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ObjectiveTo investigate the clinical features, diagnosis, treatment, and prognosis of autoimmune pancreatitis (AIP) alone versus AIP with IgG4 sclerosing cholangitis (IgG4-SC). MethodsA retrospective analysis was performed for the clinical data of 40 patients with type 1 AIP who were admitted to The First Affiliated Hospital of Zhengzhou University from June 2015 to January 2020, among whom 29 patients had AIP alone and 11 had AIP with IgG4-SC. The two groups were compared in terms of clinical manifestations, laboratory examination, imaging findings, treatment, and prognosis. The 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 Fisher’s exact test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to calculate recurrence rate and plot recurrence curve, and the log-rank test was used for univariate analysis. ResultsCompared with the AIP group, the AIP+IgG4-SC group had significantly higher number of affected organs ［3.0(3.0-4.0) vs 3.0(1.5-3.5), Z=-2.172, P=0035］ and response index before treatment ［12.0(12.0-15.0) vs 12.0(9.0-13.5), Z=-2.157, P=0.032］. The AIP+IgG4-SC group had a significantly higher median serum IgG level than the AIP group ［21.0(15.8-23.7) g/L vs 14.8(13.3-15.7) g/L, Z=-2.711, P=0.004］. During the median follow-up time of 15.8 (6.5-31.3) months, the AIP+IgG4-SC group had a significantly higher recurrence rate than the AIP group (χ2=8.155, P=0.004). ConclusionPatients with AIP and IgG4-SC tend to have higher serum IgG4 level, number of affected organs, and recurrence rate than those with AIP alone. Early identification, diagnosis, and treatment can reduce the recurrence rate of AIP.
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Objective@#To explore the clinicopathological characteristics of primary hepatic neuroendocrine neoplasm (HNEN) and metastatic HNEN from digestive tract, to screen the risk factors of hepatic metastasis of gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) and to analyze the differences between primary and metastatic HNEN in clinical features, diagnosis, treatment and prognosis.@*Methods@#From January 2010 to June 2017, the clinical data of 182 patients with HNEN admitted at The First Affiliated Hospital of Zhengzhou University were retrospectively analyzed, including 39 cases of primary HNEN, 129 cases of metastatic HNEN and 14 cases of HNEN with unknown primary lesions. Chi-square test and t test were performed to analyze the pathologic characteristics among groups. Logistic regression method was used to analyze the risk factors of hepatic metastasis. Kaplan-Meier method and log-rank test were used for survival analysis. Cox model was used for the prognostic multivariate survival analysis.@*Results@#Metastatic HNEN from digestive tract was more common in male (70.5%, 91/129). The case number of serological tumor biomarkers neuronspecific enolase and alpha-fetoprotein positive in primary HNEN were two cases and one case, respectively, and the positive rates in metastatic HNEN were 37.2% (32/86) and 6.4% (7/110). Most primary HNEN was single lesion (61.5%, 24/39), while multiple lesions were more common in metastatic HNEN (78.3%, 90/115). Primary HNEN mainly occurred in the right lobe of the liver (44.7%, 17/38), while metastatic HNEN located simultaneously in the left and right lobes of the liver (68.4%, 78/114). There were significant differences between primary HNEN and metastatic HNEN in tumor number, pathological grading, location of tumors and maximum diameter of tumors (χ2=21.264, 11.696, 19.461 and 4.547, all P<0.05). The median survival time of patients with primary HNEN and metastatic HNEN were 17.0 months and 10.0 months, and there was a significant difference in survival curves between the two groups (χ2=7.235, P=0.007). The type of hepatic tumors (primary or metastatic)(P=0.002), pathological grading of hepatic tumors (P=0.044), lymph node metastasis (P=0.024), the growth pattern of tumors (P<0.01) and treatment methods (P=0.018) were the independent factors for the prognosis of patients.@*Conclusions@#There are significant differences between primary HNEN and metastatic HNEN in tumor number, size and location. The type of hepatic tumors, pathological grading, lymph node metastasis, growth pattern of tumors and treatment methods are the independent factors for the prognosis of patients. Early topical treatment and combination treatment can help to prolong survival time of HNEN patients.
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Nonalcoholic fatty liver disease (NAFLD) is one of the common causes for chronic liver diseases, which progress gradually from nonalcoholic type simple fatty liver disease to hepatitis, cirrhosis and even liver failure and hepatocellular carcinoma. Sarcopenia is a progressive disease characterized by reduced skeletal muscle mass and function in association to metabolic dysfunctions. Recent studies have shown that the occurrence and development of NAFLD and sarcopenia are related, and there is a common base for the pathogenesis between the two, which may promote each other for mutual risk factors. This article reviews the current research progress of this field in order to clinically further understand the pathogenesis and intrinsic links between the two to look for appropriate interventions.
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To investigate the potential risk factors for hepatocellular carcinoma in primary biliary cholangitis (PBC) patients. Methods:The data of 670 PBC inpatients between January 2011 and December 2016 were collected from the database of The First Affiliated Hospital of Zhengzhou University. The potential risk factors were evaluated, and odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed by univariate (unadjusted OR) and multivariate [adjusted OR (AOR)] conditional Logistic regression. Results: In total, 35 PBC patients developed liver carcinoma (5.2%); of these, 4 patients (female) were excluded because of incomplete data for influencing factors and 6 (2 male; 4 female) were excluded as they were diagnosed with hepatocellular carcinoma (HCC) during or before PBC. Therefore, 25 patients were included in the case-control study. Male patients were more likely than female patients to show alcohol in-take, smoking, a family history of malignancy, and serious liver injury (all P<0.05), indicated by the increasing levels of alanine amino-transferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) (P<0.05). Conditional Logistic regression analysis revealed that body mass index (BMI) ≥25 kg/m2 (AOR=1.015, 95% CI: 1.001-1.257, P=0.032) and history of alcohol intake (AOR=10.014, 95% CI: 1.009-91.071, P=0.039) were significantly associated with increased odds of HCC development in PBC patients. Conclusions:The risk factors for PBC-associated liver carcinoma include BMI≥25 kg/m2 and history of alcohol intake. In addition to regular monitoring, PBC patients may benefit from alcohol abstinence and body weight control.
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Objective To explore the clinicopathological characteristics of primary hepatic neuroendocrine neoplasm (HNEN) and metastatic HNEN from digestive tract ,to screen the risk factors of hepatic metastasis of gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) and to analyze the differences between primary and metastatic HNEN in clinical features , diagnosis, treatment and prognosis.Methods From January 2010 to June 2017, the clinical data of 182 patients with HNEN admitted at The First Affiliated Hospital of Zhengzhou University were retrospectively analyzed , including 39 cases of primary HNEN, 129 cases of metastatic HNEN and 14 cases of HNEN with unknown primary lesions .Chi-square test and t test were performed to analyze the pathologic characteristics among groups .Logistic regression method was used to analyze the risk factors of hepatic metastasis .Kaplan-Meier method and log-rank test were used for survival analysis . Cox model was used for the prognostic multivariate survival analysis .Results Metastatic HNEN from digestive tract was more common in male ( 70.5%, 91/129 ).The case number of serological tumor biomarkers neuronspecific enolase and alpha-fetoprotein positive in primary HNEN were two cases and one case , respectively, and the positive rates in metastatic HNEN were 37.2%( 32/86) and 6.4%(7/110).Most primary HNEN was single lesion (61.5%, 24/39), while multiple lesions were more common in metastatic HNEN (78.3%, 90/115).Primary HNEN mainly occurred in the right lobe of the liver (44.7%, 17/38), while metastatic HNEN located simultaneously in the left and right lobes of the liver (68.4%, 78/114).There were significant differences between primary HNEN and metastatic HNEN in tumor number , pathological grading, location of tumors and maximum diameter of tumors ( χ2 ＝21.264, 11.696, 19.461 and 4.547, all P?0.05).The median survival time of patients with primary HNEN and metastatic HNEN were 17.0 months and 10.0 months, and there was a significant difference in survival curves between the two groups (χ2 ＝7.235, P＝0.007).The type of hepatic tumors (primary or metastatic) ( P＝0.002), pathological grading of hepatic tumors (P＝0.044), lymph node metastasis ( P ＝0.024), the growth pattern of tumors ( P ?0.01) and treatment methods (P＝0.018) were the independent factors for the prognosis of patients .Conclusions There are significant differences between primary HNEN and metastatic HNEN in tumor number , size and location. The type of hepatic tumors, pathological grading , lymph node metastasis, growth pattern of tumors and treatment methods are the independent factors for the prognosis of patients .Early topical treatment and combination treatment can help to prolong survival time of HNEN patients .
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Objective To investigate the role and mechanism of circular RNA-vimentin (circ-VIM) in the proliferation and apoptosis of colorectal cancer cells.Methods From December 2016 to December 2017, at Department of General Surgery of The First Affiliated Hospital of Zhengzhou University, the clinical data of 100 patients who underwent radical resection of colorectal cancer and were confirmed by pathological examination after operation were collected.The tumor tissues and corresponding paracancerous tissues (negative control) were also collected.The expression of circ-VIM in the colorectal cancer tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR).The proliferation of HCT-116 and HT29 colorectal cancer cells was detected by cell counting kit-8 assay.The ratio of apoptosis of HCT-116 and HT29 cells was measured by annexin Ⅴ/propidium iodide double staining assay.The mitochondrial membrane potential of HCT-116 and HT29 cells was examined by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide (JC-1) assay.The expression changes of protein kinase B and mammalian target of rapamycin were tested by Western blotting.The target miRNA of circ-VIM was predicted by miRDB software.T-test and chi-square test were performed for statistical analysis. Results The expression of circ-VIM in colorectal cancer tissues was 2.387 ±0.536, which was higher than that in corresponding paracancerous tissues (1.110 ±0.134), and the difference was statistically significant (t =23.096, P <0.01).And the expression levels of circ-VIM were significantly different in patients with different tumor size, TNM stage and lymph node metastasis (all P <0.05).The proliferation of HCT-116 cells and HT29 cells in lenti-circ-VIM group was 0.737 ±0.023 and 0.835 ±0.025, respectively, which were both higher than those in control group (0.449 ±0.020 and 0.531 ±0.019), and the differences were statistically significant (t =20.706 and-15.374, both P <0.01).The proliferation of HCT-116 cells and HT29 cells in lenti-circ-VIM-shRNA group was 0.236 ±0.027 and 0.243 ±0.019, which were lower than those in control group, and the differences were statistically significant (t =24.557 and -23.197, both P <0.01).The ratio of apoptosis of HCT-116 cells and HT29 cells in lenti-circ-VIM-shRNA group was (18.00 ±1.82)％ and (20.80 ±0.61)％, which was higher than those in control group ((6.64 ±2.01)％ and (7.35 ±1.36)％), and the differences were statistically significant (t =8.826 and 17.454, both P <0.01).The fluorescence intensity ratio of JC-1 aggregate and JC-1 monomer of HCT-116 cells and HT29 cells in lenti-circ-VIM-shRNA group was 2.21 ±0.12 and 1.40 ±0.11, which was lower than those in control group (14.54 ±1.00 and 9.24 ±1.18), and the differences were statistically significant (t =-19.558 and-15.685, both P <0.01), which indicated mitochondrial membrane potential decreased.After treated with lenti-circ-VIM-shRNA, the expression of phosphorylated protein kinase B, phosphorylated mammalian target of rapamycin, B-cell lymphoma-2 and mitochondrial cytochrome C at protein level were all down-regulated, however the expression of cytoplasmic cytochrome C, B-cell lymphoma-2 associated X protein and cleaved caspase-3 at protein level were all up-regulated.When the expression of circ-VIM was up-regulated, the expression of miRNA-147b, miRNA-4447 and miRNA-3656 was down-regulated.When the expression of circ-VIM was down-regulated, the expression of miRNA-147b, miRNA-4447 and miRNA-3656 was up-regulated.Conclusion The expression of circ-VIM in colorectal cancer is abnormally increased, which is involved in the proliferation and apoptosis of colorectal cancer cells.
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Microglia, a type of neuroglia, has a variety of functions such as phagocytosis, clearance, antigen presentation,promotion of repairment of injury and secretion of extracellular signaling molecules,in which phagocytosis of microglia plays a crucial role in maintaining brain tissue,remodeling synapses,clearance of several aberrant proteins such as amyloid β in neurodegenerative diseases, and in neurodevelopment. This review briefly summarizes the phagocytic function of microglia with underlying regulatory mechanism in neurodevelopment and neurodegenerative diseases,aiming to provide a new thought for the therapy of neurodegenerative diseases.
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Cytochrome P450 (CYP450) is a superfamily of heme-thiolate proteins, which is involved in the metabolism and activation of various endogenous and exogenous substances, including food, drugs and pollutants. Previous studies of the CYP450 genes mainly focused on their function in drug metabolism. However, in recent years, studies have found that CYP450 are also involved in the development and progression of various diseases, including Parkinson's disease (PD), cancer, cardiomyopathy and heart failure (HF). By far, the process and related mechanisms of CYP450 in the metabolism of endogenous substances in brain tissues has not been clarified yet. In this paper, we summarized the research progress of CYP450 genes involved in the metabolism of endogenous substances, in order to provide a new idea for the exploration of the functions of CYP450 genes expressed in the brain.
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Macrophages acquire distinct phenotypes during tissue stress and inflammatory responses. Macrophages are roughly categorized into two different subsets named inflammatory M1 and anti-inflammatory M2 macrophages. We herein identified a unique pathogenic macrophage subpopulation driven by IL-23 with a distinct gene expression profile including defined types of cytokines. The freshly isolated resting mouse peritoneal macrophages were stimulated with different cytokines in vitro, the expression of cytokines and chemokines were detected by microarray, real-time PCR, ELISA and multiple colors flow cytometry. Adoptive transfer of macrophages and imiquimod-induced psoriasis mice were used. In contrast to M1- and M2-polarized macrophages, IL-23-treated macrophages produce large amounts of IL-17A, IL-22 and IFN-γ. Biochemical and molecular studies showed that IL-23 induces IL-17A expression in macrophages through the signal transducer and activator of transcription 3 (STAT3)-retinoid related orphan receptor-γ T (RORγT) pathway. T-bet mediates the IFN-γ production in IL-23-treated macrophages. Importantly, IL-23-treated macrophages significantly promote the dermatitis pathogenesis in a psoriasis-like mouse model. IL-23-treated resting macrophages express a distinctive gene expression prolife compared with M1 and M2 macrophages. The identification of IL-23-induced macrophage polarization may help us to understand the contribution of macrophage subpopulation in Th17-cytokines-related pathogenesis.
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Animals , Mice , Cell Polarity , Imiquimod , Interleukin-23 , Metabolism , Macrophages , Metabolism , Pathology , Mice, Inbred C57BL , Mice, Knockout , Psoriasis , Metabolism , PathologyABSTRACT
Objective: To explore the impact of knocking out wildtype p53 phosphatase 1 gene on heart function with the changes of cardiac tissue mRNA and protein expressions in experimental mice. Methods: Our research included in 2 groups: Wildtype (WT) mice group and Wip1 knockout (Wip1-KO) mice group. n=10 in each group. The heart function, ratio of heart weight to body weight (HW/BW) were examined and compared between 2 groups; cardiac tissue morphology was observed by HE staining; mRNA expressions of ANP, BNP, MCP-1 andα-SMA were determined by RT-PCR and protein expressions of Bcl-2, Bax and c-caspase3 were measured by Western blot analysis. Results: Compared with WT mice group, Wip1-KO mice group showed decreased Wip1 mRNA expression,P0.05; apoptosis related protein expressions of Bax/Bcl-2 and c-caspase3 were similar between 2 groups,P>0.05. Conclusion: Wip1 gene knockout may impair the heart function in experimental mice, while the relevant mechanism should be further investigated.
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Objective To assess the drug sensitivity of pancreatic cancer cells based on real-time cell analysis and provide a reference for individualized diagnosis and treatment of pancreatic cancer.Methods Three human pancreatic cancer cells lines SW1900, Capan-2 and PANC-1 were selected and treated with gemcitabine hydrochloride and tegafur gimeracil oteracil potassium capsules, respectively.After 24 hours of culture, the cells were treated with the two drugs in gradient concentration.The cell growth curves before and after the drug administration was monitored using a real-time cells analyzer and the growth inhibition rates (IC50) of the drugs of the pancreatic cancer cells were calculated.At the same time, the cells in the cell culture plate were treated with the drug, and acridine orange/ethidium bromide (AO/EB) staining and laser scanning confocal microscopy were performed to observe the changes of cells after the drug administration.Results 72 hours after the drug administration, IC50 values for the three cell lines were different.The IC50 values of gemcitabine hydrochloride for SW1900, Capan-2 and PANC-1 cells were 1.69 μmol/L, 10.05 μmol/L and 12.74 μmol/L, respectively.The IC50 values of tegafur capsule for SW1900, Capan-2 and PANC-1 cells were 180.29 μmol/L, 765.70 μmol/L and 95.57μmol/L, respectively.AO/EB staining confirmed the reliability of IC50.Conclusions SW1900 and Capan-2 cells can be used as the control for gemcitabine hydrochloride and tegafur gimeracil oteracil potassium capsules to establish cell models for drug screening in vitro, which provides a reference for the application of the technology in anticancer drugs screening.
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Objective To explore the clinicopathologic characteristics,to screen risk factors of metastasis and to analyze the diagnosis,treatment and prognosis of gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN).Methods From January 2010 to November 2015,the clinical data of 405 patients with GEP-NEN were retrospectively analyzed.GEP-NEN tumors were classified as neuroendocrine tumor (NET,G1 and G2 grade),neuroendocrine carcinoma (NEC,G3 grade) and mixed adenoendocrine carcinoma (MANEC,G3 grade).The clinicopathologic characteristics were summarized.The staining characteristics of synaptophysin (Syn),chromogranin A (CgA) and CD56 of tumor tissues were analyzed by immunohistochemistry.x2 and t test were performed to analyze differences in pathologic characteristics between groups.Logistics regression method was used to analyze the risk factors of metastasis.KaplanMeier method and Log-rank test were used for survival analysis.Results The mean age of patients with GEP-NEN was (54.7± 13.3) years.Gastric NEN was the most common GEP-NEN (98 cases,24.2％),followed by 95 cases (23.5％) with NEN in rectum,86 cases (21.2％) in pancreas and 50 cases (12.3％)in esophagus.Among them,47 cases (11.6％) were functional GEP NEN and 358 cases (88.4％) were non-functional GEP-NEN.According to pathologic diagnosis,227 cases (56.0％) were NET,125 cases (30.9％) were NEC and 16 cases (4.0％) were MANEC.According to tumor classification,120 cases (29.6％) were grade G1,108 cases (26.7％) were grade G2 and 177 cases (43.7％) were grade G3.Immunohistochemistry staining positive ratesof Syn,CgA and CD56 were 97.4 ％ (381/391),44.0 ％ (121/275) and 83.9％(291/347),respectively.The median (lower quartile,upper quartile) diameter of grade G1,G2 and G3 tumors were 1.0 cm (0.6 cm,1.5 cm),1.5 cm (1.0 cm,2.5 cm),4.0 cm(2.5 cm,6.0 cm),respectively,and the difference was statistically significant (Z =99.171,P ＜ 0.01).The positive rate of CgA of grade G3 tumor was lower than that of grade G1 and G2(x2 =7.078 and 11.391,both P＜ 0.01).The results of Logistic regression analysis revealed that tumor size and pathologic classification were the important predictors of metastasis.The median survival time of metastasis group and non-metastasis group of grade G3 was 12.0 months and 41.5 months,and there was a significant difference between the two groups by Log-rank test (x2 =37.075,P＜0.01).Conclusions GEP-NEN may occur at any part of the digestive system.There are differences in tumor size positive rate of,immunohistochemistry staining and the primary site of tumors with different pathological grading.The tumor diameter and pathologic classification are the important predictors of metastasis.The prognosis of metastasis group is worse than that of non-metastasis group.
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Objective To develop a more convenient and stable method for assessment of drug sensitivity of prostate cancer based on real-time cell analysis system as a reference for clinical treatment.Methods Human prostate cancer VCaP, DU145, PC-3, PC-3M-2B4 and PC-3M-IE8 cells were chosen to detect the sensitivity to three drugs, docetaxel, cabazitaxel and abiraterone acetate.Serial dilutions of the three drugs were used to treat the cell culture for 24 hours.The drug-induced effects on the cell lines after an incubation of 24 hours were recorded by the real-time cell analysis system to determine the half maximal inhibitory concentration (IC50).Results Docetaxel showd IC50 of 8.81 nmol/L, 11.61 nmol/L, 1.78 nmol/L, 1.44 nmol/L, 8.69 nmol/L for VCaP, DU145, PC-3, PC-3M-2B4, PC-3M-IE8 cells, respectively.Cabazitaxel showed IC50 of 3.73 nmol/L, 3.96 nmol/L, 10.41 nmol/L, 5.43 nmol/L, and 7.37 nmol/L, respectively, for the five cell lines.Abiraterone acetate showed IC50 of 8.34 μmol/L, 8.60 μmol/L, 24.20 μmol/L, 8.59 μmol/L, and 13.21 μmol/L for the five cell lines.Conclusions PC-3M-2B4 and DU145, VCaP and PC-3 cells can be used as control for docetaxel, cabazitaxel and abiraterone acetate to establish cell models for the drug screening in vitro and to provide reference for clinical applications.
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Objective To knock out the Abcb1 gene of rat,and establish the Abcb1 humanized rat model based on the Abcb1 knock out rat.Methods The animal model was established using BAC and CRISPR/Cas9 technology,and was analyzed by PCR, RT-PCR and real-time PCR.Results Establishing a rat model expressing human Abcb1 stably by transfer the 153 kb BAC containing human Abcb1 promoter and cDNA into rat genome, and establishing the Abcb1 knock out rat at the same time.Establishing the Abcb1 humanized model by crossing these two strains together.The expression pattern of Abcb1 in Abcb1 humanized rat is different from the wild type rat.The Abcb1 humanized model express not only the human Abcb1 gene but also has similar expression pattern as human.Conclusions The Abcb1 knock out rat and the Abcb1 humanized rat were successfully established, and this model is close to human concerning about the drug metabolism related to Abcb1.
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Objective To develop a model that could copy the pathological development of psoriasis, the triple-transgenic mice that harboring Plasminogen activator, urokinase ( PLAU) ,PLAU receptor ( PLAUR) and signal transducer and activator of transcription 3 ( STAT3 ) were generated.They are the important genes involved in the pathological development of psoriasis.Methods The transgenic plasmid was constructed by insertion of the PLAU, PLAUR and STAT3 into the downstream bovine keratin 5 promoter respectively.The transgenic mouse was produced by microinjection and the genotyping was detected by PCR.The expression level of the transgenic gene was determined by Western blotting.The pathological changes were observed by HE staining.Results One mouse line was selected with over expression of the PLAU, PLAUR and STAT3 in the tissue of skin.The transgenic mice showed decreased dermal layer, a hyperkeratinized cuticular layer and increased stratum spinosum.The number of hair follicle was reduced and developed abnormally in the transgenic mice.The Munro abscess in the dermal layer and the increased inflammatory cell infiltrates in dermal layer were also observed in the transgenic mice.Conclusions A transgenic mouse line was produced and passage stably, which expressed the PLAU, PLAUR and STAT3 in the tissue of skin and developed the psoriasis progressively.All of our results suggested that the transgenic mice were a useful animal model for psoriasis.
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Objective To develop a model that could roundly show the phenotypes of human alzheimer disease (AD), the triple-transgenic rat model harboring APP(Swe), PS1dE9, and TAU transgenes was established in view of the advantage of rat as an important animal model on the research of nerve system .Methods APPswe/PS1dE9/TAU triple transgenic rat AD rats were generated on a SD background by co-injecting rat pronuclei with two human genes driven by the mouse prion promoter:‘Swedish’ mutant human APP (APPsw) and exon 9 mutant human presenilin-1 (PS1dE9) and human microtubule-associated protein tau gene under the control of PDGF promoter .Transgene integration was confirmed by genotyping and expression levels were evaluated by western blot ( WB ) of brain homogenates .The pathological changes were detected by human Abeta, TAU and Phospho-PHF-TAU immunohistochemistry staining (IHC).The behavioral and cognitive changes were evaluated by Morris water maze .Results One transgenic rat lines with high human APP ( Swe ) , PS1dE9, and TAU transgenic expression was selected from three transgenic founders .Compared with the wild type rat , the transgenic rat showed significant learning and memory impairments in the Morris water maze at 6 months of age .The triple transgenic rat manifested hyperphosphorylated tau and obvious aggregation of amyloid -β( Aβ) in the brain cortex and hippocampus.Conclusion APPswe/PS1dE9/TAU triple transgenic rat AD model was established .The triple transgenic AD rat fills a critical need for a next-generation animal model to enable basic and translational AD research .
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Objective To study the influence of Apo E gene knockout on the lymphocytes . Methods Cells from the peripheral blood, spleen and bone marrow of Apo E knockout and wildtype mice were stained with kinds of antibodies , and analyzed by flow cytometry .Results Compared with wildtype mice , significant differences were found in B and T lymphoctes in the peripheral blood and spleen , but there was no significant difference in pre B cells , T lymphocytes in the thymus and long term hematopoietic stem cell in the Apo E knockout mice .Conclusion Numbers of B lymphocytes decreased in the peripheral blood and spleen , but there was no significant difference in B , T lymphocytes development , and numbers of long term hematopoietic stem cell in Apo E gene knockout mice .
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Objective To investigate the influence of Siraitia Grosvenori and Rehmannia Glutinosa on the Hematopoietic stem cells proliferation and function .Methods Cells from the peripheral blood , spleen and bone marrow of mice were stained with indicated antibodies , and analyzed by flow cytometry .Mice were divided 3 groups:control group, Siraitia Grosvenori treatment group and Rehmannia Glutinosa treatment group .After 4.5Gy IR treatment, mice divided 4 groups: control group, 4.5Gy IR treatment and feed with normal food, 4.5Gy IR treatment and feed with Siraitia Grosvenori and 4.5Gy IR treatment and feed with Rehmannia Glutinosa for 1 month.Results Mice fed with Siraitia Grosvenori and Rehmannia Glutinosa decreased the percentage of B cells and increased the percentage of M cell .For HSCs, the number of HSCs was increased , especially the number of LT-HSCs.After 4.5Gy IR treatment, mice fed with Siraitia Grosvenori and Rehmannia Glutinosa increase the number of HSCs , and increased the percentage of M cells . Conclusion Siraitia Grosvenori and Rehmannia Glutinosa promote the hematopoietic stem cells and progenitor cells proliferation and function and recover the damage that caused by IR treatment .
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Objective To study the effects of NRG2 on cardiac structure and function , we established the cardiac-specific human NRG2 transgenic mice and investigate the effect of NRG2 on cardiac structure and function under pressure overload situation .Methods The transgenic vector was constructed by insertion of the human NRG2 gene under the α-MHC promoter.The transgenic mice were generated by microinjection and were all maintained on a C57BL/6J genetic background .The genotype of transgenic mice was identified by PCR and the expression level of target gene was determined by western blot .Transverse aortic constriction ( TAC) was applied to prepare the pressure overload induced cardiomyopathy mice model .The cardiac structure and function of the transgenic mice were compared and analysized by echocardiographic and pathological observation .Results Transgenic mice with high level of NRG2 in heart tissues were established.The left ventricular wall thickness (LVPWD) was increased, and to 15.6% at 3 months old compared with that of the non transgenic ( NTG) mice.The hypertrophy of left ventricular wall caused by pressure overload was removed due to the expression of NRG2 .Meanwhile, cardiac disarray and fibrosis were increased obviously compared with that of the NTG mice.Conclusion The transgenic expression of NRG2 in heart tissues could shorten the pathological process of hypertrophy, but accelerated the process of heart failure (HF).
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Objective To establish the sperm specific Sleeping Beauty ( SB ) transposase-expression transgenic mouse for the study of the genetic modification mediated by transposon system in mouse .Methods Prm1 promoter was cloned from mouse genomic DNA to drive the expression of SB transposase .The transgenic mice were generated by microinjection .The gene type of transgenic line was identified by PCR .The expressing level in testis was determined by western blot and immunohistochemistry (IHC) staining.Results Five lines of transposase transgenic mice were obtained by microinjection and three can be germline .One mouse line with higher expression level of transposase in the testis was obtained.Conclusion One transgenic mouse model with Sleeping Beauty transposase - expression was successfully established .This model will greatly contribute to the research of genetic modification mediated by transposon in mouse.