Even one the same pathological type of various kinds of refractory nephrotic syndrome has great dif-ferent pathogenesis. It is more reported in recent years that new nephrotic medications(such as Ofatumumab and Eculi-zumab)or novel utilized old medications(such as CoQ10,galactose and retinoic acid)used in other diseases were re-searched and developed based on the mechanisms of nephrotic syndrome,or new mechanisms were contrarily discovered when new medications used in other diseases were effectively used in refractory nephrotic syndrome. Here,the novel medications which were successfully used in clinic patients with refractory nephrotic syndrome,or laboratory proteinuric animal models,or the old medications with new and effective actions were introduced. Their mechanisms of drug actions were also briefly described. It is hoped that these information has practical value for the medication selection by clinical nephrologist and for the collision of research idea inspiration by investigators in nephropathy research area.

It is widely accepted that diabetes is intimately linked to diet. The latest researches showed that diet-microbiota interactions acted as moderators of human diabetes. Gluten-free diet and hydrolyzed protein decreased the incidence of type 1 diabetes mellitus (T1DM)by the mechanism of changes in gut microbiota and immune micro-environment. Consuming more dairy products decreased the incidence of type 2 diabetes mellitus (T2DM). High fat diet can induce insulin resistance (IR),thus increasing the incidence of T2DM. Parental dietary affected on offspring diabetes by the epigenetic mechanism. Low carbohydrate diet,dietary fiber and legumes were effective to the treatment of diabetes. Prediction of postprandial glucose level and treatment based on gut microbiota contributed to control the glucose of diabetic patients. An in-depth understanding of these mechanisms provides new ideas for the individualized and precise treatment of diabetes.

Objective: To establish the determination method of total isofraxidin in Ciwujia Tablets. Methods: In this method phenomenex C 18 column was used, acetonitrile -0.05mol?L -1 potassium dihydrogen phosphate solution (15∶85) was used as a mobile phase. The detection wavelength was at 344nm.Results: The recovery of the added sample was 102.8% and RSD was 2.2%. Conclusion: This method is simple and the result is reliable.

Objective To investigate the retinoic acid incubation effect on proliferation of U251 cell line and effect on MAPK signal pathway. Methods ATRA solution of different concentration on the U25 1 glioma cells were incubated,the influence of ATRA on the proliferation of U25 1 cells were detected,and the proteins of MKPs and MAPK signaling pathways were detected by qRT-PCR and Western blot.Using Graph Prism 5 software for quantitative analysis of experimental results.Results Compared with control group,ATRA could effectively inhibit the proliferation of U25 1 glioma cells, in a concentration dependent manner.QRT-PCR results showed that,different concentrations of ATRA after incubation for 48 hours,the expression of MKPs mRNA changed,but the changes of MKP-5 and expression of 67LR was different,explained the main differences between the two methods of the MAPK signaling pathway was the regulation of MKP-5.Western blot results showed that the ATRA,after 48 hours of incubation,the protein MAPK pathway had changed in phosphorylation, which showed that ATRA protein in the MAPK signaling pathway through control of the degree of phosphorylation on U25 1 cell line regulation.Conclusion Retinoic acid and retinoic acid receptor play its physiological effects and regulate human glioma cell line U25 1 proliferation through different combination.Retinoic acid could not only reduce the expression of phosphorylated ERK1/2 to inhibit tumor proliferation,but also regulate three kinds of protein phosphorylation,therefore its mechanism will be more complex,at the same time that the MAPK signaling pathway plays a crucial role in tumor proliferation process.

Objective To explore the effect of subcutaneous composite flaps by crossed filling and supporting within areola combined with continuous distraction on moderate and severe inverted nipple.Methods 33 patients with 59 moderate and severe inverted nipples were involved in this study.The bilateral subcutaneous triangular composite tissue flaps pedicled with the base of the nipple were harvested within areola,the two triangular composite tissue flaps were revolved and advanced either horizontally to the opposite pedicle through the tunnel beneath the nipple and fixed as supporting.After the operation,the continuous distraction of the nipple lasted for two to four weeks,clinical effect and complications were analyzed.Results None of these 59 nipples appeared blood circulation disorder after operation.Postoperative follow-up for 6 months to 3 years showed that 54 inverted nipples were corrected completely without complications,such as nipple and areola necrosis,and there were no recurrence.The patients and doctors were satisfied with the appearance of the nipples.Conclusions Correcting the moderate and severe inverted nipple with subcutaneous composite flaps by crossed filling and supporting within areola combined with continuous distraction is simple,microinvasive,effective,and the incision scar is invisible,and it therefore is an ideal method for correcting the inverted nipple.

Objective To explore the inhibitory effect of mutant influenza A viruses to the activation of interferon regulatory factor 3 (IRF-3). Methods HEK293 cells were infected with A/FM/1/47,A/HK/1/68, A/HK/1/68-MA20, A/HK/1/68-MA20C and positive control Sendai virus (SV). Whether the slowly moved phosphorylation form Ⅲ and Ⅳ of IRF-3 appeared or not was compared by Western blot in cells infected with these viruses. Wild type of NS1 from A/HK/1/68 and mutant NS1 from A/HK/1/68-MA20 were subcloned into pcDNA3.1-flag respectively. They were transfected in HEK 293 cells respectively. At 16 hours posttransfection, cells were infected with Sendai virus for 8 hours. Whole cell extracts were analyzed by Western blot and then probed with monoclonal flag antibody to check the expression of NS1, or with anti-IRF-3 to observe the inhibitory effects of the wild and mutant NS1 to the activated IRF-3. Luciferase assay was carried out by co-transfection with reporter plasmid, pGL2B with interferon ? promoter, and wild or mutant NS1 cDNA expression plasmid. SV was used to infect these cells after the co-transfection. Results Only less virulent A/HK/1/68-MA20 and positive control SV can activate IRF-3. Activated form Ⅲ and Ⅳ of IRF-3 began to appear 9 hours post infection (h.p.i), and most significant activated IRF-3 appeared 23 and 26 h.p.i. Sequence analysis of NS1 of MA20 revealed that nucleotide position number 94 is mutated from T to C, and amino acid at position number 23 is changed from valine to alanine. Co-transfected with wild type NS1 made form Ⅲ and Ⅳ of IRF-3 almost disappear, but not mutant NS1. In the luciferase functional analysis, wild type NS1 can inhibit the luciferase activity of IFN-? promoter, which was induced by SV, to around 1/10. Again no inhibitory effects was observed of mutant NS1 in the luciferase assay. Conclusion The mechanism that A/HK/1/68-MA20 can activate IRF-3 is that point mutant NS1 abolished the inhibitory function of NS1.

The acetylation status of histones and non-histone proteins regulate chromatin remodeling and gene transcription. Histone deacetylase inhibitors (HDACi), a promising therapeutic approach to cancer, are characteristic of causing accumulation of acetylated histones and other transcriptional regulators. Recent studies demonstrate that HDACi is able to arrest the cell cycle in G1 and/or G2 phase, and to induce apoptosis in a variety form of transformed cells with little toxicity to normal cells. However, the exact antitumor mechanisms of HDACi are still unclear. This review provides an update on the current knowledge of HDACi with a focus on HDACi-regulated cell growth arrest and apoptosis.

Objective Interferon regulatory factors 3 (IRF-3) is a key transcription factor to regulate gene expression of interferon after virus infection. This study aims to look for new spliced isoforms of IRF-3 and to investigate their structures and functions. Methods RNA extracts from human embryonic kidney 293 cells were amplified by RACE and RT-PCR. New sequences were compared with published sequences of IRF-3 and murine EST database using bioinformatics method. A new sequence, IRF-3c, was subcloned into pcDNA3.1-flag. The IRF-3c/pcDNA3.1-flag plasmid was transfected in HEK 293 cells. Whole cell extract was analysed by Western blot and then probed with monoclonal Flag antibody. Luciferase assay was carried out by co-transfection with reporter plasmid, pGL2B with interferon ? promoter, and IRF-3c cDNA expression plasmid. At 16 hours posttransfection, cells were infected with Sendai virus for 8 hours. Cells were collected and assayed for luciferase activity. Results A novel spliced isoform of IRF-3, named IRF-3c was discovered. The new isoform is almost the same as IRF-3, except for the utilization of the 180 bp bases in intron 6 adjacent to exon 6. The first 2,3 and 4 bases are a stop codon, which may produce a protein with a truncated C-terminal stoped at amino acids 327. Western blot analysis confirmed an expected 44 kDa strong band. The new inserted bases can be found in murine EST database, suggesting a conservative function in evolution. The functional luciferase assay showed that IRF-3c inhibited the IFN? promoter activity to (around) 40%～50% as that of control after Sendai virus infection. Conclusions The discovery of a new isoform of IRF-3 provides a new insight into the functional regulation of IRF-3 family. It is a dominant-negative inhibitor for interferon ? promoter activity in the virus infection pathway, provides a mechanism for the fine-tuning of the virus-induced activation of the interferon response, and prevents interferon ? from its overexpression and its toxic effects. It is worthwhile to explore the role of IRF-3c in the pathogenesis of human diseases using IRF-3c’s specific sequence.

Aim To examine the in vivo effect of the antisense or/and decoy oligonucleotide of NF-?B on vessel proliferation and balloon-injured monocytes chemotactic protein-1(MCP-1) and extracellular signal regulated kinase in the carotid artery of rats.Methods Sprague-Dawley rats underwent balloon-dilation injury of the left carotid artery.The rats were divided into 7 groups(n=18) and each group were further divided into 6 sub-groups for study at 6 time points(1,3,5,7,14 days,n=3).Uninjured artery of the same rat was used as the control.Results In model group,sense group and scramble group,intima/media ratio increased after 5 days and reached the maximum after 14 days;intima/media ratio in antisense group,decoy group,antisense plus decoy group decreased significantly(P

Six compounds were isolated from the whole herb of Phyllanthus urinaria L. They were id entified as ellagic acid (Ⅰ), 3, 3', 4-tri?O-methylellagic acid (Ⅱ), succinic acid (Ⅲ ), feru lic (Ⅳ ), ?-sitosterol-glucoside (Ⅴ ) and gallic acid (Ⅵ ) by means of spectral analysis and chemical reaction- Compound Ⅱ, Ⅲ, Ⅳ, and Ⅴwere isolated for the first time from this plant