Objective To study the effect and safety of recombinant human brain natriuretic peptide (rhBNP)on hemodynamics in patients with refractory heart failure(RHF).Methods A total of 16 patients with RHF were enrolled in the study.We defined RHF as the symptoms and signs had not been improved with conventional intensive treatment.The patients started to receive the infusion of rhBNP with 1.5 μg/kg bolus intravenous injection followed by 0.007 5 μ4/(kg · min)for 24 hours.During 24 hours,the hemodynamic parameters,systolic blood pressure,heart rate and electrolyte were monitored.After rhBNP infused,echocardiography was used to measure the cardiac index(CI),left ventricular end diastolic diameter(LEVDD)and ejection fraction(EF)in the third day.Results After rhBNP infused,pulmonary capillary wedge pressure (PCWP),mean pulmonary artery pressure(MPAP)were significantly reduced at 15 minutes(PCWP[22.7 ±4.0]mm Hg vs[25.3 ±3.9]mm Hg;MPAP[31.9 ±3.6]mm Hg vs[34.6 ±7.8]mm Hg,P ＜0.05),the systolic blood pressure decreased remarkably at one hour([105.2 ± 11.5]mm Hg vs[119.0 ± 17.2]mm Hg,P ＜ 0.01),and the effect disappeared gradually,heart rate decreased remarkably([109.0 + 10.8]beat/min vs [82.2 ± 8.6]beat/min).blood K +,Na + and renal function remained unchanged(P ＞ 0.05).CI([3.7 ± 0.6]L/m2 vs[1.8 ±0.4]L/m2),LEVDD([63.6 ±5.7]mm vs[67.3 ±6.2]mm)and EF([43.1 ±8.3]％ vs [31.2 ± 6.4]％)were significantly improved(P ＜ 0.01).There was no symptomatic hypotension or other adverse events.Conclusion Injection of rhBNP is safe,feasible,and effective in patients with refractory heat failure for improving hemodynamics.

OBJECTlVE To estabIish a simpIe,sensitive and quick method for determination of B7011 in rat pIasma. METHODS The method of protein precipitation with methanoI was used for pre-treatment of pIasma sampIes determined by Iiquid chromatography mass spectrometer. The Iinear reIa-tionship,intra-batch and inter-batch precision,specificity,matrix effect,recovery rate,the accuracy and stabiIity of the pIasma sampIes were vaIidated. The concentration of B7011 in pIasma was determined by LC-mS/ mS foIIowing a singIe intravenous injection of B7011 0.5 mg·kg-1 to rats. RESULTS The Iinear range of B7011 was 30-20 000 μg·L-1 ,the Iower Iimit of quantification was 30 μg·L-1 in pIasma,the in-tra-batch precision of 60,1000,16 000 and 10 000 ng·mL-1 was 5.61% -13.31%,2.31% -8.35%, 2.02%-9.47% and 4.0%-15.0% respectiveIy,and inter-batch precision was 10.05%,2.55%,3.75% and 8.58% respectiveIy. The recovery of 60,1000,and 16 000 μg·L-1 was 114.12%,109.2% and 101.06%respectiveIy. The average peak concentrations were 8373.28 and 8564.59 μg·L-1 ,the mean AUC was 98 400 and 104 000 μg·L-1·h and the t1/ 2z for B7011 was 41.7 and 63.6 h in bIood of maIe and femaIe rats, respectiveIy. CONCLUSlON The estabIished method is sensitive, fast and simpIe and concentration of B7011 in pIasma is determined by LC-mS/ mS foIIowing a singIe intravenous injection of B7011 0.5 mg·kg-1 to rats. It can satisfy the requirements of pharmacokinetic and toxicokinetic studies.

[Objective]To explore the intracellular antimicrobial activities of erythromycin,ciprofloxacin,levofloxacin,moxifloxacin against Legionella pneumophila.[Methods]The minimum inhibition concentration(MIC)of each antibiotic was evaluated by E-test method and microdilution method respectively.The minimal extracellular concentration inhibiting intracellular multiplication(MIEC)of each antibiotic was evaluated by the MTT colorimetric assay system.[Results]The MIC concentration for each drug by E-test method were:erythromycin,0.047 μg/mL;ciprofloxacin,0.38 μg/mL;levofloxacin,0.125 μg/mL;moxifloxacin,0.125 μg/mL,the MIC concentrations for each drug by microdilution method were:erythromycin,0.125 μg/mL;ciprofloxacin,0.03 μg/mL;levofloxacin,0.016 μg/mL;moxifloxacin,0.016 μg/mL.The MIEC concentration for each drug were:erythromycin,0.25 μg/mL;ciprofloxacin,0.016 μg/mL;levofloxacin,0.016 μg/mL;moxifloxacin,0.004 μg/mL.[Conclusions]Fluoroquinolones have superior activity than erythromycin in U937 cells infected with L.pneumophila.Moxifloxacin is the most potent drug among the four tested antimicrobials.Our results indicated that the MTT assay system allows comparative and quantitative evaluations of the intracellular activities of antibiotics against L,pneumophila and efficient processing of a large number of samples.

Objective To explore the monitoring of cerebrospinal fluid (CSF) dynamics in a model of brain herniation induced by acute intracranial hypertension in Guangxi Bama-Mini pigs by phasecontrast cine magnetic resonance imaging (PC cine MRI).Methods Femoral artery blood were extracted from 10 pigs,and injected into the frontal and temporal parietal lobe to make a model of brain herniation induced by acute intracranial hypertension.The mean arterial blood pressure (MAP),intracranial pressure (ICP),and cerebral perfusion pressure (CPP) were monitored.Routine T1WI,T2WI,coronal,sagittal and cerebrospinal fluid flow sequence (fast PC cine slice) which positioned on the cervical 3 (C3) vertebral body as the center and perpendicular to the spinal scans were performed on all experimental animals before and after blood injection with 3.0T Magnetic Resonance Imaging.The ICP,MAP,CPP,the absolute values of CSF peak flow velocity and the absolute value of carotid peak flow velocity before and after blood injection were compared.Results The ICP,MAP,CPP,and the absolute value of CSF peak flow velocity before injection of autologous arterial blood were statistically significant as compared with those after blood injection [(6.80±2.044) mmHg vs (52.20±1.619) mmHg,(76.80±7.068) mmHg vs (142.80±12.399) mmHg,(70.00±6.074) mmHg vs (90.50±12.250) mmHg,and the absolute value of CSF peak flow velocity was (243.20±77.671) mm/s vs (201.40±55.482) mm/s,respectively,P＜0.01].The absolute value of the peak velocity of the carotid artery before blood injection was not statistically significant compared with that after blood injection [(876.80±239.908) mm/s vs (799.40±241.829) mm/s,P＞0.05].Conclusion After the formation of brain herniation induced by acute intracranial hypertension,the CSF flow in the C3 level spinal canal showed a low dynamic change,and the CSF flow velocity waveform was disordered and malformed.The non-invasive measurement of CSF dynamics by PC cine MRI can provide an important basis for the change of CSF dynamics in the model of brain herniation induced by acute intracranial hypertension,and provide a theoretical basis for further research on damage control neurosurgery in the future.

A novel RNA virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the ongoing outbreak of coronavirus disease 2019 (COVID-19). Population genetic analysis could be useful for investigating the origin and evolutionary dynamics of COVID-19. However, due to extensive sampling bias and existence of infection clusters during the epidemic spread, direct applications of existing approaches can lead to biased parameter estima-tions and data misinterpretation. In this study, we first present robust estimator for the time to the most recent common ancestor (TMRCA) and the mutation rate, and then apply the approach to analyze 12,909 genomic sequences of SARS-CoV-2. The mutation rate is inferred to be 8.69 × 10-4 per site per year with a 95％ confidence interval (CI) of [8.61 × 10-4, 8.77 × 10-4], and the TMRCA of the samples inferred to be Nov 28, 2019 with a 95％ CI of [Oct 20, 2019, Dec 9, 2019]. The results indicate that COVID-19 might originate earlier than and outside of Wuhan Seafood Market. We further demonstrate that genetic polymorphism patterns, including the enrichment of specific haplotypes and the temporal allele frequency trajectories generated from infection clusters, are similar to those caused by evolutionary forces such as natural selection. Our results show that population genetic methods need to be developed to efficiently detangle the effects of sampling bias and infection clusters to gain insights into the evolutionary mechanism ofSARS-CoV-2. Software for implementing VirusMuT can be downloaded at https://bigd.big.ac.cn/biocode/tools/BT007081.

On January 22, 2020, China National Center for Bioinformation (CNCB) released the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access information resource for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2019nCoVR features a comprehensive integra-tion of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline. Of particular note, 2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and their detailed statistics for each virus isolate, and congregates the quality score, functional annotation,and population frequency for each variant. Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019 (COVID-19), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with NCBI. Collectively, SARS-CoV-2 is updated daily to collect the latest information on genome sequences, variants, hap-lotypes, and literature for a timely reflection, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.