The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

[This corrects the article DOI: 10.1016/j.apsb.2021.07.006.].

Objective:To compare the differences in lung function between sanitation workers and the general population undergoing routine physical examinations, and to analyze the risk factors for restricted airflow and severity of the condition in sanitation workers.Methods:This study is a large cross-sectional study called "Shanxin Respiratory Health Screening for Ten Thousand People". A total of 1 036 sanitation workers (sanitation group) and 6 701 individuals from the general population undergoing routine physical examinations (control group) were selected as the original study subjects from June 2021 to April 2022 (before matching). Both groups underwent pre-bronchodilator lung function tests, and the differences in lung function characteristics between the two groups were compared. The sanitation group also completed a questionnaire survey. Multivariate and ordinal multinomial logistic regression analysis were used to analyze the risk factors for airflow limitation and its severity.Results:A total of 1 027 individuals from the sanitation group and 999 individuals from the control group were included in the study. There were no significant differences in age, gender, height, weight, and body mass index (BMI) between the two groups (all P>0.05). The rate of airflow restriction was significantly higher in the sanitation group compared to the control group (22.88% vs 8.81%, P<0.001). In the sanitation group, there was no statistically significant difference in a self-assessment test for chronic obstructive pulmonary disease (CAT) scores between individuals with airflow restriction (235 cases) and those without airflow restriction (792 cases) [(1.50±2.50) vs (1.15±2.03) points, P=0.084]. There were no statistically significant differences in forced vital capacity (FVC) as a percentage of predicted value (FVC%pred) between the two groups. However, the sanitation group had significantly lower %pred for forced expiratory volume in one second (FEV 1%pred), FVC/FEV 1 ratio (FEV 1/FVC%pred), forced expiratory flow at 50% of FVC (FEF 50%%pred), forced expiratory flow at 75% of FVC (FEF 75%%pred), and maximal mid-expiratory flow (MMEF%pred) compared to the control group (all P<0.05). The rates of abnormal FEF 50%%pred, FEF 75%%pred, and MMEF%pred were significantly higher in the sanitation group compared to the control group (17.62% vs 10.31%, 17.04% vs 10.01%, 27.26% vs 18.41%, all P<0.001). Small airway parameters and the rate of airflow restriction were significantly higher in past and current smokers of the sanitation group compared to never smokers (all P<0.05). Multifactorial analysis showed that high BMI ( OR=0.929, 95% CI: 0.885-0.974) was a protective factor for airflow restriction, while high smoking index was a risk factor ( OR=1.020, 95% CI: 1.011-1.030). Ordered multinomial logistic regression analysis showed that high BMI ( OR=0.925, 95% CI: 0.882-0.971) was a protective factor for the severity of airflow restriction, while high smoking index ( OR=1.020, 95% CI: 1.011-1.029) was a risk factor for the severity of airflow restriction. Conclusions:The incidences of airflow limitation and small airway abnormalities in sanitation workers are higher than that in general physical examination population. High smoking index and low BMI are independent risk factors for airflow limitation and its severity.

Objective: To investigate the effect of online and offline mindfulness training on improving anxiety and depression and sleep quality of college students,and to provide a reference for mental health promotion among college students. Methods: From October 2020, a total of 1 203 university students from North China University of Technology were screened with the Self rating Anxiety Scale (SAS), Self rating Depression Scale (SDS) and Pittsburg Sleep Quality Index (PSQI) using the whole group radom cluster sampling method. Totally 103 students who met the inclusion criteria were randomly divided into 64 online and 39 offline groups. The degree of improvement in anxiety, depression and sleep quality was assessed after the intervention. Results: The SAS, SDS and PSQI scores of college students after the online and offline the mindfulness training intervention significantly decreased compared with score before the intervention( t =5.57, 5.31, 3.99; 4.88,5.02, 5.88, P <0.01). The difference in the degree of improvement in sleep quality between the two interventions, online and offline, was statistically significant ( t =-2.55， P <0.05). The less the three symptoms of anxiety, depression and sleep were combined in university students, the higher the symptom remission rate of the positive mindfulness training (25% remission rate for all three symptoms together, 40% remission rate for two symptoms together and 100% remission rate for only one symptom). Conclusion Both online and mindfulness training can be used as an effective intervention for sleep, anxiety and depression; offline mindfulness training is more effective than online in improving sleep quality in university students; mindfulness training is more effective in relieving single symptoms.

Objective:To investigate the anatomical safety and feasibility ofposterior occipitocervical fixation with atlan-tooccipital-clivus screw.Methods:Data of 60 patients who treated in the spinal department of our hospital with upper cervical computed tomographic scans from February 2017 to November 2019 were retrospectively collected. Occipitocervical infection, injury, tumor and deformity were excluded. The Mimics software was used to reconstruct the occiput, atlas and measure the anatomical parameters, including the height and width of the anterior edge of the clivus, the height and width of the middle part of the clivus, the thinnest distance of the soft tissue in front of the clivus, the anteroposterior diameter, transverse diameter, the angle of inside tilting in coronary plane of the occipital condyle, the distance from the hypoglossal canal to the atlantooccipital articular surface, the anteroposterior diameter and transverse diameter of the superior joint of atlas, the height of the lateral mass, and the height and transverse diameter of the inferior articular process of the superior atlas joint. The three-dimensional digital modeling was performed and the screw diameter of 3.5mm was simulated. 3-Matic software were used to measure the screw placement parameters, including the inside tilting angle in coronary plane of screw, and the angle of upper tilting in sagittal plane and length of screw. The atlanto-occipital junction was exposed at the rear of 8 cadavers. According to the above parameters, the titanium alloy screws with a diameter of 3.5 mm were transferred from the inferior articular process and posterior arch of the atlas to the clivus through the atlantooccipital. Finally, the screw path was cut along the nail path with a pendulum saw, and the track of the screw was observed to confirm the safety and effectiveness of the screw.Results:The leading edge height and width of male clivus was 16.8±2.5 mm and 20.1±3.1 mm. The middle part of the clivus was 9.7±2.3 mm and 22.4±3.7 mm. The thinnest soft tissue in front of the clivus was 5.8±1.48 mm. The anteroposterior diameter of the occipital condyle was 19.1±1.9 mm, the transverse diameter was 12.6±2.0 mm, the inside tilting angle was 33.7°±4.5°, and the vertical distance from the lowest point of the neural tube to the articular surface of the occipital condyle was 9.6±1.1 mm. The height of the lateral mass of atlas was 12.9±2.4 mm, the anteroposterior diameter of the upper joint of atlas was 21.7±1.9 mm, and the transverse diameter was 11.7±1.4 mm. The width of the inferior facet was 14.9±1.4 mm and the height of the inferior facet was 5.7±0.85 mm. The distance from the screw entry point to the vertical line of the lateral mass migration midpoint was 2.5±0.6 mm; The distance from the screw entry point to the horizontal line of the midpoint was 2.3±0.7 mm.The inside titling angle of screw was 18.4°±1.6°, the upper tilting angle was 55.6°±3.1°, the length of the screw track was 53.0±2.8 mm, the adjustment range of upper tilting angle was 15.0±2.8 mm, the adjustment range of inside tilting angle was 10.4±2.4 mm. The anatomical parameters of females were slightly smaller than those of males, and the difference was statistically significant, but there was no significant difference between left and right parameters. The screws of 8 specimens could be inserted safely and effectively.Conclusion:Atlan-tooccipital-clivus screw can be implanted without damaging the nerve and vascular structure, and it can be used as a choice for occipitocervical fixation.

Objective:To investigate the characteristics of magnetic resonance imaging and clinical application of multi-modality magnetic resonance imaging (MRI) for evaluating the response of neoadjuvant chemotherapy (NACT) in inflammatory breast cancer (IBC).Methods:A total of 36 IBC patients were enrolled in the study.The morphological, hemodynamic and diffusion-weighted imaging features of MRI were analyzed. Eleven patients underwent MRI examination before and after NAT. The imaging changes were analyzed and the efficacy of NACT was evaluated.Results:There were 38 identified breast carcinoma in these 36 cases, among which abnormal skin thickening and enhancement, extensive edema was found in 37 breast lesions. Enhancement of breast lesions in 25 cases was non-mass-like enhancement. Diffusion limitation was found in all lesions. The number of vessels in affected side was more than that in healthy side in MIP images. Thirty three cases had axillary lymph node enlargement.The sensitivity and specificity of MRI in evaluating residual breast tumors and vascular thrombus were high, but the evaluation of axillary lymph nodes was relatively low.Conclusions:Multi-modal MRI can be used for early and accurate diagnosis of IBC. It can also be used to predict and evaluate the effect of neoadjuvant chemotherapy.

Objective:To explore the difference in properties of anterior occipital condyle plate screws compared with common anterior occipitalcervical fusion internal fixation.Methods:A 28-year-old healthy adult male volunteer's CT data of the occiput and neck was selected to establish finite element models：including the normal model，simple artificial vertebral fixation model（special-shaped titanium cage+clival screws），anterior occipital condyle plate and screw fixation model，and clival plate and screw fixation model，then a 50 N gravity and a torque of 1.5 N m were exerted upon the upper surface of the occipital bone to make the model produce flexion and extension，lateral bending and rotation. The motion range，internal fixation stress distribution and occipital bone stress distribution of each model under varying conditions were compared.Results:Under the conditions of flexion，extension，lateral bending and rotation，the range of motion of the normal model was 18.65°，15.35°，9.82° and 34.68°，respectively；that of the simple artificial vertebral fixation model was 3.20°，3.63°，2.94° and 3.92°，respectively；that of the clival plate and screw fixation model was 0.40°，0.50°，0.35° and 0.89°，respectively；that of the anterior occipital condylar plate and screw fixation model was 0.27°，0.33°，0.13° and 0.30°，respectively. Compared with the simple artificial vertebral fixation model，the range of motion of the clival plate and screw fixation model decreased by 87.5%，86.2%，88.1% and 77.3% in flexion，extension，lateral bending and rotation. The range of motion of the anterior occipital condylar plate and screw fixation model decreased by 91.5%，90.1%，95.6% and 92.3%，respectively. Under the conditions of flexion and extension，lateral bending and rotation，the stress peak of the simple artificial vertebral fixation model was 52.3 MPa，51.9 MPa，52.6 MPa，respectively；that of the clival plate and screw fixation was 100.1 MPa，158.1 MPa，170.6 MPa，respectively；that of the anterior occipital condylar plate and screw fixation was 114.2 MPa，62.9 MPa，132.9 MPa，respectively. Under the condition of flexion and extension，lateral bending and rotation，the stress peak of the occipital bone in the simple artificial vertebral body internal fixation model was 52.9 MPa，50.9 MPa and 62.3 MPa，respectively；that of the clival plate and screw fixation model was 19.7 MPa，55.9 MPa and 38.3 MPa，respectively；that of the anterior occipital condylar plate and screw fixation model was 37.8 MPa，15.0 MPa and 16.3 MPa，respectively. The stress in bone near the hypoglossal canal was close to 0 MPa，much smaller than the stress peak in occipital bone.Conclusion:Anterior occipital condylar plate and screw fixation in front of the special-shaped titanium cage can improve the stability of occipitocervical fusion with little effect on the occipital bone and hypoglossal canal or without obvious stress concentration，and hence is a safe and reliable anterior fixation method for upper cervical spine instability.

Objective:To provide a theoretical basis for the clinical application of the posterior route through atlas occipital articular slope screw internal fixation system through the biomechanical study.Methods:Eight cadavers of healthy adults aged 35-60 years and 155-180 cm in height were selected. The specimens with complete anatomical structure and without surgical operation were established as normal models. The model of occipito-atlantoaxial complex was established by breaking the articular capsule, ligament and other connecting structures and cutting the dentate process. The device was established as an internal fixation model through the specimen of atlantooccipital joint slope screw internal fixation system. Given normal model and internal fixation of 1.5 N·m in the moment of flexion, lateral bending and axial rotation and to measure the specimen C 0-C 1 and C 0-C 2 segment of the range (range of motion, ROM), comparative analysis of pillow neck area within the normal model and fixed model changes the range of movement, after the evaluation through the slope between atlas and the occipital screw internal fixation system of mechanical properties. Results:In the normal model, the flexion, flexion and extension, lateral bend and axial rotation ranges of C 0-C 1 segments were 23.85°±2.43°, 4.74°±0.55°, 5.77°±0.75°, respectively; the corresponding activity ranges of C 0-C 2 segments were 30.66°±3.05°, 9.09°±1.37°, 70.97°±9.48°, respectively; in the internal fixation model, the flexion and extension, lateral bend and axial rotation ranges of C 0-C 1 segments were 0.71°±0.24°, 0.24°±0.06°, 0.34°±0.09°, respectively. The corresponding activity range of C 0-C 2 segment was 3.09°±0.82°, 0.74°±0.07°, 1.22°±0.10°, respectively. Compared with the normal model, the range of activity of the internal fixation model in all directions was significantly reduced (<3°), and the reduction ratio of activity was more than 90%. Conclusion:The posterior route through pillow slope screw internal fixation system can effectively reduce the range of motion of the occipital neck in flexion, extension, lateral bending and rotation, and has safe and reliable biomechanical stability.

Objective:To analyse the pathogenic bacteria distribution and clinical characteristics of late-onset sepsis (LOS) among premature infants with gestational age less than 34 weeks in Henan Province.Methods:The clinical data of 6 590 premature infants admitted to 17 medical institutions in Henan Province from January 2019 to December 2020 were retrospectively analyzed. The gestational age of infants was less than 34 weeks and was admitted to the neonatal ward within 7 days after birth. SPSS 19.0 statistical software was used for data analysis.Results:Among 6 590 premature infants LOS developed in 751 cases (11.40%), of whom the diagnosis was confirmed in 276 cases (36.75%) and 475 cases (63.25%) were diagnosed clinically. The fatality rate related to LOS was 13.58%. There were significant differences in the incidence of LOS and infection-related mortality among infants with different gestational ages and body weights ( χ2=388.894 and 13.572, χ2=472.282 and 9.257, P<0.05 or <0.01). Among 276 children with confirmed LOS, 286 strains of pathogenic bacteria were isolated. Gram-negative bacteria were most prevalent (178 strains), accounting for 62.24% of all infections, followed by fungi (58 strains, 20.28%). Klebsiella pneumoniae was most frequently detected Gram-negative bacteria (117 strains, 40.91%), among which 32.48% (38/117) was carbapenem-resistant Klebsiella pneumoniae. The proportion of diagnosed sepsis, the proportion of catheterization, and the infection-related mortality of infants with LOS in tertiary hospitals were all higher than those in secondary hospitals ( χ2=6.212, 5.313 and 4.435, all P<0.05). The proportion of exclusive breastfeeding in secondary hospitals was lower than that in tertiary hospitals ( χ2=19.216, P<0.05). The time of antibacterial drug use before infection in specialized hospitals was longer than that in general hospitals ( χ2=3.276, P<0.05). Conclusion:The incidence of LOS among preterm infants in Henan Province is high, which was mainly caused by Gram-negative bacteria. The clinical characteristics of LOS caused by different pathogens and in different health institutions are different, the prevention and control strategy should be developed accordingly to reduce the incidence LOS of preterm premature infants.

Given the opposing effects of Akt and AMP-activated protein kinase (AMPK) on metabolic homeostasis, this study examined the effects of deletion of Akt2 and AMPKα2 on fat diet-induced hepatic steatosis. Akt2–Ampkα2 double knockout (DKO) mice were placed on high fat diet for 5 months. Glucose metabolism, energy homeostasis, cardiac function, lipid accumulation, and hepatic steatosis were examined. DKO mice were lean without anthropometric defects. High fat intake led to adiposity and decreased respiratory exchange ratio (RER) in wild-type (WT) mice, which were ablated in DKO but not Akt2−/− and Ampkα2−/− mice. High fat intake increased blood and hepatic triglycerides and cholesterol, promoted hepatic steatosis and injury in WT mice. These effects were eliminated in DKO but not Akt2−/− and Ampkα2−/− mice. Fat diet promoted fat accumulation, and enlarged adipocyte size, the effect was negated in DKO mice. Fat intake elevated fatty acid synthase (FAS), carbohydrate-responsive element-binding protein (CHREBP), sterol regulatory element-binding protein 1 (SREBP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), peroxisome proliferator-activated receptor-α (PPARα), PPARγ, stearoyl-CoA desaturase 1 (SCD-1), phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase), and diglyceride O-acyltransferase 1 (DGAT1), the effect was absent in DKO but not Akt2−/− and Ampkα2−/− mice. Fat diet dampened mitophagy, promoted inflammation and phosphorylation of forkhead box protein O1 (FoxO1) and AMPKα1 (Ser485), the effects were eradicated by DKO. Deletion of Parkin effectively nullified DKO-induced metabolic benefits against high fat intake. Liver samples from obese humans displayed lowered microtubule-associated proteins 1A/1B light chain 3B (LC3B), Pink1, Parkin, as well as enhanced phosphorylation of Akt, AMPK (Ser485), and FoxO1, which were consolidated by RNA sequencing (RNAseq) and mass spectrometry analyses from rodent and human livers. These data suggest that concurrent deletion of Akt2 and AMPKα2 offers resilience to fat diet-induced obesity and hepatic steatosis, possibly through preservation of Parkin-mediated mitophagy and lipid metabolism.