Objective Differentially expressed genes in oral squamous cell carcinoma (OSCC) were subjected to bioinformatic and Mendelian randomization analyses to elucidate their prognostic significance in OSCC. Methods The TCGA database and dataset GSE138206 were used to screen the common differential genes of OSCC, and their relationship was analyzed by using Mendelian randomization. The prognostic value of differential genes was further analyzed by Cox risk regression. The biological function of genes with high prognostic value was further evaluated by single gene differential analysis. Results A total of 147 common differential genes were screened from the two databases. Results of two-sample Mendelian randomization showed that GREM2 was associated with the increased risk of OSCC. In addition, SH3BGRL2 was associated with a decreased risk of OSCC, and DKK1, CCL11, and HOXC6 were considered as independent prognostic markers of OSCC. The predicted results of DKK1 were consistent with the actual results. KEGG enrichment analysis indicated the potential involvement of DKK1 in arachidonic acid and linoleic acid metabolism. Furthermore, DKK1 showed positive correlations with Tgd and Th2 cells, while displaying negative associations with PDC, Cytotoxic cells, Mast cells, CD8 T cells, TFH cells, B cells, T cells, and Th17 cells. Conclusion GREM2 is associated with an increased risk of OSCC. DKK1 is highly expressed in OSCC and associated with poor prognosis, which may be involved in regulating the metabolism of arachidonic acid and linoleic acid and immune cell invasion in OSCC.

Objective To analyze the role and mechanism of PD-L1 in oral cancer metastasis based on TCGA and GEO databases.Methods The expression characteristics and clinical significance of the PD-L1 in oral cancer were analyzed using the TCGA database.PD-L1 mRNA levels were detected by quantitative reverse transcription-polymerase chain reaction(RT-qPCR)in various oral cancer cell lines.CCK-8,scrath test,Transwell-migration,and matrigel-invasion assays were employed to assess the effects of PD-L1 on proliferation,migration,and invasion of oral cancer cells.The interaction network between PD-L1 and functional genes in patients with oral cancer was constructed using STRING software and the GEO database,and key pathways were screened by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.The regulatory relationship between PD-L1 and key genes was validated by RT-qPCR.Results TCGA data revealed that PD-L1 was highly expressed in patients with oral cancer and was correlated with lymph node metastasis(P＜0.01).PD-L1 was also highly expressed in oral cancer cell lines and its inhibition significantly inhibited the proliferation,migration,and invasion of Cal27 and SCC25 cells(P＜0.05).KEGG analysis indicated that PD-L1 activated the Janus kinase(JAK)/signal transducer and activator of transcription(STAT)pathway by upregulating C-X-C motif chemokine ligand(CXCL)9 and CXCL10,thereby promoting STAT1 expression to regulate oral cancer metastasis.Inhibition of the JAK/STAT pathway further suppressed the proliferation,migration,invasion,and expression of STAT1,CXCL9,and CXCL10 in Cal27 and SCC25 cells(P＜0.05).Conclusions PD-L1 may promote oral cancer cell proliferation,migration,and invasion by upregulating CXCL9 and CXCL10 to regulate the JAK/STAT pathway and enhance STAT1 expression,ultimately driving oral cancer growth and metastasis.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

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

Objective To analyze the role and mechanism of PD-L1 in oral cancer metastasis based on TCGA and GEO databases.Methods The expression characteristics and clinical significance of the PD-L1 in oral cancer were analyzed using the TCGA database.PD-L1 mRNA levels were detected by quantitative reverse transcription-polymerase chain reaction(RT-qPCR)in various oral cancer cell lines.CCK-8,scrath test,Transwell-migration,and matrigel-invasion assays were employed to assess the effects of PD-L1 on proliferation,migration,and invasion of oral cancer cells.The interaction network between PD-L1 and functional genes in patients with oral cancer was constructed using STRING software and the GEO database,and key pathways were screened by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.The regulatory relationship between PD-L1 and key genes was validated by RT-qPCR.Results TCGA data revealed that PD-L1 was highly expressed in patients with oral cancer and was correlated with lymph node metastasis(P＜0.01).PD-L1 was also highly expressed in oral cancer cell lines and its inhibition significantly inhibited the proliferation,migration,and invasion of Cal27 and SCC25 cells(P＜0.05).KEGG analysis indicated that PD-L1 activated the Janus kinase(JAK)/signal transducer and activator of transcription(STAT)pathway by upregulating C-X-C motif chemokine ligand(CXCL)9 and CXCL10,thereby promoting STAT1 expression to regulate oral cancer metastasis.Inhibition of the JAK/STAT pathway further suppressed the proliferation,migration,invasion,and expression of STAT1,CXCL9,and CXCL10 in Cal27 and SCC25 cells(P＜0.05).Conclusions PD-L1 may promote oral cancer cell proliferation,migration,and invasion by upregulating CXCL9 and CXCL10 to regulate the JAK/STAT pathway and enhance STAT1 expression,ultimately driving oral cancer growth and metastasis.

Objective: To identify core acupoint patterns and elucidate the molecular mechanisms of acupuncture for primary depressive disorder (PDD) through data mining and network analysis. Methods: A comprehensive literature search was conducted across PubMed, Embase, Ovid Technologies (OVID), Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), China National Knowledge Infrastructure Database (VIP), Wanfang Data, and SinoMed Database from database foundation to January 31, 2025, for clinical studies on acupuncture treatment of PDD. Descriptive statistics, high-frequency acupoint analysis, degree and betweenness centrality evaluation, and core acupoint prescription mining identified predominant therapeutic combinations for PDD. Network acupuncture was used to predict therapeutic target for the core acupoint prescription. Subsequent protein-protein interaction (PPI) network and molecular complex detection (MCODE) analyses were conducted to identify the key targets and functional modules. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses explored the underlying biological mechanisms of the core acupoint prescription in treating PDD. Results: A total of 57 acupoint prescriptions underwent systematic analysis. The core therapeutic combinations comprised Baihui (GV20), Yintang (GV29), Neiguan (PC6), Hegu (LI4), and Shenmen (HT7). Network acupuncture analysis identified 88 potential therapeutic targets (79 overlapping with PDD), while PPI network analysis revealed central regulatory nodes, including interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, toll-like receptor 4 (TLR4), IL-10, brain-derived neurotrophic factor (BDNF), transforming growth factor (TGF)-β1, C-X-C motif chemokine ligand 10 (CXCL10), mitogen-activated protein kinase 3 (MAPK3), and nitric oxide synthase 1 (NOS1). MCODE-based modular analysis further elucidated three functionally coherent clusters: inflammation-homeostasis (score = 6.571), plasticity-neurotransmission (score = 3.143), and oxidative stress (score = 3.000). GO and KEGG analyses demonstrated significant enrichment of the MAPK, phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and hypoxia-inducible factor (HIF)-1 signaling pathways. These mechanistic insights suggested that the antidepressant effects mediated through mechanisms of neuroinflammatory regulation, neuroplasticity restoration, and immune-oxidative stress homeostasis. Conclusion This study reveals that acupuncture alleviates depression through a multi-level mechanism, primarily involving the neuroinflammation suppression, neuroplasticity enhancement, and oxidative stress regulation. These findings systematically clarify the underlying mechanisms of acupuncture’s antidepressant effects and identify novel therapeutic targets for further mechanistic research.

Objective To analyze the effects of miR-181a-5p overexpression on metabolites in the small intestines of mice with subcutaneous oral cancer by detecting changes in metabolites and metabolic pathways.Methods Three groups were included in study:Control group,negative control and miR-181a-5p overexpression group.To establish a subcutaneous oral cancer model in mice,variously treated cell suspensions were subcutaneously injected into the upper right of the groin in female M-NSG severely immunodeficient mice.Changes in pathology and small intestinal tissues were assessed by HE staining.Changes in mouse body weight were also assessed.Tandem orbitrap mass spectrometry and ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry,were used to examine metabolites in the small intestines.By pre-analyzing the original data and quality rating sample data,XCMS was able to assess which metabolites were different among the groups.To identify unique metabolic pathways,KEGG enrichment analysis was used.Results A total of 170 distinct metabolites were found in the small intestinal tissues of Control and NC groups.Choline metabolism,alanine,aspartate,and glutamate metabolism,GABA synaptic metabolism,glycerophospholipid metabolism,cAMP signaling route,cancer center carbon metabolism,and niacin and niacin amine metabolic pathways were important signaling pathways for metabolite enrichment.In the NC group,16 distinct metabolites with VIP values larger than 2 were found in the small intestines compared with the OE group overexpressing miR-181a-5p.Glycerin phosphorylcholine,palmitic acid,3-hydroxybutyl carnitine,and β-hydroxybutyric acid were among the metabolites that significantly varied.The primary enhanced metabolic pathway was the choline pathway.Conclusions Mouse small intestines underwent slight changes from subcutaneous oral cancer with the greatest effect on metabolites critical for energy metabolism.The choline metabolic pathway was the pathway that selected absolutely metabolites in mouse small intestines with subcutaneous grafts of oral cancer.

Objective To investigate the effects of Gli2 on the proliferation,growth,migration,and invasion of oral cancer cells(Tca8113)at the cellular level,and to clarify the molecular mechanism of how Gli2 regulation affects the migration and invasion of oral cancer cells.Methods Small interfering(si)RNA was used to inhibit Gli2 expression in Tca8113 cells.The effects of Gli2 on the proliferation,growth,migration,and invasion of Tca8113 cells were examined by CCK-8,platb cloning,and transwell chamber assay.Further qRT-PCR and Western blot assays were used to explore the mechanism of how Gli2 regulation effects the malignant proliferation and metastasis of Tca8113 cells.Results The mRNA and protein expression of Gli2 in oral cancer cells(Tca8113)increased.Interference of Gli2 expression inhibited the proliferation,growth,migration,and invasion of Tca8113 cells.Further experiments showed that interfering with Gli2 expression inhibited the mRNA and protein expression of key factors in the Hedgehog(Hh)pathway.In addition,interference of Gli2 expression significantly affected the mRNA and protein expression of key factors in epithelial mesenchymal transformation(EMT)pathways.Conclusions Gli2 is abnormally activated during oral cancer,and interference of Gli2 expression significantly inhibits the proliferation,growth,migration,and invasion of oral cancer cells.Gli2 influences the migration and invasion of oral cancer cells by regulating the Hh and EMT pathways.This study has provided a new way to elucidate the pathogenesis of oral cancer and new perspectives on the clinical treatment of oral cancer.

Objective To explore the effect of oral neuromuscular training combined with intermittent theta burst stimulation(iTBS)on dysphagia of nasopharyngeal carcinoma patients after chemoradiotherapy.Methods Seventy-six nasopharyngeal carcinoma patients with dysphagia who received chemoradiotherapy in The Second Affiliated Hospital of Air Force Medical University from March 2021 to March 2022 were enrolled and divided into two groups by random number table methods.Control group received conventional swallowing training,and observation group received oral neuromuscular training combined with iTBS.The swallowing function was assessed by video fluoroscopic swallowing study(VFSS)and Rosenbek penetration aspiration scale(PAS)at the baseline and after treatment.The quality of life and treatment effect were compared between the two groups.Results After intervention,the PAS score was decreased and the Swallowing Quality-of-Life Questionnaire(SWAL-QOL)score was increased in both groups(P＜0.05),with significant differences between the two groups(P＜0.05).The treatment efficacy of dysphagia in the observation group was significantly higher than that in the control group(86.84%vs 44.74%,P＜0.05).Conclusion Oral neuromuscular training combined with iTBS can effectively ameliorate dysphagia and improve the quality of life of patients with nasopharyngeal carcinoma after chemoradiotherapy.

Objective:To analyze the factors influencing patients′ medical experience, to provide reference for medical institutions to improve patients′ medical experience.Methods:A stratified sampling method was employed nationwide to select 32 patients and 20 medical staff. From May to August 2023, semi-structured interviews were conducted with them regarding the factors influencing patients′ medical experience. The data from the interviews were analyzed using programmed grounded theory, which led to the identification of factors affecting patients′ medical experience.Results:After three-level coding, four main categories of demographic characteristics, self health characteristics, medical outcome experience, and medical process experience, two core categories of patient related influencing factors and hospital related influencing factors were obtained. Additionally were also obtained.Conclusions:The factors influencing patients′ medical experience are multifaceted and jointly dominated by multiple stakeholders. Medical institutions should adopt a variety of measures to continuously improve patients′ medical experience. When assessing patients′ medical experience, the impact of individual differences among patients on the assessment results should be fully considered.