Objective To explore the relationship between vascular endothelial growth factor (VEGF) concentration in urine and renal vascular damage in children with Henoch Schonlein purpura nephritis (HSPN).Methods The kidney pathological lesion of 78 biopsy-proven HSPN children was assessed with renal vascular damage, glomerular pathological damage, and tubulointerstitial pathological damage semi-quantitative points. The children were divided into 3 groups (light, medium, and heavy group) according to the renal vascular, glomerular, tubulointerstitial, glomerular and tubulointerstitial total pathological points. Blood and urine vascular endothelial growth factor concentration was detected by enzyme linked immunosorbent assay;the localized renal VEGF expression and microvessel density were detected by immunohistochemistry assay in the kidneys. Results The semi-quantitative points of glomerular, tubulointerstitial, renal vascular, and glomerular and tubulointerstitial total points in different groups had significant difference (all P＜0.01);the minor renal vascular damage, the higher light microvessel density, blood and kidney concentration of VEGF, and the VEGF excretion in the urine were also lower in different groups, and there were significant differences (all P＜0.01). Glomerular points were positively related with tubular points, vascular points, kidney total score (r=0.596,0.612, and 0.728;P＜0.05, 0.05, and 0.01 respectively). Microvessel density was highly positively related with blood VEGF and renal VEGF, and negatively rela-ted with urine VEGF (r=0.601, 0.696, and -0.639,all P＜0.01). Conclusion The urinary excretion of VEGF leads to the decrease of local kidney VEGF concentration resulting in the renal vascular injury, which may be the important reason for renal vascular damage and pathology chronic progress in HSPN children.

BACKGROUND: It has been widely reported that the most types of cancer are probably originated from cancer stem cells (CSCs) which are subpopulations of tumor cells. Recent studies also suggested that lung cancer could arise from CSCs. However, the phenotypic characteristics of CSCs in lung cancer have not been precisely described.OBJECTIVE: To systematically analyze the expression of the most common CSC markers in cell line A549.METHODS: A549 cells were cultured for 1 week under the condition of conventional high glucose. After that, flow cytometry was used to assess the expression of putative stem cell markers, including CD133, CD24, CD44 and ABCG2.Cells were then sorted according to the expression of CD44 and CD24 markers by fluorescence-activated cell sorting (FACS) and characterized using their sphere-forming capacity in serum free medium supplemented with several growth factors.RESULTS AND CONCLUSION: A549 cells expressed the CSC markers CD44 and CD24 at 64.23％ and 58.62％,whereas the expression of both ABCG2 and CD133 was around 0.9％. Double-positive CD44/133 populations were rare.CD44+/CD24+ and CD44+/CD24- subpopulations respectively exhibited 54.64％ and 23.38％ expression. CD44+/CD24+ and CD44+/CD24- subsets were sorted by FACS. Both isolated subpopulations formed spheres in the serum free medium supplemented with basic fibroblast growth factor and epidermal growth factor. However, there was no significant difference in the sphere formation efficiency among CD44+/CD24+ and CD44+/CD24- subsets as well as A549 cells. Our findings suggest that CD44 and CD24 cannot be considered as potential markers for isolating lung CSCs in cell line A549, and further investigation using in vivo assays is required.

Objective To investigate the effects and underlying mechanism of the scavenger receptor CD36 in high glucose-induced rat glomerular mesangial cells apoptosis.Methods The mesangial cells of rats were divided into 4 groups:control group (5.6 mmol/L glucose),mannitol group (24.2 mmol/L mannitol+5.6 mmo]/L glucose),high glucose group (30 mmol/L glucose),CD36 monoantibody group (30 mmol/L glucose+CD36 mono-antibody).The intracellular ROS level was detected by confocal microscopy with fluorescent probe CM-H2DCFDA.MDA,GSH-PX,8-OHDGA in cell supernatant were detected.Apoptosis was determined by flow cytometry followed by Annexin V-FITC/PI double stains.The expression of CD36,Bax and Bcl-2 were detected by RT-PCR and Western blotting.Results The expression of CD36 was detected in glomerular mesangial cells.The highest level was found in high glucose group in 24 hours.There was no significant difference found between control group and mannitol group with respect to intracellular ROS generation,MDA,8-OHDG,GSH-PX level,apoptosis rate,expression of CD36,Bax and Bcl-2 (all P ＞ 0.05).There was no significant difference in the expression of CD36 between CD36 mono-antibody group and high glucose group (P ＞ 0.05).Compared to control group,the intracellular ROS generation,MDA and 8-OHDG levels,apoptosis rate,the expression of CD36 and Bax were significantly increased,the GSH-PX level and the expression of Bcl-2 were significantly lower in high glucose group (all P ＜ 0.05).Compared to the high glucose group,the intracellular ROS generation,MDA and 8-OHDG levels,apoptosis rate,the expression of Bax were suppressed but the GSH-PX level and the expression of Bcl-2 increased in CD36 mono-antibody group (all P ＜ 0.05).The intracellular ROS level was positively correlated with apoptosis rate,protein expression of CD36 and Bax gene,was negatively correlated with Bcl-2 protein expression.Conclusions CD36 was involved in the high glucose induced apoptosis of mesangial cells which was potentially mediated by an increased level of oxidative stress.

New drug research and development is a technology-intensive industry with high investment, high cycle and high risk. In recent years, with the rapid development of modern disciplines such as omics technology, bioinformatics, high-throughput and high-content screening, and artificial intelligence, the research and development of small-molecule drugs has presented a new paradigm characterized by "integrated medicinal chemistry". This review summarizes new enabling drug discovery technologies, the emergence of new subfields formed through integration innovations and practical chemistry toolbox in the field of medicinal chemistry.

Virus infection is a serious threat to human health and social development. The increase in pandemics caused by emerging and re-emerging viruses highlights the urgent need for broad-spectrum antivirals. In this perspective, we highlight recent case studies and summarize the universal strategies and methodologies in broad-spectrum antiviral drug discovery from common targets, common steps in viral life cycle, universal strategies, and broad-spectrum molecules, hoping to provide valuable guidance for the current and future development of antiviral drugs.

ObjectiveTo compare liver pathology changes of patients with Budd-Chiari syndrome (BCS) and intrahepatic portal hypertension (IPH) after portosystemic shunt surgery. MethodsFrom January 2010 to December 2011,liverbiopsy was taken during shunt surgery (9 BCS patients,4 IPH patients),and 6-9 months after surgery on follow-up.Collagen type Ⅳ ( Col Ⅳ ),procollagen m (PC Ⅲ ),matrix metalloproteinase (MMP-1),tissue inhibitors of metalloproteinase(TIMP-1) were tested using SABC (immuonohistochemistry) method,and HE staining to observe the morphology of liver tissue.Free portal vein pressure before and after shunt was measured. ResultsIn BCS group,Col Ⅳ,PC 1Ⅲ and TIMP-1expression downregulated after surgery (127 ±15) vs.(137 ±16),t =4.896,P-0.013; (115.2 ± 10.6) vs.(127.3±9.5),t=4.877,P=0.003; (119.2±11.3) vs.(131.2±l9.6),t=2.841,P=0.023.MMP-1expression did not change ( P ＞ 0.05 ),while MMP-1/TIMP-1was not significantly correlated with liver fibrosis (0.95 ±0.16) vs.(0.98 ±0.15),t =-0.710,P =0.504.In IPH group,the expression of Col Ⅳ,PCⅢ,MMP-1,and MMP-1/TIMP-1did not change significantly after surgery (P ＞0.05).Compared with that in IPH group the expression of PC Ⅲ,Col Ⅳ and TIMP-1downregulated significantly in BCSgroup (127±15) vs.(150 ±12),U=3.000,P=0.038; (115.2 ±10.6) vs.(128.1±2.8),U=2.000,P=0.023; (119.2 ± 11.3) vs.(131.4 ±2.5),U=3.000,P =0.038.By HE staining in BCS group there was significant intrahepatic congestion which alleviated after surgery.While in PHT group liver pathology did not change significantly after surgery.FPP in BCS and IPH patients significantly decreased after shunt surgery (25 ±8) vs.(41±8) cmH20,t=17.816,P=0.000;(31±8) vs.(45 ±9) cmH20,t =5.745,P =0.010 ). Drop of FPP of BCS group plays a key role in reversal of liver fibrosis.ConclusionsIn BCS group liver pathology improved after shunt surgery probably by removing the intrahepatic obstruction,but in IPH group liver pathology remained unchanged after shunt.

OBJECTIVE:To prepare Xuangui zhitong dispersible tablets and optimize its formulation technology. METHODS:Using disintegration time as index,single factor test was conducted for filler,disintegrating agent,the types and amount of adhe-sives and compression pressure. The amount of mixed disintegrating agent,avicel and gum arabic were optimized by orthogonal test. The tablet quality by optimized formulation was detected,and disintegration time,the content and dissolution rate of tetrahy-dropalmatine were determined;the similarity of in vitro dissolution rate of dispersible tablets and dropping pills were evaluated by similarity factor test. RESULTS:The optimized formulation was composed of 25% MCC as fillers,9% PVPP and 9% L-HPC as mixed disintegrants,85% ethanol solution as adhesives,micro-silica gel 2%,compression pressure of 3.0 kg/cm2. The average dis-integration time was 1.22 min,and the content of tetrahydropalmatine was 1.097 mg/g. The accumulative dissolution rate was more than 80% at 10 min and more than 90% at 15 min. The similarity factor f2 of dissolution curve was 62,using dropping pills as ref-erence preparation. CONCLUSIONS:Xuangui zhitong dispersible tablet had a rapid disintegration and the behavior of dissolution is similar to Xuangui zhitong dropping pills.

Objective:To observe the effect of Er Chen Tang on CYP2E1 and mitochondrial energy metabolism in nonalcoholic fat-ty liver disease ( NAFLD) to explore the role of Pinellinae Rhizoma Praeparata ( PRP) and Citri reticulatae pericarpium ( CRP) in the treatment of nonalcoholic fatty liver disease. Methods:Er ChenTang and the prescription without PRP or CRP was respectively given the animal models by gastric gavage. The serum levels of ALT, AST, triglyceride, cholesterol, SOD and MDA in hepatic tissue, and the contents of liver tissue CYP2E1 and ATP were detected in the mice. Results:The CYP2E1 levels in NAFLD mice increased signif-icantly with abnormal mitochondrial energy metabolism. Compared with those in the model group, the levels of ALT, AST, triglyceride and cholesterol were significantly reduced by Er Chen Tang, meanwhile, the content of CYP2E1 was reduced and also restored liver en-ergy metabolism. The treatment effect significantly decreased when the lack of PRP or CRP, and the ability of restoring liver mitochon-drial energy metabolism of Er Chen Tang decreased significantly when the lack of PRP (P<0. 05). After the removal of CRP, the in-hibition ability of Er Chen Tang to CYP2E1 levels significantly decreased (P<0. 05). Conclusion:Er Chen Tang can effectively im-prove nonalcoholic fatty liver diseases, and effectively reduce the content of CYP2E1 in liver tissue of mice and restore the mitochondri-al energy metabolism.

Objective To assess the effectiveness of Bankart repair under arthroscope in treatment of recurrent anterior shoulder joint instability. Methods From February 2010 to February 2015, 63 patients with recurrent anterior shoulder dislocation under arthroscipic Bankart repair, and 53 patients (28 male, 25 female) were available for follow-up. The mean age at the time of surgery was 27.9 years (range, 16 ~ 51). All of the 63 patients underwent surgical treatments, and the effectiveness was evaluated with University of California at Los Angeles (UCLA), American Shoulder and Elbow Surgeon scores (ASES), Constant-Murley scores, forward elevation, abduction and external rotation and X-ray. Results The ASES scores, UCLA scores were (97.0 ± 6.8), (29.6 ± 2.5) respectively, improved significantly higher after the surgery (P < 0.05). No significant change was found regarding Constant-Murley scores (99.1 ± 2.4), forward elevation (168.7 ± 2.7)°, abduction and external rotation (72.6 ± 8.7)° compared with the pre-operation. Conclusions Significant difference between pre-operation and post-operation suggests that Arthroscopic Bankart repair is a good option for the treatment of recurrent anterior shoulder dislocation without large glenoid bone loss and poor quality Ligament and joint capsule. Risk factors of recurrence should be evaluated before the surgery to reduce the recurrence rate of dislocation.

Objective To conduct a case-control study on the association of the nucleotide polymorphisms in the promoter region of the matrix metalloproteinase-9 (MMP-9) gene with phenotype of esophageal cancer. Methods All subjects were unrelated residents in northern regions of China. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to determine the MMP-9 genotypes. Results The overall distribution of genotypes in the patients was not different from that in the controls (OR=0.77, 95% CI=0.45-1.34; P=0.36). There were no significant differences between the patients and the control subjects in terms of the distributions of sex and age, smoking status, alcohol dependence, pickled diet status, or history of environmental exposure. The patients were further examined with stratifications by age, sex, grade, depth of tumor invasion, lymphatic invasion, venous invasion and TNM staging. The results showed no pronounced association among the stratifications. Conclusion There is no significant association between the MMP-9 single nucleotide polymorphism genotypes and phenotype of esophageal cancer.