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.

General practice standardized residency training is a crucial part of postgraduate education for cultivating general practitioner. The factors influencing the quality of general practice residency training cover various aspects such as the residents themselves, teaching staff, management and decision-making levels, as well as teaching resources. Guided by the goal of "fostering virtue through education", and integrated the spirit of Norman Bethune and modern innovation theories and the educational philosophy, the China-Japan Union Hospital of Jilin University has carried out comprehensive reforms in this field. It has constructed a PDCA cycle management system based on the concept of total quality management to improve the quality of education from multiple links such as quality planning and process monitoring. In terms of faculty development, based on the dissipative structure theory, a mechanism of "selection, evaluation, incentive, and elimination" has been established. Teacher communities have been formed and a training college has been established to strengthen the teaching team. In terms of platform construction, the linkage between "teaching base-community" and "on campus-off campus" has been strengthened and resources have been integrated. The reform has achieved remarkable results, and our practice may provide a reference for general practice medical education.

Objective To construct intrauterine adhesion (IUA) mouse models induced by two different concentrations of ethanol injury, compare the phenotypes, and optimize a more stable IUA modeling method. Methods Twenty 8-week-old female C57BL/6N mice were randomly divided into two groups: the 95% ethanol injury group and the 50% ethanol injury group. Using a self-control method, the left uterine horn was infused with ethanol to establish the IUA model, while the right uterine horn was infused with saline as the sham operation. Five mice from each group were euthanized on day 7 and 15 after modeling, and uterine tissues were collected. Hematoxylin-eosin (HE) staining was used to observe the endometrial pathology, and Masson staining was used to assess the degree of endometrial fibrosis. Quantitative real-time PCR was employed to detect the expression levels of fibrosis markers and pro-inflammatory factors in the uterine tissues. Results Compared to the sham operation, these two ethanol injury led to a significant reduction in elasticity of the uterus, an increase in inflammatory infiltration, and a marked increase in the degree of fibrosis on day 7 after modeling (P<0.05). The 95% ethanol injury group showed a significant decrease in endometrial thickness (P<0.05), whereas no significant change was observed in the 50% ethanol injury group when compared to the sham operation (P>0.05). The expression levels of fibrotic marker molecules collagen type Ⅳ alpha 1 chain (Col4A1), α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and pro-inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were significantly elevated in the 50% ethanol injury group when compared to the sham operation (P<0.05), although there was an increasing trend of the same markers in the 95% ethanol injury group, the differences were not statistically significant (P>0.05). On day 15 after modeling, the histopathological changes in both ethanol injury groups were not significant when compared to the sham operation, the expression levels of Col4A1, TGF-β, TNF-α and IL-1β remained significantly higher in the 50% ethanol injury group (P<0.05), while only IL-1β was significantly elevated in the 95% ethanol injury group (P<0.05). Conclusion Uterine infusion with 95% ethanol results in more marked histopathological changes in the IUA mouse model compared to the 50% ethanol injury group. The 95% ethanol injury model is suitable for histopathological studies. However, the 50% ethanol injury group shows higher expression levels of fibrosis markers and pro-inflammatory factors compared to the 95% ethanol injury group, suggesting that the 50% ethanol injury model is more suitable for molecular pathological study.

To assess the cross-contamination risk and genetic evolution ofStaphylococcus aureus(S.aureus)at various stages in a swine slaughterhouse,and to provide a reference for risk evalua-tion and control measures of S.aureus contamination during swine slaughtering,we conducted whole-genome sequencing on 31 isolates of S.aureus collected and preserved from the slaughter-house.Bioinformatics analyses were performed to investigate the genomic characteristics and genet-ic relationships of these isolates.Results revealed cross-contamination across different slaughter-house stages,predominantly with ST398-t1451 strains.Additionally,highly virulent ST9-t899 strains and ST398-t11 strains with numerous resistance genes were detected at various stages.The strains predominantly carried virulence genes such as hlgA,hlgB,and hlgC,with varying num-bers of resistance genes.Notably,two strains carried the optrA gene and three strains carried the cfr gene;the presence of the optrA gene is relatively rare among S.aureus.These genes confer re-sistance to novel synthetic antibiotics such as oxazolidinones and florfenicol and have the potential for horizontal gene transfer,increasing the risk of dissemination both within and beyond the slaughterhouse.Importantly,the study also detected a LA-MRSA-ST9 strain in water samples from the slaughterhouse,which could potentially infect humans.This strain exhibits zoonotic char-acteristics,highlighting the need for stricter protective measures for slaughterhouse workers to mitigate occupational exposure and infection risks.

Objective:To analyze the effects of Yiqi Tongluo Decoction combined with acupuncture on hemorheology and neurological function in patients with ischemic stroke due to qi deficiency and blood stasis syndrome. Methods:This study was designed as a prospective study. It included 120 patients with ischemic stroke due to qi deficiency and blood stasis syndrome, all of whom received treatment at Sun Simiao Hospital, Beijing University of Chinese Medicine between April 2021 and May 2023. The patients were randomly assigned to either an observation group ( n = 60) or a control group ( n = 60) using a random number table method. Both groups received standard conventional treatment. The control group received acupuncture, while the observation group was treated with both acupuncture and Yiqi Tongluo Decoction. Neurological function deficits were evaluated for both groups before and after treatment, and hemorheological indices, antioxidant enzyme levels, and markers of brain injury were measured to evaluate treatment efficacy. Results:After treatment, the scores on the China Stroke Scale and the National Institutes of Health Stroke Scale in the observation group were (11.37 ± 1.25) points and (6.18 ± 0.73) points, respectively, which were significantly lower than those in the control group [ (15.31 ± 1.59) points, (8.31 ± 0.92) points, t = 15.09,14.05, both P < 0.001]. After treatment, the plasma and whole blood viscosity levels in the observation group were (1.41 ± 0.15) mPa·s and (9.05 ± 1.01) mPa·s, respectively, which were significantly lower than those in the control group [(1.75 ± 0.18) mPa·s, (10.28 ± 1.14) mPa·s, t = 11.24,6.26, both P < 0.001]. The levels of serum catalase and glutathione peroxidase in the observation group were (160.85 ± 17.11) U/L and (40.31 ± 4.08) U/L, respectively, which were significantly higher than those in the control group [(139.64 ± 14.52) U/L, (34.85 ± 3.61) U/L, t = -7.32,-7.76, both P < 0.001]. The serum levels of high mobility group protein-1 and neuron-specific enolase in the observation group were (4.25 ± 0.43) μg/L and (18.57±1.92) μg/L, respectively, which were significantly lower than those in the control group [(5.84±0.61) μg/L, (22.63±2.31) μg/L, t = 10.47, 16.50, both P < 0.001]. The overall response rate in the observation group was significantly higher than that in the control group ( χ2 = 6.51, P < 0.05). Conclusions:Yiqi Tongluo Decoction combined with acupuncture has demonstrated significant benefits in treating patients with ischemic stroke due to qi deficiency and blood stasis syndrome. This approach can enhance hemorheology, increase antioxidant enzyme levels, minimize brain tissue damage, and improve neurological function in patients.

The drugs used to improve brain metabolism mainly include ergotamine derivatives,GABA derivatives,vitamin B6 derivatives,neuropeptides,morpholines,hormones and other.However,these drugs may have adverse reactions during clinical application.This article focuses on the adverse effects of commonly used drugs for brain metabolism,and reviews the studies on the new state of pharmaceutical substances,such as drug combination,chiral resolution of isomers,crystal form of dominant drugs,co-crystal drugs and nanodrugs,with the aim of reducing adverse reactions.By summarizing the research on modifying the solid state of drugs to mitigate adverse reactions,this article provides new research insights for obtaining new drug with less adverse reaction and greater clinical value.

In order to cultivate high-level medical talents, introducing information technology into medical teaching, the teaching faculty of the "Medical Functional Experiment" course constructed and explored an online-offline hybrid experimental problem-based learning (PBL) model guided by hypoxia pathophysiology problems. We explore the teaching method, implementation process, assessment, and effect evaluation of the experimental PBL model from the aspects of teaching objects, online teaching platform setting, and offline application, and also discuss its academic innovation points and application value. We hope to provide ideas for integrating the PBL concept into experimental teaching and help cultivate excellent innovative medical talents.

Treatment-resistant depression (TRD) remains a major challenge in psychiatric clinical practice. However, there is still substantial controversy in the academic community regarding how to define and assess it, and treat and manage these patients effectively. This paper reviews the evolution of the concept of "treatment resistance"in depression with a particular focus on comparing the conventional concept of TRD with the recently proposed concept of "Difficult-to-Treat Depression (DTD)". It explores the underlying rationale and logic behind this conceptual shift, and discusses the practical challenges associated with implementing the "DTD" framework in clinical practice. Finally, the paper provides targeted recommendations to address these challenges, aiming to serve as a reference for psychiatric clinicians and researchers in China.

Anticipatory anxiety is a negative emotion that arises when individuals encounter potential threats or uncertainties in the future. It is the core symptom of a variety of anxiety disorders, and is closely associated with the occurrence, severity, treatment outcome, and prognosis of anxiety disorders, which has garnered a growing amount of focus in clinical practice. Nevertheless, scientific research on anticipatory anxiety continues to face obstacles such as unclear pathological mechanisms, the absence of simple and consistent self-assessment tools, and effective interventions. To improve understanding of the role of anticipatory anxiety in the diagnosis and treatment of anxiety disorders, this study reviews pertinent domestic and international literature, and briefly introduces the concept, assessment and measurement, activation paradigm, pathological mechanisms, and interventions of anticipatory anxiety.

Objective To investigate the effects of Yiqi Bushen Huoxue Jiangzhuo Formula on residual renal function(RRF),serum interleukin-6(IL-6),and C-reactive protein(CRP)levels in maintenance peritoneal dialysis(PD)patients with chronic renal failure(CRF).Methods Eighty CRF patients requiring maintenance PD treatment and meeting the traditional Chinese medicine diagnostic criteria of spleen-kidney qi deficiency and damp-phlegm stasis stagnation syndrome were enrolled from the Nephrology Department of Lu'an Traditional Chinese Medicine Hospital between July 2022 and July 2024.Patients were randomly divided into an observation group(n=40)and a control group(n=40)using a random number table.Both groups received standard maintenance PD and conventional western medical treatment,while the observation group additionally received Yiqi Bushen Huoxue Jiangzhuo Formula.The treatment duration for both groups lasted 6 months.Changes in RRF,serum levels of inflammatory markers(IL-6,CRP),and nutritional status indicators(hemoglobin[Hb],prealbumin[PA],albumin[ALB])were evaluated before and after treatment.Clinical efficacy was assessed.Results(1)After 6 months of treatment,the overall response rate in the observation group was 90.00％(36/40),while that in the control group was 67.50％(27/40).The intergroup comparison(by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group,with a statistically significant difference(P＜0.05).(2)After treatment,the levels of blood urea nitrogen(BUN),serum creatinine(SCr),and RRF in both groups decreased compared to pre-treatment levels(P＜0.05).And the reduction in BUN and SCr of the observation group was significantly greater than that in the control group,while the reduction in RRF was significantly smaller than that in the control group,with all differences being statistically significant(P＜0.01).(3)After treatment,serum IL-6 and CRP levels in both groups decreased compared to pre-treatment levels(P＜0.05).And the reduction in serum IL-6 and CRP levels in the observation group was significantly greater than that in the control group,with statistically significant differences(P＜0.01).(4)After treatment,serum Hb,PA,and ALB levels in both groups increased compared to pre-treatment levels(P＜0.05).And the increase in serum Hb,PA,and ALB levels in the observation group was significantly greater than that in the control group,with statistically significant differences(P＜0.01).Conclusion Yiqi Bushen Huoxue Jiangzhuo Formula effectively preserves residual renal function,mitigates inflammation,and improves nutritional status in CRF maintenance PD patients with spleen-kidney qi deficiency and damp-phlegm stasis stagnation syndrome.