1.Role and possible mechanism of pseudogene FMO6P in inhibiting invasion and metastasis of gastric cancer
Xiongyan WU ; Zhen LI ; Zhenjia YU ; Liping SU
Journal of Surgery Concepts & Practice 2024;29(2):161-169
Objective To determine the expression and clinical significance of pseudogene FMO6P in gastric cancer,and explore its functions and underlying molecular mechanism in regulating the invasion and metastasis of gastric cancer cells.Methods The expression level of FMO6P in gastric cancer tissues and cell lines was detected by quantitative real time polymerase chain reaction(qRT-PCR).The migration and invasion abilities of gastric cancer cells were detected by transwell assay.The effect of FMO6P on the tumor formation and peritoneal dissemination of gastric cancer cells were evaluated by injecting FMO6P-overexpressing gastric cancer cells into the subcutaneous or peritoneal cavity of nude mice respectively.The expression levels of epithelial-mesenchymal transition(EMT)markers,including E-cadherin,N-cadherin,ZEB1,MMP2,and the activation of AKT/mTOR pathway in FMO6P-overexpressing or knockdown gastric cancer cells were measured by Western blot.Results The expression of FMO6P was significantly reduced in tumor tissues compared to its adjacent non-tumor tissues of gastric cancer,FMO6P expression level in tumor tissues was correlated with tumor size and TNM stage.Overexpression of FMO6P significantly inhibited the invasion and migration abilities of gastric cancer cells,while downregulation of FMO6P expression promoted the invasion and migration ability of gastric cancer cells.Overexpression of FMO6P in gastric cancer cells significantly inhibited the subcutaneous tumor formation and peritoneal dissemination of gastric cancer cells in nude mice.Moreover,overexpression of FMO6P promoted the expression of E-cadherin,and inhibited the expression of N-cadherin,ZEB1,and MMP2 in gastric cancer cells.The phosphorylation levels of AKT and mTOR were also downregulated in gastric cancer cells overexpressing FMO6P.Conclusions All these findings suggested that pseudogene FMO6P suppresses the invasion and migration potential of gastric cancer cells in vitro and in vivo,which is possibly through the inhibition of the AKT/mTOR signaling pathway.
2.Progress of circulating tumor DNA methylation for gastric cancer screening and management
Qinxing CAO ; Li YAN ; Nengyi HOU ; Jinfeng CHEN ; Song YU ; Hejiang LU ; Zhenjia DAN ; Minghui PANG
Chinese Journal of Gastrointestinal Surgery 2024;27(5):535-544
Circulating tumor DNA (ctDNA) is cell-free DNA released by tumors or circulating tumor cells, containing abundant tumor-specific information that can serve as biomarkers for cancer early screening, monitoring, prognosis, and prediction of treatment response. This is particularly attractive in the field of gastric cancer, where high-quality screening, monitoring, and prediction methods are currently lacking. Gastric cancer exhibits significant tumor heterogeneity, with large differences in genetic and epigenetic characteristics among different subgroups. Methylated ctDNA has high sensitivity and specificity, which can help clarify tumor genotyping and facilitate the formulation of precise diagnostic and therapeutic strategies. Furthermore, numerous studies have confirmed the unique advantages of methylated DNA in predicting treatment response, adjuvant therapy, and drug resistance assessment, which may be used in the future to enhance the efficacy of chemotherapy regimens and improve patient chemotherapeutic response, and even treat multidrug resistance. However, there are several challenges associated with methylated ctDNA, such as low sensitivity and specificity at single-target sites, limited association between some gastric cancer subtypes and ctDNA, off-target risks, and the lack of large-scale and high-quality clinical research evidence. This review mainly summarizes current research on the methylation status of ctDNA in gastric cancer and connects these findings to early screening, recurrence monitoring, and potential treatment opportunities for gastric cancer. With advances in technology and the deepening of interdisciplinary research, ctDNA detection will reveal more disease information and become an essential foundation for gastric cancer research and precision medicine treatment.
3.Progress of circulating tumor DNA methylation for gastric cancer screening and management
Qinxing CAO ; Li YAN ; Nengyi HOU ; Jinfeng CHEN ; Song YU ; Hejiang LU ; Zhenjia DAN ; Minghui PANG
Chinese Journal of Gastrointestinal Surgery 2024;27(5):535-544
Circulating tumor DNA (ctDNA) is cell-free DNA released by tumors or circulating tumor cells, containing abundant tumor-specific information that can serve as biomarkers for cancer early screening, monitoring, prognosis, and prediction of treatment response. This is particularly attractive in the field of gastric cancer, where high-quality screening, monitoring, and prediction methods are currently lacking. Gastric cancer exhibits significant tumor heterogeneity, with large differences in genetic and epigenetic characteristics among different subgroups. Methylated ctDNA has high sensitivity and specificity, which can help clarify tumor genotyping and facilitate the formulation of precise diagnostic and therapeutic strategies. Furthermore, numerous studies have confirmed the unique advantages of methylated DNA in predicting treatment response, adjuvant therapy, and drug resistance assessment, which may be used in the future to enhance the efficacy of chemotherapy regimens and improve patient chemotherapeutic response, and even treat multidrug resistance. However, there are several challenges associated with methylated ctDNA, such as low sensitivity and specificity at single-target sites, limited association between some gastric cancer subtypes and ctDNA, off-target risks, and the lack of large-scale and high-quality clinical research evidence. This review mainly summarizes current research on the methylation status of ctDNA in gastric cancer and connects these findings to early screening, recurrence monitoring, and potential treatment opportunities for gastric cancer. With advances in technology and the deepening of interdisciplinary research, ctDNA detection will reveal more disease information and become an essential foundation for gastric cancer research and precision medicine treatment.
4.Hemagglutinin occlusion of needle passage for preventing complications of pulmonary puncture biopsy
Duwang QIU ; Lei ZHAO ; Lei SU ; Zhenjia LI ; Fei GAO
Chinese Journal of Interventional Imaging and Therapy 2024;21(6):329-333
Objective To observe the value of hemagglutinin occlusion of needle passage for preventing complications of pulmonary puncture biopsy.Methods Data of 155 patients with single pulmonary nodule who underwent CT-guided percutaneous lung puncture biopsy were retrospectively analyzed.The patients were divided into observation group(n=78,injected hemagglutinin when withdrawing the needle)and control group(n=77,directly withdrawn the needle).Chest CT examination was performed immediately after completion of the procedure.Pulmonary hemorrhage grades were evaluated,and the proportions of compressed lung area were measured and compared between groups.Results Puncture and sampling were successfully performed in all 155 patients,and definite pathological diagnose was acquired in 150 cases(150/155,96.77%).High-grade hemorrhage was detected in 20 cases(20/78,25.64%)of observation group and 38 cases(38/77,49.35%)of control group,while pneumothorax was noticed in 18 cases(18/78,23.08%)with lung compression area proportion of(0[0,0])in observation group,and in 31 cases(31/77,40.26%)with lung compression area proportion of 0[0,0.76%]in control group,respectively,in observation group were better than in control group(all P<0.05).Conclusion Occlusion needle passage when withdrawing needle with hemagglutinin after pulmonary puncture biopsy could reduce the risk of hemorrhage and pneumothorax.
5.Predictive value of peripheral blood NLR and PLR in perioperative period on the prognosis of patients with intrahepatic cholangiocarcinoma
LI Zhenjia ; MA Ruirui ; WANG Congjun ; SHEN Yanbing
Chinese Journal of Cancer Biotherapy 2021;28(6):605-610
[摘 要] 目的:探讨肝内胆管癌(intrahepatic cholangiocarcinoma,ICCA)围手术期外周血中性粒细胞与淋巴细胞比率(neutrophil-to-lymphocyte ratio,NLR)和血小板与淋巴细胞比率(platelet-to-lymphocyte ratio,PLR)对患者预后的预测价值。方法:收集2015年1月至2018年1月在上海市松江区中心医院接受肝切除术治疗的ICCA患者97例作为ICCA组,选择同期在本院做健康体检的志愿者100例作为正常对照组。检测两组受试者术前1 d、术后3 d和7 d外周血的NLR、PLR,采用单因素、多因素分析ICCA患者术后随访期死亡的危险因素,采用Kaplan-Meier生存曲线分析术后3 d的NLR和PLR对ICCA患者术后生存时间的影响,采用受试者工作特征曲线(receiver operating characteristic curve,ROC)分析术后3 d的NLR和PLR水平对患者术后随访期死亡的预测价值。结果:ICCA组患者术前1 d、术后3和7 d外周血的NLR、PLR均高于正常对照组(均P<0.05),术前1 d和7 d外周血NLR、PLR差异无统计学意义(P>0.05),术后3 d外周血NLR、PLR水平最高(P<0.05)。多发肿瘤、合并淋巴结转移、TNM分期Ⅲ~Ⅳ、CA199水平增高、术后3 d的NLR和PLR较高分别是ICCA患者随访期死亡的独立危险因素(均P<0.05)。ROC曲线显示,术后3 d的NLR和PLR高低对ICCA患者术后生存时间具有预测价值。Kaplan-Meier生存曲线显示,低NLR[(50.32±3.69) vs (30.12±2.36)个月]和低PLR[(53.6±3.75) vs (37.6±2.96)个月]患者生存时间均长于高NLR和PLR的ICCA患者(均P<0.05)。结论:ICCA术后3 d的NLR和PLR异常增高是患者肝切除术后死亡的独立危险因素,其对患者生存时间具有早期预测价值。
6.Expression and clinical significance of Flotillin-2 in gastric cancer tissues
LI Zhenjia ; XU Suming ; CHEN Ruoxi ; LI Jiaxi ; YU Fanqi ; LI Yimin ; YU Mengqi ; ZOU Zhenhong ; LIANG Bo ; YU Liming
Chinese Journal of Cancer Biotherapy 2018;25(6):629-633
Objective: To investigate the expression of Flotillin-2 (Flot-2) protein in gastric cancer tissues and its relationship with clinicopathological features and prognosis of gastric cancer (GC) patients. Methods: 112 samples of gastric cancer tissue and the corresponding paracancerous tissue that resected at the gastrointestinal surgery department of the Second Affiliated Hospital of Nanchang University between January 2009 andApril 2010 were collected for this study. The expression of Flot-2 protein in tumor tissues was detected by immunohistochemistry. The survival data were analyzed by Kaplan-Meier and Log-Rank test, and the survival curve was plotted. Spearman correlation analysis was used to examine the relationship between Flot-2 protein expression and clinicopathological characteristics and prognosis of GC patients. Results: In gastric cancer tissues, Flot-2 was primary stained in cytoplasm. Level of Flot-2 was significantly higher in gastric cancer tissues compared with that in paracancerous tissues (53.57% vs 46.43%, P<0.05). Expression of Flot-2 in tumor tissues was significantly associated with tumor size, depth of invasion, lymph node metastasis, distant metastasis and AJCC stage (all P<0.01), but not with gender, age, differentiation degree and tumor location (P>0.05). Moreover, survival analysis showed that the overall survival of patients with low Flot-2 expression was significantly higher than that of the patients with high level (P<0.01). Cox regression analysis indicated that distant metastasis, AJCC stage and Flot-2 expression were the independent risk factors for the prognosis of GC patients. Conclusion: Flot-2 protein was highly expressed in gastric cancer tissues and closely correlated with the poor prognosis of GC patients; Flot-2 is an independent risk factor for GC prognosis and may be served as a potential therapeutic target for gastric cancer.
7.The effect of siRNA targeted against Bcl-xl on the expression of apoptosis relevant factors Bcl-xl,Bax, Caspase-3
Wei GAO ; Xin FENG ; Zhenjia YANG ; Yunxia LI ; Libing REN
Chinese Journal of Rheumatology 2013;(1):37-40,封3
Objective To investigate the effect of siRNA targeted against Bcl-xl on cell proliferation of rheumatoid arthritis (RA) and the effect on expres-ion of apoptosis relevant factors Bcl-xl,Bax,Caspase-3.Methods Human RA synovial cells were cultured and passed by tissue block collagenase digestion method.The siRNA plasmid targeting Bcl-xl gene was constructed by Bcl-xl cDNA sequence provided by gene banks,while single missense sequences were used as negative controls.LipofectamineTM 2000 was used to transfect synovial cells.The effect of Bcl-xl silencing on proliferation of synovial cells was evaluated by MTT at 24,48,72 hours after transfection.The expressions of Bcl-xl,Bax,Caspase-3 protein,synovial apoptosisrelated factors were determined by Western blotting after transfected at different time points.The average of multiple-sample average was analyzed by single-factor x2 test or LSD-t and Tamhane's T2 test was used for twotwo comparison.Results MTT result s showed that RNA interference that specifically silent Bcl-xl could obviously suppress the proliferation of sliding film cells,which was most eveident at 48 hours.This inhibition was gradually weakened with prolonged time,but when compared was the control group,differences was significant (P<0.05).Western blotting results displayed that when compared to the control group,Bcl-xl protein expression obviously declined after transfection P<0.01,which was the least at 48 h time point.Bax,Caspase3 protein expression were obviously increased when compared to the coutrol group.Conclusion The expression of Bcl-xl,a RA synovial cell anti-apoptotic factor,is significantly reduced by specific RNA interference silencing Bcl-xl,which may play an important role in inhibiting the excessive proliferation of synovial cells.
8.In vitro susceptibility of commonly used antibiotics on community-acquired uncomplicated urinary tract infection pathogens in Beijing
Chunxia YANG ; Shan CHEN ; Yong YANG ; Yingmei LIU ; Hui WANG ; Zhanwei WANG ; Qiwen YANG ; Binbin LI ; Fang LI ; Shanshan WANG ; Chunlei WANG ; Jiuxin QU ; Zhenjia LIU ; Ludong QIAO ; Bin CAO
Chinese Journal of Urology 2012;33(2):132-137
Objective To investigate the distribution and susceptibility patterns of common uropathogens causing community-acquired urinary tract infection (UTI) in Beijing.MethodsA total of 300non-duplicate isolates were randomly collected from 3 hospitals in Beijing between Jan,1 2010 and Mar,312011.Minimal inhibitory concentrations (MICs) were determined by the broth microdilution methods,which were performed and interpreted according to the guidelines established by the Clinical and Laboratory Standards Institute (CLSI).A panel of 8 antimicrobial agents were tested:amikacin,cefaclor,cefepime,cefoperazone/sulbactam,ciprofloxacin,levofloxacin,gentamicin and nitrofurantoin. Fosfomycin trometamol MICs were determined by the agar-dilution method in cation-adjusted MH agar supplemented with glucose 6-phosphate at a concentration of 25 mg/L as detailed in the guidelines issued by 2010 CLSI. All the Escherichia coli,Klebsiella pneumoniae and Proteus mirabilis strains were screened and confirmed by double-disk synergy test for extended-spectrum β-lactamase (ESBLs).Results Among the organisms cultured,E.coli wasthepredominantpathogen(65.0% ), followedby Enterococcus(11.7% ),Staphylococcus( 6.3% ), Klebsiella pneumoniae( 5. 3% ), Proteus mirabilis( 4. 7% ), and Pseudomonas aeruginosa (3.0%).Lower susceptibility rates to ciprofloxacin and levofloxacin (31.4% -47.4% ) were observed among all the stains.Amikacin,cefoperazone/sulbactam,nitrofurantoin and fosfomycin trometamol were the most active drugs (92.1%,92.1%,88.4% and 87.9% susceptible strains,respectively) among the Gram-negative strains.Isolates of Staphylococcus were highly sensitive to amikacin ( 100.0% ),cefoperazone/sulbactam (94.7%),nitrofurantoin ( 100.0% ).Higher susceptibility rates to nitrofurantoin (91.4%) and fosfomycin trometamol (90.0%) were observed in Enterococcus.ESBLs-producing strains accounted for 52.3% (102/195) in E.coli,43.8% (7/16) in K.pneumoniae and 14.3%(2/14) in P.mirabilis,respectively.ConclusionsResistance is most common to ciprofloxacin and levofloxacin of all the stains.Currently,the most appropriate agents for the empirical management of uncomplicated UTI seems to be amikacin,cefoperazone/sulbactam,nitrofurantoin and fosfomycin trometamol.
9.Anus-preserving rectectomy using telescopic anastomosis for middle and lower rectal cancer, report of 402 cases
Shiyong LI ; Zhenjia LIANG ; Shujun YUAN ; Gang CHEN ; Xue BAI ; Fuyi ZUO ; Bo YU ; Guang CHEN ; Xiaojun WEI ; Yishi XU ; Junfeng DU ; Wei CUI
Chinese Journal of General Surgery 2011;26(7):537-539
Objective To study the clinical efficacy of anus-preserving rectectomy by using telescopic anastomosis of colon and rectal mucosa for the middle and lower rectal cancer. Methods A retrospective analysis was carried out in 402 cases with middle and lower rectal cancer undergoing telescopic anastomosis for anus-preserving procedure, including 241 males and 161 females, age ranging from 21 to 99 years, averaging at 55. 7 years. The distal margins of the tumors were within 6 - 9 cm to anal verge. According to TNM staging, there were 123 cases in Stage Ⅰ , 244 cases in Stage Ⅱ , 31 cases in Stage Ⅲ,and 4 cases in Stage Ⅳ. Results 345(345/402, 85. 8% ) cases were followed up, the median time of the follow-up was 6. 1 years. Postoperative complications included 17(4.2%) cases of stomal leakage, 11(2.7% ) cases of stomal stenosis. All patients recovered normal defecating function 12-24 weeks post operation. Local recurrence rate was 6. 3% (22/345). Hepatic and lung metastasis was 13. 6% (47/345) and 2. 6% (9/345)respectively. The five year survival rate was 68. 7% (112/163). Conclusions Anuspreserving rectectomy by using telescopic anastomosis is safe and effective procedure to treat middle and lower rectal cancer, with the preservation of anal function and without the increasing rate of local recurrence.
10.Effect of the formulae for calming the liver and suppressing YANG on lymphocyte proteome in migraine rats with syndrome of hyperactivity of liver-YANG
Guangwei ZHONG ; Jianjun HU ; Zeqi CHEN ; Yanhong LUO ; Ying ZHANG ; Yaohui YIN ; Wei LI ; Zhenjia YI ; Guolin CHEN
Journal of Central South University(Medical Sciences) 2010;35(1):70-76
Objective To explore the molecular mechanism of the formulae for calming the liver and suppressing YANG in migraine rat model with syndrome of hyperactivity of the liver-YANG.Methods A rat model of migraine with hyperactivity of liver-YANG was established through electrical trigeminal ganglion stimulation and syndrome of oral administration of Fuzi decoction. The total proteins of the lymphocyte in the rats were separated by immobilized pH gradient-based 2-dimensional gel electrophoresis(2-DE), and the 2-DE image was analyzed by PDQuest 7.0 software. Matrix-assisted laser desorption/ionzation-time of flight mass spectrometry (MALDI-TOF-MS) and the SWISS-PORT and MSDB database were used to identify differential proteins.Results The formulae for calming the liver and suppressing YANG could also improve headache. Well-resolution and reproducible 2-DE patterns of rat lymphocyte from normal, model, and therapy tissues were obtained. Eleven of the total 13 differential protein spots were successfully identified by MALDI-TOF-MS. These proteins were alcohol dehydrogenase 3(ADH3), glycogen phosphorylase, ATP synthase D chain, annexin-3, ubiquitin, neutrophil defensin 4 precursor, melanoma-associated antigen E2, heat shock protein-27, annexin-A1, peroxirdoxin-Ⅱ, MU class glutathione S-transferase (Fragment)(GSH). Conclusion Differences occur in the expression of lymphocyte proteins in migraine rats with syndrome of hyperactivity of liver-YANG after treatment with the formulae for calming the liver and suppressing YANG, and the 11 identified protein spots may be associated with its mechanism.

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