Objective To establish a method for simulataneous determination of 18 free amino acids in snake venom. Methods Preparation of free amino acid samples by membrane. HPLC analysis was performed after derivatization by using phenyl isothiocyanate (PITC) as a derivative reagent, samples were analyzed on Ultimate LP-C18 column with gradient elution column of 0.05 mol/L sodium acetate buffer and methanol-acetonitrile- water (40:40:20), and current speed was1.0 mL/min, and the column temperature was set at 35℃, and detection wavelength was 254nm. Results The 18 kinds of amino acids showed a good linearity with the correlation coefficients ≥0.99. The recovery rate was 74.59%~110.62%. Snake venom contained 17 kinds of amino acids, the total content of amino acids was 0.2%. Conclusion The method was accurate, reproducible and reliable, and can be used for the determination of amino acids in snake venom and related products.

[Abatract] In order to improve the result of clinical practice for undergraduate students of clinical medicine, combined with the professional characteristics of hematology and teaching syllabus, Hematology Department in the First Affiliated Hospital of Dalian Medical University developed practi-cal teaching content and tried using a variety of teaching methods and teaching means such as multi-media aided teaching, case teaching and simulation teaching method and so on. Besides, multiple station examination was established; teaching feedback and supervision were strengthened. The prac-tice proved that the reform measures were conducive to the cultivation of medical students' practical skills and clinical thinking, which helped to speed up the transformation from the students to the role of doctors.

Besides regulating lipid, statins can inhibit inflammatory response, improve the function of endothelial cells, and protect intestinal mucosal barrier. Therefore, it can be used to relieve the clinical symptoms of acute pancreatitis, shorten the course of treatment, and improve the prognosis, and can play an important role in treatment. With the wide application of statins, their adverse effects are gradually being recognized, including acute pancreatitis. The World Health Organization database lists a variety of statins that can cause acute pancreatitis, but related mechanisms remain unknown. In view of the contradictory results mentioned above, this article reviews the current status, mechanisms of action, and roles of statins in acute pancreatitis and points out that further double-blind trials are needed to investigate the association between statins and acute pancreatitis.

Objective:To translate the Attention to Positive and Negative Inventory(APNI)and analyze the validity and reliability in Chinese undergraduates sample,to offer a convenient and reliable tool of measuring the cognitive bias for national researchers. Methods:The English-version APNI went through translation into Chinese, retroversion into English,translation into Chinese again,and revision several stages. Two parts of samples (1450 Chinese college students)were surveyed. Sample one (n=1000)was used for item analysis,exploratory factor a-nalysis (EFA),concurrent validity and reliability analysis,while sample 2 (n=450)was used for confirmatory fac-tor analysis (CFA). Totally 68 subjects of sample 1 were randomly chosen and resurveyed with an interval of one week. Beck depression inventory (BDI-II)and patient health questionnaire (PHQ-9)was used for concurrent validi-ty. Results:Item analysis indicated that the 22 items of Chinese APNI had good discriminability. EFA focused onattention to positive information(API)and attention to negative information(ANI)two factors. CFA showed good model fit (χ2 =1376,RMESA=0. 09,CFI=0. 94). Concurrent validity result showed that the total scores of BDI-II and PHQ-9 was negatively correlated with total scores of API (r=-0. 24,-0. 29,Ps<0. 01 ),and posi-tively correlated with total scores of ANI (r=0. 36,0. 31,Ps<0. 01). The Cronbach'αcoefficients of API and ANI sub-scale were 0. 86 and 0. 82,while the retest reliability coefficients were 0. 79 and 0. 62. Conclusion:It suggests that the Chinese APNI has good validity and reliability in a sample of college students,which could be used to eval-uate the cognitive bias of Chinese college students.

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.

Heme/metabolism* ; Cryoelectron Microscopy ; Membrane Transport Proteins ; Escherichia coli Proteins/metabolism*

Inhibition of Mycobacterium tuberculosis (Mtb) cell wall assembly is an established strategy for anti-TB chemotherapy. Arabinosyltransferase EmbB, which catalyzes the transfer of arabinose from the donor decaprenyl-phosphate-arabinose (DPA) to its arabinosyl acceptor is an essential enzyme for Mtb cell wall synthesis. Analysis of drug resistance mutations suggests that EmbB is the main target of the front-line anti-TB drug, ethambutol. Herein, we report the cryo-EM structures of Mycobacterium smegmatis EmbB in its "resting state" and DPA-bound "active state". EmbB is a fifteen-transmembrane-spanning protein, assembled as a dimer. Each protomer has an associated acyl-carrier-protein (AcpM) on their cytoplasmic surface. Conformational changes upon DPA binding indicate an asymmetric movement within the EmbB dimer during catalysis. Functional studies have identified critical residues in substrate recognition and catalysis, and demonstrated that ethambutol inhibits transferase activity of EmbB by competing with DPA. The structures represent the first step directed towards a rational approach for anti-TB drug discovery.

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