Objective To investigate the roles of Arsenic Trioxide to the lupus nephritis in MRL/ lpr mice and the effect on the expression of TGF-pl in the renal tubule. Methods 45 MRL/lpr mice were chosen for such experiment, then separated in 3 different groups, including arsenic trioxide ( ATO) group, cyclophosphamide (CYC) group and sodium chloride (NS) group. Urine of these mice was kept after the treatment to detect the urine protein levels. The pathological changes and the expression of IgG were observed , and the complement 3 of the nephridial tissue as well as the TGF-pl were detected by immunohisto-chemistry. Result The levels of urine protein in ATO group and CTX group were lower than NS group after the treatment ( P <0.05). The expression of IgG along the glomerular mesangium and capillary loop in ATO and CTX groups was less than NS group ( P <0.05). The expression of C3 had no significant difference within three groups ( P > 0.05). The glomcrulus spherulous cells and the integral of activity in ATO group and CTX group were less than that in NS group ( P <0.05). TGF-β1 wildly presented in the epithelial cells endochylema of the nephric tubule, but it was rarely seen in glomcrulus in NS group. The expression in the nephric tubule of ATO group was less than NS group (20.28 ± 1. 90 vs 68. 23 ± 2. 87, P < 0.01) , and the expression in the nephric tubule in CTX group was less than that in NS group (23. 26 ± 1.71 vs 68. 23 ±2. 87, P <0. 01). Conclusion TGF-pl may take part in the immunopathogenesis of lupus nephritis in MRI/lpr mice. ATO can relieve the inflammation of nephric tubule by down regulation the expression of TGF-β1. ATO can also relieve the tissue damage of kidney in lupus nephritis through reducing the inflammation of glomcrulus and interstitial substance,as well as the expression of the immunocomplex.

Objective:To clone the human cell death-inducing DFF45-like effectors 3(CIDE3) full length cDNA for construction the eukaryotic expression vector pcDNA3.l(+)-CIDE3 and to study its bioactivity.Methods:① Total RNA was extracted from human white adipose tissues and the desired cDNA fragment was obtained by RT-PCR.After the fragment had being inserted into an eukaryotic expression vector pcDNA3.l(+),the resulted recombinant plasmid pcDNA3.l(+)-CIDE3 was transformed into DH5?.The positive clone was selected and confirmed to contain full length of CIDE3 cDNA by agarose gel and DNA sequence analysis.②After the pcDNA3.l(+)-CIDE3 plasmid was transfected into HeLa cells under lipofectamine mediation,the effect of target gene expression on growth of HeLa cells was analysed by TUNEL staining. Results:① The recombinant eukaryotic expression plasmid pcDNA3.l(+)-CIDE3 was constructed successfully and the sequence of CIDE3 was consistent with that of genebank.②After transfected pcDNA3.l(+)-CIDE3,HeLa cells presented distinguished apoptosis(about 15%),compared with that of transfected plasmid pcDNA3.l(+)(

Objective:To investigate the expression and significance ofβ1 integrin, Rac1, and RhoA in invasive micropapillary breast carcinoma (IMPC). Methods:Immunohistochemical staining was performed to detect the expression ofβ1 integrin, Rac1, and RhoA in 89 patients with IMPC and 90 patients with invasive ductal carcinoma-not otherwise specified (IDC-NOS) who were treated between January 2007 and December 2008 in Tianjin Medical University Cancer Institute and Hospital. The relationship among the three proteins and the expression ofβ1 integrin, Rac1, and RhoA with clinicopathological features were determined. Results:β1 integrin (78.7%) and Rac1 (76.4%) were highly expressed in patients with IMPC. This expression was significantly higher than that in patients with IDC-NOS (63.3%and 54.4%). Statistical difference was found between the two groups (P<0.05). Positive rate of RhoA (68.5%) in patients with IMPC was also statistically higher than that in patients with IDC-NOS (44.4%, P=0.001). In patients with IMPC, the expression ofβ1 integrin and Rac1 was positively associated with lymph node metastasis (P<0.05), while the expression ofβ1 integrin was positively correlated with Rac1 expression (P=0.006). Expression of RhoA was positively correlated with lymph node involvement and ER and PR status (P<0.05). However, no correlation was found between RhoA expression and the expression ofβ1 integrin and Rac1 (P>0.05). Conclusion:Thus,β1 integrin, Rac1, and RhoA were overexpressed and might play an important role in the high frequency of metastasis in patients with IMPC. These proteins could be considered as biomarkers for the prognosis and new targets for IMPC therapy.

Breast cancer is one of the major causes of death in women,and its incidence has been increasing year after year.The Rho GTPases,their regulatory proteins and Rho GTPases play an important role in promoting the occurrence and distant metastasis of breast cancer.Here we summarized the current knowledge of the regulation network of Rho GTPases,their regulatory proteins and Rho GTPases on the occurrence and development of breast cancer,and targeted therapy for RHO GTP enzyme pathway in breast cancer.

BACKGROUND:Researches showed that the enriched environment could improve the cognitive dysfunction of rats with vascular dementia. However, there are few reports regarding its mechanism of action.
OBJECTIVE:To explore the effect of enriched environment on the cognitive dysfunction of rats with vascular dementia from the behavioral level.
METHODS:Vascular dementia models weremade by permanent ligation of bilateral common carotid arteries and were divided into vascular dementia group (n=8) and enriched environment group (n=12). Vascular dementia group was taken care under conventional breeding environment for 30 days, while the enriched environment group was subjected to the enriched environment for 30 days. Morris water maze test was adapted to test the cognitive function of rats between two groups. Immunohistochemistry and immunoblotting were applied to observe the number ofDCX+cels and DCX protein level in both groups. The number of DCX-labeled cels co-expressing NeuN was observed using immunofluorescence technique.
RESULTS AND CONCLUSION:(1) The escape latency in the vascular dementia group was longer than that in the enriched environment group (P< 0.05). The times across the platform was less in the vascular dementia group than that in the enriched environment group (P< 0.05). (2) In comparison with the enriched environment group, the number of DCX-positive cels andits protein level in the piriform cortex were significantly decreased in the vascular dementia group (P< 0.05). (3) The number of DCX/NeuN co-labeled cels in the piriform cortex was significantly less in the vascular dementia group than in the enriched environment group (P< 0.05). (4) These findings suggested that enriched environment could improve the cognitive dysfunction of rats with vascular dementia through promoting the expression and differentiation of the immature neurons.

Objective:To explore the correlation between medication adherence and quality of life (QOL) in aged pa‐tients with hypertension from communities .Methods :Chinese questionnaire of quality of life in patients with cardi‐ovascular disease (CQQC) and Morisky medication adherence scale were used to investigate and analyze 197 aged pa‐tients with hypertension from communities .Results:Total score of CQQC was (78.69 ± 9.36) scores in the 197 aged patients with hypertension from communities .In which ,77 cases (39.09% ) possessed good medication adherence , and 120 cases ( (60. 91% )) with poor adherence to medication . Compared with those with poor adherence to medi‐cation,therewassignificantriseintotalscoreofCQQC [(75.73±8.52)scoresvs.(83.31±8.76)scores ,P<0.01] .Pearson correlation analysis indicated that QOL was significant positively correlated with medication adher‐ence (r=0.397 , P<0.01) .Conclusion:Community health staff should pay attention to influencing factors of med‐ication adherence in aged patients with hypertension ,take individualized and targeted interventional measures to im‐prove their adherence to medicationand quality of life .

AIM: To investigate the effect of advanced glycosylation end products(AGEs) modified protein on morphological changes of actin cytoskeleton in primary endothelial cells and the role of MAPK signaling pathways in this pathological procedure.METHODS: Human umbilical vein endothelial cells(HUVECs) were incubated with AGEs modified human serum albumin(AGE-HSA) at concentrations of 12.5,25,50,and 100 mg/L,respectively,for 2,4,8,12 and 24 hours.The cells were treated with different chemical compounds of inhibitors,or adenoviral deliver approach(either dominant positive or negative adenoviral constructs) of MAP kinases to specifically block or activate certain signal transduction pathways under above situations.As control,HSA of the same concentration was administered to cells at the same time.The treated cells were incubated with FITC-phalloidin to stain F-actin.RESULTS: F-actin in HUVECs was rearranged greatly by AGEs in a concentration and time-dependent manners.The unmodified HSA did not influence Factin distributions.The AGEs-induced changes were blocked by pretreatment with SB203580,PD98059 for 30 min,or pre-infection with recombinant virus of dominant negative form of MKK 6b [MKK6b(A)],MEK1 [MEK1(A)] for 24 h,while SP600125 and dominant negative form of MKK7 [MKK7(A)] failed to inhibit the effects of AGEs.Furthermore,the infection of recombinant virus of constitutive active form of MKK6b [MKK6b(E)] or MEK1 [MEK1(E)] could also induced re-arrangement of F-actin,respectively,while the effect elicited by [MKK6b(E)] was abolished by co-infection with recombinant adeno-virus of dominant negative p38?. CONCLUSION: AGEs-induced morphological changes of F-actin in endothelial cells are mediated by p38-and ERK MAPK signal pathways.

OBJECTIVE To investigate the dynamic changes in urine metabolic profiles in rats induced by D-galactose (D-Gal),and to study the correlations between the differential metabolites and behavior indicators using the proton nuclear magnetic resonance (1H-NMR)-based metabonomics.METHODS Subcutaneous injection of D-Gal 100 mg· kg-1 for 10 weeks was adopted in the model group.The sample of urine was collected at day 0 (dO),d14,d28,d42,d56 and d70.NMR metabonomics technique was used for acquisition of data,which was analyzed by multivariate statistical analysis.The ability of learning and memory were measured by Morris water maze test from d70.After the behavioral test,the rats were sacrificed and the hippocampus was observed by hematoxylin-eosin staining.RESULTS Principal component analysis (PCA) results revealed that there was considerable difference between the model group and the normal control group at d70.According to the varible importance plot (VIP) calculation and S-plot scores,a total of 12 metabolites were screened and identified as potential biomarkers at d70.The differences of metabolites and Morris water maze test were subjected to correlation analysis,and the results showed that the levels of choline,lactate and dimethylglycine in the model group were significantly increased and negatively correlated with the times of crossing the platform (r =-0.90,-0.50 and-0.52;n=10).Formate was significantly negatively correlated with the time spent in the target area (r =-0.51,n=10),but choline and formate were significantly positively correlated with the escape latency (r =0.72 and 0.53;n=10).However,the levels of creatine and taurine decreased in the model group,which was significantly positively correlated to the times of acrossing platforms (r =0.89 and 0.71;n=10),while alanine was significantly positively correlated to the time spent in the target area(r =0.74,n=10).Taurine,alanine and creatine were significantly negatively correlated with the escape latency (r =-0.66,-0.50 and-0.85;n=10).The correlations between the differential metabolites and the behavioral indicators were further proved.CONCLUSION The metabolic profile changes in urine from D-Gal induced aging model rats are significantly correlated with impairement of ability in learning and memory.1H-NMR metabonomics in urinary metabolic profile changes may be used as an evaluation index in the D-Gal induced aging rats model.

Objective:To analyze the differentally expressed long non-coding RNA (lncRNA) among mice of different ages and explore the mechanism of kidney aging.Methods:Male C57BL/6 mice aged 3-month-old ( n=5), 12-month-old ( n=5) and 24-month-old ( n=5) (each weighting about 25 g) were randomly selected. PAS staining, Masson staining and senescence associated β-galactosidase (SA-β-gal) staining were used to detect the pathology and cell senescence of mice kidney. High throughput sequencing was performed to detect the differentially expressed lncRNA and their fragments per kilobase million. Real-time quantitative PCR was used to verify the differentially expressed lncRNA. Competitive endogenous RNA (ceRNA) network, which consisted of lncRNA, miRNA and mRNA was built. GO and KEGG enrichment analysis method were used to predict the biological function of differentially expressed lncRNA. Results:PAS staining and Masson staining showed the development of kidney fibrosis, and SA-β-gal staining positive region was increased significantly as age increased. There were 938 known lncRNA and 542 novel lncRNA differentially expressed among different ages' mouse kidney. Compared with 3-month-old mice, 33 lncRNA were up-regulated and 43 lncRNA were down-regulated in 12-month-old mice. Compared with 3-month-old mice, 130 lncRNA were up-regulated and 91 lncRNA were down-regulated in 24-month-old mice. Compared with 12-month-old mice, 36 lncRNA were up-regulated and 22 lncRNA were down-regulated in 24-month-old mice. The results of qRT-PCR about verified 10 lncRNAs with larger differential expression multiples and higer expression levels were consistent with the sequencing data. GO enrichment analysis showed that the target genes of lncRNA differentially expressed in the three groups were mostly located in the nucleus and cytoplasm, and might play a role by binding to proteins or participate in various protein phosphorylation, cell cycle, transcription, transcription regulation and other processes. KEGG enrichment analysis showed that the target genes of lncRNA differentially expressed in the three group were significantly enriched in Rap1 signaling pathway, FOXO signaling pathway and MAPK signaling pathway, which were closely related to kidney aging.Conclusion:There are significant differences in expression of lncRNA among the kidney of different ages mice, which are involved in the occurrence of renal senescence.

The incidence of primary intestinal lymphoma (PIL) in primary gastrointestinal lymphoma (PGIL) is much lower than that of primary gastric lymphoma (PGL). Treatment strategies for PGL have been normalized, but there are still controversies concerning about the diagnosis criteria and optimal treatment of PIL. The lesions are mainly found in intestinal tract, and the most common involvement is ileocecal junction. The pathological types are derived from B-cell and diffuse large B-cell lymphoma (DLBCL) is the most common type, followed by extra-nodal marginal zone lymphoma of mucosa-associated lymphoid tissue. Surgery, chemotherapy, radiotherapy, antibiotics and monoclonal antibody therapy could be used as the monotherapy or different combined therapies, however, the final conclusion has not been reached in the treatment of PIL, accompanied by various influencing factors for prognosis. This review discusses the diagnosis criteria, clinical features, optimal treatment and prognostic factors of PIL. The diagnosis criteria and the optimal treatment will be put more emphasis.