This research investigates the regulatory role of the transcription factor PU.1 in type 1 conventional dendritic cells (cDC1) and its therapeutic potential of modulating the nuclear factor kappaB (NF-κB) cells signaling pathway in non-small cell lung cancer (NSCLC). Utilizing single-cell transcriptome sequencing and comprehensive bioinformatics tools, including the CIBERSORT algorithm, we analyzed the immune cell landscape within NSCLC tissues. Our analysis revealed distinct NSCLC subtypes and delineated the developmental trajectories and functional distinctions of cDC1 cells. Key differentially expressed genes (DEGs) and pivotal functional modules within these cells were identified, highlighting PU.1 as a critical mediator underexpressed in NSCLC samples. Functionally, PU.1 demonstrated the induction of the NF-κB pathway, which led to inhibited tumor proliferation and enhanced activation of cDC1, thereby suggesting its role in tumor immune surveillance. In vivo models confirmed the suppressive effect of PU.1 on NSCLC progression, mediated through its influence on cDC1 functionality via the NF-κB pathway. These findings propose PU.1 as a promising target for NSCLC therapeutic strategies, emphasizing the importance of transcriptional regulators in the tumor microenvironment.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

OBJECTIVES: To elucidate the underlying mechanisms of macrophage-mediated inflammation and tissue injury in diabetic foot ulcer (DFU). METHODS: Skin tissue samples were collected from patients with DFU and with non-DFU. A total of 79 272 high-quality cell transcriptomes were obtained using single-cell RNA sequencing. An unbiased clustering approach was employed to identify cell subpopulations. Seurat functions were used to identify differentially expressed genes between DFU and non-DFU groups, and gene ontology (GO) enrichment analysis was used to reveal gene function. Furthermore, cell-cell communication network construction and ligand-receptor interaction analysis were performed to reveal the mechanisms underlying cellular interactions and signaling regulation in the DFU microenvironment from multiple perspectives. RESULTS: The results revealed a significant expansion of myeloid cells in DFU tissues, alongside a marked reduction in structural cells such as endothelial cells, epithelial cells, and smooth muscle cells. Major cell types underwent functional reprogramming, characterized by immune activation and impaired tissue remodeling. Specifically, macrophages in DFU skin tissues exhibited a shift toward a pro-inflammatory M1 phenotype, with upregulation of genes associated with inflammation and oxidative stress. Cell communication analysis further demonstrated that M1 macrophages served as both primary signal receivers and influencers in the COMPLEMENT pathway mediated communication network, and as key signal senders and mediators in the secreted phosphoprotein 1 (SPP1) pathway mediated communication network, actively shaping the inflammatory microenvironment. Key ligand-receptor interactions driving macrophage signaling were identified, including C3-(ITGAM+ITGB2) and SPP1-CD44. CONCLUSIONS This study establishes a comprehensive single-cell atlas of DFU, revealing the role of macrophage-driven cellular networks in chronic inflammation and impaired healing. These findings may offer potential novel therapeutic targets for DFU treatment.
Humans ; Macrophages/immunology* ; Diabetic Foot/pathology* ; Single-Cell Analysis ; Transcriptome ; Gene Expression Profiling ; Inflammation ; Skin ; Cell Communication ; Signal Transduction ; Cellular Reprogramming

Objective:To observe the efficacy and safety of Tianchan capsule on chemotherapy-induced peripheral neuropathic pain (CIPNP) .Methods:A total of 120 CIPNP patients with Karnofsky performance status (KPS) score higher than 60 admitted to the Nantong Tumor Hospital, Jiangsu Province and Suzhou Hospital of Traditional Chinese Medicine from April 2023 to April 2024 were selected as study objects. Patients were divided into control group (cisplatin/paclitaxel) and observation group (cisplatin/paclitaxel+Tianchan capsule) according to random number table method, with 60 cases in each group. After 28 days of treatment, the clinical efficacy, adverse reactions, numberical rating scale (NRS) score, quality of life score, Traditional Chinese Medicine (TCM) syndrome score and neurotoxicity grading score before and after treatment were observed and compared between the two groups.Results:Twenty-eight days after treatment, the total effective rate of the control group was 0 (0/60) , while the total effective rate of the observation group was 83.33% (50/60) , with a statistically significant difference ( χ2=85.71, P<0.001) . The NRS scores of the control group before treatment and at 7, 14, and 28 days after treatment were 6.18±1.71, 6.17±1.72, 6.20±1.70 and 6.22±1.70, respectively, with no statistically significant difference ( F=-1.43, P=0.160) . The NRS scores of the observation group before treatment and at 7, 14, and 28 days after treatment were 6.05±1.76, 5.17±1.42, 3.76±1.16, and 2.00±0.80, respectively, with a statistically significant difference ( F=22.89, P<0.001) . The NRS scores of the observation group at 7, 14, and 28 days after treatment were all lower than those of the control group, with statistically significant differences (all P<0.001) . Further pairwise comparison showed that, NRS scores in the observation group gradually decreased from before treatment to after 7, 14 and 28 days of treatment (all P<0.05) . Before treatment and 7, 14, and 28 days after treatment in the control group, the KPS scores were 67.33±6.43, 67.25±6.29, 67.08±6.14 and 66.75±5.80, respectively, with no statistically significant difference ( F=2.18, P=0.340) . Before treatment and 7, 14, and 28 days after treatment in the observation group, the KPS scores were 67.17±6.49, 68.33±6.32, 71.25±7.68 and 79.42±5.30, respectively, with a statistically significant difference ( F=-19.33, P<0.001) . The KPS scores of the observation group at 14 and 28 days after treatment were both higher than those of the control group, with statistically significant differences ( t=-3.33, P<0.001; t=-12.66, P<0.001) . Further pairwise comparison showed that, the KPS scores of the observation group were higher at 28 days after treatment compared to pre-treatment levels, as well as to those at 7 and 14 days after treatment (all P<0.05) . The scores of TCM syndrome showed that the scores of burnout and fatigue were 3.03±0.66 before treatment and 3.03±0.66 after 28 days of treatment in the control group, respectively, with no statistically significant difference ( t<0.01, P>0.999) . In the observation group, the scores were 3.02±0.60 and 1.97±0.52, respectively, with a statistically significant difference ( t=21.00, P<0.001) . The scores of hypochondriac pain were 3.05±0.68 before treatment and 3.07±0.63 after 28 days of treatment in the control group, respectively, with no statistically significant difference ( t=-0.57, P=0.568) . In the observation group, the scores were 3.03±0.66 and 2.02±0.57, respectively, with a statistically significant difference ( t=18.25, P<0.001) . The scores of pale complexion were 2.87±0.50 and 2.85±0.48 in the control group before treatment and 28 days after treatment, respectively, with no statistically significant difference ( t=-0.57, P=0.568) . In the observation group, the scores were 2.93±0.55 and 1.93±0.55, respectively, with a statistically significant difference ( t=24.29, P<0.001) . The scores of loss of appetite were 2.90±0.60 and 2.90±0.63 in the control group before treatment and after 28 days of treatment, respectively, with no statistically significant difference ( t<0.01, P>0.999) . In the observation group, the scores were 2.95±0.57 and 1.98±0.60, respectively, with a statistically significant difference ( t=20.42, P<0.001) . After 28 days of treatment, the scores of burnout and fatigue, hypochondriac pain, pale complexion and loss of appetite in the observation group were lower than those in the control group (all P<0.001) . Comparison of neurotoxicity grading showed that the scores of peripheral sensory nerve disorder were 2.54±0.50 before treatment and 2.58±0.49 after 28 days of treatment in the control group, respectively, with no statistically significant difference ( t=-0.40, P=0.690) . The scores in the observation group were 2.52±0.50 and 2.00±0.00, respectively, with a statistically significant difference ( t=7.29, P<0.001) . The scores of peripheral motor nerve disorder were 2.44±0.51 before treatment and 2.36±0.48 after 28 days of treatment, respectively, with no statistically significant difference ( t=0.81, P=0.419) . In the observation group, the scores were 2.46±0.50 and 2.00±0.10, respectively, with a statistically significant difference ( t=6.49, P<0.001) . Neuralgia score: Before treatment and after 28 days of treatment, the scores in the control group were 2.14±0.49 and 2.18±0.48, respectively, with no statistically significant difference ( t=-0.41, P=0.683) . The scores in the observation group were 2.16±0.51 and 1.72±0.46, respectively, with a statistically significant difference ( t=4.56, P<0.001) . After 28 days of treatment, the scores of peripheral sensory nerve disorder, peripheral motor nerve disorder and neuralgia in the observation group were lower than those in the control group (all P<0.001) . Patients in both control group and observation group had different degrees of diarrhea, nausea and vomiting, but there was no statistically significant difference in total incidence of adverse reactions between the two groups ( χ2=0.22, P=0.637) . Conclusions:Tianchan capsule can effectively reduce the pain degree of patients with CIPNP, improve the quality of life of patients and has good safety.

Natural killer cells(NK)are important innate immune cells that do not require prior antigen exposure and can directly recognize and attack virus-infected cells and tumor cells.The activation and effector functions of NK cells are regulated by a balance of signals delivered through their surface activating receptors and inhibitory re-ceptors,which bind to ligands on target cells to achieve cytotoxicity via"induced self"and"missing self"recogni-tion models.The killing mechanisms of NK cells primarily include release of cytotoxic granules such as perforin and granzymes to induce target cell lysis,death receptor-mediated apoptosis,secretion of various cytokines,chemokines and growth factors to coordinate with other immune cells in killing tumor cells,thereby generating secondary im-mune responses and antibody-dependent cellular cytotoxicity(ADCC).

Objective To explore the influencing factors of cognitive impairment in non-dialysis patients with chronic kidney disease(CKD).Methods A total of 60 hospitalized non-dialysis patients with CKD in the Department of Nephrology of Northern Jiangsu People's Hospital Affiliated to Yangzhou University from September 2022 to September 2023 were enrolled as research objects.According to the estimated glomerular filtration rate(eGFR),they were divided into stage 1 to 2 of CKD group[eGFR ≥60 mL/(min·1.73 m2)]with 23 cases,the stage 3 of CKD group[eGFR 30～＜60 mL/(min·1.73 m2)]with 20 cases,and stage 4 to 5 of CKD group[eGFR＜30 mL/(min·1.73 m2)]with 17 cases.The Montreal Cognitive Assessment Scale(MoCA)was used to evaluate the cognitive function of the patients.Basic data and common clinical laboratory in-dicators on hospital admission were collected to analyze the differences in cognitive function levels under different renal function statuses and to explore the influencing factors of cognitive impairment.Results The incidence rates of cognitive impairment in the stage 1 to 2 of CKD group,stage 3 of CKD group,and stage 4 to 5 of CKD group were 47.8％,85.0％,and 94.1％respectively,the median MoCA scored 26,24 and 20 respectively,with statistically significant between-group differ-ences(P＜0.05).Cognitive function was significantly negatively correlated with age(r=-0.634,P＜0.001),blood urea nitrogen(BUN)(r=-0.574,P＜0.001),serum creatinine(Cr)(r=-0.417,P＜0.001),cystatin C(Cys-C)(r=-0.327,P=0.011),serum β2-microglobulin(β2-MG)(r=-0.259,P=0.046),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(r=-0.474,P＜0.001),and was significantly positively correlated with hemoglobin(HB)(r=0.401,P=0.001)and eGFR(r=0.485,P＜0.001).Multivariate Logistic regression analysis showed that age(P=0.006)and NT-proBNP(P=0.041)were influencing factors of cognitive im-pairment in non-dialysis patients with CKD.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of age for prediction were 0.860,0.864 and 0.812 respectively,the AUC,sensitivity,and specificity of NT-proBNP for pre-diction were 0.808,0.795 and 0.875 respectively,and the combined prediction of age and NT-proBNP had an AUC,sensitivity,and specificity of 0.893,0.955,and 0.750,respectively.Conclusion As renal function deteriorates,the incidence rate and severity of cognitive impairment in non-dialysis patients with CKD tend to increase.Advanced age,renal function deterioration,high NT-proBNP level,and anemia are associated with the occurrence of cognitive impairment in non-di-alysis patients with CKD,among which age and NT-proBNP are influencing factors for cognitive im-pairment.

Objective: To determine the association between the intake of five major types of prepackaged foods and the growth and development of school aged children, so as to provide a theoretical basis for guiding school aged children and their parents to make healthy prepackaged food choices. Methods: Based on data from the South West China Childhood Nutrition and Growth Cohort (SCCNG), 381 children (6-11 years of age) were selected by stratified cluster sampling. Dietary intake and pubertal development were collected using questionnaires, and anthropometric measurements were obtained. Children were followed up until November 2022. Binary Logistic regression models were used to analyze the prospective association between prepackaged food intake and the growth and development of school aged children. Results: The total intake of the five major types of prepackaged foods was 316.1 (197.1,501.4) g/d. After 2 years of follow up evaluations, 16.5% of school aged children were shown to be overweight and obese. Early spermarche occurred in 12.6% of boys and early menarche occurred in 15.4% of girls. The following findings were suggested after adjusting for the mothers education level, average gross monthly family income, whether or not the family had one child only, geographic area of residence, body mass index Z score, average duration of daily exercise, and total dietary energy intake: convenience food intake might increase the risk of early spermarche ( OR =9.37); fruit and vegetable intake might decrease the risk of early spermarche and menarche ( OR =0.33,0.17); and fish, poultry, meat, and egg intake might increase the risk of early menarche ( OR =7.59)( P <0.05). Intake of the five types of prepackaged foods was not associated with being overweight or obese after adjusting for confounders ( OR =1.40, 0.57, 0.73, 1.33,1.57, P >0.05). Conclusions The relationship between intake of the five major types of prepackaged foods and pubertal development is inconsistent and no significant correlation was detected between the intake of prepackaged foods and overweight or obese children. Nutrition education should be strengthened to help children and their parents choose healthy prepackaged foods.

Objective To observe the protective effects of codonopsis pilosulae polysaccharide on lung tissues in mice with acute lung injury(ALI)induced by lipopolysaccharide(LPS)and its mechanism.Methods Fifty male Kunming mice were randomly divided into control group,model group,dexamethasone group,codonopsis polysaccharide high-dose group(300 mg/kg)and codonopsis polysaccharide low-dose group(150 mg/kg).The ALI model was established by intraperitoneal injection of LPS.All mice were given gavage administration according to the grouping except for the control group.0.3 s force expiratory volume(FEV 0.3)and force spirometry(FVC)and their ratios were measured using multiparametric lung function test system.The histopathology change of mouse lung was detected by hematoxylin-eosin(HE)staining,and the classification and count of inflammatory cells in alveolar lavage fluid(BALF)was detected by Richter-Giemsa staining.Levels of IL-1β,IL-6,MPO and TNF-α were measured by ELISA in BALF,and Western blot was used to detect the protein expression level of p-p38,p-IκB-α and p-p65.Results Compared with those in the control group,lung histopathological damage was more pronounced in the model mice,with significantly lower FEV 0.3,FVC,FEV0.3/FVC assay value,but signifi-cantly higher lung tissue wet mass/dry mass(W/D),neutrophils,lymphocytes,IL-1β,IL-6,MPO,TNF-α,p-p38 MAPK,p-IκB-α,and p-p65(P<0.05);while codonopsis pilosulae polysaccharide could significantly reverse these effects.Conclusion Codonopsis pilosulae polysaccharide plays a protective role against LPS-induced ALI via inhibiting MAPK/NF-κB pathway to reduce the pathological damage of lung tissue,and the level of inflammatory factors,thus to improve lung function in ALI model mice.

Objective: To investigate the prospective effects of intake of each food group on the development of lung function of pupils,so as to provide theoretical basis for promoting the healthy development of lung function and preventing chronic respiratory diseases in Chinese children. Methods: A cluster stratified sampling method was used to select a total of 893 pupils in grades 2-5 from Chengdu in November 2021. Dietary data of respondents were collected using a food frequency questionnaire within the past year,then the food group intake was categorized into T1, T2 and T3 from low to high by the trichotomous method, and anthropometric measurements including lung capacity were obtained in 2022. Logistic regression models and test for trend were used to analyze the prospective effects of intake of each food group on lung function development of pupils. Results: Among male students, consumption of vegetables [118.6(50.5, 188.2)g/d] and milk and dairy products [200.0(73.3, 250.0)g/d] were higher in the excellent lung capacity group than in the non excellent lung capacity group [90.0(37.1, 192.9), and 178.6(35.7, 250.0)g/d],with statistically significant differences ( Z =-1.98, -2.24); among girls, the group with excellent lung capacity consumed less staple food [391.1(273.6, 511.4)g/d] than the group with non excellent lung capacity [407.4(309.5, 594.3)g/d], and the group with excellent lung capacity consumed more aquatic products [31.2(14.6, 69.8)g/d] and milk and dairy products [215.0(107.1, 250.1) g/d ] than that of the non excellent lung capacity [19.4(10.7, 58.3), 114.3(35.7, 250.0)g/d] ( Z =-2.01, -3.33, -5.10)( P < 0.05 ). After adjusting for energy, body mass index Z score(BMI Z ), mother s education level, averge family income monthly, whether presence of smokers in the living environment, and whether participation in physical activities during the past week, among male students, T3 group of vegetable intake ( OR =0.48, 95% CI = 0.27-0.86), T2 group of bean and soy product intake ( OR = 0.52 , 95% CI =0.27-0.96)，T2 and T3 groups of milk and dairy products intake (T2： OR =0.54, 95% CI =0.31-0.93; T3： OR = 0.52 , 95% CI =0.30-0.90) were negatively associated with non excellent lung capacity ( P <0.05). Among girls, T3 group of aquatic product intake( OR =0.52, 95% CI =0.28-0.97), T2 and T3 groups of milk and dairy product (T2: OR =0.44, 95% CI =0.25- 0.76 ;T3: OR =0.33, 95% CI =0.19-0.59) were negatively associated with nonexcellent lung capacity, whereas the T2 group of red meat intake ( OR =2.51, 95% CI =1.37-4.67) was positively associated with non excellent lung capacity. Non excellent lung capacity was found to be negatively associated with vegetable and milk and dairy product intake in boys by test for trend; in girls, milk and dairy products intake was negatively associated with non excellent lung capacity, whereas red meat intake was positively associated with non excellent lung capacity ( t =-1.13，-0.44；-3.03，1.95, P trend <0.05). Conclusions Milk and dariy products intakes reduce the risk of non excellent lung capacity in pupils, vegetables intakes reduce the risk of non excellent lung capacity in boys, and the intake of red meat increases the risk of non excellent lung capacity in girls. Promoting rational food choices is necessary for children to improve healthy lung development.

Objective Photoelectric volumetric tracing(PPG)exhibits high sensitivity and specificity in flap monitoring.Deep learning(DL)is capable of automatically and robustly extracting features from raw data.In this study,we propose combining PPG with 1D convolutional neural networks(1D-CNN)to preliminarily explore the method's ability to distinguish the degree of embolism and to localize the embolic site in skin flap arteries.Methods Data were collected under normal conditions and various embolic scenarios by creating vascular emboli in a dermatome artery model and a rabbit dermatome model.These datasets were then trained,validated,and tested using 1D-CNN.Results As the degree of arterial embolization increased,the PPG amplitude upstream of the embolization site progressively increased,while the downstream amplitude progressively decreased,and the gap between the upstream and downstream amplitudes at the embolization site progressively widened.1D-CNN was evaluated in the skin flap arterial model and rabbit skin flap model,achieving average accuracies of 98.36%and 95.90%,respectively.Conclusion The combined monitoring approach of DL and PPG can effectively identify the degree of embolism and locate the embolic site within the skin flap artery.