Objective: To evaluate the malignant potential of oral lichen planus (OLP) by measuring and analyzing the dimensions of spinous cell in mucosal epithelium.Methods:Paraffin-embedded samples of oral mucosa, including normal (N,7 cases), OLP(16 cases), oral leukoplakia(12 cases) with mild and moderate epithelial dysplasia (LK) and well differentiated oral squamous cell carcinoma (SCC,10 cases), were analyzed by MIAS-99 System.The planar and stereoscopic dimensions of spinous cells were measured and compared.Results:The values of morphometric and stereologic parameters in OLP were between those in normal mucosa and in LK, significantly different from those in SCC and not significantly different from those in normal epithelium.Conclusion:Based on the changes of cell morphometric parameter value, OLP is generally a benign lesion with some degree of malignant potentiality that is less than LK.Nucleus/cytoplasm volume ratio and volume density of cell nucleus of spinous cells in mucosal epithelium are of value in distinguishing benign from maliganant lesions.

Objective To explore the curative effect of modified closed negative pressure drainage on abnormal abdominal incision. Methods Sity-three patients with abnormal healing of abdominal incision in our hospital from January 2012 to June 2013 were selected as the observation group. Another 50 patients from January to December 2011 were assigned to the control group. The former was treated after debridement with human recombinant surface growth factor and modified closed negative pressure drainage,while the latter after debridement with anti-infection and dressings of ethacridine or gentamicinsolution as well as with infrared therapy. The two groups were compared in terms of the frequency,time and cost of changed dressings,and the healing time of the incisions.Results There was insignificant difference in the cost of changed dressings between the two groups(P>0.05). However,the differences were statistically significant in terms of the frequency and time of changed dressings and the healing time of the incisions(P<0.05). The observation group was significantly superior to the control group.Conclusions Modified closed negative pressure drainage is effective in accelerating the healing in abnormal abdominal incisions,reducing the frequency and the time of changed dressings,and easing the economic burdens of the patients,which is suggested to be popularized and applicable in the pimary hospitals.

Objective To investigate the laparoscopie resection of the adrenal tumor effects and clinical experience. Methods Among the 24 cases of Laparoscopic adrenalectomy tumors, there were 8 cases of adrenal adenoma, 7 cases of pheochromoeytoma and 9 eases primary aldosteronism. Results One ease was transit to open operation, the other 23 were successful,each surgerical time was 40～130 min with an average of 98 rain. Hemorrhage was 50～300 mL, 140 ml average, no blood transfusion. It was 1～2 d after sur- gery to remove drainage tubes, and could take some activities and have fresh flow in the second day. The pa- tients didn't appear complications and discharged after 5～7 d. Follow-up of 6～24 months, there was no recurrence and long-term complications. Conclusion Laparoscopic adrenalectomy has the advantages of minor trauma surgery, less bleeding, good demonstrating, convenient operation, fewer complications and quick recovery.

Objective To investigate the expression and the significance of toll-like receptor 3 (TLR-3)in placenta,tumor necrosis factor-α(TNF-α)in maternal and cord blood of idiopathic fetal growth restriction(IFGR),and their correlation with the pathogenesis of symmetric and asymmetric IFGR.Methods From April 2008 to April 2009,42 primiparae of singleton pregnancy and their IFGR babies,who delivered at term through cesarean section, in the Third Affiliated Hospital of Zhengzhou University were enrolled. All subjectects were divided into symmetric IFGR group (n=20) and asymmetric IFGR group (n =22). Another 42 non-IFGR pairs were randomly selected as the control group. The polink-2 plus polymerized horseradish peroxidase (HRP) immunohistochemical method and the enzyme linked immunosorbent assay (ELISA) were applied to detect TLR-3 and TNF-α levels. Results (1) The expression of TLR-3 protein were observed in all maternal placenta of the three groups. TLR-3 essentially expressed in syncytiotrophoblasts and hofbouer cells in the symmetric IFGR and control group, but expressed mostly in hofbouer cells and less in syneytiotrophoblasts in the asymmetric IFGR group. (2) The expression of TLR-3 in the syncytiotrophoblasts of the symmetric and asymmetric IFGR group was significantly lower than in the control group (111±14 and 118±11 vs. 156 ± 9, P<0. 01). The number of TLR-3 positive in Hofbourer cell in the symmetric IFGR group was lower than the control group (8. 9±2. 8 vs 17.5±2. 8, P <0. 01 ), but the number in the asymmetric IFGR group was higher (23.8±3.7) compared with the control group (P <0. 01). (3) The TNF-α levels in the maternal and cord blood of the symmetric and the asymmetric group were higher than that of the control group [maternal : (90±10) μg/L and ( 86±11 ) μg/L vs. (73±9) μg/L;cord blood: (92±12) μg/L and (96±8) μg/L vs. (79±9) μg/L;P<0.01]. (4) Neither symmetric nor the asymmetric IFGR group showed any correlations between the maternal and cord blood levels of TNF-α (P>0. 05). (5) Significant correlation was found between the TNF-α level of the cord blood and TLR-3 expression in the placenta in both the symmetric and asymmetric IFGR group(P<0. 05),but no relationship was found between the maternal blood TNF-α level and TLR-3 expression in the placenta (P>0. 05). Conclusions The variantions of TLR-3 expression in placenta and the increased expression of TNF-α in cord blood are associated with the genesis IFGR. The reduced expression of TLR-3 may related to symmetric IFGR, while the increased TLR-3 level in hofbouer cells may lead to asymmetric IFGR.

Objective To compare the therapeutical effect of puerarin, ligustrazine, ginsenoside Rb1, Hydroxysafflor yellow A on cerebral ischemia reperfusion mice. Methods The mice were randomly assigned for sham group, model group, puerarin group, ligustrazine group, ginsenoside Rb1 group, and Hydroxysafflor yellow A group, 24 mice for each group. All the groups were subjected to middle cerebral artery occlusion (MCAO) by 1 h ischemia and 24 h of reperfusion except the sham group. The puerarin, ligustrazine, ginsenoside Rb1, Hydroxysafflor yellow A were administrated by tail vein injection with 3μmol/kg at the onset of 1 h of ischemia. The neurologic deficit score, infarct area calculated by TTC staining, cerebral cortex blood flow monitored by laser doppler flowmetry, NO content measured by chemical colorimetry and western blot were applied to determine the expression for cleaved-caspase-3 and nuclear transcription factor NF-κB for each group. Results Compared with the model group, the infarct area (15.83%± 1.83%, 22.00%± 2.53%, 22.83%± 1.83%, 17.83%± 1.72%vs. 34.67%± 2.66%) in the puerarin group, ligustrazine group, ginsenoside Rb1 group, Hydroxysafflor yellow A group was significantly decreased (P<0.01 or P<0.05);the cerebral cortex blood flow (598.81 ± 9.90 μl/kg?min-1, 614.78 ± 9.20 μl/kg?min-1, 577.83 ± 5.55 μl/kg?min-1, 583.54 ± 7.98 μl/kg?min-1 vs. 548.43 ± 1.97 μl/kg?min-1) significantly increased (P<0.01 or P<0.05);the NO content (17.09 ± 1.18μmol/L, 18.54 ± 0.54μmol/L, 18.17 ± 0.49μmol/L, 15.10 ± 0.73μmol/L vs. 20.63 ± 0.73μmol/L) ignificantly decreased (P<0.01 or P<0.05);the expression of cleaved-caspase-3 (1.02 ± 0.08, 1.12 ± 0.04, 0.87 ± 0.08, 1.07 ± 0.08 vs. 1.30 ± 0.06) and NF-κB p-p65/NF-κB p65 (1.03 ± 0.19, 1.15 ± 0.05, 1.12 ± 0.08, 0.72 ± 0.08 vs. 1.45 ± 0.08) ignificantly decreased (P<0.01 or P<0.05) Conclusions Four Chinese herbal monomers could improve nerve and cerebral dysfunctions and ameliorate ischemia symptoms with varying degrees. The mechanisms were involved with the enhancement of cerebral cortex blood flow and inhibition of cell apoptosis and the activation of inflammatory signaling pathways.

The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-∞) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol x L(-1) Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol x L(-1). The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94)% and (63.61 ± 3.94)%, respectively, by Danshensu at 1 and 10 μmol x L(-1). While transport of rosuvastatin was reduced by (8.22 ± 2.40)% and (11.56 ± 3.04)% and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATPJBI. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.

Objective: To observe and analyze the role of intestinal barrier in the pathognesis of autoimmune hepatitis (AIH), to explain the pathogenesis of AIH and to explore the intestinal based new treatment strategies. Methods: A total of 14 AIH patients from January to December 2017 at Tianjin Medical University General Hospital (six patients without liver cirrhosis, and eight patients with liver cirrhosis) and 10 healthy controls were enrolled. The serum levels of D-lactic acid (D-Lac) and diamine oxidase (DAO) were detected by enzyme-linked immunosorbent assay. Real time fluorescence quantitative polymerase chain reaction was used to detect the relative expression levels of connexin (zonula occluden-1 (ZO-1), occludin), cytokines (interleukin(IL)-2, interferon(IFN)-γ, IL-4, IL-10) and Toll-like receptor 4 (TLR4) in terminal ileal tissues of each group. The relative expression of secretory immunoglobulin A (sIgA) in the terminal ileum was determined by Western blotting. Thirty BALB/c mice were selected and divided into blank control group, dextran sulfate sodium (DSS) group, concanavalin A (ConA) group, DSS+ ConA group, and DSS+ bacterium+ ConA group, with six mice in each group. The relative expression levels of ZO-1, occludin in mouse colonic tissues, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and inflammatory activity degree of liver tissues (Knodell score) of each group were measured. T-test and one-way analysis of variance were performed for statistical analysis. Results: The serum D-Lac and DAO levels of AIH with liver cirrhosis group and AIH without liver cirrhosis group were both higher than those of healthy control group ((1 768.2±147.1) μg/L, (436.2±197.0) μg/L vs. (100.2±10.9) μg/L, and (11.5±2.5) U/L, (5.4±0.9) U/mL vs. (3.5±0.9) U/mL), and the levels of D-Lac and DAO of AIH with liver cirrhosis group were the highest; and the differences were statistically significant (t=5.512, 36.010, 4.088 and 9.443, F=396.958 and 46.640, all P<0.01). The relative expression levels of ZO-1 and occludin in the terminal ileal mucosa of AIH with liver cirrhosis group were lower than those of healthy control group (0.20±0.14 vs. 1.67±0.51, 0.12±0.09 vs. 0.90±0.21), and the relative expression of ZO-1 in AIH without liver cirrhosis group was lower than that in healthy control group (0.99±0.37 vs. 1.67±0.51); and the differences were statistically significant (t=8.641, 7.407 and 2.295, all P<0.05). The relative expression levels of IL-2 and IFN-γ in terminal ileal tissues of AIH with liver cirrhosis group were higher than those of healthy control group (1.11±0.43 vs. 0.24 ±0.16, and 3.50 ± 1.90 vs. 0.32±0.30), however the relative expression of sIgA in terminal ileal tissues was lower than that of healthy control group (0.506±0.024 vs. 1.081±0.102); and the differences were statistically significant (t=4.679, 3.981 and 5.493, all P<0.05). While the relative expression levels of IL-10 in AIH with liver cirrhosis group and AIH without liver cirrhosis group were lower than that in healthy control group (0.30±0.20, 0.42±0.24 vs. 0.84± 0.23), and the relative expression levels of TLR4 in ileum mucosa of the both groups were higher than that of healthy control group (8.74 ±5.13, 6.74 ±3.65 vs. 0.89 ± 0.70); and the differences were statistically significant (t=3.095, 4.816, 3.856 and 3.685, all P<0.05). The relative expression levels of ZO-1 and occludin of DSS+ ConA group were lower than those of ConA group (0.14±0.08 vs. 0.98±0.13, and 0.09±0.02 vs. 0.98±0.16), however serum ALT, AST levels and the Knodell score were all higher than those of ConA group ((5 496.67±618.83) U/L vs. (3 325.00±1 030.06) U/L, (8 825.00±1 165.35) U/L vs. (5 433.33±1 691.14) U/L, and 18.00±2.00 vs. 9.33±3.01); and the differences were statistically significant (t=13.480, 13.520, 4.227, 4.045 and -2.892, all P<0.05). The relative expression levels of ZO-1 and occludin in DSS+ bacterium+ ConA group were higher than those in DSS+ ConA group (0.46±0.08 vs. 0.14±0.08, and 0.53±0.15 vs. 0.09±0.02), while serum ALT and AST levels were lower than those of DSS+ ConA group ((4 343.33±252.16) U/L vs. (5 496.67±618.83) U/L, and (6 123.33±1 086.60) U/L vs. (8 825.00±1 165.35) U/L); and the differences were statistically significant (t=6.928, 7.122, 4.228 and 4.153, all P<0.01). Conclusions AIH patients have increased intestinal permeability and impaired intestinal barrier which is more serious in patients with liver cirrhosis than in patients without cirrhosis. The intestinal barrier injury can aggravate ConA-induced immune-mediated liver injury. While the protection and repair of intestinal barrier can alleviate immune-mediated liver injury induced by ConA.

Objective:To explore the potential Hub genes, key miRNAs, biological processes and related signaling pathways in the pathogenesis of osteoarthritis (OA), and provide bioinformatics basis for the pathogenesis and treatment of OA.Methods:The expression profiling chip of OA synovial tissue sample from Gene Expression Omnibus (GEO) were downloaded, differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. A protein-protein interaction network (PPI) was constructed. STRING and Cytoscape was used for module analysis, and the Hub gene was further identified, and further miRNAs mining of the Hub gene was carried out.Results:Finally, 9 Hub genes (SOCS3, BTRC, FBXO32, KLHL22, UBE3A, HUWE1, UBR4, ANAPC5, TRIM50) and 2 key miRNAs (hsa-miR-103a-3P, hsa-miR-107) related to the progression of OA were identified .They might be potential biomarkers for the pathogenesis of OA. We also found that signal transduction, the transcriptional positive regulation of RNA polymerase Ⅱ promoter, and protein serine/threoninase activity had a certain correlation with the pathogenesis of OA. In addition, our analysis results showed that cAMP signaling pathway and Rap1 signaling pathway were also involved in the progression of OA.Conclusion:The potential biological molecules, biological processes and related pathways identified in this study may guide us for the further research on the etiology and treatment of OA.

T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.