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.

Objective To determine the incidence and risk factors of iatrogenic retinal breaks in eyes undergoing pars plana vit- rectomy for idiopathic macular pucker.Design Retrospective case series.Participant 88 consecutive vitrectomies performed on eyes with idiopathic macular pucker.Method Consecutive vitrectomies performed on eyes with idiopathic macular pucker at Beijing Tongren Eye Center between 2002 and 2006 were retrospectively reviewed.Cases with iatrogenic retinal breaks were recorded and analyzed. Main Outcome Measure Number and location of retinal breaks,and anatomic outcome after surgical managements.Result A total of 88 consecutive vitrectomies were included in the study.Of the 88 eyes,8 eyes had 14 iatrogenic retinal breaks detected,with an aver- age incidence of 9.1%.Peripheral retinal breaks(8.0%)were more common than posterior retinal breaks(1.1%).All peripheral retinal breaks occurred around the selerotomy sites(100%)and the quadrant of predominant hand was involved most commonly(62%).Most of the breaks(88%)were detected during the surgery.All eyes with iatrogenic retinal breaks obtained anatomic retinal reattachment (100%).Conclusion Despite improvements in instrumentation and surgical techniques,iatrogenic retinal break continues to be an im- portant complication of pars plana vitrectomy in eyes with idiopathic macular pucker.This complication tends to occur more commonly at peripheral retina and is mainly selerotomy-related.

Calcinosis ; complications ; Decalcification Technique ; Humans ; Meningeal Neoplasms ; complications ; Meningioma ; complications ; Specimen Handling ; methods ; Ultrasonics

Objective:To understand the application status of precursor drugs in the outpatients of our hospital. Methods:Totally 12 kinds of precursor drugs were included in the management. The data of prescriptions in HIS were collected from July 1 to September 30 in 2015. The defined daily dose (DDD), frequency of drug use (DDDs), drug utilization index (DUI) and the other parameters were calculated and the influencing factors were analyzed by the Pareto method. Results: Among the twelve precursor drugs, DUI of seven kinds was less than or equal to 1. Paracetamol tablets, pseudoephedrine hydrochloride tablets, dextromethorphan hydrobromide and chlorphenamine maleate tablets, nicergoline tablets and compound dextromethorphan hydrobromide tablets II displayed lower DUI, indicating their clinic application was more reasonable. Conclusion:The data showed that the use of precursor drugs in our hospital is basically reasonable.

The purity of 4,4′-dimethoxy-5,6,5′,6′-bis (methylenedioxy)-2′-morpholine methylenebiphenyl-2-methyl formate methanesulfonate (IMH), a new drug for fatty liver treatment, was determined through differential scanning calorimetry (DSC). Analysis of two-factor non repeatability method was performed in the investigation the effects of two factors (heating rate and sample weight) on purity determination. The DSC experimental parameters were optimized as follows: heating rate was 10 ℃·min^-1, temperature range was 150-300 ℃, sample weight was 2.0-4.1 mg, and N₂ flow rate was 80 mL·min^-1. The linear correlation coefficient (r) of this DSC method was 0.999 8. The RSD value (n = 6) of precision was 0.03%. The standard value and uncertainty of the purity results of the multiple batches of IMH drugs were (99.74 ± 0.29)%, (99.91 ± 0.28)%, (99.90 ± 0.28)%, and (99.81 ± 0.28)% with inclusion factor (K) of 2 and confidence probability (P) of 0.95. The results were basically consistent with the results of the mass balance method. The DSC mehod is a simple, rapid and accurate method, and provides a new reference method for determining the purity of IMH drugs, improves the accuracy and reliability of purity determination.

To study chemical constituents of the leaves of Nauclea officinalis, eight alkaloids were isolated from 95% ethanol extract by various chromatographic methods. The structures were elucidated on the basis of spectroscopic data (IR, UV, ESI-MS, 1D and 2D NMR) and identified as naucleactonin C (1), strictosamide (2), vincosamide (3), pumiloside (4), angustoline (5), angustine (6), 18, 19-dihydroangustine (7) and naucleofficine D (8). Compound 1 is a new indole alkaloid. Compounds 6 and 7 were isolated from this plant for the first time.
Alkaloids ; chemistry ; isolation & purification ; Camptothecin ; analogs & derivatives ; chemistry ; isolation & purification ; Indole Alkaloids ; chemistry ; isolation & purification ; Indoles ; chemistry ; isolation & purification ; Molecular Structure ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; Rubiaceae ; chemistry ; Vinca Alkaloids ; chemistry ; isolation & purification

OBJECTIVETo investigate the pharmacokinetic interaction among three major bioactive compounds of Shengmai formula.

METHODSAfter oral administration of ginsenoside Rg(1), ginsenoside Rb(1) and schisandrin with the same dose(100 mg.kg(-1)) individually or in combination, rat serum samples were extracted, then these three compounds were determined by liquid chromatography-mass spectrometry(LC-MS). The pharmacokinetic parameters of three compounds in single or combination form were calculated by WinNonLinu6.0 using non-compartment model.

RESULTSCompared with single drug group, the peak concentration of ginsenoside Rg(1) in combined group increased from(0.476 ±0.238) μg.ml(-1) to (1.946 ±1.432) μg.ml(-1), AUC(0-∞) increased from(0.523 ±0.238) μg.h.ml(-1) to (1.908 ±1.319) μg.h.ml(-1), CL decreased from(226311 ± 96819) ml.h(-1).kg(-1) to(90650 ±73684) ml.h(-1).kg(-1) and Vd decreased from(317110 ±154009) ml.kg(-1) to(130967 ±78306) ml.kg(-1). While the pharmacokinetic parameters of ginsenoside Rb(1) and schisandrin showed no significant change.

CONCLUSIONCombined oral administration of three compounds of Shengmai formula can improve the bioavailability of ginsenoside RgRg(1), however it does not change the pharmacokinetic behavior of ginsenoside RbRg(1) and schisandrin.

Animals ; Biological Availability ; Chromatography, Liquid ; Cyclooctanes ; administration & dosage ; blood ; pharmacokinetics ; Drug Synergism ; Ginsenosides ; administration & dosage ; blood ; pharmacokinetics ; Lignans ; administration & dosage ; blood ; pharmacokinetics ; Male ; Polycyclic Compounds ; administration & dosage ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry

OBJECTIVETo investigate the correlation of vasectomy with the risk of prostate cancer in Chinese men.

METHODSWe systematically searched the databases CNKI, VIP, Wanfang, PubMed, Embase, and Cochrane Library for the literature relating the relationship between vasectomy and the risk of prostate cancer in Chinese males up to December 2014. According to the inclusion and exclusion criteria, two investigators independently selected the eligible publications, evaluated their quality, and extracted relevant information, followed by a meta-analysis with the software STATA 12.0.

RESULTSNine studies were included in the analysis involving 1 202 cases of prostate cancer and 4,496 controls. Random-effect model analysis revealed no statistically significant correlation between vasectomy and the risk of prostate cancer (OR = 1.05; 95% CI 0.62-1.79), with an obvious heterogeneity (P < 0.001, I2 = 85.7%). No significant publication bias was found among the included studies (Egger, P = 0.824; Begg, P = 0.348).

CONCLUSIONThe results of our meta-analysis do not support the association of vasectomy with the increased risk of prostate cancer in Chinese population.

Asian Continental Ancestry Group ; China ; Humans ; Male ; Prostatic Neoplasms ; ethnology ; etiology ; Risk Assessment ; Vasectomy ; adverse effects

Objective To evaluate risk factors for central venous catheter-related bloodstream infection(CRBSI)in intensive care unit(ICU)patients by Meta analysis. Methods Literatures about risk factors of CRBSI in ICU pa-tients were retrieved from databases of Cochrane Library,PubMed,Embase,CBM,CNKI,and WanFang Data,RevMan 5.3 software was used for Meta analysis.Results There are 12 literatures in accordance with the inclusion criteria,with a total sample size of 14 422 cases,5 cohort studies and 7 case-control studies,the Newcastle-Ottawa Scale(NOS)scores were 4-6 points. According to Meta analysis,duration of indwelling catheter(WMD,12.25 [95%CI,5.55-18.94]),multi-cavity catheter(OR,3.52[95% CI,1.46-8.52]),femoral vein catheterization (OR,2.44[95%CI,1.34-4.46]),parenteral nutrition(O R,2.47[95% CI,1.18-5.21]),length of stay in ICU(WMD,10.01[95%CI,4.17-15.85]),APACHE II score(WMD,4.46[95%CI,1.25-7.66]),and dia-betes mellitus(OR,1.83[95% CI,1.08-3.09])were significantly different in each group(all P<0.05). Conclusion Risk factors for CRBSI in ICU patients are duration of indwelling catheter,multi-cavity catheter,femo-ral vein catheterization,parenteral nutrition,length of stay in ICU,APACHE II score,and diabetes mellitus. However,due to the limitation of methodological quality of included studies,more strictly designed and large sam-ple prospective studies are needed to verify the result.

Objective:To establish an experimental model for intracellular antibacteria and endotoxin neutralization in vitro to detect the antibacterial and endotoxin neutralization activity of the muBPI_(25) protein.Methods: RAW264.7 cells were transfected with pcDNA3.1(+)muBPI_(36-259), and then were infected with intracellular bacterial of either G ~+/G~-to establish the experimental model of intracellalar antibacteria.The RAW264.7 cells were co-transfected with the pSecTag2B-muBPI_(36-259) and dual-luciferase reporter gene plasmids for establishment of the experimental model of endotoxin neutralization.Results:The experimental model of intracellular antibacteria confirmed that the muBPI_(25) protein could inhibit/kill Salmonella typhi.The experimental model of endotoxin neutralization indicated that the muBPI_(25) protein could neutralize endotoxin.Conelusion: We firstly demonstrate that murine BPI N-terminal functional fragment(muBPI_(25) protein)can inhibit/kill Salmonella typhi,and can neutralize, its lysating product, endotoxin.