Objective To investigate the relationship between the expression levels of lymphocyte activation gene-3(LAG-3)and pen-traxin-3(PTX3)and the disease severity of the patients with allergic rhinitis(AR).Methods A total of 128 AR patients visited the Department of Otolaryngology,Chengdu Integrated TCM and Western Medicine Hospital from January 2021 to June 2023 were retro-spectively selected as the research subjects(AR group).According to the severity of the condition,the patients were further divided into the mild group(n=40),moderate group(n=42),and severe group(n=46).In addition,80 healthy volunteers who underwent physical examinations in our hospital were selected as the control group.The clinical data such as the gender,age,body mass index(BMI),allergens,and disease onset time of all subjects were recorded and analyzed,and all patients were scored using the Score For Allergic Rhinitis(SFAR).The enzyme linked immunosorbent assay(ELISA)was used to detect the expression levels of serum LAG-3 and PTX3 in all subjects.The correlation between the expression levels of serum LAG-3 and PTX3 was analyzed by the Pearson correla-tion analysis.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of serum LAG-3 and PTX3 levels,both individually and in combination,for AR.Results The expression levels of serum LAG-3 in the AR group(468.74±104.32 μg/L)were significantly lower than that in the control group(691.53±184.65 μg/L,t=7.795,P<0.05),while those of ser-um PTX3 in the AR group(24.83±7.54 ng/L)were significantly higher than that in the control group(17.34±5.37 ng/L,t=7.793,P<0.05).The expression levels of serum LAG-3 in the AR patients with positive immunoglobulin(IgE)and SFAR score≥7 were 442.46±92.37 μg/L and 448.27±103.24 μg/L,respectively,which were significantly lower than that in the AR patients with negative IgE(497.61±115.32 μg/L)and SFAR score<7(498.66±112.76 μg/L,P<0.05).While the expression levels of serum PTX3 in the AR patients with positive IgE and SFAR score≥7 were 28.24±8.17 ng/L and 26.43±8.73 ng/L,respectively,which were significantly higher than that in the AR patients with negative IgE(21.08±6.25 ng/L)and SFAR score<7(22.51±6.89 ng/L,P<0.05).Com-pared with the mild group,the expression levels of serum LAG-3 in both the moderate and severe groups were reduced,and that of ser-um LAG-3 in the severe group was significantly lower than that in the moderate group.While the expression levels of serum PTX3 showed an opposite trend,and the levels of serum PTX3 in the severe group were significantly higher than that in the moderate group(P<0.05).The Pearson correlation results showed a significant negative correlation between serum LAG-3 and PTX3 levels in AR pa-tients(r=-0.402,P=0.000).The analysis of the ROC curve showed that the area under the ROC curve(AUCROC),sensitivity,and specificity of the combination of serum LAG-3 and PTX3 in the diagnosis of AR were 0.881,89.80％,and 73.80％,respectively,which were better than that of serum LAG-3 and PTX3 alone.Conclusion The combined detection of serum LAG-3 and PTX3 for the diagnosis of AR has higher clinical application value and may be used to evaluate the severity of the disease.

Objective·To investigate the changes in transcriptome and chromatin accessibility during the differentiation of human embryonic stem cells(hESCs)into neural progenitor cells(NPCs)using in vitro differentiation models and high-throughput multi-omics sequencing technologies.Methods·hESCs were first induced to differentiate into NPCs in vitro using the embryoid body formation method,and cells at both stages were collected.The cell phenotypes were identified by reverse transcription-quantitative real-time PCR(RT-qPCR)and immunofluorescence(IF)staining.Transcriptome sequencing(RNA-seq)was conducted to detect and analyze the differentially expressed genes(DEGs)between hESCs and NPCs.The assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)was employed to assess chromatin accessibility changes between hESCs and NPCs.Motif enrichment analysis was performed on differentially accessible chromatin regions to discover potential regulatory transcription factors.Finally,an integrated analysis of RNA-seq and ATAC-seq data and the protein-protein interaction(PPI)network were performed to identify key genes and regulatory pathways involved in the early stages of neural differentiation in vitro.Results·Both RT-qPCR and IF results indicated that the expression levels of pluripotency markers(NANOG and POU5F1)were high at the hESC stage but significantly decreased at the NPC stage,while early neural differentiation markers(PAX6,SOX1,and NES)were minimally expressed at the hESC stage but markedly upregulated at the NPC stage.RNA-seq analysis revealed that compared to the hESC stage,there were 5 597 genes upregulated and 3 654 genes downregulated at the NPC stage.Gene function enrichment analysis showed that the upregulated genes at the NPC stage were enriched in the functions related to neural development.ATAC-seq analysis demonstrated a total of 27 491 genomic regions had significant changes in chromatin accessibility during the differentiation from hESC to NPC,with 12 381 regions showing increased accessibility and 15 110 regions showing decreased accessibility.Motif enrichment analysis revealed that transcription factor genes such as DLX1 and LHX2 might play an important role in the differentiation process from hESCs into NPCs.Integrated analysis of RNA-seq and ATAC-seq data revealed that overlapping genes with high expression at the NPC stage were mainly enriched in axon guidance,forebrain development,and neuron migration.After neural differentiation,the expression levels of CTNND2 and LHX2 genes increased,and the chromatin accessibility of related genomic regions also increased.PPI network analysis indentified candidate downstream genes including PRKACA,CDH2,and ERBB4.Conclusion·The in vitro differentiation model of hESCs combined with high-throughput multi-omics sequencing technologies can be used to depict the changes in transcriptome and chromatin accessibility during the differentiation of hESCs into NPCs.In this process,the expression levels of genes related to axon guidance,forebrain development,and neuronal migration pathways increase and related chromatin accessibility is enhanced.

Objective:To investigate the utility of a computational pathology-based tumor microenvironment(TME)score derived from whole slide images(WSIs)in predicting the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)in patients with EGFR mutation-positive non-small cell lung cancer(NSCLC).Methods:This retrospective study collected 240 EGFR-mutant NSCLC pa-tients treated with EGFR-TKIs at The First Affiliated Hospital of Wannan Medical College and analyzed hematoxylin-eosin(H&E)-stained WSIs of biopsy specimens,along with clinical and imaging data.The patients were randomly assigned into a training cohort(n=160)and an inde-pendent validation cohort(n=80)in a 2:1 ratio.Treatment response was assessed based on CT findings at 3 months after EGFR-TKIs initi-ation.Computational pathology was employed to automatically quantify the proportions of four TME components(tumor epithelium,stroma,lymphocytes,and vasculature)within the tumor regions of WSIs.Multivariate Logistic regression in the training cohort identified TME components independently predictive of treatment response(P<0.05),which were then integrated into a TME-score.The predictive performance was evaluated using receiver operating characteristic(ROC)curve analysis and area under the curve(AUC).The TME-score model was compared with a clinical-feature-based model and a combined model(TME-score+clinical features).Finally,the models were val-idated in the independent cohort.Results:In the training cohort,the TME-score,incorporating epithelial and stromal proportions,achieved an AUC of 0.827(95%CI:0.749-0.892)for predicting treatment response,while the validation cohort yielded an AUC of 0.845(95%CI:0.735-0.937).Both outperformed the clinical model(AUCs=0.730[95%CI:0.645-0.804]and 0.712[95%CI:0.586-0.824],respectively).The combined model(TME-score+clinical features,including cytokeratin 19 fragment and non-contrast CT values)further improved predictive performance(AUCs=0.884[95%CI:0.827-0.932]and 0.882[95%CI:0.798-0.950],respectively).Delong's test for pairwise model comparis-ons showed significant differences(all P<0.05)except TME-score and the combined model in the validation cohort(P=0.289).Conclusions:TME-score outperformed clinical models in predicting EGFR-TKIs efficacy in EGFR mutation-positive NSCLC patients and may serve as a novel tool for identifying patients likely to benefit from targeted therapy.

Objective To compare the efficacy of recombinant human interleukin-11(rhIL-11)and herombopag olamine tablets on chemotherapy-induced thrombocytopenia(CIT)in breast cancer.Methods Eighty-six prospectively selected breast cancer patients with CIT were randomly divided into the control group(administered rhIL-11)and the study group(administered herombopag olamine tablets),with 43 cases in each group.Before treatment and 14 days after treatment,platelet parameters[platelet count(PLT),plateletcrit(PCT),platelet distribution width(PDW)and mean platelet volume(MPV)]and flow cytometry were measured by automated hematology analyzer.Cellular immune indicators(CD3+,CD4+,CD8+and CD4+/CD8+)were detected by flow cytometer.Enzyme-linked immunosorbent assay was used to determine the levels of thrombopoietin(TPO)and interleukin-11(IL-11).The above parameters were compared between the two groups,and the incidence of adverse reactions in the two groups was recorded.Results After treatment,PLT,PCT,CD3+,CD4+,CD4+/CD8+,TPO and IL-11 in both groups were higher than before treatment,and which was higher in the study group than the control group(P＜0.05).After treatment,PDW,MPV and CD8+of both groups were lower than before treatment,and the study group was lower than the control group(P＜0.05).There was no significant difference in the overall incidence of adverse reactions between the two groups(P＞0.05).Conclusion Both rhIL-11 and herombopag olamine tablets are effective in treating breast cancer with CIT.Compared with rhIL-11,herombopag olamine tablets have more advantages in improving platelet parameters,cellular immune indicators,TPO and IL-11,and do not increase the adverse reactions.

Cancer stem cells (CSCs) are proposed to account for the progression, metastasis, and recurrence of diverse malignancies. However, the disorganized vasculars in tumors hinder the accumulation and penetration of nanomedicines, posing a challenge in eliminating CSCs located distantly from blood vessels. Herein, a pair of twin-like small-sized nanoparticles, sunitinib (St)-loaded ROS responsive micelles (RM@St) and salinomycin (SAL)-loaded GSH responsive micelles (GM@SAL), are developed to normalize disordered tumor vessels and eradicate CSCs. RM@St releases sunitinib in response to the abundant ROS in the tumor extracellular microenvironment for tumor vessel normalization, which improved intratumor accumulation and homogeneous distribution of small-sized GM@SAL. Sequentially, GM@SAL effectively accesses CSCs and achieves reduction-responsive drug release at high GSH concentrations within CSCs. More importantly, RM@St significantly extends the window of vessel normalization and enhances vessel integrity compared to free sunitinib, thus further amplifying the anti-tumor effect of GM@SAL. The combination therapy of RM@St plus GM@SAL produces considerable depression of tumor growth, drastically reducing CSCs fractions to 5.6% and resulting in 78.4% inhibition of lung metastasis. This study offers novel insights into rational nanomedicines designed for superior therapeutic effects by vascular normalization and anti-CSCs therapy.

Objective To analyze the effects of nasal endoscopic low temperature plasma ablation combined with nasal dynamical system-assisted resection on inflammatory markers in peripheral blood of sinonasal inverted papilloma(SINP)and their correlations with recurrence.Methods A retrospective analysis was performed on 60 SINP patients admitted to Chengdu First People's Hospital from May 2021 to May 2023,all of whom were treated with endoscopic low temperature plasma ablation and nasal dynamical system-assisted resection;and another 60 healthy persons who underwent physical examination in the same period were enrolled and set as control group.The changes of peripheral blood inflammatory markers before and at various time points after operation were compared between control group and SINP patients.General data of patients were collected by self-made scales.The recurrence was recorded,and its influence factors were analyzed for further exploring and the correlation between recurrence and levels of peripheral blood inflammatory factors.Results Statistically significant differences between control group and SINP group were found in serum tumor necrosis factor-α(TNF-α),C-reactive protein(CRP),interleukin-6(IL-6),interleukin-8(IL-8),eosinophilic cationic protein(ECP)and eosinophilic granulocytes(EOS)before operation,3 days and 1 month after operation(all P<0.001).Univariate analysis identified that TNF-α,CRP,IL-6,IL-8,mitotic counts,atypical hyperplasia and course of disease were associated with postoperative recurrence in SINP patients.Spearman correlation analysis showed that the postoperative recurrence in SINP patients showed no correlation with IL-6 level(P>0.05),but positively correlated with TNF-α,CRP and IL-8 levels(P<0.05).Conclusion Nasal endoscopic low temperature plasma ablation combined with nasal dynamical system-assisted resection is effective for SINP,with a low postoperative recurrence rate.Moreover,peripheral blood inflammatory markers are closely related to the occurrence and development of SINP,which may be involved in the recurrence,and there is a synergistic effect.

Objective To explore the independent risk factors influencing the poor prognosis after transnasal-intestinal obstruction catheterization under endoscopic ultrasound,construct a nomogram for predicting poor postoperative prognosis,and conduct external validation of the nomogram.Methods Clinical data of 451 patients with intestinal obstruction who underwent endoscopic ultrasound transnasal-intestinal obstruction catheterization from February 2019 to February 2022 were collected to establish a nomogram.Then,194 sets of data with the same conditions from February 2022 to February 2024 were collected as the external validation group to validate the model externally.The recovery at 30 d after operation was observed and divided into good prognosis group and poor prognosis group.Multivariate Logistic regression model was used to analyze the independent risk factors influencing the poor prognosis after transnasal-intestinal obstruction catheterization under endoscopic ultrasound.Using R 3.6.3 software and the RMS package,a nomogram model for predicting the risk of poor prognosis after intestinal obstruction catheterization under endoscopic ultrasound was constructed..The discrimination and consistency of the model were evaluated using receiver operator characteristic curve(ROC curve)and calibration curve.Results The patients in the poor prognosis group were older than those in the good prognosis group,the levels of C-reactive protein(CRP),procalcitonin(PCT)and neutrophil to lymphocyte ratio(NLR)were higher than those in the good prognosis group,the length of hospital stay was longer than that in the good prognosis group,and the proportion of diabetes,abdominal pain and hormone using were higher than those in the good prognosis group,body mass index(BMI),preoperative albumin level and preoperative nutritional support ratio were lower than those of the good prognosis group,with statistical significance(P<0.05).Multivariate Logistic regression analysis(introduction level was 0.05,exclusion level was 0.107)showed that:age≥68 years(OR＾=2.631,95%CI:1.927～3.593),BMI<22.31 kg/m2(OR＾=2.142,95%CI:1.436～3.195),preoperative albumin<32.47g/L(OR＾=1.962,95%CI:1.506～2.556)and preoperative nutritional non-support(OR＾=2.814,95%CI:1.401～5.654)were independent risk factors affecting the poor prognosis after endoscopic transnasal-intestinal obstruction catheterization(P<0.05).The column nomogram showed that old age,low BMI,low preoperative albumin,and no preoperative nutritional support all increased their corresponding weights.Internal and external validation results indicated good consistency and discrimination of the model.Conclusion age≥68 years,BMI<22.31 kg/m2,preoperative albumin<32.47 g/L,and no preoperative nutritional support are all independent risk factors affecting the ineffective of intestinal obstruction catheterization under endoscopic ultrasound.The nomogram model established in this study based on these four factors has high reliability and practicality.

Recently, intelligent care is gradually changing the traditional care way, and artificial intelligence (AI) application is gradually broadening in the field of assisted reproduction. This review systematically analyzes the AI application in multiple aspects of reproductive health care. It also indicates the challenge during the process, including data privacy, technical reliability, ethics and legal provisions, and humanistic care. Both the opportunities of AI in assisted reproduction are highlighted and the ensuing problems are analyzed in depth. The purpose is to provide ideas for future studies to ensure that AI technology can be safely, efficiently and responsibly integrated with the field of reproductive health care.

Objective:To investigate the efficacy and safety of trastuzumab deruxtecan (T-DXd) in the treatment of metastatic breast cancer.Methods:A retrospective case series study was conducted. The clinical data of 38 breast cancer patients with metastasis in other parts who received T-DXd treatment in Xi'an International Medical Center Hospital from August 2021 to August 2024 were analyzed. The clinical efficacy and incidence of adverse reactions in patients were recorded, comparison of clinical efficacy in stratified patients based on clinical characteristics was performed, and the progression-free survival (PFS) was analyzed using Kaplan-Meier method.Results:All 38 patients were female, with a median age [ M ( Q1, Q3)] of 55 (42, 60) years; according to the guidelines of the American Society of Clinical Oncology/College of American Pathologists, 13 cases (34.2%) were positive for human epidermal growth factor receptor 2 (HER2) and 25 cases (65.8%) were low in HER2 expression; the Eastern Cooperative Oncology Group (ECOG) physical status scores of 23 cases (60.5%) were 0-2 points and 15 cases (39.5%) were 3-4 points; the median number of T-DXd treatment lines was 4 (2,16) lines. According to the Response Evaluation Criteria in Solid Tumors 1.1, the objective response rate (ORR) of T-DXd treatment was 34.2% (13/38), and the disease control rate (DCR) was 78.9% (30/38); the ORR of patients aged ≤ 50 years old was higher than that of patients aged >50 years old [56.3% (9/16) vs. 18.2% (4/22)], patients with HER2 positive was lower than that of patients with low HER2 expression [100.0 (13/13) vs. 68.0% (17/25)], patients with previous tyrosine kinase inhibitor (TKI) treatment was higher than that of patients without TKI treatment [100.0% (12/12) vs. 69.2% (18/26)], and the DCR of patients with T-DXd treatment for ≥ 4 cycles was higher than that of patients with T-DXd treatment for 1-3 cycles [100.0% (25/25) vs. 38.5% (5/13)], and the differences were statistically significant (all P < 0.05). Among the 38 patients, 19 (50.0%) stopped medication due to disease progression, 11 (28.9%) stopped medication due to economic reasons, 1 (0.8%) stopped medication due to grade 3 nausea and vomiting, and 1 (0.8%) stopped medication due to grade 2 interstitial lung disease (ILD), while the remaining 6 (15.8%) were undergoing T-DXd treatment. The median follow-up time was 9.5 (3.9, 17.8) months, and 16 cases (42.1%) progressed and died; the median PFS time was 5.9 months (95% CI: 3.1-8.7 months). Adverse reactions were mostly grade 1-2; common hematological adverse reactions included leukopenia [18 cases (47.3%)], neutropenia [16 cases (42.1%)], thrombocytopenia [11 cases (28.9%)], and anemia [15 cases (39.5%)]. Non-hematological adverse reactions included nausea [28 cases (73.7%)], vomiting [15 cases (39.5%)], decreased appetite [20 cases (52.6%)], fatigue [22 cases (57.9%)], alopecia [22 cases (57.5%)], elevated aspartate aminotransferase [20 cases (52.6%)], and elevated alanine aminotransferase [15 cases (39.5%)] were more common. Two cases developed interstitial lung disease (ILD), classified as grade 1 and grade 2, respectively. After discontinuation of medication and treatment with methylprednisolone, they returned to normal. Conclusions:T-DXd ≥ 2 line therapy has good efficacy and safety in the treatment of HER2 positive or low expression metastatic breast cancer. Bone marrow suppression and gastrointestinal adverse reactions are the most common, and the occurrence of ILD should be noted in the treatment.

Objective·To investigate the changes in transcriptome and chromatin accessibility during the differentiation of human embryonic stem cells(hESCs)into neural progenitor cells(NPCs)using in vitro differentiation models and high-throughput multi-omics sequencing technologies.Methods·hESCs were first induced to differentiate into NPCs in vitro using the embryoid body formation method,and cells at both stages were collected.The cell phenotypes were identified by reverse transcription-quantitative real-time PCR(RT-qPCR)and immunofluorescence(IF)staining.Transcriptome sequencing(RNA-seq)was conducted to detect and analyze the differentially expressed genes(DEGs)between hESCs and NPCs.The assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)was employed to assess chromatin accessibility changes between hESCs and NPCs.Motif enrichment analysis was performed on differentially accessible chromatin regions to discover potential regulatory transcription factors.Finally,an integrated analysis of RNA-seq and ATAC-seq data and the protein-protein interaction(PPI)network were performed to identify key genes and regulatory pathways involved in the early stages of neural differentiation in vitro.Results·Both RT-qPCR and IF results indicated that the expression levels of pluripotency markers(NANOG and POU5F1)were high at the hESC stage but significantly decreased at the NPC stage,while early neural differentiation markers(PAX6,SOX1,and NES)were minimally expressed at the hESC stage but markedly upregulated at the NPC stage.RNA-seq analysis revealed that compared to the hESC stage,there were 5 597 genes upregulated and 3 654 genes downregulated at the NPC stage.Gene function enrichment analysis showed that the upregulated genes at the NPC stage were enriched in the functions related to neural development.ATAC-seq analysis demonstrated a total of 27 491 genomic regions had significant changes in chromatin accessibility during the differentiation from hESC to NPC,with 12 381 regions showing increased accessibility and 15 110 regions showing decreased accessibility.Motif enrichment analysis revealed that transcription factor genes such as DLX1 and LHX2 might play an important role in the differentiation process from hESCs into NPCs.Integrated analysis of RNA-seq and ATAC-seq data revealed that overlapping genes with high expression at the NPC stage were mainly enriched in axon guidance,forebrain development,and neuron migration.After neural differentiation,the expression levels of CTNND2 and LHX2 genes increased,and the chromatin accessibility of related genomic regions also increased.PPI network analysis indentified candidate downstream genes including PRKACA,CDH2,and ERBB4.Conclusion·The in vitro differentiation model of hESCs combined with high-throughput multi-omics sequencing technologies can be used to depict the changes in transcriptome and chromatin accessibility during the differentiation of hESCs into NPCs.In this process,the expression levels of genes related to axon guidance,forebrain development,and neuronal migration pathways increase and related chromatin accessibility is enhanced.