1.Establishment and in vivo imaging observation of a nude mouse model of type 2 diabetes mellitus and pancreatic cancer
Yongning XU ; Xuehuan HUANG ; Zhipan TANG ; Ruohan LI ; Wen QIN
Journal of Clinical Hepatology 2024;40(6):1231-1239
Objective To establish a nude mouse model of type 2 diabetes mellitus(T2DM)and pancreatic cancer that allows dynamic observation of tumor formation process and facilitates in vivo research.Methods At first,human pancreatic cancer PANC-1 cells were transfected with lentiviral vector GV260 to construct the pancreatic cancer cell line PANC-1-Luc with stable expression of firefly luciferase.Then,36 specific pathogen-free nude mice were randomly divided into control group with 12 mice and model group with 24 mice(nude mice with T2DM and pancreatic cancer).The mice in the control group were fed with breeding diet and were then given ectopic subcutaneous implantation of PANC-1-Luc cells,and those in the model group were first given high-fat diet and intraperitoneal injection of 1%STZ,followed by ectopic subcutaneous implantation of PANC-1-Luc cells.The fluorescence in vivo imaging system and the manual measurement method were used for simultaneous and dynamic monitoring of the growth of pancreatic cancer in nude mice in the two groups,and the tumor growth curve was plotted to investigate the correlation between fluorescence value and tumor volume.Subcutaneous tumors and pancreatic islets were observed under a microscope to verify whether the model was successfully established,and immunohistochemistry was used to measure the expression of Ki-67 in tumor tissue to investigate the influence of hyperglycemia on the growth of pancreatic cancer in nude mice.The independent-samples t test was used for comparison of normally distributed continuous data between groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups.Results The optimal virus titer was determined as 5×107 TU/mL for the stable transfection of lentiviral vector in PANC-1 cells,and the optimal concentration selected with puromycin was 20 μg/mL,with an optimal selection time of 9 days.The fluorescence value of PANC-1-Luc cells was linearly and positively correlated with the number of cells,with the linear equation of y=42.56x-42 504(r=0.977,P=0.004).The blood glucose value of T2DM nude mice was 23.05(19.25-26.40)mmol/L,with a blood glucose level of>11.1 mmol/L in each nude mouse,and there was a significant difference in blood glucose value between the T2DM nude mice and the control nude[6.15(5.20-7.30)mmol/L](Z=-8.45,P<0.001).Compared with the control group,the model group had reductions in the number and volume of pancreatic islets,with irregular shapes and unclear boundaries,and pathological examination confirmed that the xenograft tumor was pancreatic cancer tissue,which showed that the model was established successfully.In the model group,there was a linear positive correlation between subcutaneous tumor size and fluorescence values,with the linear equation of y=232 348 691x-8 258 608(r=0.911,P=0.031).The model group had a significantly higher positive rate of Ki-67 than the control group(50.333%±7.808%vs 15.917%±4.055%,t=13.55,P<0.001),suggesting rapid tumor proliferation in the model group.Conclusion The T2DM nude mouse model of pancreatic cancer established in this study can simulate the pathological process of the development and progression of pancreatic cancer in the context of T2DM and dynamically observe the influence of hyperglycemia on the growth of pancreatic cancer cells in vivo,thereby providing a new experimental vector for the in vivo study of the development and progression of pancreatic cancer in the context of T2DM.
2. Clinical efficacy and modeling evaluation of He-wei-zhi-xie capsules in treating diarrhea patients
Liying XU ; Xiaomin HUANG ; Shuhua WANG ; Gaosong ZHANG ; Jihan HUANG ; Shuhua WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(1):47-55
AIM: To evaluate the clinical efficacy and safety of He-wei-zhi-xie (HWZX) capsules in diarrhea patients. METHODS: The clinical study was conducted in 35 clinical trials centers from October 2015 to December 2017 by multicenter, prospective, open and uncontrolled design methods. The primary efficacy endpoint is the effective rate of diarrhea, the secondary endpoints include recovery rate of diarrhea, recovery time of diarrhea, number of irregular stools and Leeds dyspepsia questionnaire. The pharmacodynamics model of time course was established by nonlinear mixed effect model, and the effect of covariates on pharmacodynamic parameters was investigated. The safety measures were the incidence of adverse events, adverse reactions and the laboratory test indicators. RESULTS: A total of 2 285 cases were included in full analysis set. The effective rate of diarrhea was 90.8%, and the diarrhea recovery rate was 77.3%. The median time of recovery was 3 days, and the Leeds score was reduced by 3.6 points. It is found that baseline has a significant effect on model parameter E
3.KCNJ11 rs5210 polymorphism and genetic susceptibility to nonalcoholic fatty liver disease and coronary artery disease
Yanyan XU ; Zhenzhen ZHAO ; Shousheng LIU ; Huan SONG ; Yongning XIN
Journal of Clinical Hepatology 2021;37(6):1354-1359
ObjectiveTo investigate the association of KCNJ11 rs5210 single nucleotide polymorphism with nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) in the Chinese Han population in Qingdao, China. MethodsA total of 246 patients with NAFLD who attended Qingdao Municipal Hospital from December 2018 to September 2019 were enrolled as NAFLD group, 201 patients with CAD were enrolled as CAD group, and 116 patients with NAFLD and CAD were enrolled as NAFLD+CAD group; 342 healthy individuals were enrolled as control group. Fasting venous blood samples were collected for biochemical analysis. Whole blood genomic DNA was extracted, and PCR was used to determine KCNJ11 rs5210 genotype. The chi-square test was used to analyze whether the distribution of KCNJ11 rs5210 gene frequencies met the Hardy-Weinberg equilibrium, in order to determine whether the tested samples could represent the population. The chi-square test was used to analyze the differences in sex and genotype/allele frequency between groups. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Bonferroni method was used for further comparison between two groups. The unconditional logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval. ResultsThree genotypes (AA, GA, and GG) of KCNJ11 rs5210 were found by gene sequencing. There were no significant differences in rs5210 allele frequency and genotype distribution between the control group, the NAFLD group, the CAD group, and the NAFLD+CAD group (all P>0.05), and there were still no significant differences after adjustment for sex, age, and body mass index (BMI) (all P>0.05). For all subjects, the subjects with AA genotype had a higher level of alkaline phosphatase than those with GA genotype (P=0.048); in the NAFLD group, the patients with GA genotype had significantly higher BMI and total bilirubin than those with AA genotype (P=0.042 and 0.002). The unconditional logistic regression analysis showed that elevated BMI was associated with the risk of NAFLD (OR=1.35, P<0.01), while decreased high-density lipoprotein (HDL) might indicate an increase in the risk of NAFLD (OR=0.33, P<0.01); elevated fasting plasma glucose and decreased HDL might indicate an increase in the risk of CAD (OR=1.51 and 0.11, both P<0.01) and NAFLD with CAD (OR=1.46 and 0.06, both P<0.01). ConclusionThere is no significant association between KCNJ11 rs5210 polymorphism and the risk of NAFLD and CAD in the Chinese Han population in Qingdao.
4.Correlation of serum alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and alkaline phosphatase with blood pressure in patients with nonalcoholic fatty liver disease in coastal regions of Shandong Province in China
Yijing LIU ; Zhenzhen ZHAO ; Shousheng LIU ; Yanyan XU ; Yongning XIN
Journal of Clinical Hepatology 2021;37(9):2144-2147
Objective To investigate whether there was a correlation between serum liver enzyme levels and blood pressure in the Chinese Han population with nonalcoholic fatty liver disease (NAFLD) in Shandong coastal regions in China. Methods A total of 269 NAFLD patients who lived in Shandong coastal regions and attended or underwent physical examination in Qingdao Municipal Hospital from December 2019 to June 2020 were enrolled, among whom 105 had hypertension and 164 did not have hypertension. Morning blood pressure was measured to calculate mean arterial pressure (MAP), and laboratory tests were performed to measure the serum levels of liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP)] and fasting blood glucose (FBG). The independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A Pearson correlation analysis was used to investigate the correlation of four liver enzymes with the indices including MAP, and a binary logistic regression model was used to analyze the impact of serum liver enzymes on hypertension. Results Compared with the non-hypertension group, the hypertension group had significantly higher body mass index (BMI), MAP, and GGT (all P < 0.05). For all NAFLD patients and the NAFLD patients without hypertension, male patients had significantly higher BMI, MAP, ALT, AST, and GGT than female patients (all P < 0.05), and for the NAFLD patients with hypertension, male patients had a significantly higher level of GGT than female patients ( P < 0.05). There was a significant difference in the distribution of GGT between the hypertension group and the non-hypertension group, and compared with the non-hypertension group, the hypertension group had a significantly higher proportion of patients with GGT exceeding the normal range ( χ 2 =4.781, P =0.029). Serum GGT level was correlated with MAP within the normal range (70-105 mm Hg) ( r =0.178, P =0.011), while there was no significant correlation when MAP exceeded the normal range ( P =0.415). After adjustment for age and sex, the binary logistic regression model showed that AST level was positively associated with hypertension in the population with NAFLD (odds ratio [ OR ]=1.011, 95% confidence interval [ CI ]: 1.000-1.022, P =0.040), and after further adjustment for BMI and FBG, the results showed that AST level was still positively associated with hypertension ( OR =1.011, 95% CI : 1.000-1.022, P =0.044). Conclusion In Chinese Han population with NAFLD in Shandong coastal regions, higher levels of AST may predict an increased risk of hypertension.
5.Quantitative analysis of non-alcoholic fatty liver disease based on MRI proton density fat fraction in the coastal region of Qingdao
Yueli ZHU ; Zhipeng XU ; Wanjiang YU ; Yongning XIN ; Zhenzhen ZHAO ; Shousheng LIU ; Kuirong LYU
Chinese Journal of Hepatology 2021;29(11):1077-1082
Objective:To explore the clinical application value of MRI-PDFF on different liver segments for the evaluation of non-alcoholic fatty liver disease (NAFLD).Methods:178 volunteers from March 2019 to February 2020 were included. PDFF values ??of all nine segments of the liver were measured using CSE3.0T MRI scan. The obtained average value was used to represent the average liver fat content. PDFF values of each or combined liver segment were equally compared with the average value to observe the representativeness of fat content. Receiver operating characteristic curve was used to analyze the diagnostic performance of each liver segment, and the Youden index was used to calculate the cutoff value. Paired-sample t-test or non-parametric Kruskal-Wallis test were used to compare measurement data among groups.Results:178 volunteers average liver fat content ranged from 0.89% to 42.61% with MRI-PDFF, and 71.35% (127/178) of the volunteers had PDFF > 5%. There was no significant difference between SIII, SIVb, SV, and SVIII liver segments when compared with the average value ( P > 0.05). PDFF values ??of SI, SII, and SIV a liver segments were all lower than the average value, while the PDFF values ??of SVI and SVII liver segments were all higher than the average value ( P ??< 0.05). MRI-PDFF sensitivity value for diagnosing liver steatosis of nine liver segments was 85.8% ~ 94.5%, and the specificity was higher than 96.0%. Among them, the SV liver segment had the highest sensitivity (94.5%), and the corresponding optimal diagnostic threshold value was 5.13%. Compared with single and combined liver segment, the PDFF value of SII, SV, SVI combined liver segment had the highest diagnostic performance for fatty liver, with the sensitivity and specificity of 96.9%, and 100%, respectively, and the corresponding optimal diagnostic threshold value was 5.17%. Conclusion:Compared with single and other combined liver segments, MRI-PDFF values of SII, SV, and SVI combined liver segments have higher sensitivity and specificity for the diagnosis of NAFLD, and it can be used as the first choice for the determination of liver fat content with MRI.
6. Analyze the mediating effect of the positive psychological qualities, between emotional intelligence and humanistic caring ability among the nursing interns
Pengzhu XU ; Yu LIU ; Tieying SHI ; Changli LIU ; Wei DAI ; Tongtong JIANG ; Yongning LIU
Chinese Journal of Practical Nursing 2019;35(24):1854-1858
Objective:
To explore the humanistic caring ability, and to analyze the relationship between the positive psychological qualities, emotional intelligence and humanistic caring ability among the nursing interns, and provide theoretical basis to improve nursing students’ humanistic caring ability.
Methods:
A total of 132 nursing interns from a three Level of first-class hospital in Liaoning province, were investigated by using the general questionnaire, caring ability inventory, emotional intelligence scale and Positive Mental Characters Scale for China normal university.
Results:
The score of humanistic caring ability was (180.74±18.75). Among them, the average score of cognitive was the highest (73.71±10.93) and the average score of courage was the lowest (48.43±11.91). Emotional intelligence and positive psychological qualities were positively correlated with the humanistic caring ability, and positive psychological qualities was a intermediate variable between emotional intelligence and humanistic caring ability, and the mediating effect size is 18.71%.
Conclusion
The level of humanistic caring ability in nursing interns is lower, which needs to be further improved. The emotional intelligence and positive psychological qualities have a significant positive effect on the humanistic caring ability. Schools and internship hospitals can improve their sense of humanistic caring ability by developing the emotional intelligence and positive psychological qualities to stabilize the development of nursing career.
7.Effects of PTEN over-expression on phosphatidyl inositol 3-kinase/protein kinase B signal pathway in ovarian epithelial cancer cells
Yongning ZHAI ; Lingling XU ; Yue SHEN ; Hong XIA ; Yufei SHEN
Chinese Journal of Obstetrics and Gynecology 2010;45(9):682-685
Objective To evaluate the effect of exogenous wild PTEN gene stable transfected into human ovarian cancer cell line HO-8910 on phosphatidyl inositol 3-kinase( PI3K)/protein kinase B (Akt)siganal pathway and cells proliferation. Methods Wild-type PTEN recombinant eukaryotic expression plasmid was constructed and then was transfected into HO-8910 cells by lipofectamine 2000. The expression of PTEN, Akt1, Akt2, PI3K mRNA and protein of PTEN were tested by reverse transcription( RT)-PCR and Western blot. The proliferation of HO-8910 after wild PTEN gene transfected was measured by methyl thiazolyl tetrazolium(MTT). Results Wild-type PTEN gene was successfully transfected into HO-8910 cells. The results of RT-PCR and western bolt showed that there were the significant expression high level of PTEN mRNA and protein after infected by wild-PTEN plasmid than those in the control[ ( 17 372 ±23)vs.(39±1 )vs. (78 ±4)copies/ml,P <0. 05 ]. While the expression of mRNA of Akt1, Akt2 and PI3K were decreased clearly than those in the control [ (28 ± 2 ) vs. ( 115 ± 5 ), (7 ± 1 ) vs. ( 18 ± 2), (61 ± 2 ) vs.(84 ± 2)copies/ml , all P < 0. 05 ]. The proliferation rate of HO-8910 cells was obviously slower than those in the control (90 158 ±47 vs. 148 251 ±65 vs. 250 115 ±62, P<0.05). Conclusion Transfection of PTEN may increase the expression of PTEN and inhibit the proliferation of HO-8910 cells, in which PI3K/ Akt siganal pathway is inhibit significantly.
8.The effects of olanzapine,clozapine,risperidone and quetiapine treatment on P50 sensory gating in first-ep-isode schizophrenics
Junqing WANG ; Lanxian YE ; Chongtao XU ; Yongning ZHUO
Chinese Journal of Behavioral Medicine and Brain Science 2010;19(1):24-26
Objective To compare the effects of atypical antipsyehoties treatment on PS0 sensory gating in first-episode schizophrenics. Methods The P50 auditory evoked potential was recorded by using conditioning-testing stimulus paradigm and stimulus train paradigm in 36 normal controls and 53 first-episode schizophrenics be-fore and after treatment,and compare the difference of P50 sensory gating after treatment. Results Before treat-ment, compared with control group, the atypical groups both had statistic difference of T-P50 amplitude ((1.01±0.88)μV, (0.68±0.64)μV, (0.58±0.47)μV), P50 suppression ((0.61±0.27), (0.54±0.22, (0. 59± 0.19)) in conditioning-testing stimulus paradigm and P50 amplitude,P50 suppression evoked by high frequency stimuli in stimulus train paradigm(P < 0.05), but no difference among the atypical groups (P > 0.05). After treat-ment,compared with control group, there was no statistic difference in olanzapine and elozapine groups of T-P50 amplitude and P50 suppression in conditioning-testing stimulus paradigm, but the difference in risperidone and que-tiapine groups still obviously(P<0.05). In stimulus train paradigm, there was no statistic difference of P50 ampli-tude, P50 suppression evoked by high frequency stimuli in every groups (P>0.05). Compared within atypical groups, the difference of P50 amplitude and P50 suppression were both obviously(P<0.05). Conclusion Each a-typical antipsychotic has different effect on P50 sensory gating;and the conditioning-testing stimulus paradigm and stimulus train paradigm P50 sensory gating may reflect different central neuron mechanism.
9.The effects of typical and atypical antipsychotics on P50 sensory gating in first-episode schizophrenics
Junqing WANG ; Yongning ZHUO ; Chongtao XU ; Lanxian YE
Chinese Journal of Nervous and Mental Diseases 2009;35(12):722-725
Objective To compare the effects of typical and atypical antipsychotics treatment on P50 sensory ga-ting in first-episode schizophrenics.Methods Using conditioning-testing stimulus paradigm and stimulus train paradigm to record the P50 auditory evoked potential in 36 normal controls and in 61 first-episode schizophrenics before and after treat-ment.Patients were categorized into two groups:the typical antipsychotic treatment group(typical group)and the atypical antipsychotic treatment group(atypical group).Results Before treatment,both of the typical and atypical groups had low-er levels of S2-P50 amplitude,P50 suppression in conditioning-testing stimulus paradigm and P50 amplitude as well as P50 suppression evoked by high frequency stimuli in stimulus train paradigm in comparison with controls(P<0.05).After treatment,the typical antipsychotic treatment significantly improved the levels of P50 suppression in the stimulus train para-digm but not the levels of S2-P50 amplitude,P50 suppression in the conditioning-testing stimulus paradigm(P<0.05)whereas the atypical antipsychotic treatment improve the levels of P50 amplitude,P50 suppression in both stimulus train paradigm and the conditioning-testing stimulus paradigm(P<0.05). Conclusions The typical antipsychotic treatment can ameliorate the P50 suppression in stimulus train paradigm,but not in the conditioning-testing stimulus paradigm,whereas atypical antipsychotic treatment can ameliorate P50 suppression in both paradigms.
10.Therapeutic Effect of Argon Laser Photocoagulation on Macular Choroidal Neovascularization.
Yan XIANG ; Yongping HU ; Yongning XU ;
Journal of Medical Research 2006;0(10):-
Objective To observe the therapeutic effect of Argon laser photocoagulation on macular choroidal neovascularization. Methods 57 cases(58eyes)with macular choroidal neovascularization were treated with Argon laser photocoagulation,the visual acuity, the changing of macular choroidal neovascularization and macular hemorrhage before and after treatment were observed and compared with 34 cases(34eyes)with macular choroidal neovascularization who were treated with drugs.The average follow-up was 48(from2 to 84) months.Results The retinal hemorrhage decreased evidently in cases treated with laser coagulation.The hemorrhage absorb in therapeutic group is more evident than that in control group,There are statistically difference between the two groups(0.01<P<0.05).There are sig- nificantly difference between the two groups in increased visual acuity and choroidal neovascularization disappeared(P<0.01).Couclu- sions Argon laser photocoagulation is effective on macular cloroidal neovasculurition.

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