OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.

BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.

This study aimed to design and synthesize a series of novel photocaged compounds based on the precise binding mode of cyclin-dependent kinase 2 (CDK2) inhibitor AT7519 with its target, to achieve precise optical control over molecular activity. Using AT7519 as the structural foundation, different types of photoremovable protecting groups were introduced at its key interaction sites (the NH of the pyrazole ring and the NH of the piperidine ring), resulting in the synthesis of eight dual-photocaged compounds. Their structures were confirmed by NMR and mass spectrometry, and their photochemical properties—including photolysis wavelength, photolysis time, and photolysis efficiency—were systematically evaluated. The optically controlled inhibitory effects of the compounds on HCT116 cell proliferation were assessed using MTT assay. The photoresponsive characteristics of the photocaged compounds were significantly influenced by the type of photoremovable protecting group and its introduction site. Among them, compounds 1a, 1b, and 2d exhibited excellent photolysis efficiency, each achieving a rate exceeding 90%. Particularly, compounds 1b and 2d demonstrated excellent optically controlled activity: under dark conditions, their half maximal inhibitory concentration (IC50) values were both greater than 150 µmol/L, indicating negligible cell proliferation inhibitory activity; however, upon irradiation, their cell proliferation inhibitory activity significantly increased, with IC50 values comparable to those of the positive control AT7519. The obtained compounds 1b and 2d possess excellent optically controlled properties, and can be further investigated as potential candidates for optically controlled CDK2 inhibitors.

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 analyze the factors influencing postoperative complications and survival in patients undergoing hepatectomy for primary liver cancer (PLC).Methods:Two hundred and eighty-eight patients with PLC who underwent hepatectomy at Tianjin Medical University Cancer Hospital from April 2018 to December 2020 were prospectively enrolled, including 235 males and 53 females, aged (58.5±9.5) years. Nutritional evaluations included the nutritional risk screening 2002 (NRS-2002), patient-generated subjective global assessment (PG-SGA), and physical metrics such as body mass index, handgrip strength, arm circumference, mid-arm muscle circumference (MAMC), and triceps skinfold thickness (TSF). Based on the occurrence of postoperative complications during hospitalization including abdominal infection, bleeding, bile leakage, intra-abdominal fluid accumulation, pulmonary infection, intestinal fistula, and wound dehiscence, patients were divided into two groups: the complication group ( n=205) and the non-complication group ( n=83). Multivariate logistic regression analysis was performed to identify the factors related to postoperative complications, while Cox proportional hazards regression was used to evaluate the impact of various variables on postoperative survival. Survival analysis was conducted using the Kaplan-Meier method, and differences in survival rates were compared using the log-rank test. Results:Compared with the non-complication group, patients in the complication group had a significantly longer postoperative hospital stay [13(8, 16) d vs. 7(5, 9) d], higher proportions of low MAMC [34.1% (24/83) vs. 20.0% (41/205)], lower grip strength [28.9% (24/83) vs. 17.6% (36/205)], higher incidence of intraoperative blood loss ≥200 ml [44.6% (37/83) vs. 22.0% (45/205)], and greater proportion of resection involving ≥3 liver segments [45.8% (38/83) vs. 26.3% (54/205)] (all P<0.05). Multivariate logistic regression analysis identified the low MAMC ( OR=2.01, 95% CI: 1.09-3.71, P=0.025), intraoperative blood loss ≥200 ml ( OR=2.75, 95% CI: 1.55-4.90, P=0.001), and resection involving ≥3 liver segments ( OR=2.02, 95% CI: 1.15-3.55, P=0.015) as independent risk factors for postoperative complications in patients undergoing hepatectomy for PLC. Multivariate Cox regression analysis revealed that low TSF ( HR=1.94, 95% CI: 1.01-3.72, P=0.047), low handgrip strength ( HR=2.23, 95% CI: 1.29-3.88, P=0.004), and resection involving ≥3 liver segments ( HR=1.96, 95% CI: 1.15-3.36, P=0.014) were risk factors associated with poor survival after surgery. Conclusions:Low MAMC, intraoperative blood loss ≥200 ml, and resection involving ≥3 liver segments are risk factors for postoperative complications in patients undergoing hepatectomy for PLC, while low TSF, reduced handgrip strength, and resection involving ≥3 liver segments are predictors of poor postoperative survival.

Objective:To design one kind of adjustably assistive walking wheelchair with multi postures,so as to improve the quality of life of people with motion disorders,disabilities or semi disabilities on lower limbs.Methods:The adjustably assistive walking wheelchair with multi postures composed of walking mechanism,mechanism of adjusting posture,and chair,which can achieve five postures,including sitting,low sitting,high sitting,standing and lying.One kinematic model of the wheelchair mechanism was established,and Admas software was used to conduct kinematic simulation.Aimed at key components,the statics simulation was analyzed.The test for adjustment of 5 kinds of postures,the test for the reachable range of hands and the test for the stability of adjusted postures were conducted on the physical prototype of the wheelchair.Results:The results of kinematic simulation showed that the method and formula derivation of motion analysis were correct.Static simulation showed that the seat cushion bracket of key load-bearing component did not affect the normal use of wheelchair under the effect of 100 kg load on seat posture.Experimental tests showed that all parameters of posture transformation were consistent with the design objectives and theoretical analysis.The reachable range of hands was between 500 mm and 2300 mm.The tested results of transformation between sitting and lying postures showed that the stability of the system of adjusting posture of wheelchair was favorable.Conclusion:The adjustably assistive walking wheelchair with multi postures can meet the requirement of user in getting things at low and high position through adjusts the height of sitting posture,which can suit the requirement of user at different home scenarios with larger difference at height,such as table,stove and cabinet.

Thyroid diseases are clinically prevalent endocrine and metabolic disorders, including various types such as Hashimoto's thyroiditis and thyroid nodules. Their pathogenesis is complex and influenced by numerous factors, potentially involving genetic factors, environmental factors, and immune dysfunction. With the continuous advancement of modern traditional Chinese medicine (TCM), TCM has established a unique theoretical system in the prevention and treatment of thyroid diseases, with increasingly rich clinical practical experience. This article reviews the recent application of TCM health status analysis, monitoring, early warning, and prevention in the field of thyroid diseases, aiming to provide useful references for in-depth study in this field.

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.