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.

AIM:This study aims to investigate the regulatory effects of caffeic acid phenethyl ester(CAPE)on metabotropic glutamate receptor 5(mGluR5)and tyrosine kinase Fyn,and to explore its role in alleviating neuroinflam-mation and pathological features of Alzheimer disease(AD).METHODS:In vitro,the murine neuroblastoma N2a cell line was treated with amyloid β-protein 42 oligomers(Aβ42Os;10 nmol/L to 10 μmol/L)for 24 h.Cell viability was as-sessed by MTT assay.Western blot analyzed mGluR5 expression and Fyn phosphorylation(Tyr416).Pharmacological modulators(CHPG/MPEP)were used to evaluate mGluR5-mediated inflammatory cytokine regulation(qPCR)and Fyn ac-tivation.In vivo,wild-type(WT)and 5×FAD mice(WT,WT+CAPE,5×FAD and 5×FAD+CAPE)were analyzed for AD-related proteins,neuroinflammation(ELISA),glial activation(GFAP/Iba-1 immunofluorescence),and β-amyloid deposi-tion(thioflavin S).RESULTS:(1)Treatment with 1 μmol/L Aβ42Os increased mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01)without affecting N2a cell viability.Intracerebral Aβ42Os injection similarly up-regulated hip-pocampal mGluR5 and Fyn(P<0.01).(2)MPEP reduced mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01),while suppressing tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)mRNA levels(P<0.01).(3)CAPE decreased mGluR5-Fyn activation in N2a cells,neurons,and 5×FAD mice(P<0.01).(4)CAPE-treated 5×FAD mice exhibited reduced neuroinflammation markers(GFAP,Iba-1,TNF-α,IL-1β,and IL-6),Aβ plaques,and p-APP levels(P<0.01).CONCLUSION:Treatment with CAPE inhibits Aβ42Os-induced mGluR5-Fyn signaling activation,thereby attenuating neuroinflammation and the pathology associated with AD.

Objective To explore the preventive effect of multidisciplinary collaborative evidence-based nursing on dysphagia in patients with orotracheal intubation in intensive care unit(ICU)after extubation.Methods A retrospective analysis was performed on 200 patients with orotracheal intubation in ICU who were admitted to Dongguan Traditional Chinese Medicine Hospital between January and December 2023.Of them,96 patients who were admitted to our hospital between January and May 2023 received routine nursing(routine group),104 patients who were admitted to our hospital between June and December 2023 received multidisciplinary collaborative evidence-based nursing(evidence-based group).The incidence of dysphagia after extubation,water swallowing test result,swallowing function measured with M.D.Anderson dysphagia inventory(MDADI),psychological state assessed by connor-davidson resilience scale(CD-RISC),quality of life assessed by swallowing quality-of-life questionnaire(SWAL-QOL),and the incidence of dysphagia complications(aspiration,aspiration pneumonia,and malnutrition)were compared between the two groups.Results The incidence of dysphagia after extubation and the water swallowing test class in the evidence-based group were lower than those in the routine group(both P<0.05).The total score of MDADI and CD-RISC scores in the evidence-based group were significantly higher than those in the routine group(P<0.05),while the SWAL-QOL scores were lower(P<0.05).The incidence of complications in the evidence-based group was significantly lower than that in the routine group(P<0.05).Conclusion Multidisciplinary collaborative evidence-based nursing can effectively reduce the incidence of dysphagia in patients with orotracheal intubation in ICU after extubation,improve swallowing function,psychological state and quality of life,and reduce the incidence of complications.

AIM:This study aims to investigate the regulatory effects of caffeic acid phenethyl ester(CAPE)on metabotropic glutamate receptor 5(mGluR5)and tyrosine kinase Fyn,and to explore its role in alleviating neuroinflam-mation and pathological features of Alzheimer disease(AD).METHODS:In vitro,the murine neuroblastoma N2a cell line was treated with amyloid β-protein 42 oligomers(Aβ42Os;10 nmol/L to 10 μmol/L)for 24 h.Cell viability was as-sessed by MTT assay.Western blot analyzed mGluR5 expression and Fyn phosphorylation(Tyr416).Pharmacological modulators(CHPG/MPEP)were used to evaluate mGluR5-mediated inflammatory cytokine regulation(qPCR)and Fyn ac-tivation.In vivo,wild-type(WT)and 5×FAD mice(WT,WT+CAPE,5×FAD and 5×FAD+CAPE)were analyzed for AD-related proteins,neuroinflammation(ELISA),glial activation(GFAP/Iba-1 immunofluorescence),and β-amyloid deposi-tion(thioflavin S).RESULTS:(1)Treatment with 1 μmol/L Aβ42Os increased mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01)without affecting N2a cell viability.Intracerebral Aβ42Os injection similarly up-regulated hip-pocampal mGluR5 and Fyn(P<0.01).(2)MPEP reduced mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01),while suppressing tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)mRNA levels(P<0.01).(3)CAPE decreased mGluR5-Fyn activation in N2a cells,neurons,and 5×FAD mice(P<0.01).(4)CAPE-treated 5×FAD mice exhibited reduced neuroinflammation markers(GFAP,Iba-1,TNF-α,IL-1β,and IL-6),Aβ plaques,and p-APP levels(P<0.01).CONCLUSION:Treatment with CAPE inhibits Aβ42Os-induced mGluR5-Fyn signaling activation,thereby attenuating neuroinflammation and the pathology associated with AD.

Objective To conduct a scoping review of studies related to latent class trajectory analysis of glucose metabolism indicators in diabetes mellitus patients,so as to clarify the method of latent category trajectory analysis,evaluation indicators and the changing trajectories of different glucose metabolism indicators in diabetes mellitus patients,and to establish foundation for diabetes management and research.Methods Based on Arksey's framework for scoping study,a literature search was performed in CNKI,Wanfang,CBM,Web of Science,PubMed,Embase,Cochrane Library,CINAHL database inception to January 28,2024.Totally 2 researchers independently screened the literature and extracted data.Results A total of 22 pieces of the literature were included.Latent class growth model was the most commonly used model in latent class trajectory analysis,and 4 softwares are available for implementation.The current evaluation indicators for trajectory results are various,with the Bayesian information criterion and average posterior probability as the most frequently utilized.Hemoglobin is the most commonly used glucose metabolism indicators for trajectory analysis,and the number of identified trajectories ranged from 2 to 5.Most studies showed that diabetic patients exhibited a"low-stable"pattern in glucose metabolism indicators.Conclusion Latent class trajectory analysis represents a novel longitudinal data analysis approach that can identify potential subgroups of diabetic patients with similar development trajectory.The models and evaluation indicators employed are diverse,and the stability test of the models can be enhanced in the future.Through trajectory identification,it is recommended that clinical staff pay greater attention to the longitudinal trend of the glucose metabolism indicators and incorporate it into the long-term blood glucose management goal of diabetic patients.

Objective To conduct a scoping review of studies related to latent class trajectory analysis of glucose metabolism indicators in diabetes mellitus patients,so as to clarify the method of latent category trajectory analysis,evaluation indicators and the changing trajectories of different glucose metabolism indicators in diabetes mellitus patients,and to establish foundation for diabetes management and research.Methods Based on Arksey's framework for scoping study,a literature search was performed in CNKI,Wanfang,CBM,Web of Science,PubMed,Embase,Cochrane Library,CINAHL database inception to January 28,2024.Totally 2 researchers independently screened the literature and extracted data.Results A total of 22 pieces of the literature were included.Latent class growth model was the most commonly used model in latent class trajectory analysis,and 4 softwares are available for implementation.The current evaluation indicators for trajectory results are various,with the Bayesian information criterion and average posterior probability as the most frequently utilized.Hemoglobin is the most commonly used glucose metabolism indicators for trajectory analysis,and the number of identified trajectories ranged from 2 to 5.Most studies showed that diabetic patients exhibited a"low-stable"pattern in glucose metabolism indicators.Conclusion Latent class trajectory analysis represents a novel longitudinal data analysis approach that can identify potential subgroups of diabetic patients with similar development trajectory.The models and evaluation indicators employed are diverse,and the stability test of the models can be enhanced in the future.Through trajectory identification,it is recommended that clinical staff pay greater attention to the longitudinal trend of the glucose metabolism indicators and incorporate it into the long-term blood glucose management goal of diabetic patients.

[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 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.