Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

AIM:To explore the potential of Huangqi sanqi mixture(AP)in improving renal fi-brosis by performing transcriptome sequencing of the kidneys of the unilateral ureteral ligation mouse group and the Huangqi sanqi mixture inter-vention group,and using bioinformatics to verify the signitficantly different lncRNAs mechanism.METHODS:Twenty-four C57 mice were divided in-to sham operation group,renal fibrosis group,Huangqi sanqi mixture intervention group(3.944 g/kg)and irbesartan positive control intervention group,with 6 mice in each group.A mouse model of renal fibrosis was established by unilateral ure-teral ligation(UUO).The animals were given intra-gastric administration after operation,and the ani-mals were sacrificed and the specimens were col-lected after seven consecutive days of administra-tion.The changes of Huangqi sanqi mixture on re-nal fibrosis pathological damage were analyzed by HE and Masson staining,and the protein levels of Fn and α-SMA in renal tissue of each group were detected by Western blot and immunohistochemis-try to evaluate the alleviating effect of Huangqi san-qi mixture on renal fibrosis.Subsequently,lncRNA expression information was obtained by transcrip-tome sequencing,and Quantitative Real-time PCR(qPCR)was performed after data quality,GO en-richment and differential lncRNA were analyzed.According to the differential lncRNA and target analysis results obtained by sequencing,lncRNA Gm51500/Adam12 was overexpressed in vitro,and its mechanism in the protection of renal fibrosis by Huangqi sanqi mixture was studied by immunohis-tochemistry,immunofluorescence staining and qP-CR verification.RESULTS:Compared with the mod-el group,the renal fibrosis of the mice in the Huangqi sanqi mixture intervention group was sig-nificantly reduced,and the protein levels of α-SMA and Fn and the expression of lncRNA in the renal tis-sue were significantly down-regulated(P＜0.000 1).Three lncRNAs were screened and verified to in-crease in the model group and significantly de-crease after AP intervention,namely lncRNA Gm29994,Gm51500 and Gm35391.Target analysis showed that lncRNA Gm51500 had the most signifi-cant relationship with Adam12.The results of ani-mal experiments showed that Adam12 was highly expressed in the kidney of UUO mice and was sig-nificantly inhibited after AP intervention.Subse-quent cell experiments confirmed that overexpres-sion of lncRNA Gm51500 could up-regulate TGF-β-induced renal tubular cell fibrosis and Adam12 ex-pression.Cell recovery experiments confirmed that Adam12 overexpression reversed the inhibitory ef-fect of AP on renal tubular cell injury and fibrosis.CONCLUSION:Huangqi sanqi mixture can improve renal fibrosis.Based on transcriptomic sequencing,lncRNA Gm51500/Adam12 axis may be a potential target for Huangqi sanqi mixture to improve renal fibrosis.

AIM:To explore the potential of Huangqi sanqi mixture(AP)in improving renal fi-brosis by performing transcriptome sequencing of the kidneys of the unilateral ureteral ligation mouse group and the Huangqi sanqi mixture inter-vention group,and using bioinformatics to verify the signitficantly different lncRNAs mechanism.METHODS:Twenty-four C57 mice were divided in-to sham operation group,renal fibrosis group,Huangqi sanqi mixture intervention group(3.944 g/kg)and irbesartan positive control intervention group,with 6 mice in each group.A mouse model of renal fibrosis was established by unilateral ure-teral ligation(UUO).The animals were given intra-gastric administration after operation,and the ani-mals were sacrificed and the specimens were col-lected after seven consecutive days of administra-tion.The changes of Huangqi sanqi mixture on re-nal fibrosis pathological damage were analyzed by HE and Masson staining,and the protein levels of Fn and α-SMA in renal tissue of each group were detected by Western blot and immunohistochemis-try to evaluate the alleviating effect of Huangqi san-qi mixture on renal fibrosis.Subsequently,lncRNA expression information was obtained by transcrip-tome sequencing,and Quantitative Real-time PCR(qPCR)was performed after data quality,GO en-richment and differential lncRNA were analyzed.According to the differential lncRNA and target analysis results obtained by sequencing,lncRNA Gm51500/Adam12 was overexpressed in vitro,and its mechanism in the protection of renal fibrosis by Huangqi sanqi mixture was studied by immunohis-tochemistry,immunofluorescence staining and qP-CR verification.RESULTS:Compared with the mod-el group,the renal fibrosis of the mice in the Huangqi sanqi mixture intervention group was sig-nificantly reduced,and the protein levels of α-SMA and Fn and the expression of lncRNA in the renal tis-sue were significantly down-regulated(P＜0.000 1).Three lncRNAs were screened and verified to in-crease in the model group and significantly de-crease after AP intervention,namely lncRNA Gm29994,Gm51500 and Gm35391.Target analysis showed that lncRNA Gm51500 had the most signifi-cant relationship with Adam12.The results of ani-mal experiments showed that Adam12 was highly expressed in the kidney of UUO mice and was sig-nificantly inhibited after AP intervention.Subse-quent cell experiments confirmed that overexpres-sion of lncRNA Gm51500 could up-regulate TGF-β-induced renal tubular cell fibrosis and Adam12 ex-pression.Cell recovery experiments confirmed that Adam12 overexpression reversed the inhibitory ef-fect of AP on renal tubular cell injury and fibrosis.CONCLUSION:Huangqi sanqi mixture can improve renal fibrosis.Based on transcriptomic sequencing,lncRNA Gm51500/Adam12 axis may be a potential target for Huangqi sanqi mixture to improve renal fibrosis.

After COVID -19, patients, medical workers and the whole society in COVID -19 were faced with the challenge of how to quickly return to normal life. Patients cured in COVID -19 would face mental or psychological barriers, or be discriminated against, or face problems such as overweight of local epidemic prevention policies. The front-line medical personnel experienced job burnout and a variety of mental and psychological disorders, with some even developing physical symptoms. During the epidemic, ordinary people were in a state of psychological stress, education, production and economic activities were affected, and the incidence of mental or psychological disorders increases. It was necessary to provide COVID -19 patients with mental health monitoring and counseling. Give professional guidance to front-line medical staff, arrange rotation reasonably, and pay attention to their mental health status. Local governments should strictly implement the national epidemic prevention system, formulate epidemic prevention policies with humanistic care, actively publicize epidemic related knowledge and safeguard the rights and interests of the people.

Objective To analyze and discuss the medication rule of professor Ruan Yan in the treatment of children with allergic rhinitis by using data mining method,and to provide reference for the clinical research and patented drugs development for the treatment of children with allergic rhinitis.Methods The outpatient medical records of professor Ruan Yan for the treatment of children with allergic rhinitis were collected.Microsoft Excel 2010 software was used for frequency statistics.SPSS Clementine 12.0 software was used for association rule analysis,cluster analysis and factor analysis to obtain the data.The frequency of use of various drugs and the association rules between drugs were obtained.Then the medication rules in professor Ruan Yan's prescription were analyzed.Results A total of 308 Chinese medicine compounds were included,involving 80 kinds of Chinese medicines,among which relieving drugs and qi-invigorating herbs were high-frequently used.The distribution of traditional Chinese medicine syndrome types was mainly characterized by lung-qi deficiency-cold syndrome and lung-spleen qi deficiency syndrome.The medicinal properties were mainly spicy,warm and sweet,and most of them belonged to the lung,spleen and stomach meridians.Five core prescriptions were extracted by factor analysis.Four drug combinations were obtained by systematic cluster analysis.Conclusion Ventilating lung and opening the orifices,expelling wind and removing cold,strengthening the spleen and replenishing qi are basic therapeutic principles for professor Ruan Yan in the treatment of children with allergic rhinitis.The treatment mainly focused on dispelling evil,ventilating lung and opening the orifices,expelling wind and removing cold during the acute stage of allergic rhinitis.In the remission period,according to the principle of"treating disease must be based on its origin",the treatment should enhance children's physical fitness,tonify lung and strengthen spleen,thereby reducing recurrence.

Objective To observe the value of lightweight U-Net(L-U-Net)model for segmentation of breast cancer ultrasound images.Methods A total of 1 009 ultrasound images of 779 female cases with breast cancer were retrospectively analyzed,including 807 images in training set and 202 images in test set.MobileNetV2 and MobileViT modules were embedded into encoding end of U-Net model to construct L-U-Net models,i.e.conventional lightweight L-U-Net(L-U-Net 1)and sub lightweight L-U-Net(L-U-Net 2)models.The segmentation accuracy and lightweight degree of L-U-Net models were evaluated taken manually annotating lesion areas by physicians as the reference standards.Results The pixel accuracy,intersection over union and Dice similarity coefficient of L-U-Net models for segmentation of breast cancer ultrasound images were similar to those of U-Net model,and the number of parameters,floating point operation and memory usage of L-U-Net model were lower but inference time were higher than those of U-Net model.U-Net and L-U-Net models had better segmentation efficacy for ultrasound images of breast cancer with clear boundaries.For images with blurred lesion boundaries but still recognizable,U-Net model was prone to mislabeling non lesion areas,while L-U-Net models could provide more accurate segmentation results.For images with blurred lesion boundaries difficult to identify with naked eyes,all 3 models had incomplete segmentation,among which U-Net and L-U-Net 1 models had larger missing areas but L-U-Net 2 model had smaller missing areas.Conclusion L-U-Net 2 model could be used for segmentation of breast cancer ultrasound images with good lightweight degree and segmentation accuracy.

Background and purpose:Abnormal DNA methylation is closely associated with the onset and progression of tumors.This study aimed to investigate the expression of intermediate filament family orphan 1(IFFO1),a methylation-driven gene(MDG)in pancreatic adenocarcinoma(PAAD),along with its effects on the invasion and metastasis of PAAD cells,as well as its potential as a diagnostic and prognostic biomarker.Methods:mRNA expression data(TCGA-PAAD-mRNA),DNA methylation data(TCGA-PAAD-meth,GSE53051,PACA-AU)of PAAD and adjacent normal tissues,as well as DNA methylation data of healthy individuals'blood(GSE69270),were obtained from the The Cancer Genome Atlas(TCGA),International Cancer Genome Consortium(ICGC)and Gene Expression Omnibus(GEO)databases.By performing differential expression analysis combined with differential methylation analysis,we screened for MDG in PAAD.In the TCGA database,Pearson correlation tests were employed to verify the relationship between IFFO1 promoter methylation level and its expression level.Additionally,Kaplan-Meier survival analysis was conducted to evaluate the relationship among IFFO1 promoter methylation level,expression level,and the prognosis of PAAD.Pathological sections of cancer tissues and corresponding adjacent tissues from 27 PAAD patients were obtained from Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine.All samples involved in this study were approved by the human ethics committee of Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine(ethics number:hospital ethics review[2017]No.53).Immunohistochemistry staining(IHC)was utilized to detect the expression of IFFO1 in cancer tissues and corresponding adjacent tissues from 27 PAAD patients.Based on the median expression level of IFFO1,patients in the TCGA database were classified into high-expression and low-expression groups.Subsequently,differential analysis,gene ontology(GO)enrichment analysis and gene set enrichment analysis(GSEA)were performed.Western blot and real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)were employed to assess the expression variations of IFFO1 between the normal pancreatic ductal epithelial cell line H6C7 and the PAAD cell lines MIA PaCa2,BxPC-3,AsPC-1 and Capan-2.The impact of IFFO1 overexpression on the migration and invasion capacities of PAAD cell lines AsPC-1 and Capan-2 was evaluated using scratch and invasion assays.Additionally,receiver operating characteristic(ROC)curves and Kaplan-Meier survival analysis were utilized to assess the diagnostic and prognostic significance of IFFO1 methylation levels in the TCGA pan-cancer cohort.Results:Through the cross-screening of five datasets,41 MDG in PAAD were identified.Among these,IFFO1 was found to be the gene most closely associated with the prognosis of PAAD[hazard ratio(HR)=0.28,P＜0.001].IFFO1 exhibited high methylation and low expression levels in PAAD.Moreover,a significant negative correlation was observed between the methylation level of its promoter and its expression level(r=-0.55,P＜0.001).IHC results indicated that IFFO1 expression was significantly lower in PAAD tissues than in adjacent non-tumor tissues(P＜0.05).TCGA survival analysis demonstrated that patients with high methylation or low expression of IFFO1 had poorer overall survival(P＜0.05).Both GO and GSEA analyses indicated that the pathway"Negative regulation of cell migration"was enriched in patients with high IFFO1 expression.Western blot and RTFQ-PCR results demonstrated that IFFO1 expression in normal pancreatic ductal epithelial cells H6C7 was significantly higher compared with PAAD cell lines MIA PaCa2,BxPC-3,AsPC-1,and Capan-2.Overexpression of IFFO1 significantly inhibited the migration and invasion of the PAAD cell lines AsPC-1 and Capan-2.Additionally,pan-cancer analysis revealed that IFFO1 exhibited abnormal promoter methylation and low expression across various cancer types,with its methylation levels demonstrating significant diagnostic and prognostic prediction value among different tumors.Conclusion:Promoter hypermethylation results in decreased expression of IFFO1 in PAAD.IFFO1 may suppress the invasion and migration abilities of PAAD cells.Furthermore,IFFO1 methylation holds great promise as a novel biomarker for the diagnosis and prognosis of PAAD.

Venomous snake bite is an acute systemic toxic disease, mainly manifested as: flaccid paralysis, systemic muscle lysis, coagulation disorders, bleeding, renal dysfunction, cardiac toxicity, and local tissue damage to bite segments. This article reports a rare case of spontaneous abdominal bleeding caused by a pit viper bite on the 5th day. After receiving additional anti serum injection and strengthening the correction of coagulation function,the patient's condition improved and eventually the abdominal bleeding was absorbed.

Venomous snake bite is an acute systemic toxic disease, mainly manifested as: flaccid paralysis, systemic muscle lysis, coagulation disorders, bleeding, renal dysfunction, cardiac toxicity, and local tissue damage to bite segments. This article reports a rare case of spontaneous abdominal bleeding caused by a pit viper bite on the 5th day. After receiving additional anti serum injection and strengthening the correction of coagulation function,the patient's condition improved and eventually the abdominal bleeding was absorbed.

Background: and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). Methods: We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. Results: Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. Conclusion The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.