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.

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.

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.

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.

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.

Over the course of human civilization, viral infections have been a part of human life and still represent one of the heaviest burdens for human and society, with a huge devastating socioeconomic impact. Inorganic and bioinorganic chemistry have made important contributions to medical science and human health in the past half century. In this paper, we selected the representative cases in recent years, and reviewed the research progress of antiviral drug discovery from the perspective of bioinorganic chemistry.

To address the continuous emergence of drug-resistant strains of viruses and the outbreaks of novel virus infections, developing new antiviral drugs based on novel strategies has become an important and urgent research topic. In recent years, the rapidly developing multi-specific binding strategy has become a focus and been widely applied in antiviral. This review summarizes the recent progress of the multi-specific binding strategy in the antiviral field from the perspective of medicinal chemistry and discusses existing challenges as well as future opportunities for antiviral drug discovery.

Objective To evaluate the clinical value of tomography ultrasonic imaging (TUI) in staging carcinomas of the cervix.Methods Eighty-seven patients with biopsy proven cervical cancer who underwent transvaginal TUI examination were enrolled.Clinical and ultrasonic staging were based on the FIGO staging system.Surgical-pathological or MR results was taken as golden standard.Ultrasonic staging were compared with clinical staging.Tumor sizes of 38 cases of cervical cancers measured by TUI were recorded and compared with the pathological results.Results The overall accuracy of preoperative TUI staging was higher than that of preoperative clinical staging (91.95 ％ vs 81.60 ％,P ＜0.01).Mean size of the 38 malignant tumors was 2.5 cm×2.1 cm×2.2 cm by TUI and 2.6 cm×2.1 cm×2.3 cm by pathological samples (P ＞ 0.05).Conclusions TUI technology may be useful in the noninvasive examination of preoperative staging of carcinoma cervix.

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.

ObjectiveTo investigate the expression and clinical significance of heat shock transcription factor 1 (HSF1) protein in human hepatocellular carcinoma (HCC) tissues,and deduce the probable molecular mechanism of HSF1 in the development and advancement of HCC.MethodsSixty-seven samples of HCC tissue and 21 samples of normal liver tissue were obtained from March 2006 to March 2007 at the Xijing Hospital.The expressions of HSF1 protein and heat shock protein 70 (HSP70) were detected by using immunohistochemistry.The probable molecular mechanism of HSF1 in the development and advancement of HCC was deduced according to the relationship between the expressions of HSF1 protein and HSP70.Positive rates of HSF1 protein in different tissues and the relationship between HSF1 protein expression in the HCC tissues and clinical pathological factors were analyzed by the chi-square test and by calculating Fisher exact probability,respectively.The correlation between the expressions of HSF1 protein and HSP70 in the HCC tissue was analyzed by the Spearman correlation coefficient.The survival curve was drawn by the Kaplan-Meier method,and the survival rate was analyzed by the Log-rank test.ResultsThe positive rates of HSF1 protein expression was 69％ (46/67) in the HCC tissue,which was significantly higher than 29％ (6/21) in the normal liver tissue ( x2 =10.628,P ＜ 0.05 ),The positive rates of HSP70 expression in the HCC tissue was 57％ (38/67),which was significantly higher than 24％ (5/21) in the normal liver tissue ( x2 =6.929,P ＜ 0.05 ).The expression of HSF1 protein in the HCC tissue was positively correlated with that of HSP70 (r=0.319,P ＜0.05).The high expression of HSF1 protein was correlated with the integrity of capsule of HCC,tumor differentiation and TNM stage (x2 =5.935,9.762,5.159,11.267,P＜0.05 ),while the high expression of HSF1 protein was not correlated with the gender,age,levels of hepatitis B surface antigen and alpha fetoprotein,and portal vein tumor thrombus ( x2 =0.822,0.172,2.059,P ＞0.05 ).The survival time was (21.4 ± 1.9 )months for patients with positive HSF1 protein expression and (29.8 ± 2.7 ) months for patients with negative HSF1 protein expression.There was a significant difference in the survival time between patients with positive and negative HSF1 protein expression ( x2 =4.276,P ＜ 0.05 ).Conclusions HSF1 is correlated with the development,advancement,invasion,metastasis and malignant prognosis of HCC.HSF1 takes effects by regulating the expression of HSP70,and it has a good perspective of clinical application for the diagnosis and treatment of HCC.