Objective To determine 2, 3, 4, 5, 6-pentafluorobenzyl monofluoroacetate (PFB-MFA) as the derivative of monofluoroacetate anion ion by gas chromatography, by which fluoroacetamide, one of the raticides may be analyzed. Methods The calibration curve and limit of detection were obtained by quantification of standardized PFB-MFA using GC/ECD and GC/MS. Results The linear ranges for PFB-MFA were 0.01～0.1ng/?for GC/ECD,1～100ng/?l for GC/MS SCAN and 5?10~(-3)～1 ng/?l for GC/MS SIM. The limit of detections for fluoroacetate anoin were 1.31?10~(-4)ng/?l for GC/ECD, 0.13 ng/?l for GC/MS SCAN, and 1.76?10~(-4) ng/?l for GC/MS SIM. Conclusion The monofluoroacetate anion derivative (MFAPFB) can be deterimined accurately with high sensitivity by GC/ECD and GC/MS SIM, which may be used for analysis of fluoroacetamide in forensic practice.

Objective To evaluate the effects of different doses of fentanyl on the median effective target plasma concentration (EC50) of propofol inhibiting body movement evoked by gastroscopy in the elderly patients.Methods Ninety patients of both sexes,aged 75-89 yr,with a body mass index of 19-25 kg/m2,of ASA physical status Ⅱ or Ⅲ,scheduled for elective gastroscopy,were randomly divided into 3 groups (n =30 each):control group (group C) and different doses of fentanyl groups (F0.5 and F1.0 groups).Fentanyl 0.5 and 1.0 μg/kg were injected intravenously in F0.5 and F1.0 groups,respectively.Propofol was then administered by target-controlled infusion.The initial target plasma concentrations (Cps) of propofol were 2.0,1.5 and 1.0 μg/ml in C,F0.5 and F1.0 groups,respectively.Gastroscopy was performed after the target effect-site and plasma concentrations were balanced.Body movement was defined as movement in head or four extremities during gastroscopy.The target Cp of propofol was determined by up-and-down sequential trial.Each time the Cp increased/decreased by 0.5 μg/ml in the next patient depending on whether or not body movement developed.The EC50 and 95 ％ confidence interval (CI) of propofol inhibiting gastroscopy-evoked body movement were determined using Probit analysis.Results The EC50 (95 ％ CI) of propofol was 2.24 ng/ml (1.67-2.47 ng/ml) in group C,1.79 (1.55-1.95) μg/ml in group F0.5,and 1.13 (1.08-1.62) μg/ml in group F1.0.There was no significant difference in the EC50 of propofol between F0.5 and C groups.The EC50 of propofol was significantly lower in F1.0 group than in C and F0.5 groups.Conclusion When combined with propofol,fentanyl 1.0 μg/kg is recommended for gastroscopy in the elderly patients.

Objective To evaluate the effect of age on the median-effective target plasma concentration (EC50) of propofol inhibiting body movement evoked by gastroscopy in the patients.Methods Ninety adult patients of both sexes,of ASA physical status Ⅰ or Ⅱ,with body mass index 19-25 kg/m2,scheduled for elective gastroscopy,were divided into 3 groups according to age (n =30 each):18-39 yr group (Ⅰ group),40-64 yr group (Ⅱ group) and 65-85 yr group (Ⅲ group).In Ⅰ,Ⅱ,Ⅲ groups,propofol was given by target-controlled infusion with the initial target concentrations of 2.5,2.0 and 1.5 μg/ml,respectively,and gastroscopy was performed when the target concentration was achieved.Body movement was defined as the directional movement in head or four extremities during gastroscopy.The target plasma concentration of propofol was determined by up-and-down sequential trial.Each time the plasma concentration of propofol increased/decreased by 0.5 μg/ml in the next patient depending on whether or not body movement developed.The EC50 and 95 ％ confidence interval of propofol inhibiting gastroscopy-evoked body movement were determined using Probit analysis.Results The EC50 (95 ％ confidence interval) of propofol was 4.2(3.8-4.5),4.1(3.7-4.4) and 2.4(1.8-2.7) μg/ml in Ⅰ,Ⅱ and Ⅲ groups,respectively.There was no significant difference in the EC50 of propofol between group Ⅱ and group Ⅰ.The EC50 of propofol was significantly lower in group Ⅲ than in Ⅰ and Ⅱ groups.Conclusion Age affects propofol-induced analgesia in patients with visceral pain,and the potency of propofol inhibiting visceral pain during gastroscopy in the elderly patients is significantly enhanced as compared with that in the young and middle-aged patients.

Background Laser peripheral iridoplasty (LPI) is widely used in the treatment of glaucoma by flattening the iris and widening angle of anterior chamber (AA).However,no evidence suggests the optimal site of LPI in iris.Objective This study was to compare the therapeutic effects of LPI at different sites of iris for glaucoma.Methods Glaucoma models were established in the right eyes of 40 healthy adult male pigment rabbits by intrachamber injection of 0.1 ml compound carbomer solution with 0.3％ carbomer and 0.025％ dexamethasone.The models were randomly divided into model control group,corneoscleral limbus group,one spot from corneoscleral limbus group and two spots from corneoscleral limbus group.LPI was performed at corresponding site of iris by 532 nm argon laser with the spot diameter 500 μm,energy 300 mW,exposure time 0.3 seconds and laser number 24 spots,and the rabbits in the model control group did not receive LPI.Intraocular pressure (IOP),coefficient of outflow facility (C value) were measured and calculated with Schi(o)tz tonometer before LPI and 2,4,7,14 and 30 days after LPI,and anterior chamber depth (ACD),AA,anterior chamber angle opening distance within 500 μm radius from scleral spur (AOD500) were measured with ultrasound biomicroscope (UBM).The eyeballs were extracted 30 days after LPI,and the chamber angle were observed under the optical microscope after hematoxylin and eosin staining.The use and care of the animals complied with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.Results UBM showed that compared with the model control group,the anterior chamber angle was evidently widened in all the LPI groups,with the best effectiveness in the one spot from corneoscleral limbus group and the worst one in the two spots from corneoscleral limbus group.Compared with the model control group,the IOP was evidently reduced,and C values,AA and AOD500 were significantly increased in the corneoscleral limbus group,one spot from corneoscleral limbus group and two spots from corneoscleral limbus group after LPI,showing significant differences among the four groups (IOP:Fgroup =16.848,P ＜ 0.01;C value:Fgroup =9.629,P ＜ 0.01;AA:Fgroup =62.336,P＜0.01;AOD500:Fgroup =77.779,P ＜ 0.01).IOP was reduced and C value,AA and AOD500 were increased in 2,4,7,14 and 30 days after LPI as compared with before LPI,with significant differences over time (IOP:Ftime =3.041,P =0.011;C value:Ftime =4.311,P＜0.01;AA:Ftime =14.627,P＜0.01;AOD500:Ftime =20.378,P＜0.01).Compared with the model control group,the ACD was significantly increased in the corneoscleral limbus group and one spot from corneoscleral limbus group,and that in the two spots from corneoscleral limbus group was significantly reduced,and the ACD was insignificantly increased over time after LPI (Fgroup =18.017,P＜0.01;Ftime =0.022,P =1.000).Hematoxylin and eosin staining showed that the trabecular meshwork and adhesion of tissure were reopened and the anterior chamber angle was widened after LPI.Conclusions LPI can widen anterior chamber angle and lower the IOP.The best therapeutic outcome for glaucoma is displayed when LPI is performed at the iris site corresponding to one spot from the corneoscleral limbus.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins