejiang stand close, while the one from Fujian lags behind, indicating a gap of scientific research competitiveness among the four.Conclusion:The reasons for the existing gap are potentially related to different college foundation and history, orientation and objectives, as well as the strength of scientific research team. Newly-built medical universities should keep deepening the comprehensive reform of medical education and strengthening comprehensive power of scientific research competitiveness.
10.Analysis of the correlation between preoperative factors and positive surgical margin after robot-assisted laparoscopic radical prostatectomy
Wugong QU ; Biao DONG ; Jin TAO ; Zhaowei ZHU ; Junxiao LIU ; Shuanbao YU ; Xuepei ZHANG
Chinese Journal of Urology 2021;42(4):289-293
Objective:To analyze the correlation between preoperative parametres and positive surgical margin after robot-assisted laparoscopic radical prostatectomy.Method:From October 2014 to January 2019, the clinical data of 310 patients who underwent robot-assisted laparoscopic radical prostatectomy(RARP) by single surgeon were collected retrospectively. The median age, PSA, f/t PSA and PSAD was 68(62-72)years, 26(13-63) ng/ ml, 0.12 (0.07-0.18) and 0.36(0.20-0.75) ng/ml 2, respectively. There were 115 cases with clinical T 1, 100 with clinical T 2, 41 with clinical T 3, and 15 with clinical T 4. Based on the MRI or ultrasound examination, the median value for the transverse diameter, anteroposterior diameter, vertical diameter, and volume of the prostate is 44(35-50)mm, 45(40-51)mm, 41(36-50)mm, and 76(54-118)ml, respectively. In this study, 84(27%)cases were diagnosed pathologically by transurethral resection of the prostate, and 226(73%)cases by prostate biopsy. The biopsy technique was transrectal ultrasound-guided systematic 12-point biopsy, and additional 1-5 needles were performed in regions with abnormal ultrasound echoes. The median for total number of puncture needles, number and percentages of positive needles were 12(12-13), 9(4-12)and 85%(35%-100%), respectively. Of all the patients, there were 61 cases with Gleason score≤6, 95 with Gleason score=7 and 84 with Gleason score≥8. There were 237(76%)patients undergoing neoadjuvant endocrine therapy. The patients were divided into the negative surgical margin group and positive surgical margin group. The correlation between positive surgical margin and general clinical data, PSA derivates, prostate size (transversal diameter, anteroposterior diameter, vertical diameter, and prostate volume), percentage of positive biopsy cores, Gleason score, method of pathological diagnosis, and endocrine therapy were analyzed. Results:Of all the 310 enrolled patients, the overall positive surgical margin rate was 34.2%(106/310). Univariate analysis showed that tPSA(41.3 ng/ml vs.24.8ng/ml, P=0.029), f/tPSA(0.14 vs.0.10, P=0.004), transversal diameter of prostate(46 mm vs.38mm, P=0.049), percentage of positive biopsy cores(100% vs.58%, P=0.001), and biopsy Gleason score(Gleason score≤6, =7 and ≥8: 14, 31 and 32 cases vs. 47, 64 and 42 cases, P<0.05)exhibited significant correlation with postoperative positive surgical margin. Multivariate analysis showed that transversal diameter of prostate( P=0.026) and percentage of positive biopsy cores( P=0.048) were independent risk factors for positive surgical margin. Conclusions:Transversal diameter of prostate and percentage of positive biopsy cores were independent risk factors, which help to predict the occurrence of postoperative positive surgical margin.


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