Objective To study the changes of susceptibilities of Neisseria gonorrhoeae to antibiotics in Chengdu area. Methods The MIC values of 12 antibiotics to 100 strains in 1991 and 100 strains in 1996 were determined, and the MIC values to PPNG and non PPNG strains were also compared. Results and Conclusion The MIC values of 6 antibiotics (including penicillin G, tetracycline,etc.) to the isolates in different periods changed significantly (P

Adult ; Aneurysm, Dissecting ; complications ; diagnosis ; Aortic Aneurysm ; complications ; diagnosis ; Diagnostic Errors ; Female ; Humans ; Myocardial Infarction ; complications ; diagnosis

Background Many researches confirmed that basic fibroblast growth factor (bFGF)plays an important role on the proliferation and differentiation of retinal progenitor cells,but its low intraocular permeability limits its clinical application.To explore an effective approach to enhance the intraocular permeability of bFGF has an important significance for the treatment of retinopathy. Objective This study was to investigate the effect of azone on bFGF intraocular permeability after its topical administration. Methods Eighteen New Zealand white rabbits were randomly divided into four groups on random number table method.Distilled water( blank control group),5％ bFGF eyedrops(5％ bFGF group ),0.4％ azone+5％ bFGF eyedrops (0.4％ azone + 5％ bFGF group ) and 0.4％ azone+ 10％ bFGF eyedrops (0.4％ azone + 10％ bFGF group)were topically administered in different groups at 5- minute interval for 3 times.Aqueous and vitreous fluid were extracted 30 minutes after administration of eyedrops,and those in the 0.4％ azone + 5％ bFGF group were obtained 30,60 and 120 minutes after administration.bFGF concentration in the aqueous and vitreous fluid was quantified with ELISA. Results The bFGF levels(A value)in aqueous and vitreous fluid were 0.1007±0.0100 and 0.1340±0.0100 after topical administration of the 5％ bFGF eyedrops,those in blank control group were 0.1363 ±0.0100 and 0.1130±0.0100,respectively,and those in the 0.4％ azone+5％ bFGF group and 0.4％ azone+10％ bFGF group were significantly higher than the 5％ bFGF group ( both P=0.000).However,no significant difference was found in bFGF levels between 0.4％ azone+5％ bFGF group and 0.4％ azone + 10％ bFGF groups in both aqueous and vitreous fluid ( P =0.985,0.098 ).A value of bFGF in aqueous was gradually increased with prolong of time in the 0.4％ azone+5％ bFGF group,with the values 0.9413±0.0300 at 30 minutes,0.3865±0.0300 at 60 minutes,and 0.2550±0.0300 at 120 minutes,showing a positive linear correlation between bFGF level and time( R2 =0.736,P =0.003 ),but no significant correlation was seen in vitreous sample(R2=0.196,P=0.233). Conclusions Azone can improve the intraocular penetration of bFGF eyedrops.Increasing the concentration of bFGF in eyedrop from 5％ to 10％ dose not change its intraocular distribution.The highest content of the bFGF in aqueous is at 30 minutes following the administration of 0.4％ azone+5％ bFGF eyedrops.

At present, majority of the small molecular drugs used in clinics target proteins, they exert the efficacy through the binding to specific sites on the target protein. However, the "druggable" protein targets account for a small portion of the total number of proteins, and "non-druggable" proteins account for 80%, because of not having suitable drug binding sites. In the central rule, RNA is located in the upstream of proteins and controls the transcription of proteins. The research of small molecule drugs targeting RNA can solve the problem of protein "undruggable proteins" in some extent. This review summarizes the representative research achievements of small molecular drugs targeting RNA in recent years, and the screening methods applied to this field, with the focuses on the latest progress of small molecular drugs targeting novel coronavirus RNA.

Cancer, also known as malignant tumor, is the second largest disease after heart disease, which is characterized by genomic instability and mutagenicity. Ataxia telangiectasia and RAD3-related kinase (ATR) are members of phosphatidylinositol 3-kinase (PIKK) family, belonging to serine/threonine kinase, one of the key kinases in DNA damage response (DDR) and DNA repair pathway. This paper reviews the latest progress in the ATR inhibitor field including mechanism of action (MOA), therapeutic applications, and the combination therapy from the perspective of medicinal chemistry. It also discusses the possible challenges and future directions of developing ATR inhibitor antitumor drugs, which could provide the scientists in this field the convenience for access the information and application guidance for clinical studies.

As one of the major sources of infection, viruses could infect all organisms including bacteria, plants, animals, and humans. Infectious diseases caused by viruses pose a great threat and damage to human health and economic activities all over the world. Adaptor-associated protein kinase 1 (AAK1) is a member of the Ark1/Prk1 family of serine/threonine kinases and a specific key kinase regulating the phosphorylation of AP-2 protein μ2 subunit T156. In the past, AAK1 has been regarded as a feasible biological target for the treatment of nerve pain. Recently, scientists have found that inhibiting AAK1 can regulate endocytosis and inhibit virus invasion into cells. Therefore, AAK1 could be the potential target of anti-virus therapy. This paper reviews the research progress of small molecule AAK1 inhibitors in the field of antiviral, analyzes the future research directions and challenges, and provides new ideas for the development of antiviral drugs targeting AAK1.

OBJECTIVETo compare the effect of reinforcing Shen method (RSM) and activating blood method (ABM) in treating osteoarthritis (OA) at the molecular level.

METHODSThe physical and chemical characteristics of components from respective recipes of RSM and ABM, and network features of component-target interaction network were analyzed by computer simulation methods including chemical space, molecular docking, and biological network, etc.

RESULTSThe chemical components of RSM and ABM were scarcely scattered with larger overlapping. Among established networks, the distribution of network features was partially similar in RSM and ABM. The average target number correlated with each component was 1.86 in RSM and 2.11 in ABM respectively. Each average target number was respectively correlated with 4.46 compounds and 3.93 compounds, reflecting multi-component and multi-target actions.

CONCLUSIONComputer simulation could intuitively trace out similarities and differences of two different methods and their interaction with targets, which revealed that the compatibility of RSM and ABM could have broader protein targets and potential synergism at the molecular level.

Study the serum level of HGF, Cys C and TGF-beta1 in type 2 diabetic nephropathy (DN), the infect of Pingshen decoction on those index. Selected 69 cases of 2 type DN and randomly divided into therapy group (36 cases) and control group (33 cases). The therapy group were treated with Pingshen decoction 1 dose/d, bid po. The control group were treated with NephritisShu tablet, 6 tablet, tid po. 8 weeks was a course. Before and after treatment, we examine the serum level of HGF, Cys C and TGF-beta1 by ELISA and immunonephelometry, and compare with 30 cases of healthy control group. The study demonstrates that before treatment, the serum level of HGF in both groups were significantly lower than healthy control group (P < 0.01), but Cys C, TGF-beta1 were significantly higher (P < 0.01). After treatment, the serum level of HGF of both groups were increased. The serum level of HGF of therapy group were significantly higher than of control group (P < 0.01), but the serum level of Cys C and TGF-beta1 were significantly lower than control group (P < 0.01). The serum level of HGF was correlated negatively with Cys C,TGF-beta1. In control group, the UAER, urine beta2-MG and quantity of 24-hour urine protein were significantly decreased after treatment (P < 0.01). The index of urine of therapy group were significantly lower than control group (P < 0.01). Results indicate that test of serum level of HGF and Cys C,TGF-beta1 of diabetic nephropathy have important clinical significance. Pingshen decoction can effectively intervene in the serum level of HGF and Cys C, TGF-beta1 and index of urine.
Aged ; Aged, 80 and over ; Case-Control Studies ; Cystatin C ; blood ; Diabetic Nephropathies ; blood ; drug therapy ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Female ; Hepatocyte Growth Factor ; blood ; Humans ; Male ; Middle Aged ; Transforming Growth Factor beta1 ; blood

OBJECTIVE: To set up an easy and effective method for biotinylation of small molecule drugs with long chain. METHODS: Biotinylated 6-aminocaproic acid was synthesized as intermediate by one step method, doxorubicin(DOX) with auto-fluorescence was used as the first drug, and by DCC and DMAP catalysis, biotinylated DOX was synthesized. Using the double fluorescence system of DOX, the binding ability of biotinylated DOX to avidin and its biological activity were determined. When verified to be reasonable and effective, the method was applied to catalyze biotinylated paclitexal (PTX) which didn′t have auto-fluorescence itself, and the physical and chemical characteristics, and biological activities as well as the visualization were tested. RESULTS: The binding rate of synthesized DOX to avidin was 93.7%; the cells inhibition rate and localization were the same as DOX; the purity of biotinylated PTX was 84.42%, and the structure shown by NMR was correct; the cell inhibition rate was the same as PTX; the combination of PTX with microtubules was observed by visual modification. CONCLUSION: The method supplies a temperate way for biotinylation, and can be used for the synthesis and visualization of small molecules as probes and research of drug mechanism.

BACKGROUND:Extensive studies have shown that transcutaneous electrical nerve stimulation (TENS) plays a positive role in relieving the pain caused by a variety of diseases. However, its exact effect to manage pain in patients with knee osteoarthritis is stil controversial. TENS is classified into h-TENS and l-TENS, but currently its respective role in relieving the pain caused by knee osteoarthritis is not clear yet. OBJECTIVE: To compare the efficacy of h-TENS and l-TENS on pain relieving among patients with knee osteoarthritis. METHODS: A computer-based search was performed on PubMed, Embase and Cochrane database for randomized controled trials on TENS for the treatment of knee pain in patients with knee osteoarthritis which were reported before February 2014. Methodology quality of the trials was criticaly assessed and relative data were extracted. These studies were selected independently by two reviewers according to the inclusion and exclusion criteria. Meta-analysis was performed using Revman5.2 software. RESULTS AND CONCLUSION:A total of 10 randomized controled trials involving 519 cases were included. The results of meta-analysis showed that the h-TENS group had significant effects on pain relief in knee osteoarthritis patients in comparison to the control group [MD=-0.56, 95%CI(-0.98,-0.15),P=0.008]; the l-TENS group had no significant effect on pain relief in knee osteoarthritis patients in comparison to the control group [MD=-0.13, 95%CI(-1.63, 1.38),P=0.87]; the h-TENS group had significant effect on pain relief in knee osteoarthritis patients in comparison to the l-TENS group [MD=-0.85, 95%CI(-1.32, -0.37), P=0.000 5]. These findings indicate that h-TENS performs something positive to reduce pain in knee osteoarthritis patients that l-TENS cannot do. Owing to the limitations of this study, further work is needed to determine the role of TENS in pain management among patients with knee osteoarthritis.