Objective:To explore the incidence of vascular leakage after acute hemodilution in patients with traumatic orthopedics by using 6% hydroxyethyl starch 130/0.4 (HES).Methods:Using prospective cohort study method, 48 orthopedic trauma patients in in Yantaishan Hospital from June 2018 to December 2018 were selected as the subjects of observation.The American Society of anesthesiologists (ASA) grade was divided into grade I-III.According to the degree of trauma, they were divided into two groups: general orthopedic patients group (24 cases) and severe trauma orthopedic patients group (24 cases). According to the formula of blood volume, the blood volume of the patients in the two groups was calculated.After intubation, 10% of the blood volume of HES was infused intravenously at the rate of 0.5 ml/(kg·min) for acute hemodilution.Plasma colloidal osmolality and hemoglobin were measured immediately before acute hemodilution (T0), 15 minutes (T1) and 30 minutes (T2) after acute hemodilution.The concentrations of HES in T1 and T2 plasma were measured.The urine volume from the beginning of infusion to 30 minutes after the end of infusion was saved.The urine volume and hes concentration were measured to calculate the urine hes content.Results:The amount of HES input was the same in the general orthopedic patients group and the severe trauma orthopedic patients group, which were (7.71±0.3) ml/kg and (7.70±0.2) ml/kg, and the expansion ratio was about 100%.Compared with T0, plasma colloid osmotic pressure at T1 and T2 were (27.9±1.5) mmHg(1 mmHg=0.133 kPa)) and (27.7±1.5) mmHg in the general traumatic orthopedics patients, which was higher than T0((26.5±1.5) mmHg, P<0.05). There was no significant difference of COP at T1 and T2 ((27.0±1.6) mmHg and(26.9±1.5) mmHg) compared with T0((26.3±1.7) mmHg, P>0.05) in the severe trauma orthopedic patients). The concentration of plasma HES in the severe trauma orthopedic patients ((6.8±0.6) g/L and (5.8±0.5) g/L) was lower than in the general traumatic orthopedics patients ((7.7±0.5) g/L and (7.1±0.5) g/L, t=5.660 and 6.755, all P<0.05) at T1 and T2.There was no significant difference of the urine HES content ((29.0±3.5 ) mg vs.(28.4±3.3) mg, t=0.61, P>0.05 )between the two groups after infusion. Conclusion:The ratio of acute hemodilution and volume expansion of HES was the same in the two groups.The changes of plasma colloid osmotic pressure and HES concentration were lower in patients with severe trauma orthopedics, and there was more obvious extravascular leakage in patients with severe trauma orthopedics.

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