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.

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.

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.

Objective:Since December 2019, novel coronavirus infection has occurred in Hubei province and spread throughout the country quickly. This new crown viral pneumonia was named as coronavirus disease of 2019 (COVID-19) by WHO. However, at present, there is a high incidence of acute aortic dissection in winter and spring. How to prevent the spread of the epidemic and choose the appropriate treatment is an important topic for the patients with acute aortic dissection.Methods:From January 16, 2020 to February 26, 2020, a total of 37 of acute aortic dissection operations were carried out in several cardiovascular surgery centers in Hubei Province. There were 18 cases of Stanford type A aortic dissection and 19 cases of Stanford type B aortic dissection. There were 10 cases (55.55%) with ascending aorta replacement and 7 cases (38.89%) with Bentall procedure for aortic root surgery, and total arch replacement with stented elephant trunk implantation were performed in 14 cases (77.8%). In 19 patients with Stanford type B aortic dissection, thoracic endovascular aortic repair was performed, with the left subclavian artery chimney technique in 2 cases.Results:No deaths occurred within 30 days of hospitalization. Preoperative nucleic acid testing excluded 7 cases of novel coronavirus infection, and 3 suspected cases underwent emergency surgery. the three-level protective standard was adopted in the majority of the surgeries(62.2%, 23/37), and 11 patients were negative in the reexamination of viral nucleic acid after the operation.Conclusion:During the epidemic period, patients with acute aortic dissection should be carefully identified with actife COVID-19 before surgery. The treatment principles-" prevention and control of pneumonia epidemic should be emphasized, conservative medical management should be taken in the comfirmed cases, the selective operation should be delayed as far as possible, and the operation should be reasonable performed in critical cases" should be followed, which can save patients' lives to the greatest extent and prevent the spread of the virus.

Objective To explore the protective effect of long non-coding RNA(lncRNA) metasta-sis associated in lung denocarcinoma transcript 1 (MALAT1) involved in hyperoxia-induced lung injury in preterm infants.Methods This study had downloaded chip data set GSE25286 (Mouse GEO Genome 430 2.0 Array) from gene expression database gene expression omnibus (GEO),according to the state of hyperoxia exposure,the MALAT1 mRNA expression in rats normal lung tissues and hyperoxic lung tissues was compared at day 14th and 29th.In chip data set GSE43830(Human Exon 1.0 ST Arrays) from GEO,the expression of multi-ple genes[cell division cycle 6(CDC6),death effector domain containing 2(DEDD2),and Cyclin B1 (CCNB1)] in WI38 cells(lung fibroblasts) was compared before and after MALAT1 was knockout.At the same time,the peripheral blood samples of premature infants were collected to verify.Totally 40 premature infants were hospitalized in the department of neonatology in our hospital from Jan 2015 to Dec 2016,the pe-ripheral blood samples of 40 premature infants were collected.RNA was extracted and Real time-PCR was performed after reverse transcription,clinical data of these 40 cases were retrospectively analyzed. Results (1) By using Affymetrix Expression console and Affymetrix Transcriptome analysis console software source files of the chip of pretreatment and difference expression gene screening,the expression of lncRNA MALAT1 gene in lung tissues of hyperoxia lung injury mice significantly upregulated[fold change(FC) =2.33,P=0.001].(2) After MALAT1 in WI38 cell was knockout,MALAT1 expression was significantly reduced(FC= -15.6,P=0.000),the expression of CDC6(FC= -2.37,P=0.001) and CCNB1(FC=-2.16,P=0.002) were down regulated,DEDD2 expression was up regulated(FC =2.46,P =0.000). (3) The results of peripheral blood samples from preterm infants showed that the expression of MALAT1 was significantly increased in preterm infants with hyperoxia-induced lung injury(0.375 5 ± 0.081 9,t =4.634, P=0.015),compared with normal preterm infants(0.273 4 ± 0.067 3).Conclusion Through inhibiting cell apoptosis,lncRNA MALAT1 can protect preterm infants with hyperoxia-induced lung injury,it may provide a new strategy for prevention and treatment of hyperoxia-induced lung injury in premature infants.

Tumor in the caudate lobe is difficult for surgical treatment due to its unusual local anatomy.As the development of surgical techniques,the success rate of caudate lobectomy is increased.In recent years,the concept of precision hepatectomy aiming to reduce the iatrogenic damage from hepatectomy and improving the recovery of patients on the basis of radical treatment has been raised.This article summarized the experiences of precision hepatectomy for the treatment of huge tumor in the caudate lobe which was performed in the Ruijin Hospital of Shanghai Jiaotong University.With the help of precision hepatectomy concept and techniques,a more satisfactory result both in safety and prognosis was achieved.