OBJECTIVE To investigate the effects and mechanism of modified Xiaoqinglong decoction combined with bone marrow mesenchymal stem cells （BMSCs） on nasal-pulmonary-intestinal mucosal immunity in rats with cold asthma. METHODS SD rats were randomly divided into blank group， model group， BMSCs group， BMSCs+modified Xiaoqinglong decoction （6.39 g/kg） group， and BMSCs+dexamethasone （0.125 mg/kg） group， with 10 rats in each group. The cold asthma rat model was established by sensitization and atomization challenge with ovalbumin combined with aluminum hydroxide， together with cold air stimulation from air conditioners. One hour before the initial atomization challenge， rats in all groups except the blank group and model group were injected with BMSCs suspension via the tail vein. Starting from the 15th day of the experiment， rats in each group were intragastrically administered corresponding liquid medicine or normal saline once a day for 7 consecutive days. After the last administration， the asthmatic behavioral changes and pathological morphological changes of lung tissues in rats were evaluated. The levels of interleukin-6 （IL-6） and IL-10 in nasopharyngeal lavage fluid， bronchoalveolar lavage fluid （BALF） and intestinal mucus were detected. The expression levels of proteins related to the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in nasal， lung and intestinal tissues were determined. RESULTS Compared with the blank group， the asthmatic behavioral score， lung tissue injury score， IL-6 levels in nasopharyngeal lavage fluid， BALF and intestinal mucus， PI3K protein expression and Akt phosphorylation levels in nasal， lung and intestinal tissues of rats in the model group were significantly increased （ P ＜0.05）； the IL-10 levels in nasopharyngeal lavage fluid， BALF and intestinal mucus were significantly decreased （ P ＜0.05）. Alveolar atrophy， collapse and even fusion， abnormal hyperplasia and hypertrophy of bronchial smooth muscle， and massive inflammatory cell infiltration were observed. Compared with the model group， most of the above quantitative indicators in the BMSCs group， BMSCs+modified Xiaoqinglong decoction group and BMSCs+dexamethasone group were significantly reversed （ P ＜0.05）， and pathological injuries of lung tissues were markedly alleviated. Compared with the BMSCs group， most of the above quantitative indicators were further improved in the BMSCs+modified Xiaoqinglong decoction group （ P ＜0.05）. CONCLUSIONS Modified Xiaoqinglong decoction combined with BMSCs can effectively improve nasal-pulmonary-intestinal mucosal immunity and relieve asthmatic symptoms in cold asthma rats， and its mechanism may be related to inhibiting the activation of the PI3K/Akt signaling pathway.

OBJECTIVE To investigate the effects and mechanism of modified Xiaoqinglong decoction combined with bone marrow mesenchymal stem cells （BMSCs） on nasal-pulmonary-intestinal mucosal immunity in rats with cold asthma. METHODS SD rats were randomly divided into blank group， model group， BMSCs group， BMSCs+modified Xiaoqinglong decoction （6.39 g/kg） group， and BMSCs+dexamethasone （0.125 mg/kg） group， with 10 rats in each group. The cold asthma rat model was established by sensitization and atomization challenge with ovalbumin combined with aluminum hydroxide， together with cold air stimulation from air conditioners. One hour before the initial atomization challenge， rats in all groups except the blank group and model group were injected with BMSCs suspension via the tail vein. Starting from the 15th day of the experiment， rats in each group were intragastrically administered corresponding liquid medicine or normal saline once a day for 7 consecutive days. After the last administration， the asthmatic behavioral changes and pathological morphological changes of lung tissues in rats were evaluated. The levels of interleukin-6 （IL-6） and IL-10 in nasopharyngeal lavage fluid， bronchoalveolar lavage fluid （BALF） and intestinal mucus were detected. The expression levels of proteins related to the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in nasal， lung and intestinal tissues were determined. RESULTS Compared with the blank group， the asthmatic behavioral score， lung tissue injury score， IL-6 levels in nasopharyngeal lavage fluid， BALF and intestinal mucus， PI3K protein expression and Akt phosphorylation levels in nasal， lung and intestinal tissues of rats in the model group were significantly increased （ P ＜0.05）； the IL-10 levels in nasopharyngeal lavage fluid， BALF and intestinal mucus were significantly decreased （ P ＜0.05）. Alveolar atrophy， collapse and even fusion， abnormal hyperplasia and hypertrophy of bronchial smooth muscle， and massive inflammatory cell infiltration were observed. Compared with the model group， most of the above quantitative indicators in the BMSCs group， BMSCs+modified Xiaoqinglong decoction group and BMSCs+dexamethasone group were significantly reversed （ P ＜0.05）， and pathological injuries of lung tissues were markedly alleviated. Compared with the BMSCs group， most of the above quantitative indicators were further improved in the BMSCs+modified Xiaoqinglong decoction group （ P ＜0.05）. CONCLUSIONS Modified Xiaoqinglong decoction combined with BMSCs can effectively improve nasal-pulmonary-intestinal mucosal immunity and relieve asthmatic symptoms in cold asthma rats， and its mechanism may be related to inhibiting the activation of the PI3K/Akt signaling pathway.

Objective To investigate necroptosis-related diagnostic biomarkers of bronchopulmo-nary dysplasia(BPD)and their relationships with the immune microenvironment through the analysis of necroptosis-related genes(NRGs)in BPD.Methods The dataset GSE32472 was downloaded from the Gene Expression Omnibus(GEO)database,and NRGs were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway and Gene Cards databases.Differentially expressed necroptosis-related genes(DE-NRGs)were screened,and their biological functions and pathways were explored through functional enrichment analysis.Machine learning algorithms,inclu-ding least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE),were applied to screen feature genes.The Cell-type Ⅰdentification By Estimating Relative Subsets of RNA Transcripts(CIBERSORT)algorithm and the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues using Expression Data(ESTIMATE)algo-rithm were used to explore the immune infiltration characteristics of BPD.Spearman correlation anal-ysis between feature genes and immune cells was performed using the"corrplot"package in R lan-guage.Results A total of 19 DE-NRGs were identified.The main biological functions and path-ways of DE-NRGs included the regulation of necroptosis and inflammatory responses.Three feature genes,namely flotillin-2(FLOT2),CASP8 and FADD-like apoptosis regulators(CFLAR),and charged multivesicular body protein 7(CHMP7),were further screened to construct a nomogram.In the validation sets GSE8586 and GSE188944,the area under the curve(AUC)values were all greater than 0.7.CIBERSORT analysis revealed that BPD group presented a higher proportion of naive B cells,neutrophils,eosinophils and resting mast cells compared to control group(P＜0.05).Meanwhile,the proportion of CD8+T cells,CD4+naive T cells,CD4+resting memory T cells,regulatory T cells,resting natural killer(NK)cells,M0 macrophages,M2 macrophages and activated dendritic cells was lower than that in the control group(P＜0.05).ESTIMATE analysis showed that the stromal score in the BPD group was higher than that in the control group,while the immune score was lower,with statistically significant differences(P＜0.05).Correlation analysis between the three feature genes and ESTIMATE scores indicated that FLOT2 and CFLAR were posi-tively correlated with the stromal score and negatively correlated with the immune score,whereas CHMP7 was positively correlated with the immune score and negatively correlated with the stromal score.Conclusion The three necroptosis-related feature genes can serve as diagnostic biomarkers for BPD-related necroptosis,with high diagnostic efficacy.They may play an important roles through immune mechanisms,providing new insights and theoretical references for the early diagnosis and immune intervention of BPD.

Objective To investigate the clinical value of postoperative platelet-to-neutrophil ratio(PNR)in predicting the prognosis of patients with acute anterior circulation cardiogenic large-vessel occlusion stroke after receiving endovascular treatment.Methods A total of 95 patients with acute anterior circulation cardiogenic large-vessel occlusion stroke,who were admitted to the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University of China from January 2019 to January 2022,were enrolled in this study.Venous blood sampling was performed at admission and within 24 hours after thrombectomy,and the PNR,platelet-white blood cell ratio(PWR),platelet-lymphocyte ratio(PLR),and neutrophil-lymphocyte ratio(NLR)were calculated.According to the modified Rankin Scale score at 90 days(mRS-90),the patients were divided into good prognosis group(mRS-90 ≤2 points,n=45)and poor prognosis group(mRS-90 3-6 points,n=50).The clinical data were compared between the two groups.Multivariate logistic regression analysis was used to analyze the predictors of 90-d good prognosis.The area under the receiver operating characteristic curve(AUC)was used to compare the efficacy of PWR,PNR,and NLR in predicting good prognosis.Results Compared with poor prognosis group,in good prognosis group the patients were younger,the NIHSS score at admission was smaller,the incidence of postoperative contrast extravasation was lower,the postoperative 24-hour PWR and PNR values were higher,and the postoperative 24-hour NLR value was lower,the differences in the above indexes between the two groups were statistically significant(all P＜0.05).Multivariate analysis showed that bridging therapy(OR=4.746,P=0.021,95％CI:1.262-17.856),postoperative contrast medium extravasation(OR=0.254,P=0.022,95％CI:0.079-0.824)and postoperative 24-h PNR(OR=1.087,P=0.006,95％CI:1.025-1.153)were the independent predictors for 90-d good prognosis in patients with acute anterior circulation cardiogenic large-vessel occlusion stroke after receiving endovascular treatment.AUCs of postoperative 24-h PWR,PNR and NLR for predicting a good prognosis after thrombectomy were 0.734,0.736 and 0.704 respectively.PNR had the highest predictive efficacy,with a cutoff value of 25.08,a specificity of 84.00％,and a sensitivity of 67.78％.Conclusion In patients with acute anterior circulation cardiogenic large-vessel occlusion stroke after receiving endovascular treatment,a better clinical prognosis can be expected when the patient has a higher postoperative 24-h PNR value.

Background and purpose:Amplification of the urokinase plasminogen activator receptor(uPAR)gene is closely associated with poor prognosis in pancreatic cancer patients.uPAR regulates epithelial-mesenchymal transition(EMT)and chemoresistance in pancreatic cancer cells through the mitogen-activated protein kinases(MAPK)signaling pathway,though the specific mechanisms remain unclear.This study aimed to investigate the mechanism by which uPAR promotes proliferation,invasion,and chemoresistance of pancreatic cancer cells by inhibiting autophagy.Methods:Pancreatic cancer tissue samples were collected from patients who underwent surgical resection and biopsy at the Changsha Central Hospital,Affiliated to University of South China(Changsha Central Hospital),between December 2021 and Jun 2022.The study was approved by the Ethics Committee of Changsha Central Hospital(Approval No.:2021-S0182,2022-S0084).Patient-derived organoids(PDOs)from pancreatic cancer samples were cultured in vitro.Six pancreatic cancer cell lines(AsPC-1,PANC-1,CAPAN-1,CAPAN-2,MIA PaCa-2 and PaTu8988T)were used in this study.uPAR-deficient models were constructed using clustered regularly interspaced short palindromic repeats(CRISPR)Cas9 technology.Cell proliferation and invasion abilities were measured using confocal microscopy,Western blot,enzyme-linked immunosorbent assay(ELISA),and MTS assays.Changes in MAPK and autophagy signaling pathways and gemcitabine-induced cell death were analyzed.The synergistic effects of combined treatments were evaluated using gene silencing(siRNA)or autophagy inhibitors.Results:In AsPC-1 cells,uPAR knockout significantly reduced the proliferation and migration abilities of clone cells compared to wild-type cells,as shown by MTS assays and wound healing experiments,and decreased sensitivity to gemcitabine(P＜0.05).Re-expression of uPAR restored the proliferation and invasion abilities of clone cells and partially restored sensitivity to gemcitabine(P＜0.05).Confocal microscopy revealed reduced F-actin and a rounded morphology in clone cells.Western blot analysis showed increased expressions of E-cadherin and Slug,decreased expression of vimentin,and increased expressions of phospho-focal adhesion kinase(p-FAK),p-p38MAPK,and the microtubule-associated protein light chain 3B(LC3B)in clone cells compared to wild-type cells.siRNA results indicated that silencing FAK or p38MAPK or combining autophagy inhibition could resensitize clone cells to gemcitabine(P＜0.05),with p38MAPK silencing reducing LC3B expression.Organoid studies showed varying responses to gemcitabine among 8 organoids,all expressing uPAR.uPAR expression levels were negatively correlated with gemcitabine IC50(r2=0.66,P＜0.05).Three organoids responded well to the combination of gemcitabine and autophagy inhibitors(P＜0.05).Conclusion:uPAR promotes pancreatic cancer cell activity through the p38MAPK signaling pathway,preventing FAK-mediated resistance and cell dormancy.The study suggests that pancreatic cancer patients with high uPAR expression respond better to gemcitabine,while tumors with low uPAR and high p38MAPK expressions may benefit from combined treatment with autophagy inhibitors and cytotoxic chemotherapy.

Objective To investigate the application value of point-of-care lung ultrasound (POC-LUS) scoring in selecting respiratory support treatment modalities for neonatal infectious pneumonia (NIP). Methods A total of 89 NIP patients were selected as the study subjects and divided into control group (no assisted ventilation) with 46 cases, noninvasive group (noninvasive assisted ventilation) with 28 cases, and invasive group (invasive mechanical ventilation) with 15 cases based on the degree of dyspnea and blood gas analysis results. The POC-LUS scores of the three groups were compared, and the correlations of POC-LUS scores with arterial oxygen partial pressure [p_a(O₂)] and arterial carbon dioxide partial pressure [p_a(CO₂)] were analyzed. Receiver operating characteristic (ROC) curves were plotted to assess the predictive efficacy of POC-LUS scores for the need for noninvasive assisted ventilation or invasive mechanical ventilation in NIP patients. Results The POC-LUS scores of the noninvasive group and the invasive group were (31.7±7.3) and (42.1±8.0), respectively, which were higher than (21.5±7.3) of the control group. Additionally, the score of the invasive group was higher than that of the noninvasive group (P < 0.05). Correlation analysis revealed a significant negative correlation between POC-LUS scores and p_a(O₂) (r=-0.802, P < 0.05), and a significant positive correlation with p_a(CO₂) (r=0.807, P < 0.05). ROC curve analysis showed that the area under the curve (AUC) of POC-LUS scores for predicting the need for noninvasive assisted ventilation and invasive mechanical ventilation were 0.918 (95%CI, 0.862 to 0.973) and 0.938 (95%CI, 0.889 to 0.987), respectively. The sensitivity was 0.767 and 0.933, and the specificity was 0.935 and 0.824, with optimal cutoff values of 29.5 and 31.5, respectively. Conclusion POC-LUS scoring can quantitatively assess the severity of lung lesions in NIP patients and serves as a guiding tool for clinicians in selecting assisted ventilation treatment modalities.

Objective To investigate the therapeutic effect of self-made Bitong Ointment combined with umbilical dressing of traditional Chinese medicine in the treatment of children with pediatric allergic rhinitis differentiated as type of latent heat in the lung meridian. Methods Eighty children with allergic rhinitis differentiated as type of latent heat in the lung meridian were randomly divided into observation group and control group, with 40 cases in each group. The control group was treated with loratadine, while the observation group was additionally treated with self-made Bitong Ointment and umbilical dressing of traditional Chinese medicine. After 4 weeks of treatment, the clinical effect, TCM syndrome score, airway stress response, inflammatory factors, and therapeutic safety were evaluated. Results The total effective rate in the observation group was 95.00% (38/40), which was higher than 77.50% (31/40) in the control group. After treatment, the scores of main TCM syndromes such as frequent sneezing, clear and thin nasal discharge, decreased sense of smell, shortness of breath, and reluctance to speak in the observation group were lower than those in the control group. After treatment, the levels of indicators of airway stress response such as exhaled nitric oxide (FeNO), lipid peroxide (LHP) and inducible nitric oxide synthase (iNOS) in the observation group were lower than those in the control group. After treatment, the levels of inflammatory factors such as monocyte chemoattractant protein-4 (MCP-4), cysteinyl leukotriene receptor 1 (CysLTR1), and interleukin-9 (IL-9) in the observation group were significantly lower than those in the control group (P < 0.05). The incidence rate of adverse reactions during treatment was 15.00% (6/40) in the observation groupand 10.00% (4/40) in the control group, with no significant difference between the two groups (P>0.05). Conclusion The combination of self-made Bitong Ointment combined with umbilical dressing of traditional Chinese medicine is effective in the treatment of children with pediatric allergic rhinitis differentiated as type of latent heat in the lung meridian, which can improve the TCM syndromes, inhibit the airway stress response, reduce the expression levels of inflammatory factors, and has good therapeutic safety.

Objective To evaluate the effect of structured therapy and education based on personal strength on ischemic stroke. Methods From March,2021 to September,2023,a total of 114 patients with ischemic stroke from the First People's Hos-pital of Kunshan were randomly divided into control group(n=57)and experimental group(n=57).The control group received routine medicine,rehabilitation training and standard health education,while the experimental group received routine medicine,rehabilitation training and structured therapy and education based on personal strength,for six weeks.They were compared with the scores of modified Rankin Scale(mRS),motor-evoked po-tential(MEP)latency and amplitude,modified Barthel Index and Self-Recovery Efficacy Scale score and recur-rence within three months after the start of the study.The scores of Morisky Medication Adherence Scale(MMAS)and Five Facet Mindfulness Questionaire(FFMQ)were also compared. Results After treatment,the score of mRS(t=5.002),MEP latency period(t=9.739)and amplitude(t=4.394),modi-fied Barthel Index(t=11.261),the score of Self-Recovery Efficacy Scale(Z=-2.638),and the scores of MMAS(t=19.521)and FFMQ(t=15.381)were better in the experimental group than in the control group(P<0.05). Conclusion Structured therapy and education based on personal strength could faciliate to improve the recovery and self-management of ischemic stroke patients.

Atrial functional mitral regurgitation (AFMR) is mitral regurgitation in patients with atrial fibrillation (AF), whose left atrium (LA) is enlarged, the left ventricle is not enlarged or only slightly enlarged, the left ventricular ejection fraction is preserved, and the mitral valve itself has no apparent lesion. At present, the etiology, pathophysiology and mechanism of this disease have not been completely clear yet. Existing studies have found that the causes of AFMR mainly include AF, enlargement of LA and mitral annulus, destruction of mitral annular shape, inability of mitral valve remodeling to compensate for mitral annular expansion, and hamstringing of the posterior mitral leaflet by atriogenic tethering. AFMR is demonstrated to be associated with an increased risk of mortality and readmission due to heart failure. Therefore, it serves as a primary therapeutic target for patients with heart failure and AF. However, the optimal treatment of AFMR still remains controversial. Therefore, this article will mainly expound the current definition, etiology, pathophysiological mechanism, treatment, and prognosis of AFMR.

Objective To explore the feasibility of integrated imaging of portal vein and hepatic vein with"three low-contrast agents"combined with energy spectrum CT technology.Methods A total of 100 patients with enhanced abdominal CT scans were selected.The patients were randomly divided into two groups.The patients of experimental group(n=50)were injected with the isotonic con-trast agent iodixanol(320 mg I/mL)at a flow rate of 3 mL/s and a total volume of 1.2 mL/kg,and underwent energy spectrum CT scan in the portal venous phase.The patients of control group(n=50)were injected with the sub-hypertonic contrast agent iohexol(350 mg I/mL)at a flow rate of 5 mL/s and a total volume of 1.5 mL/kg,and underwent conventional multi-phase spiral CT enhancement scan.The image quality and radiation dose of portal vein and hepatic vein were compared between the two groups.Results The CT value of main portal vein in the experimental group was higher than that in the control group,and the difference was statistically sig-nificant(P＜0.05).There was no statistical significance in main portal vein contrast-to-noise ratio(CNR),main portal vein signal-to-noise ratio(SNR),hepatic vein CT value,and hepatic vein CNR between the two groups(P＞0.05).The SNR and image standard deviation(SD)of the hepatic vein in the control group were better than those in the experimental group(P＜0.05).There was no statistical significance in the subjective scores of portal vein and hepatic vein between the two groups(P＞0.05).The volume CT dose index(CTDIvol),dose length product(DLP),and effective dose(ED)of the portal venous phase spectrum CT scan in the experimental group were lower than those of the conventional single-phase spiral CT scan in the control group(P＜0.05).Conclusion"Three low-contrast agents"combined with energy spectrum CT technology can realize integrated imaging of portal vein and hepatic vein in late portal vein,and can reduce radiation dose.