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.

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.

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.

Objective To investigate the clinical value of preoperative neutrophil to lymphocyte ratio in predicting lymph node metasta-sis after radical resection of esophageal carcinoma. Methods The clinical data of 110 patients with esophageal carcinoma who underwent radical resection of esophageal carcinoma from February 2015 to March 2017 in our hospital were retrospectively analyzed. NLR≥4 was the critical point,all patients were divided into high NLR group(NLR≥4) in 45 cases,the low NLR group(NLR<4) 65 cases,compared two groups of patients with clinical characteristics,lymph node metastasis,and regression analysis of factors influencing lymph node metastasis af-ter radical resection of esophageal carcinoma by logistic. Results There were 87 patients with lymph node metastasis in 110 cases,among which 43 cases(95. 56％) had lymph node metastasis in 45 cases of high NLR group,and 44 cases(67. 69％) had lymph node metastasis in 65 cases in low NLR group. The number of lymph node metastasis,depth of tumor invasion and distant metastasis in the high NLR group were higher than those in the low NLR group(P<0. 05),which indicated that the preoperative NLR level was related to lymph node metastasis af-ter radical resection of esophageal carcinoma. The number of lymph node metastasis and lymph node metastasis in the high NLR group were higher than those in the low NLR group(P<0. 05). The tumor T stage(OR=1. 898,95％CI:1. 151～3. 130),NLR≥4(OR=1. 919,95％CI:1. 076～3. 422) is the independent risk factors of lymph node metastasis in patients with esophageal cancer(P<0. 05). Conclusion The preoperative NLR was higher in patients with esophageal cancer and its lymph node metastasis,the greater the risk of distant metastasis tumor the deeper the infiltrating,it is more likely,to suggest it should expand the range of lymph node dissection in the operation,the lymph node metastasis,radical dissection has certain value.

The growth characteristics of hydrogen-production photosynthetic bacterial biofilm in a plate-type biofilm bioreactor were studied experimentally.The effect of hydraulic and nutritional conditions on the surface coverage,thickness,dry weight,and density of Rhodoseudomonas palustris biofilm was observed,respectively.Glucose in the influent concentration range from 0.05 to 10 g/L was used as the sole carbon source.Liquid flow rate was varied from 37.8 to 1080ml/h in the experiments.Experimental results showed that the hydraulic and nutritional conditions had significant influences on the growth rate and structure of biofilm.In a lower flow rate range,high liquid flow rate was propitious to the diffusion of substrate from liquid phase to solid-liquid interface,which resulted in the fast development of biofilm on the solid-liquid interface.However,some parts of biofilm were scraped off when the flow rate exceeded a threshold.At a fixed liquid flow rate,the biofilm density increased with the increase in the substrate concentration.The biofilm having thick and loose structure was developed under low substrate concentration condition.The biofilm structure was convenient for the nutrient transfer in the biofilm,which is a survival strategy of microorganisms facing adverse circumstances.

The aims of microbiology experiment teaching are not only to cultivate the students’ capacity of basic operation,but also to expanse their knowledge scope.We applied the bacterial diversity on the teach-ing class to make the students understand the progress of microorganism genomics research.It is helpful to cultivate the students’ innovative spirit and ability.Easy to work,clear result and low cost facilitated the spread of this experiment in the university.

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.

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.