Objective:To investigate the characteristics of cardiopulmonary exercise testing and risk factors for decreased aerobic capacity in children with non-acute asthma exacerbations, to assess their cardiopulmonary health and to provide a basis for improvement.Methods:A case-control study.Sixty-one children with non-acute asthma exacerbations treated at the Outpatient Department of Children′s Hospital of Soochow University from October 2022 to December 2023 and 22 control children during the same period were included.Binary Logistic regression was employed to assess risk factors for decreased aerobic capacity in children with asthma.Results:Among the included 61 children with non-acute asthma exacerbations, there were 33 cases in the chronic persistent phase (chronic persistent phase group) and 28 in the clinical remission phase(clinical remission group).There were 22 children in the control group.During the peak exercise phase of the cardiopulmonary exercise testing, the mean kilogram body weight oxygen uptake (VO 2/kg), the percentage of predicted kilogram body weight oxygen uptake, and metabolic equivalents (Met) in the chronic persistent phase group were lower than those in the control and clinical remission phase groups.The mean VO 2/kg recovery from the cardiopulmonary exercise testing in the first minute in the chronic persistent phase group was lower than that in the control and clinical remission phase groups.The median Met and ventilation per minute recovery in the chronic persistent phase group were lower than those in the control group.The median heart rate recovery in asthma children was lower than that in control children.The percentage of cardiopulmonary exercise testing abnormalities was higher in asthma children with symptoms after excise than that in asthma children without symptoms after excise.The percentage of decreased ventilation efficiency in asthma children with symptoms after excise was higher than that in asthma children without symptoms after excise.Multivariate regression analysis showed that a higher body mass index (BMI) ( OR=1.577, 95% CI: 1.113-2.235, P=0.010) and a higher peak respiratory reserve ( OR=1.103, 95% CI: 1.018-1.195, P=0.017) were risk factors of decreased aerobic capacity.The risk of decreased aerobic capacity in the chronic persistent phase was 7.949 times higher than that in the clinical remission phase ( OR=7.949, 95% CI: 1.290-48.996, P=0.025). Conclusions:The aerobic capacity is decreased and ventilatory recovery is slower in children with chronic persistent asthma than those in healthy children.The heart rate recovery in asthma children is slower than that in healthy children.A high BMI, a high peak respiratory reserve, and chronic persistence of asthma are independent risk factors for decreased aerobic capacity in children with non-acute asthma exacerbations.asthma.

Objective:To explore the correlation between serum uric acid/high-density lipoprotein cholesterol ratio (UHR) and the risk of hypertension in elderly physical examination populations.Methods:This study was a cross-sectional study. A total of 1 028 patients aged≥60 years who underwent physical examinations at the Health Management Center of Fuwai Central China Cardiovascular Hospital from September 2023 to February 2024 were included in this study. The general demographic data, past medical history, physical examination and laboratory examination indicators of the physical examiners were collected, and according to whether they had hypertension or not, they were divided into hypertension group (390 cases) and non-hypertension group (638 cases), and all UHR values were arranged from small to large, and the UHR was divided into three groups by tertiles of UHR, and the general data and blood biochemical indexes between the groups were compared. Spearman rank correlation was used to analyze the correlation between UHR level and body mass index, total cholesterol, triglyceride and other indexes in the elderly population. Logistic regression was used to explore the relationship between UHR level and hypertension in the elderly population, and the stratification analysis of the physical examination population was carried out according to diabetes, coronary heart disease and dyslipidemia, and the interaction test between groups was carried out.Results:Among the 1 028 geriatric physical examination cases, 580 (56.4%) were males and 448 (43.6%) were females, aged (66.7±5.8) years. UHR levels were higher in the hypertensive group compared to the non-hypertensive group [248.88 (191.19, 322.25) vs 213.52 (165.94, 275.29); Z=-5.445, P<0.05]. With the increase of UHR level, the detection rate of hypertension in the elderly population increased (accounted for 27.8%, 38.2% and 47.8%, respectively; χ2=29.211, P<0.05). Spearman rank correlation analysis showed that UHR was positively correlated with body mass index, triglycerides, serum uric acid, serum creatinine and fasting blood glucose ( r=0.318, 0.334, 0.774, 0.474, 0.080; all P<0.05), and negatively correlated with total cholesterol, glomerular filtration rate and low-density lipoprotein cholesterol ( r=-0.239, -0.303, -0.154; all P<0.05). When the confounding factors were not adjusted (model 1), the risk of hypertension in high UHR group was 2.382 times higher than that in low UHR group and 1.607 times higher than that in medium UHR group; after adjusting for all confounding factors such as age, gender, body mass index, systolic blood pressure, diastolic blood pressure, junior high school education or below, smoking, alcohol consumption, glomerular filtration rate, etc., the risk of hypertension in the high-level UHR group was 1.732 times higher than that in the low-level UHR group (95% CI: 1.139-2.635) ( P<0.05). The elderly physical examination population was further stratified according to whether there was diabetes, dyslipidemia and coronary heart disease, and it was found that there was no interaction between UHR and diabetes, dyslipidemia and coronary heart disease on the prevalence of hypertension (all P>0.05). Conclusions:Hypertension detection rate increases with higher UHR levels. UHR is closely related to the incidence of hypertension in the elderly population.

Objective:To screen broadly neutralizing antibodies in human immunodeficiency virus-1（HIV-1）chronically infected individuals and characterize their molecular features and to provide new strategies for rational vaccine development and antibody-based therapeutics.Methods:A total of 34 treatment-na?ve individuals with chronic HIV-1 infection were enrolled. Plasma antibody binding levels were measured against two HIV-1 envelope proteins. Single antigen-specific memory B cells were sorted from high-binding samples，and antibody variable region genes were amplified by PCR for paired expression. The monoclonal antibodies were evaluated for neutralizing activity using pseudovirus assays，and their structural features were analyzed by integrating AlphaFold 3 prediction with Discovery Studio molecular docking.Results:Plasma samples showed strong binding to DU422-GP140 and BG505-GP140. Eight monoclonal antibodies were isolated from two donors. Among them，antibodies 0919-A4，0919-A9 and 0808-A2 could cross-react with GP140 from HIV-1 subtypes AE，BC and B. The monoclonal antibody 0919-A9 demonstrated potent neutralizing activity against SF162（Tier 1）and CH181（Tier 2）pseudoviruses，with somatic hypermutation rates of 13.27%（heavy chain）and 15.58%（light chain）. Structural modeling revealed its specific targeting of the V1V2 region on GP120.Conclusion:The isolated antibody 0919-A9 effectively neutralizes Tier 2 pseudoviruses. Its high somatic mutation frequency and V1V2-targeting property underlie its neutralizing activity，providing both a promising candidate and mechanistic insights for HIV vaccine development and antibody-based therapeutic strategies.

Objective To investigate the effects of hypoxia on the transcriptional phenotype and ultrastructure of tumor-associated macrophages(TAMs)in glioma.Methods CD14+monocytes were isolated from healthy human peripheral blood samples collected from the Blood Bank of the First Affiliated Hospital of Army Medical University,and the cells were induced to differentiate into TAMs through co-culture with glioma cell-conditioned medium.Hypoxic TAM models were established using varying concentrations of cobalt chloride hexahydrate(CoCl2,50～400 μmol/L)or hypoxic conditions(1%,5%,10%O2)for 48 h,while normoxic TAM models(21%O2)served as controls.RT-qPCR and transcriptome sequencing were employed to analyze transcriptional changes in TAMs under normoxic and hypoxic conditions.Gene set enrichment analysis(GSEA)was applied to compare the differences in angiogenesis,glycolysis and other hypoxia-responsive pathways between the 2 conditions.Transmission electron microscopy(TEM)or immunofluorescence staining was conducted to assess the ultrastructural alterations in cytoskeleton,endoplasmic reticulum(ER),and mitochondria in normoxic and hypoxic TAMs(1%O2).Results Hypoxic TAMs exhibited up-regulated transcription of hypoxia-responsive markers(oxygen transport,glycolysis,pro-angiogenesis),with the effects correlating with hypoxia severity(P<0.05).GSEA revealed significant up-regulation of hypoxia,angiogenesis regulation,glycolysis and gluconeogenesis,and starvation stress pathways,alongside down-regulation of innate immunity,macrophage activation,cytoskeleton,and protein maturation pathways in hypoxic TAMs(P<0.05).TEM and immunofluorescence staining demonstrated obvious ultrastructure changes,including disrupted cytoskeletal organization,shortened rough ER with reduced ribosomes,mitochondrial swelling with cristae damage,and diminished ER-mitochondria contacts in hypoxic TAMs.Conclusion CoCl2 and hypoxia induce a hypoxic transcriptional phenotype in TAMs,which may potentially associated with ultrastructural remodeling of the cytoskeleton,ER,and mitochondria.

Objective:To investigate the characteristics of cardiopulmonary exercise testing and risk factors for decreased aerobic capacity in children with non-acute asthma exacerbations, to assess their cardiopulmonary health and to provide a basis for improvement.Methods:A case-control study.Sixty-one children with non-acute asthma exacerbations treated at the Outpatient Department of Children′s Hospital of Soochow University from October 2022 to December 2023 and 22 control children during the same period were included.Binary Logistic regression was employed to assess risk factors for decreased aerobic capacity in children with asthma.Results:Among the included 61 children with non-acute asthma exacerbations, there were 33 cases in the chronic persistent phase (chronic persistent phase group) and 28 in the clinical remission phase(clinical remission group).There were 22 children in the control group.During the peak exercise phase of the cardiopulmonary exercise testing, the mean kilogram body weight oxygen uptake (VO 2/kg), the percentage of predicted kilogram body weight oxygen uptake, and metabolic equivalents (Met) in the chronic persistent phase group were lower than those in the control and clinical remission phase groups.The mean VO 2/kg recovery from the cardiopulmonary exercise testing in the first minute in the chronic persistent phase group was lower than that in the control and clinical remission phase groups.The median Met and ventilation per minute recovery in the chronic persistent phase group were lower than those in the control group.The median heart rate recovery in asthma children was lower than that in control children.The percentage of cardiopulmonary exercise testing abnormalities was higher in asthma children with symptoms after excise than that in asthma children without symptoms after excise.The percentage of decreased ventilation efficiency in asthma children with symptoms after excise was higher than that in asthma children without symptoms after excise.Multivariate regression analysis showed that a higher body mass index (BMI) ( OR=1.577, 95% CI: 1.113-2.235, P=0.010) and a higher peak respiratory reserve ( OR=1.103, 95% CI: 1.018-1.195, P=0.017) were risk factors of decreased aerobic capacity.The risk of decreased aerobic capacity in the chronic persistent phase was 7.949 times higher than that in the clinical remission phase ( OR=7.949, 95% CI: 1.290-48.996, P=0.025). Conclusions:The aerobic capacity is decreased and ventilatory recovery is slower in children with chronic persistent asthma than those in healthy children.The heart rate recovery in asthma children is slower than that in healthy children.A high BMI, a high peak respiratory reserve, and chronic persistence of asthma are independent risk factors for decreased aerobic capacity in children with non-acute asthma exacerbations.asthma.

Objective:To explore the correlation between serum uric acid/high-density lipoprotein cholesterol ratio (UHR) and the risk of hypertension in elderly physical examination populations.Methods:This study was a cross-sectional study. A total of 1 028 patients aged≥60 years who underwent physical examinations at the Health Management Center of Fuwai Central China Cardiovascular Hospital from September 2023 to February 2024 were included in this study. The general demographic data, past medical history, physical examination and laboratory examination indicators of the physical examiners were collected, and according to whether they had hypertension or not, they were divided into hypertension group (390 cases) and non-hypertension group (638 cases), and all UHR values were arranged from small to large, and the UHR was divided into three groups by tertiles of UHR, and the general data and blood biochemical indexes between the groups were compared. Spearman rank correlation was used to analyze the correlation between UHR level and body mass index, total cholesterol, triglyceride and other indexes in the elderly population. Logistic regression was used to explore the relationship between UHR level and hypertension in the elderly population, and the stratification analysis of the physical examination population was carried out according to diabetes, coronary heart disease and dyslipidemia, and the interaction test between groups was carried out.Results:Among the 1 028 geriatric physical examination cases, 580 (56.4%) were males and 448 (43.6%) were females, aged (66.7±5.8) years. UHR levels were higher in the hypertensive group compared to the non-hypertensive group [248.88 (191.19, 322.25) vs 213.52 (165.94, 275.29); Z=-5.445, P<0.05]. With the increase of UHR level, the detection rate of hypertension in the elderly population increased (accounted for 27.8%, 38.2% and 47.8%, respectively; χ2=29.211, P<0.05). Spearman rank correlation analysis showed that UHR was positively correlated with body mass index, triglycerides, serum uric acid, serum creatinine and fasting blood glucose ( r=0.318, 0.334, 0.774, 0.474, 0.080; all P<0.05), and negatively correlated with total cholesterol, glomerular filtration rate and low-density lipoprotein cholesterol ( r=-0.239, -0.303, -0.154; all P<0.05). When the confounding factors were not adjusted (model 1), the risk of hypertension in high UHR group was 2.382 times higher than that in low UHR group and 1.607 times higher than that in medium UHR group; after adjusting for all confounding factors such as age, gender, body mass index, systolic blood pressure, diastolic blood pressure, junior high school education or below, smoking, alcohol consumption, glomerular filtration rate, etc., the risk of hypertension in the high-level UHR group was 1.732 times higher than that in the low-level UHR group (95% CI: 1.139-2.635) ( P<0.05). The elderly physical examination population was further stratified according to whether there was diabetes, dyslipidemia and coronary heart disease, and it was found that there was no interaction between UHR and diabetes, dyslipidemia and coronary heart disease on the prevalence of hypertension (all P>0.05). Conclusions:Hypertension detection rate increases with higher UHR levels. UHR is closely related to the incidence of hypertension in the elderly population.

Objective:To screen broadly neutralizing antibodies in human immunodeficiency virus-1（HIV-1）chronically infected individuals and characterize their molecular features and to provide new strategies for rational vaccine development and antibody-based therapeutics.Methods:A total of 34 treatment-na?ve individuals with chronic HIV-1 infection were enrolled. Plasma antibody binding levels were measured against two HIV-1 envelope proteins. Single antigen-specific memory B cells were sorted from high-binding samples，and antibody variable region genes were amplified by PCR for paired expression. The monoclonal antibodies were evaluated for neutralizing activity using pseudovirus assays，and their structural features were analyzed by integrating AlphaFold 3 prediction with Discovery Studio molecular docking.Results:Plasma samples showed strong binding to DU422-GP140 and BG505-GP140. Eight monoclonal antibodies were isolated from two donors. Among them，antibodies 0919-A4，0919-A9 and 0808-A2 could cross-react with GP140 from HIV-1 subtypes AE，BC and B. The monoclonal antibody 0919-A9 demonstrated potent neutralizing activity against SF162（Tier 1）and CH181（Tier 2）pseudoviruses，with somatic hypermutation rates of 13.27%（heavy chain）and 15.58%（light chain）. Structural modeling revealed its specific targeting of the V1V2 region on GP120.Conclusion:The isolated antibody 0919-A9 effectively neutralizes Tier 2 pseudoviruses. Its high somatic mutation frequency and V1V2-targeting property underlie its neutralizing activity，providing both a promising candidate and mechanistic insights for HIV vaccine development and antibody-based therapeutic strategies.

Purpose To explore the expression of autoph-agy-related 7(ATG7)in breast cancer and its effect on the breast cancer development.Methods Immunohistochemistry(IHC)was used to detect ATG7 protein expression in breast cancer tissues and the relationship between ATG7 and clinico-pathological features was analyzed.ShRNA was used to interfere with the expression of ATG7 in breast cancer cell line MCF-7.Puromycin was used to screen for stably transfected cells and Western blot was used to detect transfection efficiency.The effect of ATG7 knockdown cells on proliferation ability was de-tected by CCK8 and clone formation experiments.The effect of ATG7 knockdown cells on tumorigenicity in vivo was detected by subcutaneous tumor formation experiment in nude mice.Results IHC showed that ATG7 expression in breast cancer tissues was mainly localized in cytoplasm,and its expression was significant-ly correlated with tumor size and Ki67 expression(P＜0.05).ATG7-shRNA significantly interfered with ATG7 expression in breast cancer cells MCF-7.CCK8 and clone formation experi-ments showed that ATG7 knockdown promoted the cell prolifera-tion compared with the control group.The experiment of subcu-taneous tumor formation in nude mice showed that the tumor for-mation ability of mice was significantly increased after ATG7 knockdown compared with the control group.Conclusion ATG7 may inhibit the proliferation capacity of breast cancer and could be a potential target for breast cancer therapy.

Objective To explore the effect of glioma stem cells with high expression of protein tyrosin phosphatase receptor type Z1 (PTPRZ1 )on the phenotypic polarization and phagocytosis of tumor-associated macrophages and its regulatory mechanism.Methods GSCs and non-stem tumor cells (NSTCs) were screened out from human glioblastoma (GBM) specimens using flow cytometry,and the PTPRZ1 expression in paired GSCs and NSTCs were detected.Human peripheral blood mononuclear cells (PBMC)-derived CD14+monocytes were exposed to the conditioned medium from glioma cells or recombinant chemokine C-C motif ligand 20 (CCL20)for TAM polarization.Stable PTPRZ1 knockout GSCs (PTPRZ1-KO GSCs) were constructed using CRISPR/Cas9. TAM phagocytosis to GSCs,NSTCs,PTPRZ1-Control GSCs (PTPRZ1-Ctrl GSCs)and PTPRZ1-KO GSCs and the expression of immunosuppressive phenotype (M2) polarization marker CD163 were examined using flow cytometry.Differentially expressed genes (DEGs ) between paired GSCs and NSTCs were determined using a bulk RNA-sequencing dataset (GSE54791 )from Gene Expression Omnibus (GEO).A gene set informing worse outcome of patients with GBM was generated using The Cancer Genome Atlas (TCGA)-GBM cohort.By intersecting the aforementioned gene set with the gene set that encodes for human membrance proteins,the PTPRZ1 gene is obtained.Gene set enrichment analysis (GSEA)was used for pathway enrichment analysis to compare the differentially regulated pathways between GBMs with high or low PTPRZ1 expression.Bulk RNA sequencing,qRT-PCR and Western blotting were used to identify the DEGs between PTPRZ1-KO GSCs and PTPRZ1-Ctrl GSCs.Results GSCs were more capable of escaping from TAM phagocytosis than NSTCs (P<0.05 )and had specifically up-regulated PTPRZ1 expression.PTPRZ1-KO significantly suppressed GSCs escaping from TAM phagocytosis (P<0.01 ). GBMs with high PTPRZ1 expression showed significant inhibition of pathways mediating phagocytosis (P<0.05).The expression of CCL20 as a M2 TAM polarization chemokine was significantly down-regulated in PTPRZ1-KO GSCs (P<0.05 ).Treatment with recombinant CCL20 up-regulated the expression of CD163 as a M2 TAM marker in TAM.Conclusion PTPRZ1+GSCs mediate M2 TAM polarization and inhibit TAM phagocytosis,which may be related to the up-regulation of CCL20 in PTPRZ1+GSCs.

Purpose To explore the association of RIPK1 expression and Miller-Payne score after neoadjuvant therapy and its effect on chemotherapy sensitivity in breast cancer.Methods Immunohistochemistry(IHC)was used to detect RIPK1 in paraffin samples from breast cancer.Western blot was used to detect the expression of RIPK1 in different breast cancer cell lines,knockdown cell lines were constructed.CCK-8,clone for-mation experiment and flow cytometry were used to detect the effect of knockdown RIPK1 on the sensitivity of cells to chemo-therapy.Results The IHC results showed that the high expres-sion rate of RIPK1 was 69.0％(20/29)in the resistant group and 42.9％(15/35)in the sensitive group,and the expression of RIPK1 was significantly correlated with the Miller-Payne score(P=0.037).Western blot assay showed that the expression levels of RIPK1 were different in different cell lines,RIPK1 knockdown cell lines were constructed and induced apoptosis u-sing different concentrations of drugs.CCK-8,clone formation experiment and flow cytometry showed that knockdown of RIPK1 could decrease the cell survival rate,increase the apoptosis rate and decrease the colony formation rate compared with the control group.Conclusion Knockdown of RIPK1 promotes chemother-apy sensitivity of breast cancer cells.