Inosine 5'-monophosphate dehydrogenase (IMPDH) is a key enzyme of de novo GMP biosynthesis. The expression and activity of IMPDH can be affected by diseases and physiological process. It is the drug target for anticancer, antiviral, antimicrobial and immunosuppressive therapeutics. Not only catalytic action but the other biological functions of IMPDH also play an important role in diseases. The basic functions, mechanism of catalysis, classification of inhibitors, biological functions and the latest advances to IMPDH will be illustrated in this review. It is expected to be helpful to the discovery of new inhibitors and biological functions of IMPDH.
Animals ; Binding Sites ; Catalysis ; Drug Design ; Drug Discovery ; Enzyme Inhibitors ; classification ; pharmacology ; Humans ; IMP Dehydrogenase ; antagonists & inhibitors ; genetics ; metabolism ; Inosine Monophosphate ; metabolism ; Molecular Structure ; NAD ; metabolism ; Polymorphism, Genetic

[Objective] To discuss the mechanism of Kidney-notifying Compound preventing and treating menopause coronary heart disease.[Method] Copy 4 mature Henghe female monkeys into artificial menopause models,randomly divide them into Kidney-notifying Compound group(1) and Premarin control group(2),2 monkeys in one group.Every day make stomach perfusion of the of Compound decoction;take nitrate reductase to measure serum NO,radiation-immune method for plasm ET-1 concentration.[Result] The Compound and WM combined with estrogen Premarin all can raise NO and reduce ET level,two groups have statistical meaning in replying measurement(P

OBJECTIVETo compare the efficacy between eccentric fixation and internal fixation for treatment of intertrochanteric fractures of femur,to provide a theoretical basis for the selection of the treatment method of the intertrochanteric fractures of femur.

METHODSFrom February 2007 to January 2010,82 patients with femoral intertrochanteric fracture were treated by internal fixation including 39 cases of eccentric fixation involving 23 males and 6 females, aged from 41 to 81 years old with an average of (62.68±10.69), using the DHS or proximal femoral locking plate; 43 cases of intramedullary fixation involving 15 males, 28 females,aged from 43 to 78 years old with an average of (62.60±8.37),using PFN or PFNA fixed. The surgical incision length, operative time, blood loss and postoperative Harris score between two groups were compared.

RESULTSThe wound of two groups were primary healing without operative complications. All cases received follow-up for an average time of 18.3 months (12 to 28 months). The incision length, operative time and blood loss had a statistically significant difference between two groups (P<0.05). Harris scores of hip joint function at 1 month after operation had statistically significant difference between two groups (P<0.05), and Harris scores at 12 months after operation had no statistical significance difference between two groups. The rate of excellent and good was 89.7% in eccentric fixation group and 90.7% in intramedullary fixation group,the difference was not statistically significant (t=0.0613, P>0.05). In eccentric fixation group, there was 1 case of fracture nonunion with DHS loose and ensuing hip varus deformity. In intramedullary nail fixation group, there was no anti-rotation out,distal intramedullary nail of femoral refracture occurred in 1 case.

CONCLUSIONTwo treatment methods for the treatment of femoral fractures had a good therapeutic effect,but the intramedullary fixation had shorter operative time and less blood loss than the eccentric fixation,it prior to apply to osteoporosis and unstable femoral intertrochanteric fractures.

Adult ; Aged ; Aged, 80 and over ; Female ; Fracture Fixation, Intramedullary ; methods ; Fracture Healing ; Hip Fractures ; surgery ; Humans ; Male ; Middle Aged ; Operative Time

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

Transmembrane serine protease 2 (TMPRSS2) is a cell surface protease widely present in the human body. It is involved in the infection of various viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and in the cell invasion, tumor growth and metastasis processes of prostate cancer. This study used Boc-Gln-Ala-Arg-AMC as the fluorescent substrate to determine the cleavage activity of TMPRSS2 towards SARS-CoV-2 S protein. Then cell-based screening model for TMPRSS2 inhibitors was established in Vero E6 cells overexpressing TMPRSS2 (Vero E6/TMPRSS2). Seven compounds exhibiting TMPRSS2 inhibitory activities with low toxicity were obtained through high-throughput screening (HTS) from natural and synthetic compound pure product library of National Center for Screening Novel Microbial Drugs. Surface plasmon resonance (SPR) has shown that the obtained inhibitors could bind to TMPRSS2 with moderate affinity in a dose dependent manner. Cell-cell fusion experiments have shown that the obtained inhibitors can inhibit the occurrence of S protein mediated cell-cell fusion by inhibiting TMPRSS2 cleavage of SARS-CoV-2 S protein in a concentration dependent manner. Preliminary pseudovirus experiment showed that the inhibitors may reduce the pseudovirus infection into Opti-HEK-293T-ACE2 cells to varying degrees. In a word, this study successfully established a cell-based HTS model for TMPRSS2 inhibitor and preliminarily confirmed that the seven screened inhibitors possessed in vitro anti-TMPRSS2 activities, providing new structural scaffolds for the development of new drugs against SARS-CoV-2.

Objective To evaluate the association between interleukin-I(IL-1)loci polymorphisms and increased risk of gastric carcinoma in samples from northern Chinese population.Methods Blood sam- ples from 126 patients with gastric cancer and 125 controls with chronic gastritis were collected.Genomic DNA was extracted and polymorphisms at -31(C to T),-511(C to T)and at intron 2(86-bp VNTR)of IL-I RN were genotyped by PCR-CTPP,PCR-RFLP and PCR.For detection of Hp infection fast urenase test,~(14)C breath test and serum anti-Hp IgG antibody assay were used.Results Five kinds of polymorphism of IL-IRN were found as 1/1,1/3,1/4,1/2 and 2/2,and the frequencies in patients were 76.19%、4.76%、6.35%、11.90% and 0.79%,respectively.However,the frequencies in controls were 76.00%、4.00%、4.80%、13.60% and 1.60%.No significant differences were observed between cases and controls in each genotype.The polymorphism of IL-IB-31 allele was C/C,C/T and T/T.The frequencies in patients were 12.70% ,47.62% and 39.68%,and in controls 28.00%,48.80% and 23.20% respectively.IL-1B- 31 T/T carriers were at an increase risk of gastric cancer with an odds ratio of 3.772(95% CI,1.786- 7.966).IL-IB-511 alleles were C/C,C/T and T/T.The frequencies in patients were 19.20%,56.80% and 24.00% and in controls,23.38%,49.19% and 27.42% respectively.No significant differences were observed between cases and controls in each genotype.Conclusion In Chinese population,the polymor- phism of IL-1B-31 alleles may be associated with the susceptibility of gastric cancer.However,no evidence was found to support that the polymorphisms of IL-1RN and IL-I B-511 alleles had relationship with gastric cancer.

In this paper, three spoilage organisms were separated from five transmutative soy milks, and all the three spoilage bacteria could survive condition of both 1?105Pa,30min and 300mg/kg Nisin. Morpha character, physiological and biochemical characteristics, and a phylogenetic analysis based on 16S rDNA gene sequences reveal that these three strains are Bacillus licheniformis, Bacillus pumilus and Brevibacillus borstelensis respectively. GenBank accessions for these three strains are EF439666-EF439668。

Objective:To analyze morphological character of lateral tibial plateau fracture fragment, and its correlation to the presence of a meniscus injury in tibial plateau fractures.Methods:A total of 79 consecutive patients of the simple lateral tibial plateau fractures from July 201 1 to July 2015 were inclu-ded in this study,with 65 males and 14 females with an average age of (34.3 ±7.2)years and 22-61 years.According to Schatzker classification,21 cases were of Type Ⅰ,41 cases Type Ⅱ,and 17 cases Type Ⅲ.The characteristics of lateral tibial plateau fractures were evaluated by plain X-ray and magnetic resonance imaging (MRI ).The type and severity of meniscus injury were diagnosed by MRI scan. Three-dimensional measurements of the lateral fragment width (LFW),the lateral plateau depression (LPD),the coronal angulation of lateral fragment (CALF),and tibial plateau widening (TPW)were measured with Picture Archiving and Communication Systems(PACS)software.The patients with and without meniscus injuries were divided into different groups and analyzed respectively.Comparison of the above measurements between the two groups was analyzed by independent t test.Results:In all the 79 lateral tibial plateau fracture patients,26 cases (32.9%)of meniscus injuries were detected by MRI. Among all the meniscus injury cases,3 were of SchatzkerⅠ,16 SchatzkerⅡ,and 7 SchatzkerⅢ.In meniscus intact group,the average LFW was (22.0 ±2.8)mm while in meniscus injury group it was (21.3 ±3.3)mm (t =-1.008,P =0.317).The average LPD of non meniscus injury group was (5.4 ±2.8)mm,while in meniscus injury group was (8.7 ±2.8)mm (t=4.98,P=0.001).The average CALF of the two groups were 9.1°±6.1°and 10.6°±7.1°,and there was no significant dif-ference between the two groups (t=0.38,P=0.831).The average TPW was (3.0 ±1.1)mm,and (4.8 ±1 .7 )mm of the two groups.There were significant differences between the two groups (t =5.216,P=0.001).Conclusion:There was no obvious correlation between the LFD and meniscus inju-ry.The CALF of lateral tibial plateau fracture had no significant correlation with meniscus injury either. The degree of LPD and TPW may indicate injury of the meniscus in tibial plateau fractures.

Objective To compare the differences of clinical characteristics between genotype B and C chronic hepatitis B(CHB)patients and to summarize clinical factors related to genotype C hepa- titis B virus(HBV)infection.Methods Seventy eight CHB patients who were diagnosed with genotype B or C infection by liver puncture biopsy and genotyping were enrolled.Their serum HBV DNA levels were detected.Severe hepatitis,liver cirrhosis,hepatocellular carcinoma and HBeAg positive rate were analyzed to determine the pathologic inflammation and fibrosis degree of liver tissue.Chi square test and Logistic multiple regression analysis were employed for the statistical analysis.Results The serum albumin and pre-protein were lower in genotype C CHB patients than that in genotype B.The alanine aminotrans- ferase,total bilirubin and prothrombin time were higher in genotype C CHB patients than that in genotype B.The rates of genotype C patients increased significantly with the grade of liver necroin- flammation progressing from GO to G4(1.8%,11.1%,20.4%,33.3%,33.3%) and the stage of liver fibrosis progressing from SO to S4(5.6%,5.6%,14.8%,33.3%,40.7%),but the rates of genotype B patients did not change significantly with the grade of liver necroinflammation(16.7%, 25.0%,25.0%,20.8%,12.5%)and stage of liver fibrosis progressing(16.7%,29.2%%,20.8%, 16.7%,16.7%).There was statistical significance in grades of liver necroinflammation(X~2= 11.49,P=0.022)and stages of liver fibrosis(X~2=13.56,P=0.006)between genotype B and gen- otype C patients.The rates of genotype C CHB patients were higher than,similar with and lower than the rates of genotype B patients of HBV DNA level above 1.0?10~6 copy/mL,between 5.0?10~2-1.0?10~6 copy/mL and under 5.0?10~2 copy/mL,respectively(51.8% vs 12.5%,35.2% vs 45.8% and 13.0% vs 41.7%).There was statistical significance of HBV loads between genotype B and genotype C patients(X~2=13.25,P=0.001).HBeAg positive rate in genotype C patients was significantly higher than that in genotype B patients(61.1% vs 25.0%,X~2=8.67,P=0.003).The rates of decompensated cirrhosis,compensated cirrhosis and no-cirrhosis in genotype C patients were higher than,similiar with and lower than the rates in genotype B patients,respectively(40.7% vs 4.2%,22.2% vs 20.8% and 37.0% vs 75.0%).There was statistical significance of the rate of cirrhosis between genotype B and genotype C patients (X~2=12.47,P=0.002).Conclusions The degree of liver necroinflammation and fibrosis,the HBeAg positive rate and the incidence of cirrhosis are all related with genotype C HBV infection.

This study established an HPLC fingerprint of Tibetan medicine Shaji Gao from different habitats and lay a foundation for Shaji Gao varieties identification and preparation process. The chromatographic condition was as follow: Agilent zorbax SB-C18 (4.6 mm x 250 mm, 5 μm) eluted with the mobile phases of acetonitrile and 0.4% phosphoric acid water in gradient mode. The flow rate was 1.0 mL x min(-1), and the detection wavelength was set at 360 nm. The fingerprints of 15 batches Shaji Gao were carried out by similarity comparation, 7 chromatographic peaks were extracted as the common peaks of fingerprint, 3 peaks were identified, which were quercetin, kaempferol and isorhamnetin. The similarity degrees of 14 batches of samples were above 0.9 and 1 batch of samples was below 0.9. This is the first established fingerprint of Shaji Gao by using HPLC. This method has good precision, stability and repeatability that it could provide basis for quality control and evaluation of Shaji Gao.
Chromatography, High Pressure Liquid ; methods ; Medicine, Tibetan Traditional ; Quality Control