Background: Excessive growth of keratinocytes is the critical event in the etiology of psoriasis.However, the underlying molecular mechanism of psoriatic keratinocyte hyperproliferation is still unclear. Objective: This study aimed to figure out the potential contributory role of S-phase kinase-associated protein 2 (SKP2) in promoting the hyperproliferation of keratinocytes in psoriasis. Methods: We analyzed microarray data (GSE41662) to investigate the gene expression of SKP2in psoriatic lesion skins compared with their adjacent non-lesional skin. Then, we further confirmed the mRNA and protein expression of SKP2 in human psoriatic skin tissues, imiquimod (IMQ)-induced psoriatic mice back skins and tumor necrosis factor α (TNF-α), interleukin (IL)-17A and IL-6-stimulated keratinocytes by using real-time quantitative polymerase chain reaction and western blot (WB). Furthermore, we explored the potential pathogenic role and its underlying cellular mechanism of SKP2 in promoting keratinocytes hyperproliferation through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell cycle detection, 5-ethynyl-2′-deoxyuridine staining and WB. Finally, we determined whether inhibition of SKP2 can effectively alleviate the keratinocytes hyperproliferation in vivo. Results: We identified that SKP2 is aberrantly upregulated in the psoriatic lesion skin and cytokines-stimulated keratinocytes. Moreover, upregulated SKP2 augments cytokines-induced keratinocytes hyperproliferation. Mechanistically, enhanced SKP2 increased the S phase ratio through inhibiting Cyclin-Dependent Kinase Inhibitor p27 (P27 Kip1) expression. Correspondingly, suppression of SKP2 with SMIP004 can significantly ease the epidermis hyperplasia in vivo. Conclusion Our results suggest that elevated SKP2 can empower keratinocytes proliferation and psoriasis-like epidermis hyperplasia via downregulation of P27 Kip1. Therefore, targeting SKP2-P27 Kip1 axis might be a promising therapeutic strategy for the treatment of psoriasis in future.

Objective To investigate the synergistic effect of hyperhomocystinemia (HHcy) and smoking on the incidence of Coronary heart disease. Methods A total of 22 043 subjects were enrolled from health care center. Participants were classified into two groups: Non-coronary heart disease group (control group, n = 19 410) and coronary heart disease group(n=2 633).A questionnaire survey,physical examination and blood homocysteine (Hcy)test were carried out among the participants.Results After controlling the confounding factors,multivariable Logistic regression analysis showed that the risk of coronary heart disease in patients with smoking was 4.832 times higher than that of patients with normal waistline. The risk of coronary heart disease in patients with HHcy was 1.019 times higher than that of patients with normal Hcy (OR = 4.832,1.019,P < 0.05).Interaction analysis showed that the risk of patients with HHcy and smoking was 2.473 times higher than that of patients without HHcy and no-smoking.The synergy index between HHcy and smoking on the incidence of Coronary heart disease was 1.739. The pure attributable proportion due to the interaction was 42.9%. Conclusions HHcy and smoking are risk factors for coronary heart disease and there is a positive synergistic effect between HHcy and smoking on the incidence of coronary heart disease.

OBJECTIVETo assess the application value in prenatal diagnosis using karyotype analysis combined with BACs-on-Beads (BoBs) assay.

METHODSNine hundred sixty five pregnant women were subjected to amniocentesis, chromosomal karyotype analysis and detection of BoBs were employed simultaneously for abnormal number of chromosomes and 9 chromosome microdeletion syndrome in prenatal diagnosis.

RESULTSFifty cases common chromosome aneupoidies were successfully detected by both karyotype analysis and BoBs which included 31 cases of trisomy 21,10 cases of trisomy 18 and 9 cases with sex chromosome abnormality. BoBs in addition detected 1 case of DiGeorge-1 microdeletion syndrome and 1 case of 7q11.23 microduplication syndrome. All 9 fetuses with chromosome abnormalities detected by karyotyping were missed by BoBs, including 2 cases of marker chromosomes,4 cases of chromosomal translocation,1 case of chromosomal inversion, 2 cases of Sex chromosome mosaicism; 2 cases of fetal inherited from the parents,7 cases for novel mutations.

CONCLUSIONKaryotype analysis combined with BoBs dedtection is a rapid, effective and highly accurate prenatal diagnosis model that may should be widely used in clinical diagnosis.

AIM: To investigate the effect of detoxifying herbs polygonum cuspidatum, and hawthorn, herb of promoting blood flow, on pathologic morphology and inflammatory factors in apolipoprotein E gene knockout mice, in order to approach the possible regulatory mechanism of polygonum cuspidatum and hawthorn for treating artherosclerosis (AS) unstable plaque. METHODS: The animals were divided into 7 groups (12 mice in every group). The ApoE (-/-) mice fed with high fat diet were divided into polygonum cuspidatum group, hawthorn group, polygonum cuspidatum + hawthorn group, Xuezhikang group and high fat diet model group. Moreover, ApoE (-/-) mice fed with normal diet (normal diet group) and C57BL/6J mice fed with normal diet (normal control group) were set up. After intragastric administration for 17 weeks, serum hs-CRP was detected, aorta structure was observed under light microscope and NF-κB protein expression was determined by immunohistochemistry. RESULTS: The pathological change of AS in aorta in all groups fed with high fat diet and normal diet group were observed with different degree. The changes of aortic lesion in all treatment groups were reduced. The levels of NF-κB and hs-CRP in high fat diet group were significant higher than those in normal control group and normal diet group. Serum NF-κB and hs-CRP levels decreased in every treatment group, which were significant different from those in high fat diet model group (P<0.01). Among them, the changes in polygonum cuspidatum and hawthorn groups were the best. CONCLUSION: Chinese herbs of polygonum cuspidatum and hawthorn reduce inflammatory factors NF-κB and hs-CRP expression and play a role in anti-AS formation.

AIM: To investigate the mechanism of basil polysaccharide in inhibiting the invasion and metastasis ability of ovarian cancer,and to evaluate the potency of hypoxia tumour microenvironment in affecting the action of basil polysaccharide.METHODS: The human ovarian cancer cell line SKOV3 was cultured with basil polysaccharide under normoxia(21% O2,5% CO2) and hypoxia(1% O2,5% CO2,94% N2),respectively.Morphology of this cell line in different groups under different oxygen concentrations was observed under inverted phase contrast microscope.The cell invasiveness was tested by transwell method and the activities of matrix metalloproteinase-2(MMP-2) among each group were analyzed by gelatin zymography.The expressions of OPN mRNA and protein levels were detected by RT-PCR and immunohistochemistry,respectively.RESULTS: Compared to the control group,basil polysaccharide decreased the invasiveness and migrating ability and inhibited the secretion of MMP-2 in SKOV3 cells.Basil polysaccharide also reduced the expression level of osteopontin(transcriptional level and protein level) of the SKOV3 cells in both normoxic and hypoxic conditions.Moreover,these functions of basil polysaccharide were more obviously in hypoxia.CONCLUSION: The migrating ability of the SKOV3 cells is enhanced under hypoxic condition.Basil polysaccharide may inhibit the invasiveness and migrating ability of SKOV3 cells through reducing osteopontin expression and MMP-2 secretion.