OBJECTIVE:To observe the efficacy and safety of cyclophosphamide,leflunomide sequentially combined with prednisone in the treatment of membranous nephropathy in stage Ⅱ. METHODS:72 patients with membranous nephropathy in stageⅡwere randomly divided into group A(24 cases),B(24 cases)and C(24 cases). All patients were given angiotensin convert-ing enzyme inhibitor (ACEI) Benazepril hydrochloride tablet,warfarin,dipyridamole,calcium and other conventional treatment. Based on it,group A was orally given 50 mg Compound cyclophosphamide tablet,twice a day,for continuous 3 months+1.0 mg/(kg·d)Prednisone tablet,it was reduced 5 mg every 2 weeks after 2 months,then it reduced 2.5 mg every 2 weeks when 30 mg/day,and then it maintained 4-6 months when 10 mg/day,it lasted for 12 months. Group B was given 50 mg Leflunomide tablet,it changed as 20 mg/day after 2 d,and for continuous 6 months+Prednisone tablet(the same dosage and usage as group A). Group C was given Compound cyclophosphamide tablet(the same dosage and usage as group A)was orally given in 1-3 months,and Leflu-nomide tablet(the same dosage and usage as group B)in 4-9 months Prednisone tablet(the same dosage and usage as group A). Clinical efficacy,24 h urinary protein,albumin,total cholesterol,serum creatinine,alanine aminotransferase before and after 3, 6,9 and 12 months and incidence of adverse reactions in all groups were observed. RESULTS:Before treatment,there were no significant differences in the 24 h urinary protein,albumin,total cholesterol,serum creatinine and alanine aminotransferase among all groups(P>0.05). After treatment,24 h urinary protein,total cholesterol,serum creatinine and alanine aminotransferase in all groups were significantly lower than before,and they gradually decreased by treatment time,24 h urinary protein in group C was lower than group A and B,albumin was significantly higher than before and gradually increased by treatment time,and group C was higher than group A and B,the differences were statistically significant(P<0.05 or P<0.01);but there was no significant dif-ference between group A and B(P>0.05). The total effective rate in group C was significantly higher than group A and B,the dif-ference was statistically significant (P<0.05),but there was no significant difference between group A and B (P>0.05). And there was no significant difference in the incidence of adverse reactions among 3 groups (P>0.05). CONCLUSIONS:Based on the conventional treatment,the efficacy of cyclophosphamide,leflunomide sequentially combined with glucocorticoid is superior to cyclophosphamide or leflunomide alone in the treatment of membranous nephropathy in stageⅡ,with similar safety.

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 discuss the diagnostic value of CT in the hip joint dislocation.Methods We analyzed and compared 17 cases of the hip dislocation examined by X-ray and CT.Results X-ray plain film displayed hip joint dislocation in 15 cases,fractures in 10 cases,soft tissue swelling in 9 cases,widened hip joint space in 6 cases and bone fragment in 3 cases after restoration.CT showed hip joint dislocation and fractures in 17 cases,soft tissue swelling in 15 cases,widened hip joint space in 11 cases and bone fragment in 10 cases after restoration.Conclusion For the direction and the degree of hip joint dislocation,acetabulum fracture,bone fragment in articular space and soft tissue swelling,CT has distinct advantage.We find that CT may be one of a routine method in hip joint dislocation,especially after restoration.

A strain producing eggshell membrane protease (ESM protease) was isolated from the soil and identified as Pseudomonas aeruginosa. The enzyme isolated from the fermentation liquid of this strain and purified by ammonium sulfate precipitation, quadratic anion-exchange chromatography exhibited eggshell membrane degrading activity of 304.5 U/mg. By SDS-PAGE, the protein molecular mass is 32 kD. The N-terminal amino acid sequence of this protease is: Ala, Glu, Ala, Gly, Gly, Val, Ala, Gly, Lys, Glu, Asp, Ala, Ala, Glu, Leu.

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.

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.

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.

Molecular glues are a class of small molecules that induce the formation of protein-protein interactions to confer new biological function or therapeutic effects. As a unique pharmacological modality, molecular glues could target proteins without druggable binding pockets. It exhibits a variety of functions, including regulating signal transduction, stabilization or degradation of targeted proteins, through sticking different proteins together. This review will summarize the development and current status of molecular glues derived from natural products and analogs by illustrating the discovery and interaction mechanism. We hope to present a systematic view, provide valuable clues for researchers and encourage them to explore more efficient and rational molecular glue discovery strategies.

ObjectiveTo evaluate the efficacy of radical transurethral bladder tumor resection plus chemotherapy for the treatment of muscle-invasive bladder cancer. Methods Thirty-two patients,who were diagnosed muscle-invasive bladder cancer by preoperative CT and cystoscopy and not tolerating or rejecting radical cystectomy were treated by transurethral resection of bladder tumor (TURBt).The maximum diameter of tumor ranged from 1 - 5 cm,3 cm on average.After conventional intravenous chemotherapy ( docetaxel 75 mg/m2 + oxaliplatin 130 mg/m2),and given intravenous therapy (HCPT 20 mg + 20 ml saline).Regular cystoscopy was used to monitor tumor recurrence.The examination was performed quarterly in the first 2 years post operation,twice a year since the third year.ResultsThe tumors of 32 cases were resected completely.Operative time were 15 -70 min,the blood loss was 10 -150 ml,without serious complications during the operation.Pathological report showed 32 cases of transitional cell carcinoma.Clinical stages were T2a 20 cases,T2b 12 cases.Pathological grade were G2 13 cases,G3 19 cases.There was no bone marrow suppression,anemia or other severe complications was seen in 32 cases that received chemotherapy.3 of which manifested as low fever,mild nausea,and headache,respectively,having a rest 2 to 3 days the symptoms disappeared.32 patients were followed up for 3 - 60 months,a mean of 28 months.After 1 year the recurrence rate was 9.4％ (3/32),after 2 years was 12.5％ (4/32).The TNM stage of these recurrence cases were 4 cases with T2a and 3 cases with T2b.12 patients died,5 patients died of bladder cancer metastasis.Other 20 patients were survival with no recurrence.ConclusionRadical TURBt plus chemotherapy could be a treatment for the selected patients with muscle invasive bladder cancer.

Objective To investigate the protective effect of clodronate SPIO liposomes on liver injury of rats with severe acute pancreatitis(SAP)and the role of MRI in evaluating the extent of liver injury.Methods Superparamagnetic Fe3O4 nanoparticles were prepared by chemical coprecipitation.Clodronate-SPIO-containing liposomes was prepared by the thin-film method.SAP models were prepared by a uniform injection of sodium taurocholate(2 ml/kg body weight)into the subcapsular space of the pancreas.SD rats were randomly divided into control group,SAP plus SPIO group, and clodronate-SPIO-containing liposome group.Six hours after SAP models were available,T2-weighted MRI scanning(in the same plane)of the liver of rats in each group were performed.At the end of the scanning,blood samples were taken from the supcrior mesenteric vein to measure the contents of serum ALT and AST.Meanwhile, The pathological changes in the liver and pancreas were observed.Results Transmission electron microscopic examination showed that liposomes had a uniform size.No changes in the pancreas of rats in control group were noted.The pathological changes in the pancreas and liver of rats in SAP plus clodronate-SPIO-containing liposome group were significantly milder than those in SAP plus SPIO liposome group.The contents of serum ALT and AST in rats in SAP plus SPIO liposome group were significantly higher than those in control group(P＜0.01), while the contents of serum ALT and AST in rats in SAP plus clodronate-SPIO-containing group were significantly lower than those in SAP plus SPIO liposome group(P＜0.01).The MRI signal intensity of the liver in SAP plus SPIO liposome group and SAP plus clodronate-SPIO-containing liposome group was significantly lower than that in control group.The significant changes in the MRI signal intensity of the liver in SAP plus SPIO liposome group and SAP plus Clodronate-SPIO liposome group were noted(P＜0.01).Conclusion Clodronate-containing liposomes have protective effects against liver injury in SAP rats and SPIO can be used as a tracer for MRI examination.