A drug is composed of fragments with their functional and structural characteristics. Functional fragments contain structural elements known as pharmacophores which generate the bioactivity of the drugs, while structural fragments assemble the functional fragments into a specific skeleton also crucial for the activity. Although drug molecules possess structural diversity and complexity, the fragments usually have some similarity. They normally have simple texture, low molecular weight and log P. The aim of fragment-based drug discovery is to classify and screen the collections of fragments and subsequently expand, link, or merge them to obtain new chemical entities. This theory refines the traditional structure-based and the high throughput screen-based drug discovery strategy, and facilitates the reduction of molecular size and the improvement of drug-like properties, which will certainly increase the probability of developing new drugs. In this article, we reviewed the concept, methodology of fragment-based drug discovery and detailed a number of examples to illustrate the optimization strategies of this discovery method.

Objective To study the role of chronic prostatitis(CP)in the pathogenesis and development of IgA nephropathy(IgAN). Methods The incidence rate of CP was compared between the patients with IgAN and the patients with non-IgA mesangial proliferative glomerulonephritis. Furthermore, the clinical and pathological features were compared between the IgAN patients without CP and those with CP. The therapeutic effect of anti-inflammatory treatment in IgAN patients with CP was evaluated. Results Incidence of CP in IgAN patients was 44.7% and that in non-IgA mesangial proliferative glomerulonephritis patients was 21.6%. There was significant difference in the incidence of chronic prostatitis between the two groups. The incidence of glomerular sclerosis and the deposition of immune complexes in vascular wall in IgAN patients with CP were higher than that in patients without CP. The treatment of CP may be beneficial in ameliorating IgAN in some patients. Conclusion Chronic prostatitis is one of the probable pathogenetic factors in IgAN.

Objective :To study the effect and mechanism of retinoic acid(RA) on thymocytes development. Methods:Thymus tissue culture system was used to investigate the roles of RA in maturation development of thymocytes. Thymus tissues were cultured with or without retinoic acid and/or retinoic acid receptor antagonist. The cultures were harvested after 24, 48 and 72 hours, respectively. Thymocytes were stained with fluorescence labeled anti-CD3, anti-CD4, anti-CD8 antibodies and analyzed by flow cytometry. The real time quantitative RT-PCR assay was used to detect the retinoic acid receptor (RAR) mRNA expression in thymocytes. Results:The thymus tissue culture system was able to support the maturation of thymocytes. Addition of RA to the culture system promoted thymocytes differentiation from immature CD4+CD8+ cells to mature CD4+ cells, but inhibited the transformation from immature CD4+CD8+ cells to mature CD8+ cells. The effect was marked after 24h culture, and was antagonized by Ro41-5253. RA enhanced the expression of RAR mRNA in thymocytes. A positive correlation was found between the expression of RAR mRNA and the percentage of CD4+CD8+ cells and a negative correlation between the expression of RAR mRNA and the percentage of CD8+ cells. Conclusion:RA likely play an important role in thymocytes development, perhaps by affecting the relative expression of RAR gene.

Objective To explore the effect of valium and barbitone in the treatment of convulsion in neonate. Methods 156 children with convul sion were randomly divided into two groups, 77 cases in control group and 78 cases in treatment group. Results The instant and total effective rates of treatment group and control group were companed, respectively. There were significant difference between these two groups.Conclusion Valium and Barbitone is effective in treating neonate with convusion.

BACKGROUND:Due to complicated and special lumbar spinal stenosis disease and different degrees of lumbar degeneration in the elderly, it requires very careful choice of repair methods and repair technology.
OBJECTIVE:To investigate the indications and prognosis effect of the treatments of elderly lumbar spinal stenosis by selective decompression of lumbar root canal under direct vision and laminectomy.
METHODS:Clinical data of 167 elderly patients with lumbar spinal stenosis were retrospectively analyzed. A total of 82 patients were treated with selective decompression of lumbar root canal as the selective decompression group, with a clear nerve root compression but without central canal stenosis. A total of 85 patients were treated with laminectom and treated with pedicle screw fixation as the whole lamina cut group, with distinct central canal stenosis. The indications were analyzed between the two groups. Clinical effects were assessed using Japanese Orthopaedic Association and Oswestry Disability Index before and after surgery.
RESULTS AND CONCLUSION:(1) Al patients were operated successful y. There was no serious
complication during treatment. (2) Japanese Orthopaedic Association and Oswestry Disability Index were significantly improved at last fol ow-up in two groups compared with preoperation (P<0.05). No significant difference in Japanese Orthopaedic Association and Oswestry Disability Index was detected between the two groups at various time points (P>0.05). Clinical symptoms disappeared or relieved at last fol ow-up in two groups. The prognosis in two groups had significantly improved. (3) Results indicated that laminectomy and pedicle screw fixation in elderly patients with lumbar spinal stenosis and central canal stenosis obtained significant effects. For elderly patients with lumbar spinal stenosis but without central canal stenosis, selective decompression of lumbar root canal under direct vision was given, and it is effective and reliable. The two methods are suitable for different patients, and are effective and reliable way to repair.

Objective To evaluate clinical efficacy of extracorporeal shock wave lithotripsy (ESWL) for treating patients with double J (DJ) stent extubation difficulties.Methods A retrospective analysis were conducted from July 1999 to December 2013,total 30 cases (18 male and 12 female) were accepted the ESWL therapy for treating the DJ extubation difficult due to the stone scales surface.The average age in those patients was 46 years (range 24 to 83 years).The average duration of DJ stents indwelling was 8.3 months (range 1.5 to 36.0 months).There were 10 cases with single stone and 20 cases with multiple stones.The distribution of stone location included left kidney in 14 cases,right kidney in 6 cases,left ureter in 3 cases and right ureter in 7 cases.The ureteral stone scales around the DJ stent showed tubular distribution.The distribution of imaging characteristic included kidney stones around the DJ stent joint in 20 cases and surface coarse in 10 cases.The diameter of the stone ranged from 0.7 to 3.2 cm (mean 1.8 cm).All the 30 cases were treated by ESWL with the 2 000-3 300 times frequency (mean 2 800 times).Treatment voltage was 4-8 KV.Results Gravel time ranged from 40 to 70 min (mean 45 min).No intraoperative and postoperative complications occurred.Their DJ stents were easily extubated immediately after ESWL.One week after ESWL,all the patients reported the flushing of the stone.Conclusion ESWL is a simple,convenient and efficacy way to solve the DJ stent extubation difficulties due to the scales surface.

Objective To investigate the chemical constituents of red algae Hypnea charoides. MethodsThe constituents were isolated by column chromatography and their structures were elucidated by chemical properties and spectroscopic analyses. Results Three compounds were isolated and their structures were identified as 3, 6-dimethyl-8-(4-methyleneheptan-3-yloxy) octane-1-amine (Ⅰ), palmitate-K (Ⅱ), and (2R, 1′S, 2′S, 3′R)-N-(1′-hydroxymethyl-2′, 3′-dihydroxy-heptadecenyl)-2-hydroxy-12, 13-methylene-tetracosanamide (Ⅲ). Conclusion Compounds Ⅰ and Ⅲ are new compounds named as charoidesine and charoidesamide.

Due to the complicated pathogenesis of cardiac arrhythmia, the safe and effective therapeutic strategies for cardiac arrhythmia remain an urgent medical problems in the recent years. In this paper, we introduced the research practice of anti-arrhythmic agents targeting on potassium ion channel. The research progress of anti-arrhythmic agents in up-to-date literatures were also reviewed and prospected.

To study which subgroup of bone marrow derived cells formed myofibroblasts and the mechanism that transforming growth factor β1 (TGFβ1) regulates the formation of bone marrow derived macrophages into myofibroblasts during renal fibrosis.Chimeric mice were generated by lethally irradiation of C57 mice followed by transfusion of green fluorescent protein (GFP) labeled bone marrow cells.Complete marrow reconstitution was developed until 12 weeks after transplantation.The mice were randomly divided into Sham operation group,unilateral ureteral obstruction (UUO) 3 days group,UUO5 days group,UUO7 days group and UUO7 with TGFβ1 treatment group.Each group had four mice.Flow cytometry was used to evaluate cell components.Compared with Sham operation group the proportions of GFP + CD+14 oα-smooth muscle actin(α-SMA) + cells,GFP + CD+44 CD+105 α-SMA+ cells and GFP+ F4/80+ α-SMA+ cells in each UUO group were progressively increased and the transformation rate in UUO7 day group was the highest.The GFP+ F4/80 + α-SMA+ cells accounted for the largest population.TGFβ1 promoted the transformation of bone marrow derived macrophages into myofibroblasts.Compared with Sham operation group or UUO7 day group,the proportion of GFP+ F4/80+ α-SMA+ cells increased in UUO7 day TGFβ1 treatment group.Compared with Sham operation group (or UUO7 days group) the protein expressions of F4/80,oα-SMA,Collagen Ⅰ increased in UUO7 with TGFβ1 group.Bone marrow derived macrophages are considered as the main type of myofibroblast precursors during the development of renal fibrosis.TGFβ1 regulates the transformation of bone marrow-derived macrophages into myofibroblasts.This process contributes to progressive renal fibrosis and deterioration of renal function.

Objective To explore the clinical effect of extracorporeal shock wave lithotripsy (ESWL) for the treatment of horseshoe kidney stones.Methods A total of 42 cases of horseshoe kidney stones from March 1987 to January 2015 were enrolled.Among them,33 cases were male and 9 cases were female.Their age range was 19 to 71 years,average age was 42 years old.25 cases got left renal pelvis stone,17 cases were on the right renal pelvis side.The diameter range of stone was 0.4-3.7 cm,the average was 1.8cm.ESWL was applied to treat whole group.The prone position was used to removing calculus.The frequency of treatment was 2000-2700 times,with an average of 2500 times;the treatment voltage was 4-7KV.The gravel time of the treatment was 30-45min,the average was 35min.Results One time for ESWL was 29 cases,two times for ESWL was 8 cases,three times for ESWL was 3 cases,four times for ESWL was 2 cases.The first discharge stones time was 3 to 10 days.There was no special discomfort after operation.40 cases got hematuria after operation,which occurred in 1 to 3 days after ESWL Renal colic was in 7 cases which happened on 1-3 days after ESWL.Condusions Calculi in horseshoe kidney may be treated by ESWL.It is a safe and simple operation.The prone position may bring satisfactory effect.