Objective:To investigate the efficacy and safety of dupilumab in the treatment of elderly patients (≥ 60 years old) with atopic dermatitis (AD), with particular attention paid to rare adverse reactions.Methods:A single-center retrospective analysis was conducted on data collected from 281 elderly AD patients who received the standard regimen of dupilumab at the Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2020 to May 2024. Clinical characteristics such as gender, disease duration, skin lesion manifestations, and itch severity were analyzed. Changes in skin lesions and itch severity, as well as related adverse events were recorded during the follow-up period of 0 - 16 weeks. The efficacy and safety of dupilumab in the treatment of elderly AD patients were evaluated.Results:Among the 281 elderly AD patients, 214 were males (76.16%) and 67 were females (23.84%), with the age being 71.13 ± 7.91 years and the age at onset being 59.92 ± 15.72 years. The disease duration ( M[ IQR]) was 5.00 (13.00) years. After standard-regimen dupilumab treatment, the improvement rates of clinical outcome indicators SCORing Atopic Dermatitis (SCORAD) and pruritus numerical rating scale (NRS) scores gradually increased. At week 16, the improvement rates of SCORAD and NRS scores ( M[ IQR]) reached the maxima of 72.37% (23.89%) and 75.00% (29.72%), respectively. The overall incidence of adverse events was relatively low, with only 16 patients (6.05%) reporting adverse events. Common adverse reactions such as conjunctivitis (2 cases, 0.71%) and facial erythema (1 case, 0.36%) were mild and well-tolerated. Phenotype switching occurred in 10 cases (3.56%) . Conclusion:Dupilumab was an effective and safe treatment for elderly AD, but phenotype switching may occur.

Objective:To construct a sizeable naive human Fab phage display antibody library to screen high-affinity specific antibodies in vitro. Methods:Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 126 healthy individuals, subsequently reverse-transcribed into cDNA, and used as a template. PCR amplification was performed to obtain the V H from IgG, IgM and light chain κ, λ, separately, with the initial PCR products serving as templates for a second round of PCR. Overlap extension PCR was employed to generate fragments of the κ and λ light chains. These fragments were ligated with the phage vector pNC3, which harbors the variable region 1 of the heavy chain, to construct a recombinant phage plasmid. This plasmid was then electroporated into competent Escherichia Coli TG1 cells to establish a naive human Fab phage display antibody library. One hundred clones were randomly selected for identification and sequencing, and antibody gene polymorphisms were analyzed using the IMGT database and MAFFT software. Recombinant α-hemolysin from Staphylococcus aureus was utilized to screen Fab antibody fragments through biopanning of the antibody library, followed by random selection of phage ELISA-identified clones. The positive clones (antigen A450∶blank control A450≥2.1) were sequenced. Results:Two large naive Fab phage display antibody libraries were successfully constructed, in which the capacity of κ and λ chain antibody libraries were 1.25×10 11 and 1.54×10 11, respectively. The titers for two antibody libraries were 6.04×10 13 CFU/ml and 3.50×10 13 CFU/ml. The positive transformation insertion rates for κ and λ chain antibody libraries were 96% (96/100) and 100% (100/100), respectively. Sequence analysis revealed that all antibody sequences were unique. The amino acid sequences in the skeletal region were relatively conserved. In contrast, significant variations in the length of the complementarity determining region (CDR) were found, and the diversity of amino acid sequence of the complementary determining region was high, especially the CDR3. Analysis using the IMGT database indicated that the sequences exhibited a broad distribution across variable-diversity-joining gene families. After six rounds of panning, specific phage antibodies enrichment targeting α-hemolysin were achieved. A total of 142 monoclonal antibodies were sequenced, yielding 8 distinct Fab antibody sequences. Conclusion:This study successfully constructed two naive human Fab phage display antibody libraries with large capacity and good diversity, which can be used for screening human antibodies for serum epidemiology.

To investigate the effect of capsaicin(CAP)on the replication of bovine viral diarrhea vi-rus(BVDV).Bovine nasal turbinate osteoblasts(BT)infected with BVDV served as the research model,and viral gene and protein levels were evaluated using RT-qPCR and Western blot.Moreo-ver,molecular docking,molecular dynamics simulation,and oil red O staining were applied to ana-lyze the mechanism by which CAP inhibits BVDV replication.The results revealed no significant effect of CAP at 6.25,12.5,25,and 50 mg/L on the viability of BT cells.CAP was found to signifi-cantly inhibit BVDV 5′UTR RNA and E2 protein levels,according to the antiviral effect study.Molecular docking and molecular dynamics simulations indicated that CAP could bind with high affinity to the active site of PI3K.Additional mechanistic studies indicated that CAP significantly reduced the activation of the PI3K/AKT signaling pathway triggered by BVDV.Furthermore,CAP notably decreased the mRNA levels of FASN,SREBP-1,and ACC-1,which are crucial fatty acid synthesis enzymes in the downstream PI3K/AKT signaling pathway,as well as the levels of lipid droplets.Interestingly,the addition of exogenous oleic acid greatly diminished the antiviral effec-tiveness of CAP and significantly lowered the mRNA levels of IFN-α and IFN-β.The results reveal for the first time that CAP can inhibit BVDV replication,establishing a foundation for its preven-tion and the development of feed additives.

Objective:To explore dynamic changes of CD4+T lymphocytes in peripheral blood of patients with bronchial asthma at different periods and its correlation with control level.Methods:A total of 108 patients with bronchial asthma who received medical treatment in Beijing Jishuitan Hospital,Capital Medical University from September 2020 to October 2022 were selected as study objects,and CD4+T level in peripheral blood of patients with asthma at different periods were compared.According to control level,patients were divided into control group(n=68)and uncontrolled group(n=40).Factors affecting control level of patients with bronchial asthma were analyzed,and prediction model of column graph was constructed and evaluated.Results:CD4+T level in periph-eral blood of patients with acute attack of bronchial asthma was significantly lower than that in chronic duration stage and clinical control stage,CD8+T and CD3+T levels were significantly higher than that in chronic duration stage and clinical control stage(P<0.05).Allergic rhinitis,smoking history,acute respiratory tract infection and residential air pollution were uncontrolled risk factors of patients with bronchial asthma,CD4+T and regular use of inhaled corticosteroids were protective factors(P<0.05).The above indexes were used to construct a line chart model.After internal verification(Bootstrap resamplage 1 000 times),it was found that AUC of this model was 0.845(95%CI:0.734～0.885),sensitivity and specificity were 85.7%and 88.6%,respectively.Conclusion:CD4+T lymphocytes in peripheral blood of patients with acute asthma are significantly lower than patients with chronic asthma and healthy people.Allergic rhinitis,smoking history,acute respiratory tract infection and residential air pollution are uncontrolled risk factors of patients with bronchial asthma,CD4+T and regular use of inhaled corticosteroids are protective factors.

Objective This study aims to develop and evaluate an emergency medical information management system for the medical rescue of mass casualties in public health emergencies at civil airports,focusing on on-site triage and emergency treatment.Methods A retrospective analysis was conducted to compare the effects of on-site emergency drills for mass-casualty rescue in public health emergencies at the Guangzhou Baiyun International Airport Emergency Center in 2018 and 2024.The 2018 drills involving 21 casualties for which conventional emergency medical rescue equipment and procedures were utilized were set as a control group,while the 2024 drills involving 19 casualties for which an emergency medical information processing system were set as an experimental group.Data were analyzed using descriptive epidemiology,chi-square test,and t-test in terms of in-jury conditions,triage time,and total transfer and handover time.By integrating the entire process and all elements to achieve in-formation-based handling in the practical emergency medical rescue drills,the role and advantages of the emergency medical in-formation processing system in scientific command,rapid response,rapid triage,and emergency treatment for mass casualties in public health emergencies were examined.Results The two drills had no difference in the number of casualties(x2=0.054,P=0.973).The time spent on casualty triage and the total time for transfer and handover in 2024 were significantly reduced com-pared with those in 2018(t′=18.992,14.787,both P＜0.001).Conclusion The emergency medical information management system enhances the command,response capabilities and rescue efficiency and level of emergency medical rescue of mass casual-ties in public health emergencies at civil airports.It has promoted the informatization,digitalization and intelligence construction of emergency medical rescue for public health emergencies at civil airports in China,thereby offering a reference for optimizing the informatization model of emergency medical rescue at civil airports in China.

Microvascular invasion is one of the critical factors influencing the prognosis of patients with hepatocellular carcinoma.Accurate preoperative prediction for its occurrence holds pivotal significance for the formulation of clinical individualized treatment decisions.Traditional diagnosis primarily relies on the evaluation of postoperative histopathological results,which exhibits a certain degree of lag.However,the emergence of radiomics features and biomarkers offers new insights for the preoperative prediction of mi-crovascular invasion.The preoperative prediction model based on radiomics and biomarkers is capable of precisely analyzing and efficiently predicting the occurrence risk of microvascular invasion from both macro-scopic imaging features and microscopic molecular levels,thereby providing multi-dimensional and precise scientific evidence for clinical decision-making.

Objective:To construct a sizeable naive human Fab phage display antibody library to screen high-affinity specific antibodies in vitro. Methods:Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 126 healthy individuals, subsequently reverse-transcribed into cDNA, and used as a template. PCR amplification was performed to obtain the V H from IgG, IgM and light chain κ, λ, separately, with the initial PCR products serving as templates for a second round of PCR. Overlap extension PCR was employed to generate fragments of the κ and λ light chains. These fragments were ligated with the phage vector pNC3, which harbors the variable region 1 of the heavy chain, to construct a recombinant phage plasmid. This plasmid was then electroporated into competent Escherichia Coli TG1 cells to establish a naive human Fab phage display antibody library. One hundred clones were randomly selected for identification and sequencing, and antibody gene polymorphisms were analyzed using the IMGT database and MAFFT software. Recombinant α-hemolysin from Staphylococcus aureus was utilized to screen Fab antibody fragments through biopanning of the antibody library, followed by random selection of phage ELISA-identified clones. The positive clones (antigen A450∶blank control A450≥2.1) were sequenced. Results:Two large naive Fab phage display antibody libraries were successfully constructed, in which the capacity of κ and λ chain antibody libraries were 1.25×10 11 and 1.54×10 11, respectively. The titers for two antibody libraries were 6.04×10 13 CFU/ml and 3.50×10 13 CFU/ml. The positive transformation insertion rates for κ and λ chain antibody libraries were 96% (96/100) and 100% (100/100), respectively. Sequence analysis revealed that all antibody sequences were unique. The amino acid sequences in the skeletal region were relatively conserved. In contrast, significant variations in the length of the complementarity determining region (CDR) were found, and the diversity of amino acid sequence of the complementary determining region was high, especially the CDR3. Analysis using the IMGT database indicated that the sequences exhibited a broad distribution across variable-diversity-joining gene families. After six rounds of panning, specific phage antibodies enrichment targeting α-hemolysin were achieved. A total of 142 monoclonal antibodies were sequenced, yielding 8 distinct Fab antibody sequences. Conclusion:This study successfully constructed two naive human Fab phage display antibody libraries with large capacity and good diversity, which can be used for screening human antibodies for serum epidemiology.

Objective:To explore dynamic changes of CD4+T lymphocytes in peripheral blood of patients with bronchial asthma at different periods and its correlation with control level.Methods:A total of 108 patients with bronchial asthma who received medical treatment in Beijing Jishuitan Hospital,Capital Medical University from September 2020 to October 2022 were selected as study objects,and CD4+T level in peripheral blood of patients with asthma at different periods were compared.According to control level,patients were divided into control group(n=68)and uncontrolled group(n=40).Factors affecting control level of patients with bronchial asthma were analyzed,and prediction model of column graph was constructed and evaluated.Results:CD4+T level in periph-eral blood of patients with acute attack of bronchial asthma was significantly lower than that in chronic duration stage and clinical control stage,CD8+T and CD3+T levels were significantly higher than that in chronic duration stage and clinical control stage(P<0.05).Allergic rhinitis,smoking history,acute respiratory tract infection and residential air pollution were uncontrolled risk factors of patients with bronchial asthma,CD4+T and regular use of inhaled corticosteroids were protective factors(P<0.05).The above indexes were used to construct a line chart model.After internal verification(Bootstrap resamplage 1 000 times),it was found that AUC of this model was 0.845(95%CI:0.734～0.885),sensitivity and specificity were 85.7%and 88.6%,respectively.Conclusion:CD4+T lymphocytes in peripheral blood of patients with acute asthma are significantly lower than patients with chronic asthma and healthy people.Allergic rhinitis,smoking history,acute respiratory tract infection and residential air pollution are uncontrolled risk factors of patients with bronchial asthma,CD4+T and regular use of inhaled corticosteroids are protective factors.

Objective To understand the facilitating and obstacle factors for pediatric nurses in implementing interventions for children's medical fears and to provide a foundation for exploring intervention strategies for pediatric nurses to effectively tackle children's medical fears.Methods By purposive sampling,face-to-face interviews were conducted with 20 pediatric nurses in a tertiary-level A children's hospital in Wenzhou City from December 2023 to February 2024.Traditional content analysis was used for data analysis.Results Facilitators and obstacle factors to the implementation of medical fear interventions by pediatric nurses were extracted.The 4 sub-themes of the facilitator theme include awareness of the importance of medical fear intervention,the drive of individual empathy,positive peer support,and the construction of a suitable hospital environment.The 3 sub-themes of the obstacle theme include the lack of individualized intervention skills for medical fear,heavy workload,interference from negative emotional behavior of family members.Conclusion There are many factors influencing paediatric nurses to implement medical fear interventions for children.It is recommended that clinical nursing administrators should strengthen the systematic training of pediatric nurses'knowledge about medical fear interventions for children,unite with multidisciplinary experts,and recruit medical social workers or volunteers to collaborate with nurses and children's families to cope with children's medical fears together and to promote physical and mental health of hospitalized children.

Purpose To investigate the functional connectivity(FC)pattern between the bilateral lower limb sensorimotor cortex(LSM)and the whole brain in type 2 diabetic peripheral neuropathy(DPN).Materials and Methods A total of 44 DPN patients and 43 healthy controls admitted to Shaanxi Provincial People's Hospital from February 2021 to December 2022 were enrolled prospectively and underwent neuropsychological assessment and resting-state fMRI scans.Using bilateral LSM as the regions of interest,the differences of bilateral LSM and whole brain FC between DPN patients and healthy controls were compared.FC in different brain areas were extracted and correlated with clinical/neuropsychological scores.Results Compared with healthy controls,DPN patients had reduced FC of the LSM with the right cerebellar lobule Ⅵ,the right lateral occipitotemporal cortex,the bilateral rostral prefrontal cortex and the bilateral anterior cingulate gyrus.The FC between LSM and right cerebellar Ⅵ in DPN patients were significantly negatively correlated with fasting blood glucose(r=-0.490,P=0.001).The FC between LSM and bilateral anterior cingulate gyrus in DPN patients were significantly positively correlated with Montreal cognitive assessment scores(r=0.479,P=0.001).Conclusion Abnormal FC between LSM and multiple brain regions,suggesting that DPN may have extensive effects on brain regions that maintain motion and motor control function in type 2 diabetes mellitus patients.