Mechanical stimulation is a key biomechanical characteristic of the tumor microenvironment and is involved in tumor progression, immune microenvironment remodeling, and therapy resistance. This study aimed to develop a mechanical stimulation-related gene (MSRG)-based prognostic signature for survival prediction and to explore its association with the tumor immune microenvironment in lung adenocarcinoma (LUAD).

We used a multifaceted approach to analyze MSRGs in LUAD. The AUCell algorithm was used to calculate mechanical stimulation scores at the single-cell level, while CellChat and NicheNet analyses were applied to reveal cell-cell communication and ligand-target regulatory patterns under high mechanical stimulation. Mechanical stimulation activity in TCGA-LUAD samples was quantified by ssGSEA, and WGCNA was then performed to identify key gene modules associated with this trait. An integrated machine learning framework was then used to develop a prognostic risk model. Immune infiltration, stromal and immune scores, immune checkpoint-related features, and immune evasion potential were further evaluated. Finally, the selected key gene, COL22A1, was validated using multiple approaches.

Analysis of scRNA-seq data demonstrated that mechanical stimulation (MS) scores varied considerably across different cell types. The high-MS subgroup showed enhanced intercellular communication, suggesting active tumor microenvironment remodeling. Furthermore, a prognostic model for LUAD with robust predictive performance was constructed using WGCNA and machine learning algorithms. Notably, the high-risk group showed reduced immune infiltration, higher tumor purity, elevated CD276 expression, and increased TIDE scores, suggesting an immune-cold and immune-evasive microenvironment. In vitro experiments further showed that COL22A1 enhanced the malignant behavior of LUAD cells, indicating its potential as a therapeutic target.

We established an MSRG-based prognostic signature that not only predicts survival in LUAD but also reflects tumor immune microenvironment remodeling and potential immune escape. Our preliminary findings also suggest that COL22A1 is involved in LUAD progression and may have potential as a therapeutic target.

Puerarin is a bioactive isoflavone with reported anti-tumor and immunomodulatory activities; however, its candidate molecular targets and associations with the immune microenvironment in lung adenocarcinoma(LUAD) remain incompletely defined. This study integrated computational analyses with a murine LUAD model to prioritize candidate puerarin-associated targets and evaluate their relationships with immune-cell changes.

We first identified puerarin targets, non-small cell lung cancer (NSCLC)-associated genes, and differentially expressed genes (DEGs). An integrative strategy combining network pharmacology, multi-omics, and machine learning algorithms (Least Absolute Shrinkage and Selection Operator, Support Vector Machine-Recursive Feature Elimination, and Random Forest) was employed to screen feature genes. Feature genes were further evaluated by molecular docking, molecular dynamics simulations, Mendelian randomization(MR), cellular origins and immune infiltration analyses, and in vivo animal experiments using an orthotopic LUAD xenograft model.

A comprehensive analysis identified 130 targets associated with puerarin, 10,871 genes related to NSCLC, and 4,690 DEGs, resulting in an intersection comprising 39 candidate genes. Five feature genes (ABCG2, ALDH2, MIF, PTGS1, and SELP) were retained by three machine-learning approaches and ABCG2, ALDH2, MIF, and SELP showed consistent diagnostic performance in the training and validation cohorts. Docking and molecular dynamics simulations predicted favorable and stable modeled interactions of puerarin with ABCG2 and ALDH2, but did not establish direct target engagement. MR using a LUAD outcome dataset suggested an inverse association between genetically predicted ALDH2 expression and LUAD risk. Single-cell analysis indicated relative enrichment of ALDH2 transcripts in macrophages. In vivo, puerarin reduced orthotopic tumor burden and was accompanied by increased total ALDH2 expression and higher proportions of F4/80⁺CD11b⁺ cells in peripheral blood and tumor tissue.

Puerarin suppressed tumor growth in a murine LUAD model and was associated with ALDH2 upregulation and increased macrophage infiltration. Integrated analyses prioritize ALDH2 as a candidate molecule potentially linking puerarin treatment to changes in the tumor immune microenvironment. Direct puerarin-ALDH2 binding, macrophage-specific ALDH2 regulation, and the functional consequences for macrophage polarization require further experimental validation.

Glioblastoma (GBM) is a grade IV astrocytoma characterized by extensive intratumoral heterogeneity, with malignant cells existing in distinct malignant transcriptional states within the same tumour. DPP8 and DPP9 are intracellular serine proteases implicated in tumour progression and regulated cell death; however, their cell state-specific expression in GBM remains poorly understood. This study aimed to characterize the expression of DPP8 and DPP9 across malignant transcriptional states in GBM using single-cell RNA sequencing and to identify biological pathways associated with DPP8-high malignant cells.

Single-cell RNA sequencing data (GSE131928) generated by Neftel et al. was retrieved from Gene Expression Omnibus (GEO). This study was conducted from June to August 2026. All analysis was performed in R (v4.6.1) using Seurat (v5.5.1). Following quality control and preprocessing, malignant cells were classified into four established transcriptional states (AC-like, MES-like, NPC-like, and OPC-like) using published meta-module gene signatures. DPP8 and DPP9 expression was evaluated across these cellular states. Differential expression analysis between DPP8-high and DPP8-low malignant cells, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment to identify the biological processes associated with DPP8-high malignant cells.

Malignant cells were successfully classified into four transcriptional cellular states: astrocyte-like (AC), mesenchymal-like (MES), neural progenitor-like (NPC), and oligodendrocyte progenitor-like (OPC) . DPP8 and DPP9 expression differed significantly across these cellular states. AC-like cells demonstrated the highest DPP8 expression followed by MES-like cells, while NPC-like and OPC-like cells exhibited comparatively lower expression. Cell-cycle analysis demonstrated significant differences across transcriptional states, with DPP8-high malignant cells showing enrichment of G2/M-associated signatures while largely comprising non-cycling cells. Differential expression identified distinct transcriptional programmes associated with DPP8-high cells. Functional enrichment analyses revealed significant enrichment of extracellular matrix organization, cell adhesion, and multiple signaling pathways.

Single-cell transcriptomic analysis demonstrates that DPP8 exhibits transcriptional state-specific expression of DPP8 in glioblastoma, with predominant expression in AC-like malignant cells. The identified molecular programmes provide biologically relevant hypotheses for the mechanisms underlying DPP8 function.

Diffuse intrinsic pontine glioma (DIPG) is a lethal paediatric brainstem tumour with a median survival under one year and no effective therapy. Although non-coding RNAs (ncRNAs) regulate tumour progression, their regulatory networks in DIPG remain poorly characterised. This study aimed to identify dysregulated lncRNA- miRNA-mRNA axes in DIPG through integrated transcriptomic analysis, computationally validate these networks, and investigate their downstream impact on cancer-related pathways to reveal novel therapeutic targets for RNAbased precision medicine.

This study was conducted at the Precision Medicine Lab, National Centre in Big Data and Cloud Computing (NCBC), Peshawar, from 1st July to 22nd August 2025. RNA-seq datasets comprising 25 DIPG and 45 normal brain samples were obtained from GEO. Following normalization and differential expression analysis (padj < 0.05, |log2FC| > 2), dysregulated lncRNAs, miRNAs, and mRNAs were integrated into a ceRNA network using LncBase and miRTarBase. KEGG pathway enrichment, STRING protein-protein interaction analysis, Cytoscape network visualization, and Spearman correlation analysis were performed to identify and validate functionally relevant regulatory interactions.

PCA demonstrated clear separation between DIPG and control transcriptomes. PVT1 was significantly upregulated (log2FC = 3.44), whereas miR-34a was downregulated (log2FC = -3.66). Eleven oncogenic mRNAs, including NOTCH1, PDGFRA, CDK4, SOX2, and MYC, were identified as predicted targets and formed a highly connected STRING interaction network. KEGG enrichment highlighted "MicroRNAs in cancer," while correlation analysis supported an inverse PVT1-miR-34a relationship and positive associations with these oncogenes, consistent with a ceRNA regulatory mechanism.

The PVT1-miR-34a axis appears to promote oncogenic pathways in DIPG. Targetting PVT1 or restoring miR-34a may represent potential RNA-based therapeutic strategies, warranting further experimental validation through reporter and knockdown assays.

Squamous Cell Carcinoma (SCC) is among the most frequently reported malignancies in XP; however, intracranial extension is exceedingly rare and may pose a significant diagnostic challenge when radiologic findings mimic those of cerebral abscess.

The case of a 7-year-old male child with XP who developed an ulcerative lesion on the scalp and underwent surgical excision is reported. Xeroderma Pigmentosum (XP) is a rare autosomal recessive genodermatosis characterized by extreme sensitivity to ultraviolet radiation and an increased predisposition to cutaneous malignancies..

The excised tissue from the Histopathology confirmed moderately differentiated SCC with lymphovascular invasion and involvement of the deep margins. He subsequently presented with fever, vomiting, and seizures at National Institute of Child Health (NICH), Karachi, on 3rd March 2026. Contrast-Enhanced Computed Tomography (CECT) revealed bone destruction with an overlying mass and multiloculated intracranial lesions with a "bunch of grapes" appearance. The differential diagnosis included cerebral abscess and tumour extension. The family declined further evaluation and treatment, and the patient Left Against Medical Advice (LAMA). The patient deteriorated clinically and subsequently died as informed by his parents.

XP-associated scalp SCC may behave aggressively and extend intracranially, even in children. In patients with a history of malignancy, intracranial lesions with an apparent infectious appearance should prompt careful consideration of tumour extension in the differential diagnosis. Recognition of suspicious neuroimaging features, careful radiologic-pathologic correlation, early multidisciplinary evaluation, and timely management are essential to optimize outcomes.The parents consented to publish the child's report in detail.

Testicular cancer is the most common malignancy among men 15 to 45 years of age, with 5-year relative survival exceeding 95% when all stages are combined. Early detection may reduce treatment intensity, preserve fertility, and protect quality of life. Testicular self-examination (TSE) has historically been recommended as a secondary prevention strategy; however, the US Preventive Services Task Force issues a D recommendation against routine TSE, citing insufficient evidence of mortality benefit and potential harms. The National Cancer Institute Physician Data Query (PDQ) levels-of-evidence framework offers a complementary approach, grading certainty of effects while decoupling evidence assessment from prescriptive policy. This article contrasts the 2 frameworks, examines the available evidence for TSE, and considers whether elements of the PDQ approach could usefully inform guidance for low-incidence, high-survivability cancers. We argue that current evidence does not support a strong recommendation for or against routine TSE, but that mortality-only frameworks may understate outcomes that matter to patients, including treatment burden, fertility, and psychosocial function, and that more transparent communication of uncertainty would better support shared decision-making.

Improving adherence to inhaled medication is crucial for optimal treatment outcomes and effective disease management in chronic obstructive pulmonary disease (COPD) patients. This study aimed to investigate adherence to inhaled medication and its association with medication beliefs among COPD patients in Xi'an, China.

A cross-sectional study was conducted with 448 COPD inpatients recruited from two large tertiary hospitals in Xi'an, China, between May 1, 2024, and January 31, 2026. The Beliefs about Medicines Questionnaire Specific (BMQ-Specific) was used to assess inpatients' beliefs about inhalers, and the Medication Adherence Report Scale (MARS-5) was employed to evaluate adherence to inhaled medication. Logistic regression analyses were performed to examine the associations between independent variables and medication non-adherence. Three sensitivity analyses were conducted in this study to confirm the model's reliability. Model discrimination was assessed using ROC analysis, and internal validation was performed using 1,000 bootstrap resamples.

A total of 266 (59.4%) inpatients were non-adherent to inhaled medication. Overall, 243 (54.2%) inpatients expressed strong necessity beliefs about inhaled medication, while 203 (45.3%) held strong concern beliefs. Multivariable logistic regression analysis revealed that inpatient who expressed weaker necessity beliefs about inhaled medication had 4.79-fold odds (95% CI = 3.044-7.520; p < 0.001) of non-adherence compared with those who expressed stronger necessity beliefs. Inpatient who received dual therapy with LABA-ICS had 2.00-fold odds (95% CI = 1.027-3.900; p = 0.042) of non-adherence compared with those who received triple therapy with LAMA-LABA-ICS, whereas inpatient who was unemployed or retired was more likely to be adherent to inhaled medication (adjusted OR 0.534 [0.320, 0.889]; p = 0.016) than those in physical labor occupations. The association between necessity beliefs and medication adherence remained statistically significant upon validation in three sensitivity analyses.

The relatively low adherence to inhaled medication among inpatients with COPD in Northwestern China highlights the urgent need for effective strategies to improve adherence. These findings suggest a potential clinical implication wherein pharmacists and nurses could play a supportive role in promoting medication adherence among patients with COPD.

Smoking and secondhand smoke (SHS) exposures are established modifiable risk factors for premature mortality, but their joint associations with recorded idiopathic pulmonary fibrosis (IPF) remain uncertain. We examined active and passive smoking exposures in relation to all-cause and cause-specific mortality and evaluated departures from additivity with recorded IPF history.

This prospective UK Biobank cohort included 270,644 participants. Exposures comprised baseline smoking status, cumulative pack-years, maternal smoking around birth, adult SHS, and a composite passive SHS indicator. Multivariable Cox models, additive and multiplicative interaction analyses, and restricted cubic spline models were used after adjustment for demographic, socioeconomic, lifestyle, and genetic covariates.

During a median follow-up of 13.8 years, 20,959 deaths occurred. Ever-recorded IPF history was associated with all-cause mortality (HR 4.255, 95% CI 3.937-4.597), and active and passive smoking measures were also associated with mortality. In the additive interaction analyses, a positive departure from additivity was observed only between maternal smoking around birth and recorded IPF in relation to respiratory mortality (RERI 16.969, 95% CI 2.935-31.002; AP 0.248, 95% CI 0.082-0.414; SI 1.337, 95% CI 1.068-1.673). Corresponding positive RERI estimates were observed in analyses restricted to White participants, among participants with complete covariate data, and after excluding deaths occurring within the first 2 years of follow-up. The confidence intervals for the other RERI estimates in the primary analysis included zero. Dose-response associations were nonlinear among participants without recorded IPF and approximately linear among those with recorded IPF, although estimates in the latter group were less precise.

Active and passive smoking measures and ever-recorded IPF history were associated with mortality in this cohort. Evidence for positive additive interaction was confined to maternal smoking around birth and respiratory mortality and should be interpreted as hypothesis-generating. The observational findings do not establish causal or biological synergy and require replication in independent cohorts.

This study aimed to compare maternal and umbilical cord blood pro-BNP levels in pregnant women with a history of COVID-19 infection and to evaluate possible cardiac effects during pregnancy. In this prospective case-control study conducted between January and October 2023, 88 pregnant women were included: 44 with a history of COVID-19 infection after the second trimester and 44 healthy controls. Women with diabetes, hypertension, heart disease, or severe pregnancy complications were excluded. Maternal venous and umbilical cord arterial blood samples were collected immediately after delivery, and pro-BNP levels were measured using standard laboratory procedures. Maternal pro-BNP levels were significantly higher in the COVID-19 group, whereas cord blood pro-BNP levels did not differ significantly between groups. Obstetric and neonatal outcomes were similar. These findings suggest that prior COVID-19 infection may cause subclinical maternal cardiac stress, while placental mechanisms may protect the fetus from cardiac involvement.

Bronchiectasis is a common structural lung disease associated with pulmonary nocardiosis (PN), but the differences between PN patients with and without bronchiectasis remain insufficiently characterized.

We conducted a single-center retrospective study of hospitalized patients with PN at Beijing Chaoyang Hospital from January 2012 to December 2024. Patients were grouped by bronchiectasis status, and their clinical, radiological, and microbiological features were compared. Multivariable logistic regression was used to identify factors independently associated with bronchiectasis.

Among 154 patients, 86 (55.8%) had bronchiectasis. Of 162 Nocardia isolates, N. cyriacigeorgica, N. farcinica, and N. abscessus were the most commonly identified species. Patients with bronchiectasis more frequently had hemoptysis (40.7% vs. 13.2%, P<0.001) and tree-in-bud signs (11.6% vs. 2.9%, P=0.046), but less frequently had respiratory failure (10.5% vs. 26.5%, P=0.022) and had shorter hospital stays (12.62 ± 9.01 vs. 16.96 ± 10.84 days, P=0.007). Patients without bronchiectasis more frequently had type 2 diabetes, bronchial asthma, and several parenchymal or pleural imaging findings. In multivariable analysis, hemoptysis was positively associated with bronchiectasis [adjusted odds ratio (OR), 5.407; 95% confidence interval (CI), 2.185-13.382], whereas type 2 diabetes (adjusted OR, 0.320; 95% CI, 0.115-0.888) and bronchial asthma (adjusted OR, 0.166; 95% CI, 0.030-0.928) were negatively associated with bronchiectasis.

PN showed distinct clinical and radiological patterns according to bronchiectasis status. Greater diagnostic attention may be warranted in patients without bronchiectasis.