1. Therapeutic effect of triple regulated adenovirus vector expressing mda7/IL24 on liver cancer in vitro
Tumor 2008;28(5):382-385
Objective: To construct an E1 A-deleted 24-bp triple regulated replicative adenovirus vector SG600/interleukin24 (IL24), which was driven by both hTERT promoter and HRE promoter. The level of IL24 in liver cancer cells was determined and the replication capacity of SG600/ IL24 and its killing effects on liver cancer cells were observed. Methods: SG600-IL24 vector was constructed using DNA cloning and recombination techniques. The IL24 gene expression in liver cancer cell lines SMMC-7721 and BEL-7404 and normal cell line BJ was detected by ELISA assay. The replications of SG600/IL-24 in different cell lines were determined by evaluating TCID50 (50% tissue culture infectious dose) at 49 and 96 h. In vitro cell-killing effects of SG600/IL24 on the three liver cancer cell lines were analyzed by MTT assay and CPE (cytopathic effect) staining method at different MOI values. Results: IL24 was over-expressed in both SMMC-7721 and BEL-7404 cells but was weakly expressed in BJ cells. At 48 and 96 h post infection the replication of SG600/IL-24 were 794 and 7940 folds in SMMC-7721 cells; 622 and 7 810 folds in BEL-7404 cells; 20 and 200 folds in BJ cells. MTT assay showed that the MOI values of SG600/IL24 for killing 50% and 90% cells were 0.3 and 5 for SMMC-7721 cells; 3 and 20 for BEL-7404 cells; 50 and 150 for BJ cells. CPE staining demonstrated that SG600/IL24 had significant killing effects on both liver cancer cells SMMC-7721 and BEL-7404 but had no significant influence on BJ cells. The cell-killing capability of SG600/IL24 was superior than that of replicative adenovirus ZD55/IL24 and non replicative adenovirus Ad-IL24. Conclusion: After SMMC-7721 and BEL-7404 liver cancer cells are infected with SG600/1124 at high efficiency, the virus replication is active and the expression of IL24 increases greatly. SG600/IL24 has specific cell-killing effects on the two liver cancer cell lines but has no significant influence on normal cells. This study provides a basis for further investigating the effect of SG600/IL24 on liver cancer in vivo.
2.The relationship between nutrition status and renal function in renal disease patients
Yuqin DING ; Sannan KONG ; Jinfeng ZHENG ; Xinyuan DONG
Parenteral & Enteral Nutrition 1997;0(03):-
Objectives:To study the relationship between nutrition status and renal function in renal disease patients. Methods: Body weight, height and the outcomes of blood biochemistry and routine were analyzed in 110 renal patients. Results: Body weight distribution in renal failure group had marked difference compared with nomal renal function group, and the number of patients whose actual body weight being lower than ideal body weight was obviously increased. The levels of RBC, Hb and TLC were significantly decreased(P
3.Correlation of sarcopenia and metabolic risk factors
Yu WANG ; Mingxia JIANG ; Qi XU ; Mengmeng WU ; Yinan ZHOU ; Xinyuan DONG ; Jinfeng ZHENG
Journal of Medical Postgraduates 2017;30(2):181-185
Objective Sarcopenia and metabolic syndrome share similar pathophysiological mechanisms. The aim of this study was to investigate the prevalence of sarcopenia among health examination population, and to analyze the relationship between sar-copenia and blood pressure, blood glucose, uric acid and lipids. Methods Physical examination data of 1191 healthy persons in the medical examination center of the hospital from Mar 2011 to Jun 2011 were collected. The weight, skeletal muscle, body fat, body mass index ( BMI) , waist circumference,body fat percentage, waist-hip ratio and visceral fat area were analyzed by human body compositionanalyzer and the prevalence of sarcopenia was observed. At the same time, triglyceride (TG), total cholesterol (TC), high density lipo-protein-cholesterol ( HDL-C ) , low density lipoprotein-cholesterol ( LDL-C) , uric acid and fasting blood glucose were also detected. Results The prevalence rate of sarcopenia of the subjects was 5.21%, and the highest incidence was found in ≥60 years group( 11.11%) . The prevalence rates of overweight and obesity were 33.8% and 10.2%, respectively. The prevalence of sarcopenia is grad-ually higher along with increasing BMI. The prevalence rates of sarcopenia of overweight and obesity subjects were 5.47% and 26.23%, respectively. Compared with the normal control group, the level of weight[(66.34±11.75)kg vs (76.71±12.84)kg ], BMI[(23.37± 3.13) vs (28.05±3.66)], body fat percentage[(25.33±6.06)% vs (36.76±4.47)%], waist circumference[(83.19±9.56)cm vs (95.45±13.74)cm] and visceral fat area[(88.96±29.74)cm2 vs (136.91±25.56)cm2] were higher in the sarcopenia group (P<0.05). Compared with the normal control group, the incidence of systolic blood pressure[(125.59±30.04)mmHg vs (139.39±19.79) mmHg], diastolic blood pressure[(75.82±11.95)mmHg vs (82.34±10.96)mmHg ] TG[(1.56±1.12)mmol/L vs (1.98±1.72)mmol/L] and uric acid[(313.75±83.07)mmol/L vs (335.55±96.07)mmol/L] were higher in the sarcopenia group (P<0.05). Compared with the normal subjects, the detectable rates of abnormal diastolic blood pressure, fasting blood glucose, uric acid, and LDL-C were increased in the sarcopenia, obesity and sarcopenia combined with obesity subjects (P<0.05). The odds ratio of abnormal systolic blood pressure, diastolic blood pressure, uric acid, and LDL-C increased in the sarcopenia, obesity and sarcopenia combined with obe-sity subjects using logistic regression analyses after correction of gender and age. Conclusion The sarcopenia may have some con-nection with metabolic risk factors. Early detection of sarcopenia can help to distinguish people predisposed to metabolic syndrome, and it has important significance for prevention of chronic disease.
4.Hereditary spastic paraplegia with SPG30 mutation: A report from North East China
Chunkui Zhou ; Lijun Zhu ; Xinyuan Li ; Heqian Du ; Shanshan Dong ; Qun Liu ; Shaokuan Fang
Neurology Asia 2017;22(2):161-163
Hereditary spastic paraplegia is a heterogeneous group of genetic neurodegenerative disorders of the
nervous system. It is classified into four subtypes based on the mode of inheritance; and among them,
most autosomal recessive hereditary spastic paraplegia cases are due to type SPG11 and SPG15 gene
mutations. Autosomal recessive hereditary spastic paraplegia cases with SPG30 gene mutation have
never been reported in China. Herein, we present our experience with a case of hereditary spastic
paraplegia with SPG30 gene mutation in our hospital from North East China. In this patient we detected
a missense mutation of c.499 C>T (p.Arg167Cys) in gene KIF1A, a causative gene of type SPG30.
5.Pathogen distribution and risk factors of pulmonary infection after acute cervical spinal cord injury
Axiang HE ; Dong XIE ; Chenhui XU ; Xinyuan LIAO ; Lili YANG ; Xiongsheng CHEN ; Lianshun JIA
Chinese Journal of Trauma 2016;32(5):449-452
Objective To investigate the pathogen distribution and risk factors of pulmonary infection after acute cervical spinal cord injury (ACSCI) in an attempt to offer reference for early antiinfection therapy.Methods The study comprised 223 cases who were admitted from October 2011 to October 2014.There were 149 males and 74 females,at (43.3 ± 13.5) years of age.Species of pathogens identified were gram-positive,gram-negative and mixed.Effects of age,gender,injury types and tracheotomy on pathogen distribution were analyzed.Results Gram-negative infection was found in 114 cases (51.1%),with tracheotomy accounting for 7.0% of the cases and death accounting for 1.8% of the cases,and the main causative pathogens were Klebsiella pneumonia,Escherichia coli,Pseudomonas aeruginosa and Acinetobacter baumannii.Gram-positive infection was found in 41 cases (18.4%),with tracheotomy accounting for 12.2% of the cases and death accounting for 7.3% of the cases,and the main causative pathogens were Staphylococcus aureus and Streptococcus pneumonia.Mixed infection was found in 68 cases (30.5%),with tracheotomy accounting for 22.1% of the cases and death accounting for 13.2% of the cases.Gender had no significant correlation with pathogen distribution.For the cases of complete spinal cord injury and tracheotomy,the ratio of mixed infection increased significantly (P < 0.05).For the cases younger than 30 years,the pathogens were mainly gram-positive bacteria (P < 0.05).Conclusions Main pathogens of pulmonary infection after ACSCI are gram-negative bacteria.The cases younger than 30 years are associated with higher risk of grampositive infection,while the cases with complete injury or tracheotomy are associated with higher risk of mixed infection.
6.Primary clinical study of hippocampal-sparing prophylactic cranial irradiation in limited-stage small-cell lung cancer
Xin DONG ; Zongmei ZHOU ; Junjie MIAO ; Xinyuan CHEN ; Zhihui HU ; Peng HUANG ; Yin ZHANG
Chinese Journal of Radiation Oncology 2015;24(2):131-136
Objective To preliminarily observe the clinical efficacy of hippocampal-sparing prophylactic cranial irradiation (HS-PCI) using helical tomotherapy (HT) in patients with limited-stage small-cell lung cancer (LS-SCLC) after chemoradiotherapy,and compare HT with intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) in dose distribution.Methods From April to June,2014,six patients with LS-SCLC who had achieved a complete remission after chemoradiotherapy were assigned to HS-PCI using HT within a month after brain metastasis was ruled out using brain magnetic resonance imaging (MRI).After fusing CT images and MRI images,the hippocampus was contoured in the fusion images and hippocampal avoidance regions were created using a volumetric expansion of 3 mm around the hippocampus.A dose of 25 Gy in 10 fractions to 95% of planning target volume (PTV) was prescribed in HT,IMRT,and VMAT.The clinical efficacy,adverse reactions,neurocognitive function,and brain metastasis were evaluated for HT.The dose distribution in PTV and hippocampus were compared between HT,IMRT,and VMAT.Results There were one patient with abdominal wall and abdominal lymph node metastases,one patient with local recurrence,and no patient with brain metastasis during the observation period.The numbers of patients with grade 1 and grade 2 headache,dizziness,and hair loss reactions were 3 and 1,3 and 1,and 4 and 2,respectively.There were no significant differences in the average score of the Mini-Mental State Examination before treatment and at 3 and 6 months after treatment (29.7,29.2,and 29.3 ; P =0.083,0.317,and 0.157).The mean dose to the hippocampus was 16.85 Gy for IMRT and 17.59 Gy for VMAT.For HT,the mean doses to the hippocampus and avoidance regions were reduced to 5.26 Gy and 6.21 Gy,respectively.The prescribed dose for HT was reduced by 79% and 71% compared with IMRT and VMAT,respectively.The average coverage rate of the prescribed dose was 94.48% for HT.Conclusions HT achieves promising dose distribution and target coverage in sparing of the hippocampus.Moreover,HT dose not increase the incidence of adverse reactions.The change in neurocognitive function needs to be further studied with longterm observation and large-scale sampling.
7.Effect of maternal high fat diet on intestinal barrier function in early life of offspring mice
Runxiang XIE ; Hailong CAO ; Xinyuan HUANG ; Tianyu LIU ; Sinan WANG ; Wenxiao DONG ; Bangmao WANG
Chinese Journal of Clinical Nutrition 2018;26(6):361-365
Objective To observe the effects of maternal high fat diet (MHFD) during pregnancy and lactation on intestinal barrier function in offspring mice.Methods C57BL/6 pregnant mice were divided into high fat diet (MHFD) group and normal diet group (MND) randomly and were given high fat diet and normal diet during pregnancy (3 weeks) and lactation (3 weeks) respectively.Both groups of offspring mice were naturally given and bodyweight of pups was monitored at birth and weekly.After weaning,the intestinal permeability of offspring mice was detected by fluorescein isothiocyanate conjugated-dextran method (FITC-D).Immunofluorescence was used to detect the expression of ZO-1 in intestinal tissues.HE staining was used to assess the villus length and crypt depth.The intestinal cell proliferation (expression of Ki-67) and Mucin 2 (MUC2) were assessed by immunohistochemistry.PAS staining was used to evaluate the goblet cells.The expression of inflammatory cytokines including IL-1β,IL-6,and TNF-α in intestinal tissue were measured by real-time PCR.Results At the age of 2 and 3 weeks,the offspring in MHFD group were significantly heavier than those in MND group.HE staining showed no obvious microscopic inflammation in both groups of 3 weeks old offspring mice,however,the relative expression levels of IL-1β (1.95±0.53 vs.1.13±0.15;t =3.65,P=0.005),IL-6 (1.40±0.71 vs.0.73±0.17;t=2.72,P=0.04),and TNF-α (1.63±0.53 vs.1.04±0.12;t=2.64,P=0.02) mRNA were significantly higher in the MHFD group.Compared with the 3 weeks old offspring mice in MND group,MHFD significantly increased the permeability of intestine and decreased the expression of ZO-1 in membrane.The number of Ki-67 positive cells (18.00±4.74 vs.24.60±4.17;t =3.31,P=0.004) in each villus,goblet cells (14.70±2.91 vs.28.10±4.95;t =7.38,P<0.001) and MUC2 positive cells (20.60± 3.13 vs.30.00±3.33;t=6.50,P<0.001) in each crypt were significantly lower than those in MND group.Conclusion Maternal high fat diet in early life of offspring mice can induce intestinal low grade inflammation and lead to the disruption of intestinal mucosal barrier in offspring mice,which may be involved in the progeny diseases.
8.Study on the relationship between CHFR and MACC1 expressions and sensitivity of patients with rectal cancer for neoadjuvant concurrent chemoradiotherapy
Xinyuan ZHANG ; Yongfeng FU ; Lili BAI ; Sen YANG ; Lixin DONG
China Medical Equipment 2024;21(2):98-103
Objective:To investigate the relationship between the expressions of checkpoint with forkhead-associated and ring finger(CHFR)and metastasis-associated protein 1(MACC1)and the sensitivity of patients with rectal cancer for neoadjuvant concurrent chemoradiotherapy(nCRT).Methods:The medical documents of 166 patients with rectal cancer admitted to First Hospital of Qinhuangdao from March 2017 to February 2022 were collected.All patients only received nCRT before surgery,and the radiotherapy adopted three-dimensional conformal intensity modulated radiotherapy,and chemotherapy adopted Capeox scheme.All patients successfully completed total mesorectal excision after 4-6 weeks of nCRT treatment.Immunohistochemical SP staining method was used to detect the protein expressions of CHFR and MACC1 in rectal cancer and its adjacent tissues.According to the tumor regressive grading(TRG)standard of the Joint Committee on Cancer Staging in the United States,75 patients who were grade 0-2 as TRG after nCRT were included in the nCRT insensitive group,and 91 patients who were grade 3-4 as TRG were included in the nCRT sensitive group.The expression levels of CHFR and MACC1 proteins in cancer tissues before and after treatment between the two groups were compared.And then,the relationship between clinically pathological characteristics of patients and nCRT sensitivity was analyzed,and the influencing factors of nCRT sensitivity were analyzed.The receiver operating characteristic(ROC)curves of them were drawn,and area under curve(AUC)values were calculated,and the predictive values of CHFR and MACC1 for the sensitivity of patients with rectal cancer to nCRT were further analyzed.Results:The CHFR positive expression rate in rectal cancer tissue was significantly lower than that in adjacent tissues of rectal cancer,and the MACC1 positive expression rate in rectal cancer tissue was significantly higher than that in adjacent tissues of rectal cancer(x2=81.373,87.150,P<0.05),respectively.After 166 patients completed the nCRT treatment,there were 6 cases of TRG grade 0,8 cases of TRG grade 1,61 cases of TRG grade 2,59 cases of TRG grade 3 and 32 cases of TRG grade 4.The sensitivity rate of nCRT was 54.82%(91/166).The CHFR positive expression rate in the nCRT sensitive group was significantly higher than that in the nCRT insensitive group,and the MACC1 positive expression rate in the nCRT sensitive group was significantly lower than that in the nCRT insensitive group(x2=4.613,37.509,P<0.05).The proportions of T4 stage and N+stage in the nCRT sensitive group were higher than those in the nCRT insensitive group,and the differences were statistically significant(x2=54.432,28.912,P<0.05),respectively.The expressions of CHFR and MACC1 were respectively independent risk factor affected the sensitivity of patients with rectal cancer to nCRT[OR=2.456(95% CI:1.294-4.563),OR=3.281(95% CI:1.472-6.479),P<0.05].The sensitivity and specificity of the combined detection of CHFR and MACC1 were respectively 65.89% and 69.46% in predicting the nCRT sensitivity for rectal cancer.The predictive value of the combined detection was higher than that of single CHFR detection and single MACC1 detection(AUC values of them were respectively 0.713,0.564,0.589,P<0.05),respectively.Conclusion:CHFR and MACC1 are related to the sensitivity of patients with rectal cancer to nCRT,which means patients with high expression of CHFR and low expression of MACC1 are more sensitive to nCRT.Therefore,both of them may be indicators that predict the sensitivity of patients with rectal cancer to nCRT.
9.Effects of butylphthalide on hydrogen peroxide induced retinal pigment epithelial cells injury
Xiaoli XING ; Liangyu HUANG ; Zhe ZHANG ; Xinyuan HUANG ; Qiong WANG ; Xiaorong LI ; Lijie DONG
Chinese Journal of Ocular Fundus Diseases 2019;35(5):480-487
Objective To investigate the protective effect of butylphenyphthalein (NBP) on RPE apoptosis induced by H2O2.Methods The human RPE cell line (human ARPE-19 cell line) were used as the experimental cells and were divided as control group, model group, NBP group. Complete medium was used in control group. The model group was stimulated with 200 μmol/L H2O2 for 2 h, and the cells were cultured in complete medium. The NBP group was cultured with 200 μmol/L H2O2 and 1 μmol/L NBP for 2 h. After changing the medium, complete medium was combined with 1 μmol/L NBP to continue the culture of the cells. Cell viability were detected by MTT assay while the morphology of RPE were observed by HE staining. Moreover, Hoechst 33258 was used to detect RPE cell apoptosis. Mitochondrial membrane potential (JC-1) staining were performed to monitor changes in cell membrane potential and the characteristic change of apoptosis in RPE cells. Furthermore, 2′,7′-Dichlorofluorescin diacetate (DCFH-DA) staining were used to analyze the effect of NBP treatment on the expression of ROS. The effect of NBP on the expression of Heme oxygenase-1(HO-1) was analyzed by cellular immunofluorescence and western blotting.Results The results of MTT assay showed that the cells were cultured for 24 and 48 hours, cell viability of control group (t=17.710, 13.760;P<0.0001,<0.0001) and treatment group (t=4.857, 9.225;P=0.0007,<0.0001) were stronger than that of model group, and the difference was statistically significant. HE staining and Hoechst33258 staining showed that compared with the control group, the number of cells in the model group was significantly less, and the cell morphology was incomplete. Compared with the model group, the number of cells in the treatment group was significantly increased, and the cell morphology was better. The results of JC-1 assay showed that the number of apoptotic cells in the model group was significantly higher than that in the control group, and the number of apoptotic cells in the treatment group was significantly lower than that in the model group. DCFH-DA staining showed that the ROS accumulation in the model group was more than that in the control group, and the ROS accumulation in the treatment group was less than that in the model group. Immunostaining observation showed that the HO-1 fluorescence intensity of the cells in the treatment group was significantly higher than that of the control group, and the difference was statistically significant (t=10.270,P=0.0005). Western blot analysis showed that NBP up-regulated the expression level of HO-1 in a time-dependent manner. The relative expression of HO-1 at 4, 8, and 12 h of NBP showed a clear increase trend compared with 0 h, and the difference was statistically significant (F=164.91,P<0.05).Conclusions Oxidative stress injury can down-regulate the viability of RPE cells and induce apoptosis. NBP can increase the antioxidant capacity of RPE cells, reduce cell damage and inhibit cell apoptosis by up-regulating HO-1 expression.
10.Interferon-related secretome from direct interaction between immune cells and tumor cells is required for upregulation of PD-L1 in tumor cells.
Yuan-Qin YANG ; Wen-Jie DONG ; Xiao-Fei YIN ; Yan-Ni XU ; Yu YANG ; Jiao-Jiao WANG ; Su-Jing YUAN ; Jing XIAO ; Jonathan Howard DELONG ; Liang CHU ; Hai-Neng XU ; Xiu-Mei ZHOU ; Ru-Wei WANG ; Ling FANG ; Xin-Yuan LIU ; Kang-Jian ZHANG
Protein & Cell 2016;7(7):538-543