Animals ; Atherosclerosis ; etiology ; metabolism ; Gene Expression Regulation ; Humans ; Lipase ; analysis ; genetics ; physiology ; Lipoproteins ; metabolism ; Lipoproteins, HDL ; metabolism ; Lipoproteins, LDL ; metabolism ; Polymorphism, Genetic ; Tissue Distribution

AIM: To study the effect of the subretinal fluid (SRF) on proliferation of retinal pigment epithelium (RPE) cells and retinal glial (RG) cells and associated activation and translocation of protein kinase C (PKC) as well as the application of PKC inhibitor.MTEHODS: RPE and RG cells were disintegrated to obtain PKC activity of cytoplasm and cellular membrane after being treated by the subretinal fluid (SRF) from the different stages of PVR patients (grade B and C) or being treated with PKC specific activator [phorbol-12-myris-tate-13-acetate (PMA)] or normal vitreous or DMEM culture medium. PKC activity in cytoplasm and cellular membrane was measured using radioactive isotope 32P labeling in a specific reaction of phosphorylation on PKC substrate. In addition, the PKC inhibitor, dequalinium chloride, was used to pretreat the RPE and RG cells before the cells exposed to SRF or PMA or normal vitreous. 3H-TdR (tritiated thymidine) was used to measure the levels of proliferation of RPE and RG cells with or without the activation and translocation.RESULTS: SRF and PMA promoted the proliferation of RPE and RG cells. SRF and PMA activated PKC in the cytoplasm of RPE and RG cells and the activated cytoplasm PKC translocated to the cellular membrane of RPE or RG cells. The cell proliferation or PKC activation or translocation were not equally active in RPE as in RG cells. However, PKC inhibitor which attenuated the cell proliferation did not show significant difference on inhibition of RPE and RG cell proliferation. (P ＞0.05).CONCLUSION: SRF can lead to the activation and translocation of PKC in RPE and RG cells, which promote the proliferation of RPE and RG cells. Dequalinium chloride can inhibit PKC activation and translocation hence slow down the cells proliferation.

Objective To find an internal quality controlling method for 17-OHP determination by time-resolved fluoroimmuno-assay .Methods 20 quality control data were collected .The data were analyzed by using L-J method ,instant method and improved instant method .Results were used for the construction of quality control charts .Result The first three quality control data had a great impact on the following judgments of internal quality controlling when instant method was used .The subsequent results might be false acceptance .Improved instant method could effectively reduce the situations of false run-away and false acceptance ,which was suitable for the internal quality control of 17-OHP determination by time-resolved fluoroimmunoassay in newborn screening . Conclusion There are many steps of manual operations in 17-OHP determination of time-resolved fluoroimmunoassay .The details of these operations have great impacts on the experimental results .Thus ,the operations of 17-OHP test should be specified and exe-cuted strictly according to requirement .

Recently,increasing cancer researches focus on antibody-drug conjugates(ADCs) which can improve the anti-tumor potency with less adverse effect while benefiting patients in the future. However,safety evaluation of ADCs is a big challenge because of complex components as well as in experience in preclinical studies. In this review,the authors reviewed the mode of action,hazard risks,and toxicity observed in preclinical/clinical studies of ADCs,summarized the preclinical studies of Adcetris(brentuximab vedotin)and Kadcyla(ado-trastuzumab emtansine),and suggested a better strategy of ADCs in preclinical safety evaluation.

Objective To investigate the changes of T cells and disease development in the mice with Smad3 deficiency in the bone marrow cells.Methods Bone marrow cells obtained from Smad3 null(Smad3~(-/-))mice and wild type(Smad3~(+/+))mice were injected to Co~(60)-irradiated GFP mice,respectively.The general states of the bone marrow recipients were observed.The mice were sacrificed at the sixth week and the histopathological changes in the intestines were examined.The changes of T cells from lymph nodes were detected by flow cytometry.Results Smad3~(-/-) bone marrow recipient mice appeared a wasting syndrome and intestinal inflammation.The amount of CD4~+ CD62L~(lo) T cells in lymph nodes was significantly increased.Conclusion These results indicate that the mice with Smad3 deficiency in the bone marrow cells present an inflammatory disorder and their T cells are activated.

BACKGROUND:Corneal stromal fibroblasts have been shown to express interleukin-8 in the stimulation of lipopolysaccharide. Different reactions of fibroblasts to lipoprotein or other inflammatory mediators may constitute different characteristics of different tissues in the inflammatory response. OBJECTIVE:To observe the inhibitory effect of IKK-2 receptor blocker TPCA-1 on human corneal stromal fibroblasts to secrete inflammatory cytokines, chemokines and cel adhesion molecules under the stimulation of lipopolysaccharide and its signal transduction pathway, to compare with dexamethasone, and to explore alternative or synergistic effects after their combination. METHODS:This study measured the secretion of interleukin-1, tumor necrosis factor alpha, interleukin-6, and interleukin-8 from cultured human corneal stromal fibroblasts under the action of basic state and lipopolysaccharide, and their changes after the intervention with IKK-2 receptor blocker TPCA-1 and dexamethasone. We also detected expression level of intercelular adhesion molecule-1 and interleukin-6 in cel surface, and verified the changes in expression levels of intercelular adhesion molecule-1, interleukin-6, and interleukin-8 from mRNA level, as wel as examined the expression of nuclear factor kappa B under above conditions.

ObjectiveTo evaluate the therapeutic efficacy of bleeding cupping with different acupoints and frequencies in treating acne vulgaris.MethodSixty-four patients were divided by using stratified randomization method into Dazhui (GV14) group of 32 cases (16 cases in the subgroup of once every week, and the other 16 cases in the subgroup of twice every week) and Geshu(BL17) group of 32 cases (16 cases in the subgroup of once every week, and the rest 16 cases in the subgroup of twice every week). Dazhui group received bleeding cupping once every week or twice every week, while Geshu group also received bleeding cuppingonce every week or twice every week. The acne symptoms scores and total score were observed before and after intervention to evaluate the therapeutic efficacy.ResultThe symptoms scores including oily condition, skin lesion nature, counts, color, and swelling pain were decreased after intervention in the two groups (P<0.01). The improvement of oily condition in Geshugroup was more significant than that in Dazhuigroup (P<0.05). The symptoms scores including oily condition, skin lesion nature, counts, color, and swelling pain were decreased after intervention in all the subgroups of different frequencies (P<0.01). The improvements of skin lesion nature and swelling pain were more significant in the subgroups of twice a week than that in the subgroups of once a week (P<0.05).ConclusionBleeding cupping with different acupoints and frequencies all can produce satisfactory efficacies; bleeding cupping at Geshucan produce a more significant efficacy than that at Dazhui;treatment at a frequency of twice a week can produce a more significant effect than once a week in improving skin lesion nature and swelling pain.

Adenoma, Acidophil ; metabolism ; Adult ; Angiomyolipoma ; genetics ; metabolism ; pathology ; Carcinoma, Renal Cell ; metabolism ; Codon ; Diagnosis, Differential ; Exons ; Female ; Follow-Up Studies ; Gene Deletion ; Genes, p53 ; Humans ; Kidney Neoplasms ; genetics ; metabolism ; pathology ; Male ; Melanoma-Specific Antigens ; metabolism ; Middle Aged ; Retrospective Studies ; Tumor Suppressor Protein p53 ; genetics ; metabolism

Female ; Granulomatosis with Polyangiitis ; complications ; diagnosis ; Humans ; Otitis Media ; diagnosis ; etiology ; Young Adult

Background Proliferative vitreoretinopathy (PVR) is one of the major causes of retinal detachment surgery failure.Based on proteomic studies of PVR vitreous,the insulin-like growth factor binding protein-6 (IGFBP-6) protein was specifically expressed in the vitreous and serum of PVR patients.Furthermore,its expression level is higher in the vitreous and serum in severe PVR patients than that in mild PVR patients.Objective This experiment was to detect the expression of IGFBP-6 in a PVR rat model.Methods Seventy 7-week old male SPF Wistar rats were included and were randomized into the PVR model group and control group.A mixture of RPE-J cell suspension(5 μl) and platelet-rich plasma (5 μl) was intravitreally injected in the left eyes of adult Wistar rats to establish the PVR model,and normal saline solution was administered in the same way in the control group.The rat eyes were clinically examined 1 week,2,3 and 4 weeks after injection,and PVR was graded based on the criteria of Francine.The animals were sacrificed after 1 week,2,4 or 8 weeks for the preparation of retinal sections and liver extraction.Expression levels of IGFBP-6 mRNA in the rat retina and liver were assayed by real-time Q-PCR.The expression of IGFBP-6 protein in the rat serum and vitreous was detected by ELISA.The use of animals complied with the Regulations for the Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission.Results Purified IGFBP-6 RNA was extracted from the liver and retina of Wistar rat and quantified by real-time Q-PCR.The expression level of IGFBP-6 mRNA in retina was (3.79± 1.33) × 10-4 in the PVR model rats,showing a significant decline in comparison with the control rats with a level of(8.32±2.96) × 10 4,4 weeks after injection (t =3.42,P＜0.01).The expression of IGFBP-6 mRNA in the 4th week was significantly lower than that of 1 week,2 or 8 weeks after the establishment of the PVR model(P＜0.05).No significant difference was found in the IGFBP-6 mRNA level in the liver between the PVR group and control group(27.60± 14.01 × 10 4 vs.25.01 ± 12.04 ×10-4,respectively),as well as among the different time points(P＞0.05).IGFBP-6 mRNA content in the retina was significantly reduced in grades 1,2 or 3 of the PVR groups compared with the control group(P＞0.05),but there was no significant difference among the different grades of PVR groups (P＞0.05).Concentrations of IGFBP-6 protein in grades 1,2 and 3 of the PVR model group were (221.00 ± 19.32),(229.63 ± 18.89) and (225.70 ± 26.71) μg/L,with a significant elevation in comparison with (173.25 ±21.11) μg/L of the control group (t =2.14,P＜0.05).However,there was no significant change among the different grades of PVR groups(t=1.24,1.46,P＞0.05).The concentrations of IGFBP-6 protein in the vitreous and serum were higher in PVR rat samples (vitreous:225.44±19.36 μg/L;serum:108.48 ± 15.78 μg/L) than in control rats (vitreous:173.25 ± 21.11 μg/L,serum:95.96 ±17.40 μg/L)(P＜0.05).Conclusions The concentrations of IGFBP-6 protein in the vitreous and serum increase in PVR rats.The results indicate that the increased IGFBP-6 in the vitreous might be a localized autocrine secretion of the eye.