The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

Child ; Electroacupuncture ; adverse effects ; instrumentation ; Electrolysis ; Equipment Failure ; Equipment and Supplies ; adverse effects ; Humans ; Male

Long-term endurance training or physical activity has been confirmed not only to improve physical performance, but to bring about an obvious beneficial effect on human health; however, the mechanism of this effect is not clear. The most studied health adaptations in skeletal muscle response to endurance exercise are increased muscle glycogen level and insulin sensitivity, fiber type transformation toward oxidative myofibers, and increased mitochondrial content/function. Mitochondria are dynamic organelles in eukaryotic cells critical in physical performance and disease occurrence. The mitochondrial life cycle spans biogenesis, maintenance, and clearance. Exercise training may promote each of these processes and confer positive impacts on skeletal muscle contractile and metabolic functions. This review focused on the regulation of these processes by endurance exercise and discussed its potential benefits in health and disease. We presented evidence suggesting that exercise training potentiates not only the biogenesis of mitochondria but also the removal of old and unhealthy mitochondria through mitochondrial quality control.
Adaptation, Physiological ; Exercise ; Humans ; Mitochondria ; physiology ; Muscle Contraction ; Muscle, Skeletal ; physiology

Apolipoprotein A5(ApoA5)level and other indices were determined in patients with type 2 diabetes mellitus and healthy individuals.Compared to control group,ApoA5 level in the diabetic group was lower (P

From the perspective of clinical doctors, in the teaching idea, national policy, school policies and different stages of clinicians cultivation , the article introduced the concept of translational medicine in the process of the clinical doctors tralning in the United States. It described US medical schools' (U.S. Virginia University School of medicine, for example) implementation ap-proach of translational medicine ideas in different stages, such as before entering school, during the period of school, practice exam and physician clinician tralning. It provided the reference for the de-velopment of translational medicine education in the process of China clinician education and tralning, including:medical students' integration into the related clinical research in preschool through volunteer service, the choice of multiple combination model of clinical science and basic research, interdisci-plinary examination of medical practitioners and the provisions of the research work in resident and specialist tralning stage.

Objective: To compare the efficacy of moxibustion with different doses for knee osteoarthritis (KOA), and explore the correlation between moxibustion dose and clinical efficacy. Methods: Sixty-eight patients with KOA who met the inclusion criteria were randomly divided into a 20-minute moxibustion group and a 40-minute moxibustion group by the random number table method, with 34 cases in each group. Dubi (ST 35), Neixiyan (EX-LE 4) and Heding (EX-LE 2) were used for moxibustion in the two groups. Each treatment lasted 20 min or 40 min for each point in the 20-minute moxibustion group and 40-minute moxibustion group, separately; the treatment was given 3 times a week and lasted for 4 weeks. The visual analog scale (VAS), Western Ontario and McMaster University osteoarthritis index (WOMAC) and traditional Chinese medicine (TCM) symptom scores were evaluated before and after treatment to compare the efficacy between different moxibustion doses for KOA. Results: After treatment, the total effective rate was 87.5％ in the 40-minute moxibustion group, versus 70.0％ in the 20-minute moxibustion group, and the difference in the total effective rate between the two groups was statistically significant (P<0.05). After treatment, the VAS scores, the total WOMAC scores and the component scores of pain, stiffness and dysfunction, and the TCM symptom scores in both groups all changed significantly when compared with those before treatment (all P<0.05). After treatment, the between-group differences in the VAS score, the total WOMAC score and the component scores of pain and dysfunction, and the TCM symptom score were statistically significant (all P<0.05), while the difference in the stiffness score in WOMAC showed no statistical significance (P>0.05). Conclusion: Either 20-minute moxibustion or 40-minute moxibustion can relieve pain, improve stiffness, dysfunction, and TCM symptoms for KOA; and 40-minute moxibustion is better in relieving pain, improving dysfunction and TCM symptoms.

Objective: To observe the effects of electroacupuncture (EA) on uterine prostaglandin F2α (PGF2α), cyclooxygenase 2 (COX-2) and nuclear factor κB (NF-κB) in rats with primary dysmenorrhea (PD) and to discuss the possible mechanism in EA intervening PD. Methods: Forty Sprague-Dawley female rats were randomly divided into a blank group, a model group, an EA group and an ibuprofen group, with 10 rats in each group. The PD model was established using estradiol benzoate combined with oxytocin in the model group, EA group and ibuprofen group. At the same time of modeling, rats in the EA group were given EA at Guanyuan (CV 4) and Sanyinjiao (SP 6) once a day for 20 min each time for 10 consecutive days. Ibuprofen was intragastrically administered once a day for 10 consecutive days in the ibuprofen group. The same amount of normal saline was intragastrically administered once a day for 10 consecutive days in the blank group and model group. The number of writhing of rats in each group within 30 min was compared on the 11th day just after the interventions. The uterine homogenate supernatant was separated and the PGF2α level was detected by enzyme-linked immunosorbent assay. Western blot was applied for the detection of the expression levels of COX-2, phospho-NF-κB p65 and NF-κB p65 proteins in uterine tissues. Results: Compared with the blank group, the number of writhing in the model group increased significantly (P<0.01), and the expression levels of PGF2α, COX-2, phospho-NF-κB p65 and NF-κB p65 proteins in uterine tissues were significantly increased (all P<0.01). Compared with the model group, the number of writhing in the EA group and ibuprofen group were significantly reduced (both P<0.01), and the expression levels of PGF2α and COX-2 protein in uterine tissues were significantly reduced (both P<0.01). Compared with the model group, the phospho-NF-κB p65 level in uterine tissues in the EA group was significantly reduced (P<0.01). Compared with the ibuprofen group, the phospho-NF-κB p65 level in the EA group was significantly reduced (P<0.01). Conclusion: The mechanism of EA for PD rats may be related to inhibiting the phosphorylation of NF-κB and reducing the levels of COX-2 and PGF2α in uterine tissues.

The effects of androgen on lipid and the cardiovascular system are very important. The relationship between androgen and lipoprotein is rather complicated and influenced by many factors. The effects of endogenous androgen on the metabolism of lipoprotein vary with age, environment, nutrition and gender, while the effects of exogenous androgen on lipoprotein vary with different androgen preparations, administration methods and diseases to be treated. Androgen can impact the metabolism of lipoprotein, vascular endothelium, macrophage, vascular smooth muscle, angiotasis, blood coagulation, platelet and so on. The effects of polymorphism of the androgen receptor gene CAG on the cardiovascular system are important and yet somehow controversial and have to be further investigated.
Androgens ; pharmacology ; physiology ; Cardiovascular System ; drug effects ; Female ; Humans ; Lipoproteins ; metabolism ; Male ; Polymorphism, Genetic ; Receptors, Androgen ; genetics ; physiology

As the importance of clinical risks management grows hospital management,reducing hospital medical errors for patients safety has become a key quality management process.Failure Mode and effect analysis( FMEA) is a proactive technique for error detection and reduction.In this paper,based on a brief review of it's history of development,described in detail the implementation method and steps of FMEA,mainly introducing the research progress for using FMEA in reducing hospital medical errors.

OBJECTIVETo analyze the clinical effect and related risk factors of Gartland type II-III supracondylar fractures of humerus in children in the emergency closed reduction and percutaneous Kirschner wire fixation.

METHODSFrom January 2008 to June 2013,112 children of Gartland type II to III supracondylar humeral fractures were treated in children in emergency closed reduction and percutaneous K-wire fixation, including 72 males and 40 females with an average age of 6.2 years old ranging from 2 to 11 years old. Among them,74 cases were in Gartland type II fractures,38 cases were in type III; The duration from injury to surgery time was 2.5 to 8 hours (averaged 4.6 hours). Elbow cast was applied after operation with the elbow extended of 100 degrees for 4 to 6 weeks, then the gypsum and Kirschner wires were removed.

RESULTSAll patients were follow-up from 6 to 60 months (averaged 12 months). All fractures reached clinical healing. The final follow-up was assessed by Flynn criteria, the result was excellent in 86 cases, good in 23 cases, general in 3 cases, excellent and good rate was 97.3%. Three patients had mild cubitus varus deformity without orthopedic treatment. No pin tract infections, iatrogenic ulnar nerve injury, compartment syndrome, and complications such as Volkmann ischemic contracture occurred.

CONCLUSIONClosed reduction and percutaneous Kirschner wire fixation had advantages of exact reduction, firm fixation, fewer complications ,less pain in children undergoing emergency surgery, and.high success rate, so it is a safe and efficient treatment for humeral supracondylar fracture in children.

Bone Wires ; Child ; Child, Preschool ; Female ; Fracture Fixation, Internal ; instrumentation ; methods ; Humans ; Humeral Fractures ; surgery ; Male ; Reconstructive Surgical Procedures