Investigating the species/biovars,distribution patterns,and genetic correlations of Brucella from sheep in north-west China is critical to reveal the population and epidemiological characteristics of the Brucella melitensis.In this study,con-ventional identification and AMOS-PCR were used to determine the species/biovars of Brucella isolated from 13 regions in northwest China.MLST and MLVA-16 genotyping methods were used to analyze the genetic characteristics of the strains.Con-ventional identification and AMOS-PCR detection revealed that 59 Brucella melitensis were isolated in this study,in-cluding 22 strains from Inner Mongolia,17 strains from Xin-jiang,13 strains from Gansu,and 7 strains from Qinghai,of which 58 strains were B.melitensis biovar 3,and one strain was B.melitensis biovar 1.MLST analysis indicated that 90％(53/59)of B.melitensis were of ST8 sequence type,the dominant epidemic population.The MLVA-11 survey demonstrated that 59 B.melitensis strains clustered into six MLVA-11 genotypes,and 87％of the strains were of MLVA-11 genotype 116.Therefore,the predominant strains in the northwest region were from the Eastern Mediterranean lineage.MLVA-16 divided 59 strains of B.melitensis into 40 gen-otypes,eight of which were shared genotypes.Each genotype was composed of two to seven strains from the same region,thereby indicating that the cases of each shared genotype were outbreaks from a common source of infection.All shared MLVA-16 genotypes comprised strains from the same province,thus indicating apparent regional clustering characteristics of strains in each province.In a genetic comparison between populations and isolated strains from the spleens of sheep,multiple identical MLVA-16 genotypes were found to be composed of strains from different hosts.These findings indicated a transmission path-way from sheep/goats to humans.B.melitensis biovar 3 was the main pathogen causing animal brucellosis in the northwest re-gion,and infected sheep were the main brucellosis infection source in the regional population.The ST8 strains were the domi-nant epidemic population,and the MLVA genotype of strains in each region showed clear regional clustering characteristics.

Obvious epigenetic differentiation occurred on Lycium barbarum in different cultivation areas in China. To investigate the difference and change rule of DNA methylation level and pattern of L. barbarum from different cultivation areas in China, the present study employed fluorescence-assisted methylation-sensitive amplified polymorphism(MSAP) to analyze the methylation level and polymorphism of 53 genomic DNA samples from Yinchuan Plain in Ningxia, Bayannur city in Inner Mongolia, Jingyuan county and Yumen city in Gansu, Delingha city in Qinghai, and Jinghe county in Xinjiang. The MSAP technical system suitable for the methylation analysis of L. barbarum genomic DNA was established and ten pairs of selective primers were selected. Among amplified 5'-CCGG-3' methylated sites, there were 35.85% full-methylated sites and 39.88% hemi-methylated sites, showing a high degree of epigenetic differentiation. Stoichiometric analysis showed that the ecological environment was the main factor affecting the epigenetic characteristics of L. barbarum, followed by cultivated varieties. Precipitation, air temperature, and soil pH were the main ecological factors affecting DNA methylation in different areas. This study provided a theoretical basis for the analysis of the epigenetic mechanism of L. barbarum to adapt to the diffe-rent ecological environments and research ideas for the introduction, cultivation, and germplasm traceability of L. barbarum.
China ; DNA Methylation ; DNA Primers ; Epigenesis, Genetic ; Lycium/genetics*

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use* ; Binding Sites ; COVID-19/virology* ; Coronavirus Papain-Like Proteases/metabolism* ; Crystallography, X-Ray ; Drug Evaluation, Preclinical ; Drug Repositioning ; High-Throughput Screening Assays/methods* ; Humans ; Imidazoles/therapeutic use* ; Inhibitory Concentration 50 ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Naphthoquinones/therapeutic use* ; Protease Inhibitors/therapeutic use* ; Protein Structure, Tertiary ; Recombinant Proteins/isolation & purification* ; SARS-CoV-2/isolation & purification*

Background: The aortic arch replacement and cardiopulmonary bypass (CPB) are both associated with the early mortality after cardiothoracic surgery. This study aimed to investigate the relationship between CPB time and 90-day post-operative mortality in patients undergoing aortic arch surgery using the frozen elephant trunk (FET) technique with selective ante-grade cerebral perfusion (SACP). Methods: We retrospectively reviewed data of 377 adult patients undergoing aortic arch surgery via FET with SACP from July 1, 2017 to December 31, 2018 at Beijing Anzhen Hospital. The baseline characteristics, intra-operative data, and post-operative data were collected. Univariate and multivariate Cox regression analyses were used to determine independent predictors of 90-day postoperative mortality. Results: The 90-day post-operative mortality was 13.53%. The 78.51% of patients were men. There were 318 (84.35%) type A aortic dissections and 28 (7.43%) aortic aneurysms. Among those, 264 (70.03%) were emergency operations. Median CPB time was 202.0 (176.0, 227.0) min. Multivariate Cox regression analysis revealed that CPB time was independently associated with 90-day post-operative mortality after adjusting confounding factors (hazard ratio: 1.21/10 min increase in CPB time, 95% confidence interval: 1.15–1.27, P < 0.001). Kaplan-Meier analysis based on CPB time tertiles revealed that the top tertile (median 236.0 min) was associated with reduced survival rate compared with middle and bottom tertiles (P < 0.001). Each sub-group analysis based on the complexity of the underlying disease process showed similar associations between CPB time and 90-day post-operative mortality. Conclusions CPB time remains a significant factor in determining 90-day post-operative mortality in patients undergoing aortic arch surgery using FET with SACP. Surgeons should be aware of the relationship between CPB time and 90-day post-operative mortality during operative procedures and avoid extended CPB time as far as possible.

Objective: To investigate the success rate and safety of percutaneous vasoseminal vesiculography with the disposable vasographic interventional therapy kit (VITK). METHODS: This study included ninety-six 19－65 (mean 43) years old male patients with infertility, hematospermia, seminal vesicle cyst, ejaculatory duct cyst, ejaculatory dysfunction, or vas deferens injury, with disease courses varying from 1 month to 7 years. With an open, multi-centered, single-group, self-controlled design and using the disposable VITK, we treated the patients by percutaneous vasoseminal vesiculography via injection of contrast medium into the vas deferens cavity under local anesthesia. RESULTS: Percutaneous vasoseminal vesiculography was successfully performed in 92 (97.87%) of the patients, which revealed abnormal seminal ducts in 51 cases (54.3%). Among the 28 infertile patients, 3 were found with bilateral and 5 with unilateral vas deferens obstruction. Vesiculitis was detected in 36 (81.8%) of the 44 hematospermia patients and bilateral vas deferens abnormality in 5 (38.5%) of the 13 patients with ejaculatory dysfunction. Transectional damage was observed in 2 patients with vas deferens injury induced by bilateral inguinal hernia repair. Three cases of seminal vesicle cyst and 4 cases of ejaculatory cyst were definitely diagnosed by vasoseminal vesiculography. CONCLUSIONS The disposable vasographic interventional therapy kit, with the advantages of simple operation and high safety, deserves a wide clinical application in vasoseminal vesiculography.
Adult ; Aged ; Contrast Media ; administration & dosage ; Cysts ; diagnostic imaging ; Ejaculatory Ducts ; diagnostic imaging ; Genital Diseases, Male ; diagnostic imaging ; Hemospermia ; diagnostic imaging ; etiology ; Hernia, Inguinal ; surgery ; Humans ; Infertility, Male ; diagnostic imaging ; Injections ; Male ; Middle Aged ; Postoperative Complications ; diagnostic imaging ; etiology ; Radiography ; methods ; Seminal Vesicles ; diagnostic imaging ; Vas Deferens ; diagnostic imaging ; injuries ; Young Adult

Objective: To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control. Methods: A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed. Results: A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group. Conclusion In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.

OBJECTIVETo perform a prospective,multicenter,open,randomized study to determine a treatment regimen for treatment-naive patients with refractory chronic hepatitis C (RHC) using the predictive value (PV) of early virological response (EVR).

METHODSA total of 438 patients from 18 hospitals were recruited between December 2008 and December 2010 and administered peg-interferon/ribavirin treatment for 12 weeks. Patients who achieved complete EVR (cEVR) were assigned to group A for a 48-week course of treatment, while patients without cEVR were randomly allocated to either group B 1 for a 72-week course of treatment or to group B2 for a 96-week course of treatment. Serum hepatitis C virus RNA levels at baseline,treatment weeks 4, 12 and 24, end of treatment, and post-treatment week 24 were measured and used to evaluate the efficiency of therapy.

RESULTSThe overall sustained virological response (SVR) rate was 85.1%. In all, 91.0% of patients achieved cEVR and were assigned to group A, which had an SVR rate of 90.8%. There was no statistically significant difference in the SVR rates of groups B1 and B2 (29.4% vs. 25.0%, P more than 0.05). The positive PV of rapid virological response (RVR), cEVR and delayed virological response (DVR) for SVR was 93.4%, 90.8% and 77.8% respectively, and the negative PV of RVR, EVR and DVR for SVR was 28.0%, 93.3% and 100% respectively. Overall, 66.9% of the patients experienced adverse events (AEs), but only 1.9% of patients experienced sevcre AEs.

CONCLUSIONThe majority of Chinese RHC treatmentna(i)ve patients (91.0%) can achieve cEVR and a high SVR rate with a low rate of severe AEs using the cEVR guided personal treatment regimen.

Objective To investigate the effects of N -acetylcystein ( NAC) on the cardiac hypertrophy in pressure -overload rats and the relationship with the expression of inflammatory cytokines.Methods The SD rats were randomly divided into four groups:sham group, model group , drug group in sham and drug group in model.Pressure-overload rat model was established by abdominal aortic coarctation.Rats in drug group were treated with NAC ( 0.2 g? kg-1? d -1 , ig ) for 8 weeks. Cardiac hypertrophy was evaluated by heart histological analysis and echocardiography.The collagen content was determined by chromatome-try.RT-PCR and ELISA were used to determine the expression of in-flammatory cytokines.The production of reactive oxygen species ( ROS) were measured by Fenton reaction.Results Compared with sham rats, blood pressure, left ventricular weight index( LVWI) , myocyte diameter, left ventricular wall thick(LVWT) as well as the collagen content( CC) in model rats significantly elevated ( P <0.05 ) .In model rats treated with NAC, LVWI, LVWT and CC were significantly decreased as well as the production of ROS ( P <0.05 ) . Furthermore, the expression of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)but IL-10 was elevated in myocardium of pressure-o-verload rats, which was inhibited by NAC( P<0.05).NAC had no effects on the expression of IL-10.Conclusion NAC could improve the cardiac hypertrophy induced by pressure-overload.The effects of NAC probably relates to the decrease of pro-inflammatory cytokines expression in rat myocardium.

Objective To compare the hypnotic effects of propofol administered by target-controlled infusion (TCI in daytime and nighttime,in order to explore the effect of circadian rhythm on the sedative effect of propofol.Methods Sixty-five male ASA Ⅰ or Ⅱ patients,aged 18-55 years,with the body mass index (BMI) of 18.5-24.9 kg/m2,undergoing emergency minor hand surgery were divided into two groups according to the time of the day when they received TCI of propofol:daytime group (from 07:01 to 19:00) and nighttime group (from 19:01 to 07:00).The pharmacokinetic parameters proposed by Schnider et al.which suggested the effect-site concentration (Ce) was used.Four Ces of propofol were set at 0.8,1.2,2.0 and 4.0 μg/ml,respectively.Ce was increased step by step and each Ce was maintained for 5 minutes.The level of sedation at each Ce was assessed by bispectral index (BIS) and observer's assessment of alertness/sedation (OAA/S) scores.BIS values and Ces of propofol were recorded and compared between the two groups when the patients lost consciousness (OAA/S score =2).Results There were 28 and 30 patients in daytime and nighttime groups,respectively.When Ces were 1.2 and 2.0 μg/ml,the BIS values were significantly lower in the nighttime group than in the daytime group.There was no significant difference in BIS values between the two groups when Ces were 0.8 and 4.0 μg/ml.When the patients lost consciousness (OAA/S =2),the BIS value was comparable between the two groups,but Ce was significantly lower in the nighttime group than in the daytime group.Conclusion The hypnotic effect of propofol is greater during night time than during day time.