1.Impact of down-regulation of histone methyltransferase enhancer of zeste homolog 2 on RUNX3 expressions, proliferation and apoptosis in human pancreatic cancer
Jian DU ; Guang TAN ; Haifeng LUO ; Peng GONG ; Zhongyu WANG
Chinese Journal of Hepatobiliary Surgery 2016;22(4):249-252
Objective To investigate the impact of down-regulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2) on RUNX3 expressions,proliferation and apoptosis in human pancreatic cancer.Methods The expressions of EZH2 and RUNX3 in 38 pancreatic cancer patients and human pancreatic cancer AsPC-1,PANC-1 and BxPC-3 cells were detected by immunohistochemistry and western blot,respectively.Cells were transfected with siEZH2 by lipofectamin 2000.Real time-PCR and western blot were used to detect EZH2 and RUNX3 expressions.Cell growth and apoptosis in vitro and vivo were assessed by MTT,flow cytometry and nude mice experiments,respectively.The correlation among the expressions of EZH2,clinical pathological features and overall survival rate were analyzed.Results Elevated EZH2 and decreased RUNX3 expressions were observed in human pancreatic cancer tissues and cells (P < 0.05).Knockdown of EZH2 reduced cell growth and induced apoptosis in vitro and vivo by upregulating RUNX3 protein expression (P < 0.05).In addition,the EZH2 expressions were correlated with tumor stage,lymph node metastasis and poor prognosis (P < 0.05).Conclusions EZH2 expressions were correlated with malignancy and poor prognosis in pancreatic cancer.Tumor cell proliferation was promoted by EZH2 through down-regulation of RUNX3.EZH2 may be a potential therapeutic target for pancreatic cancer.
2.Vitamin D Levels and Risk of Male Factor Infertility: A Mendelian Randomization Study
Chi YUAN ; Liyuan XIANG ; Zhongyu JIAN ; Banghua LIAO
The World Journal of Men's Health 2023;41(3):640-648
Purpose:
No consensus exists about the causal relationship between vitamin D (VD) and male factor infertility due to heterogeneity and confounding factors even in randomized controlled trials (RCTs). This study aimed to investigate the causal association between 25 hydroxyvitamin D (25OHD) levels and male factor infertility through Mendelian randomization (MR) and provide complementary information for optimization of future RCTs.
Materials and Methods:
Two-sample MR analyses with four steps were performed. Single-nucleotide polymorphisms (SNPs) for VD were extracted from 417,580 Europeans in the UK Biobank, and the summary-level data of male factor infertility (825 cases and 85,722 controls) were extracted from the FinnGen.
Results:
Totally 99 SNPs robustly associated with the 25OHD were included, and a 1-unit increase in genetically predicted natural-log transformed 25OHD levels was associated with decreased risk of male factor infertility (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.44–0.89; p=0.010), which was consistent in all three sensitivity analyses (MR-Egger, weighted median, and weighted mode methods). The conclusion still stands after removing SNPs which explained more variation in the male factor infertility than the 25OHD (OR, 0.61; 95% CI, 0.42–0.88; p=0.009; n=62), and which were associated with confounders (body mass index, type 2 diabetes, smoking, and coronary artery diseases) of male factor infertility (OR, 0.58; 95% CI, 0.39–0.85; p=0.005; n=55).
Conclusions
VD supplement to increase serum 25OHD levels may be clinically beneficial for male factor infertility in the general population. The well-designed RCTs should be performed in priority to address this question.
3.Comparing the safety and efficacy of robotic-assisted, laparoscopic and open dismembered pyeloplasty: a Meta-analysis
Zhongyu JIAN ; Jixiang CHEN ; Hong LI ; Kunjie WANG
Chinese Journal of Urology 2019;40(6):456-461
Objective This systematic review and Meta-analysis was conducted to clarify the safety and efficacy of robotic-assisted (RP),laparoscopic (LP) and open (OP) dismembered pyeloplasty.Methods A systematic literature search on MEDLINE,Cochrane Central Register of Coutrolled Trials,and Web of Science was conducted to identify the relevant studies published before December 2018.Information was extracted from each eligible article.All statistical analyses of this Meta-analysis were performed with Stata 14 and RevMan 5.3 software.Results A total of 24 studies met the inclusion criteria and were included in this Meta-analysis.Compared with OP,LP showed similar results on success rate (OR =0.89,95 % CI 0.47-1.69,P =0.729) and complication rate (OR =0.89,95% CI0.58-1.36,P =0.585).LP had a longer operative time(WMD =53.86,95% CI 13.23-94.29,P =0.009) and shorter length of stay (WMD =-2.32,95% CI-3.48--1.16,P < 0.001).Our study found that RP was superior to LP with respect to success rate (OR =2.53,95 % CI 1.03-6.19,P =0.043),complication rate (OR =0.54,95 % CI 0.31-0.96,P =0.034),operative time (WMD =-25.94,95% CI-47.56--4.23,P =0.019) and length of stay (WMD =-25.94,95% CI-47.56--4.23,P =0.019).Conclusions RP has some advantages,it may be applied for UPJO routinely in the future if the costs can be decreased.
4.Imaging and clinical features of NUT gene-related carcinoma in the nasal cavity and sinus
Zhongyu YAN ; Zongrui ZHANG ; Zheng LI ; Jian GUO ; Xiao WANG ; Shijun WANG ; Jiuyang WANG ; Junfang XIAN
Chinese Journal of Radiology 2022;56(8):849-854
Objective:To assess the clinical and imaging features of NUT gene-related sinonasal carcinomas (NUT midline carcinome).Methods:The clinical data and pretreatment imaging findings of 5 cases with pathologically proven NUT sinonasal carcinomas were analyzed retrospectively in Beijing Tongren Hospital, Capital Medical University from January 2016 to December 2020. Of 5 cases, the tumors affected 4 females and 1 male with an age range of 15 to 48 years (median 19 years). Clinical data of all cases were available before surgery with both CT and MR examination. Tumor location, CT density, boney change, calcification, tumor size, T 1WI, T 2WI and diffusion weighted imaging (DWI) signal intensity, appearance diffusion coefficient (ADC), type of time intensity curve (TIC) of dynamic contrast-enhanced (DCE)-MRI were evaluated. Results:All five cases belonged to T4 stage of the clinic TNM system. The locations were nasal cavity ethmoid, sphenoid and maxillary sinus ( n=1), nasal and maxillary sinus ( n=1), nasal cavity and ethmoid sinus ( n=3). Iso-attenuated in 3 cases, heterogeneous with local necrosis in 2 cases, and heterogeneous with calcification in 3 cases on CT imaging. Bone erosion was found in 4 cases, and bone erosion with destruction in 1 case. The tumor sizes ranged from 4.2 to 4.9 cm (median 4.5 cm) on MR axial imaging. On T 1WI, 5 cases showed isointense compared with adjacent temporal muscles, with focal hypointense in 2 cases. On T 2WI, the tumor was graded as isointense in 3 cases, and hyperintense in 2 cases. Heterogeneous enhancement in all cases with mild in 3 cases, and moderate in 2 cases on postcontrast MR imaging. On DCE-MRI of 5 cases, there were 3 cases of type Ⅲ (washout-shaped curves), and 2 cases of type Ⅱ of the TIC (plateau-shaped curves). The range of ADC values was from 0.63×10 -3 to 1.17×10 -3 mm 2/s, and median ADC value was 0.84×10 -3 mm 2/s, of 5 cases with varying degrees of high signal on DWI. The Ki-67 index ranged from 30% to 80% of the tumor. An immunohistochemical study showed that the tumor cells of 5 cases were all positive for both NUT and INI-1 genes. One case was performed with biopsy and followed by chemotherapy, four cases were performed with surgery, combined with the following chemotherapy, and one also was implemented with radiation therapy. The follow-up time was 7-16 months. Five cases were all alive during the follow-up. Conclusions:The NUT midline sinonasal tract carcinoma is a rare, gene-related solid malignant tumor. The tumor is more commonly seen in young patients, mostly centered in the nasal and ethmoid region with invasive growth, more calcification on CT, and heterogeneous enhancement on MRI. These findings are some characteristics of the tumor.
5.Clinical and imaging features of the SMARCB1-de?cient sinonasal carcinoma
Zhongyu YAN ; Zongrui ZHANG ; Zheng LI ; Jian GUO ; Jiuyang WANG ; Junfang XIAN
Chinese Journal of Radiology 2023;57(5):498-503
Objective:To assess the clinical and imaging features of SMARCB1-deficient sinonasal carcinoma.Methods:Form January 2016 to November 2021, the clinical data and pretreatment imaging findings of 16 cases with pathologically proven SMARCB1-de?cient sinonasal carcinomas were analyzed retrospectively in Beijing Tongren Hospital, Capital Medical University. Immunohistochemistry for SMARCB1 showed loss of the protein in the tumor nuclie. Clinical and imaging features, including tumor location, TNM stage, size, density of CT, bone change, MRI signal intensity, enhancement pattern, type of time-intensity curve (TIC) of dynamic contrast enhanced MRI (DCE-MRI), apparent diffusion coefficient (ADC) value and diffusion weighted imaging (DWI) were evaluated. For 14 cases, correlation of the ADC value and Ki-67 index was subsequently evaluated with Pearson correlation analysis.Results:For the 16 cases SMARCB1-deficient sinonasal carcinomas, clinical stage of T4 was 12 cases and T3 was 4 cases. The location included ethmoid sinus ( n=4), nasal cavity only ( n=1), both nasal cavity and ethmoid ( n=8), ethmoid and maxillary sinus ( n=1), ethmoid and frontal sinus ( n=1), ethmoid and sphenoid sinus ( n=1). The tumor size was (4.5±1.2) cm. Iso-attenuated of CT images was showed in 13 cases and heterogeneous with necrosis was showed in 3 cases. Focal bone erosion was found in 13 cases and extensive bone destruction was found in 3 cases. Compared with adjacent muscles, T 1WI of all 16 cases showed isointense, with focal hypointense in 3 cases. On T 2WI, the tumor was graded as isointense in 9 cases, hyperintense in 7 cases, with lower inner septal in 6 cases. Enhancement was graded as mild in 11 cases, moderate in 5 cases.MRI Enhancement images showed mild enhancement in 11 cases, moderate enhancement in 5 cases, heterogeneous enhancement in 6 cases, and homogeneous enhancement in 10 cases. For DCE-MRI of 14 cases, there were 10 cases of Ⅲ type and 4 cases of Ⅱ type of the TIC. The ADC value of 14 cases was (1.02±0.27)×10 -3 mm 2/s. The Ki-67 index was 48%±21%. No correlation was observed between Ki-67 index and ADC value ( r=-0.38, P=0.183). Conclusions:SMARCB1-deficient carcinomas are mostly centered in the nasal and ethmoid region of anatomic distribution. Tendency to be infiltrative the adjacent bone structure with invasive bone reaction, mild to moderate heterogeneous enhancement, T 2WI with lower inner septal, and Ⅲ types of TIC are certain suggestive imaging features of the entity.
6.Fe3O4 nanoparticles enhance the sonodynamic therapy effect of chlorin e6 on glioma U251 cells
ZHANG Peng ; CHEN Zihan ; REN Zhongyu ; CHEN Jianjiao ; CHEN Hanren ; WEN Jian
Chinese Journal of Cancer Biotherapy 2021;28(7):702-708
[摘 要] 目的:探讨四氧化三铁(Fe3O4)纳米粒子(PION)作为药物载体增强二氢卟吩e6(chlorin e6,Ce6)在胶质瘤中的增效作用。方法:采用高温降解法和相转移法制备PEG-Fe3O4@Ce6复合纳米粒子(PION@E6),用水合粒径分析、透射电镜、胶体稳定性分析、紫外可见光吸收光谱等方法对PION@E6进行鉴定。CCK-8法检测胶质瘤U251细胞的增殖活性,流式细胞术检测细胞的凋亡水平,DCFH-DA探针法检测细胞中活性氧(reactive oxygen species,ROS)的水平。构建BALB/c-nu裸鼠胶质瘤U251细胞移植瘤模型,动物活体荧光成像术及磁共振成像(MRI)观察PION@E6及Ce6在移植瘤中的潴留时间,比较PION@E6声动力治疗组及Ce6声动力治疗组的第28天生存情况及肿瘤体积。结果:PION@E6的核心粒径为10 nm、水合粒径为(37.86±12.90)nm,具有良好的水溶性和稳定性;吸收光谱及XRD图谱显示Ce6已经负载到Fe3O4纳米粒子上。与Ce6声动力组比较,PION@E6声动力组U251细胞的增殖活性显著下降(P<0.05),细胞凋亡率显著升高(均P<0.05),细胞中ROS水平显著升高(P<0.05)。荷瘤裸鼠胶质瘤U251细胞移植瘤治疗实验结果显示,与Ce6声动力治疗组比较,PION@E6声动力治疗组裸鼠移植瘤组织中潴留时间显著延长(P<0.05),存活的裸鼠数显著增多,移植瘤体积显著缩小(P<0.01)。结论:Fe3O4纳米粒子对Ce6介导的胶质瘤U251细胞声动力治疗具有明显的增效作用。
7.Ultrasmall iron oxide nanoparticles inhibit the migration and invasion of human hepatocellular carcinoma HepG2 cells by enhancing autophagy
CHEN Hanren ; JIANG Shulian ; ZHANG Peng ; REN Zhongyu ; CHEN Jianjiao ; WEN Jian
Chinese Journal of Cancer Biotherapy 2021;28(8):783-789
[摘 要] 目的:探讨超微氧化铁纳米粒子(ultrasmall iron oxide nanoparticle,USIONP)对人肝细胞癌HepG2细胞迁移和侵袭的影响及其可能的机制。方法:采用粒径分析仪和透射电镜分别分析USIONP的水合粒径和核心粒径,Zeta电位和胶体稳定性实验分析USIONP的分散性及其稳定性以鉴定USIONP的成功制备;用不同质量浓度USIONP(0、50、100、200 μg/ml)或200 μg/ml USIONP+5 mmol/L 3-MA(自噬抑制剂)联合处理HepG2细胞,CCK-8法检测HepG2细胞的增殖活力,Transwell法检测细胞的迁移和侵袭能力,WB实验检测自噬标志物Beclin1、LC3、p62的表达,2’,7’-二氯二氢荧光素二醋酸(DCFH-DA)法测定细胞内活性氧(ROS)水平,铁离子比色法检测细胞内铁离子水平。结果:USIONP的平均水合粒径为(37.86±12.90) nm、核心粒径约10 nm,Zeta电位为–23.8 mV,有良好的水溶分散性,证实了USIONP的成功制备。随USIONP质量浓度升高和处理时间延长,HepG2细胞的增殖活力明显降低(均P<0.05);与对照组相比,200 μg/ml USIONP处理HepG2细胞24 h后,迁移、侵袭细胞数量均显著减少(均P<0.05),而3-MA能够部分抵消上述影响(均P<0.05)。与对照组相比,100、200 μg/ml USIONP处理组的HepG2细胞中Beclin1和LC3Ⅱ蛋白相对表达水平均显著升高(均P<0.05),而p62蛋白表达水平下降(均P<0.05);200 μg/ml USIONP可显著提高细胞内ROS水平与铁离子水平,而加入3-MA可阻断其作用(均P<0.05)。结论:USIONP能促进HepG2细胞发生自噬,而自噬通路激活后降解USIONP释放铁离子和导致细胞ROS水平升高,从而抑制HepG2细胞的迁移和侵袭。