OBJECTIVE To establish a comprehensive evaluation system for lipid-lowering drugs aligned with the clinical reality of Liaoning province， and to assess the commonly used lipid-lowering drugs in medical institutions within Liaoning province. METHODS A comprehensive evaluation system for lipid-lowering drugs of Liaoning province was established using literature analysis and the Delphi expert consultation method. A calculation method of “indicator weighted score” to “step-by-step aggregation” to “percentile standardization” was employed to enable horizontal comparison of 49 commonly used lipid-lowering drugs. RESULTS This study successfully established a comprehensive clinical evaluation system for lipid-lowering drugs of Liaoning province， comprising 7 first-level indicators， 35 second-level indicators， and 116 scoring criteria. Among the first-level indicators， effectiveness （23%） had the highest weight， followed sequentially by safety （22%）， innovativeness （15%）， economy （13%）， suitability （13%）， accessibility （10%）， and other attributes （4%）. Among the 49 evaluated lipid-lowering drugs， the top 10 in overall score were all statins， with rosuvastatin calcium tablet B having the highest total score of 79.22. Inclisiran sodium injection had a total score of 57.14， performed outstandingly in safety （16.27） and innovativeness （11.27）. CONCLUSIONS This study established a relatively comprehensive and detailed clinical evaluation system for lipid-lowering drugs of Liaoning province. Statins remain the cornerstone of lipid management. Most patients can primarily choose drugs like rosuvastatin tablet B， while PCSK9 inhibitors and fixed-dose combinations can be considered for patients with conventional treatment failure or statin intolerance.

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

The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 to 3.5 Å. The structure of IrtAB bound ATP-Mg2+ shows a "head-to-tail" dimer of nucleotide-binding domains (NBDs), a closed amphipathic cavity within the transmembrane domains (TMDs), and a metal ion liganded to three histidine residues of IrtA in the cavity. Cryo-electron microscopy (Cryo-EM) structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB. Moreover, the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle. This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.
Siderophores/metabolism* ; Iron/metabolism* ; Mycobacterium tuberculosis/metabolism* ; Cryoelectron Microscopy ; Adenosine Triphosphate/metabolism* ; ATP-Binding Cassette Transporters

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.