OBJECTIVE: This study aims to elucidate the therapeutic potential of osthole for the treatment of atopic dermatitis (AD), focusing on its ability to alleviate chronic pruritus (CP) and the underlying molecular mechanisms. METHODS: In this study, we investigated the anti-inflammatory effects of osthole in both a 2,4-dichloronitrobenzene (DNCB)-induced AD mouse model and tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) stimulated huma immortalized epidermal (HaCaT) cells. The anti-itch effect of osthole was specifically assessed in the AD mouse model. Using methods such as hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), western blot (WB), quantitative real-time PCR (qRT-PCR), and immunofluorescence staining. RESULTS: Osthole improved skin damage and clinical dermatitis scores, reduced scratching bouts, and decreased epidermal thickness AD-like mice. It also reduced the levels of interleukin (IL)-31 and IL-31 receptor A (IL-31 RA) in both skin tissues and HaCaT cells. Furthermore, Osthole suppressed the protein expression levels of phosphor-p65 (p-p65) and phosphor-inhibitor of nuclear factor kappa-Bα (p-IκBα). Meanwhile, it increased the protein expression levels of peroxisome proliferator-activated receptor α (PPARα) and PPARγ in HaCaT cells. CONCLUSION These findings indicated that osthole effectively inhibited CP in AD by activating PPARα, PPARγ, repressing the NF-κB signaling pathway, as well as the expression of IL-31 and IL-31 RA.

Antibody (Ab) humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic Abs originated from animal models. Computational suggestions have long been desired, but available tools focused on immunogenicity calculation of whole Ab sequences and sequence segments, missing the individual residue sites. This study introduces Site-specific Immunogenicity for Therapeutic Antibody (SITA), a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody, but also individual residues, based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures. A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Ab-Ab structural complexes. On an independent testing dataset derived from 13 Ab-Ab structural complexes, SITA successfully predicted the epitope sites for Ab-Ab structures with a receiver operating characteristic (ROC)-area unver the ROC curve (AUC) of 0.85 and a precision-recall (PR)-AUC of 0.305 at the residue level. Furthermore, the SITA score can significantly distinguish immunogenicity levels of whole human Abs, therapeutic Abs and non-human-derived Abs. More importantly, analysis of an additional 25 therapeutic Abs revealed that over 70% of them were detected with decreased immunogenicity after modification compared to their parent variants. Among these, nearly 66% Abs successfully identified actual modification sites from the top five sites with the highest SITA scores, suggesting the ability of SITA scores for guide the humanization of antibody. Overall, these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

The mutual transformation and intertweaving of qi stagnation and blood stasis exist through the development and progression of pediatric pneumonia.Based on the pathogenic mechanism of qi stagnation and blood stasis obstructing the lungs and by analyzing the progression of pneumonia,this paper proposed that the traditional Chinese medicine(TCM)pathogenesis of pediatric pneumonia can be divided into three stages:early,middle,and late.In the early stage,external pathogens invade and then lead to lung qi stagnation and blockage.In the middle stage,qi stagnation and blood stasis block the lungs and then cause blood vessel stagnation.In the late stage,qi stagnation and blood stasis linger,and then result into the residual pathogens lurking in the lungs.Accordingly,the principles of treating pediatric pneumonia are proposed,i.e.,ventilating the lungs and dispelling pathogens,activating blood circulation and resolving stasis,relieving qi stagnation and unblocking blockage.The strategies for treating pediatric pneumonia in three stages are also introduced:for the early stage of pneumonia characterized by lung qi stagnation and blockage,the formula Yinqiao San combined with Wuhu Erchen Decoction are used for clearing lung-heat,resolving phlegm,and relieving wheezing;for the middle stage of pneumonia characterized by the intertweaving of qi stagnation and blood stasis,the formula Xuefu Zhuyu Decoction combined with Xuanfei Baidu Prescription are used for activating blood circulation and resolving stasis,ventilating the lungs and removing toxins,relieving qi stagnation and unblocking blockage;for the late stage of pneumonia characterized by qi stagnation and blood stasis lingering in the lungs,Qinghao Biejia Decoction and Qingfei Touxie Prescription are used by modification for clearing heat and nourishing yin,resolving blood stasis and relieving qi stagnation,nourishing yin and subduing yang.The approach to treating pediatric pneumonia from the pathogenic mechanism of qi stagnation and blood stasis obstructing the lung show significant efficacy on improving clinical symptoms in children with pediatric pneumonia and preventing the progression of pneumonia,and will provide reference to the clinical prevention and treatment of pediatric pneumonia.

Antibody humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic antibodies originated from animal models.Computational suggestions have long been desired,but available tools focused on immunogenicity calculation of whole antibody sequences and sequence segments,missing the individual residue sites.This study introduces Site-specific Immunogenicity for Therapeutic Antibody(SITA),a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody,but also individual residues,based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures.A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Antibody-Antibody structural complexes.On an independent testing dataset derived from 13 Antibody-Antibody structural complexes,SITA successfully predicted the epitope sites for Antibody-Antibody structures with a receiver operating characteristic(ROC)-area unver the ROC curve(AUC)of 0.85 and a precision-recall(PR)-AUC of 0.305 at the residue level.Furthermore,the SITA score can significantly distinguish immunogenicity levels of whole human antibodies,therapeutic antibodies and non-human-derived antibodies.More importantly,analysis of an additional 25 thera-peutic antibodies revealed that over 70％of them were detected with decreased immunogenicity after modification compared to their parent variants.Among these,nearly 66％antibodies successfully iden-tified actual modification sites from the top five sites with the highest SITA scores,suggesting the ability of SITA scores for guide the humanization of antibody.Overall,these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

Objective To explore the mechanism of Baihu Decoction in the treatment of acute lung injury based on network pharmacology and molecular docking technology;To carry out experimental verification.Methods The active components and targets of Baihu Decoction were searched through TCMSP and BATMAN-TCM databases,and human gene searches were conducted in GeneCards,NCBI,and OMIM databases.PPI network construction and GO and KEGG pathway enrichment analysis were conducted to determine the important signaling pathways of Baihu Decoction and acute lung injury.Molecular docking of main active components and core target proteins was performed.The effects of Baihu Decoction on survival rate and inflammatory cytokine content in acute lung injury lethal model mice were observed through animal experiments.Results Totally 211 common targets for Baihu Decoction and acute lung injury were screened,and identified effective components such as quercetin,kaempferol,and stigmasterol,etc.Analysis of KEGG pathway enrichment indicated that Baihu Decoction exerted its pharmacological effects in acute lung injury through a variety of signal pathways,including Toll-like receptor signaling pathway,NOD-like receptor signaling pathway,T cell receptor signaling pathway,and MAPK signaling pathway.Molecular docking results showed that Baihu Decoction had good binding strength with MAPK14,STAT3,JUN,MAPK1,MAPK3,FOS and RELA.The results of animal experiments showed that compared with the model group,the survival rate of mice in the Baihu Decoction group was significantly increased,the degree of pathological injury in the lung tissue was reduced,and serum IL-6,TNF-α contents decreased significantly(P<0.05).Conclusion Baihu Decoction can treat acute lung injury by reducing pathological injury to lung tissue and releasing of inflammatory factors.

Objective To systematically analyze the research hotspots and development trends of drug resistance mechanisms in renal cell carcinoma(RCC),and to provide a reference for research in this field.Methods The literature related to drug resistance in treatment of RCC was obtained from Web of Science core collection.CiteSpace software was used for keyword clustering and trend analysis,and VOSviewer software was used for keyword co-occurrence network analysis.Results In total,1 392 literature were incorporated,including 736 regarding targeted therapy,158 in immunotherapy,and 369 in chemotherapy.The overall research trend in this field was on the rise,in which the research on targeted therapy resistance occupies a dominant position,and immunotherapy resistance was a new research direction.Key words in this field were focused on molecular mechanisms of drug resistance,potential signaling pathways,combination therapy,indicators,and novel therapy.The evolution of keywords and theme words suggests that the research tendency of RCC targeted therapy resistance in recent years focuses on the exploration of new mechanisms of drug resistance and the application of multi-target drugs.The research trend of immunotherapy resistance highlights combination therapy,tumor microenvironment,and metastasis correlation.The research trend of chemotherapy resistance focused on pharmacokinetic-related factors,multidrug resistance genes.Conclusion To provide references for researchers to accurately grasp the research status and development trend of drug resistance in RCC.

Objective To construct a deep learning-based target detection method to help radiologists perform rapid diagnosis of lesions in the CT images of patients with novel coronavirus pneumonia(NCP)by restoring detailed information and mining local information.Methods We present a deep learning approach that integrates detail upsampling and attention guidance.A linear upsampling algorithm based on bicubic interpolation algorithm was adopted to improve the restoration of detailed information within feature maps during the upsampling phase.Additionally,a visual attention mechanism based on vertical and horizontal spatial dimensions embedded in the feature extraction module to enhance the capability of the object detection algorithm to represent key information related to NCP lesions.Results Experimental results on the NCP dataset showed that the detection method based on the detail upsampling algorithm improved the recall rate by 1.07%compared with the baseline model,with the AP50 reaching 85.14%.After embedding the attention mechanism in the feature extraction module,86.13%AP50,73.92%recall,and 90.37%accuracy were achieved,which were better than those of the popular object detection models.Conclusion The feature information mining of CT images based on deep learning can further improve the lesion detection ability.The proposed approach helps radiologists rapidly identify NCP lesions on CT images and provides an important clinical basis for early intervention and high-intensity monitoring of NCP patients.

An adult female patient of internal nuclear inclusion disease(NIID)with a major clinical manifestation of decreased intelligence and recurrent disturbance of consciousness was followed up for nearly 4 years.In particular,the evolution of the video-electroencephalogram(VEEG),the auxiliary diagnosis of VEEG,and the prediction value of VEEG for clinical outcome were summarized.We found that(1)the background rhythm in NIID patients evolved with the progression of the disease;(2)electroencephalogram reactivity could predict the outcome of NIID coma;(3)VEEG helped to determine whether the consciousness disturbance caused by NIID was due to non-convulsive status epilepticus,This case provides a new idea to explore the application of VEEG in NIID.

OBJECTIVE To discuss the factors affecting the blood concentration of high-dose methotrexate （HD-MTX） and the occurrence of adverse drug reactions （ADR） when treating lymphoma with HD-MTX. METHODS From July 2020 to November 2021， the information of HD-MTX patients who had been monitored for HD-MTX blood drug concentration in the First Affiliated Hospital of Guangdong Pharmaceutical University was collected by retrospective analysis， such as medical record number， age， sex， height， body mass， chemotherapy plan， dosage； test indexes such as alanine transaminase， aspartate transaminase， total bilirubin， creatinine clearance （CrCl）， albumin （ALB） and other indexes were also collected before and after administration. The blood concentrations （c6 h， c24 h， c48 h） of HD-MTX were recorded， drug information of proton pump inhibitors （PPIs） was extracted and used， and ADR occurring within 48 h after administration were all evaluated. Single factor analysis， multiple linear regression and χ2 test were used to analyze the influential factors. RESULTS A total of 133 patients were included in this paper. The results of the single factor analysis of HD-MTX blood drug concentration showed that age， CrCl had an effect on c 6 h （P＜0.05）； age， CrCl and ALB had an effect on c24 h （P＜0.05）； age， body mass index （BMI）， CrCl， combined use of PPIs and ALB had an effect on c48 h （P＜0.05）. The results of multiple linear regression analysis showed that age and CrCl had no effect on c 6 h （P＞0.05）， age was the main influential factor of c 24 h （P＜0.05）， and CrCl and combined use of PPIs were the main influential factors of c48 h （P＜0.05）； the coefficient of variance expansion was between 1 and 3.5， indicating that the analysis results were acceptable. The overall incidence of adverse reactions was 51.13%， of which the blood and lymphatic system reactions were the most common. The results of the influential factors of ADR showed that age， BMI， liver function and CrCl had effect on the incidence of ADR （P＜0.05）. CONCLUSIONS During the process of HD-MTX in the treatment of lymphoma， the patient’s age， CrCl and combined use of PPIs should be considered， and the patient’s blood concentration should be monitored； at the same time， the age of patients， BMI， liver function and CrCl have an impact on the incidence of ADR.

Background: Patients with dyspepsia are the major group of outpatient department of gastroenterology. Dyspeptic symptoms are closely related to anxiety and/or depression. However, the relationship of anxiety and/or depression to dyspeptic symptoms in outpatients undergoing gastroscopy is still unclear. Aims: To investigate the incidence of anxiety and/or depression in outpatients undergoing gastroscopy and its correlation with the severity of dyspepsia. Methods: Outpatients underwent gastroscopy from November 2021 to December 2021 at West China Hospital, Sichuan University were recruited. Generalized anxiety disorder-7 (GAD-7), patient health questionnaire-9 (PHQ-9) were used to evaluate anxiety and depression, respectively. Rome diagnostic questionnaire for functional gastrointestinal disorders, severity of dyspepsia assessment questionnaire, visceral sensitivity index were used to evaluate dyspepsia. The correlation of anxiety and/or depression with dyspepsia was analyzed. Results: A total of 458 questionnaires were collected effectively, including 146 (31.9%) patients with anxiety and/or depression. Compared with the non-anxiety and depression group, the number of gastroscopy in the anxiety and/or depression group was significantly higher (P<0.05). Compared with the non-anxiety and depression group, the incidences of extremely mild/mild dyspepsia, moderate/severe epigastric fullness, postprandial fullness, epigastric pain and belching were significantly increased in the anxiety and/or depression group (P<0.05). Anxiety and/or depression was significantly correlated with the severity of dyspepsia and visceral sensitivity (r=0.421, r=0.143; P< 0.05). Conclusions: Anxiety and/or depression is common in outpatients undergoing gastroscopy; anxiety and/or depression may lead to repeated endoscopic examinations; anxiety and/or depression is significantly correlated with dyspepsia and visceral sensitivity.