Background Non-small cell lung cancer (NSCLC) shows substantial heterogeneity across age groups and tumor locations. However, the relationship between age, lobar distribution, and the pulmonary immune microenvironment remains insufficiently understood. This study aimed to identify age-specific patterns of NSCLC occurrence and explore potential immune mechanisms underlying these differences. Methods We retrospectively analyzed 121,436 surgically treated NSCLC cases from Shanghai Pulmonary Hospital between 2015 and 2024. Tumor location and age at onset were assessed across World Health Organization age categories. To investigate potential mechanisms, we analyzed 15 tumor-adjacent single-cell RNA sequencing samples from the E-MTAB-13526 dataset and validated cell-type composition changes using TCGA bulk RNA-seq deconvolution. Cell–cell communication, pseudotime trajectory, transcription factor activity, and functional enrichment analyses were performed to characterize immune alterations. Results The upper-to-lower lobe incidence disparity of NSCLC followed a curved age-related pattern and was most pronounced in the young-old (YO, 60–74 years) group, reaching an approximate ratio of 7:3. Single-cell analysis revealed that the YO group had distinct immune microenvironment features, especially abnormal proportions of myeloid cells and T cells. Among myeloid subsets, alveolar macrophages were markedly increased in the YO group and showed enrichment of metabolic remodeling, oxidative stress, senescence-related signatures, and M2-like polarization. STAT1 and STAT3 activity was elevated, suggesting involvement of the JAK/STAT pathway. In parallel, T-cell composition shifted toward higher CD4 + T-cell proportions and relatively lower CD8 + T-cell proportions in the YO group. Cell–cell communication analysis indicated prominent myeloid–T cell interactions, with MHC-II, prostaglandin, and galectin signaling among the key pathways. Conclusions The YO group exhibits a unique pulmonary immune microenvironment that may contribute to its distinct upper-versus-lower lobe NSCLC distribution. Altered alveolar macrophage abundance and T-cell polarization, potentially mediated through JAK/STAT-related immune remodeling, may represent important mechanisms linking age and tumor location in NSCLC.
Background & aimsBacterial and fungal infections are major drivers of acute decompensation and acute-on-chronic liver failure (ACLF) in cirrhosis, but real-world data on the effectiveness of empiric antibiotic therapy in China are scarce. We evaluated clinical response to empiric antibiotics, identified predictors of non-response, and assessed the impact of response and secondary infection on short-term outcomes in Chinese patients with cirrhosis.Approach & resultsIn this multicenter retrospective cohort from 24 tertiary centers, 1,401 adults with cirrhosis and bacterial or fungal infections were included. Clinical response to first-line empiric therapy occurred in 913 patients (65%). Non-responders had higher MELD/MELD-Na scores, more organ failures and ACLF, and more intense systemic inflammation. In multivariable models, greater ACLF grade 2-3, systemic inflammatory response syndrome, higher neutrophil-to-lymphocyte ratio, C-reactive protein, bilirubin, culture positivity, and lower albumin and mean arterial pressure independently predicted non-response. Non-response was independently associated with 28-day and 90-day mortality (HR 4.20 and 3.16, respectively), with consistent findings in time-dependent and center-clustered sensitivity analyses. Secondary infection developed in 7.0% of patients, was four-fold more frequent in non-responders (13.9% vs 3.3%), and nearly doubled 90-day mortality, whereas microbiological features at secondary infection did not clearly distinguish second-course responders from non-responders. Comparative analyses revealed substantial center-to-center and China-global differences in etiology, infection profile, and multidrug-resistant (MDR) burden.ConclusionsIn Chinese patients with cirrhosis, lack of early clinical response to empiric antibiotics independently predicts short-term mortality and is associated with a higher risk of clinically distinct secondary infection. Our findings support risk-adapted, locally informed empiric strategies.
Circular RNAs (circRNAs) are aberrantly expressed in various human cancers and regulate tumor cell proliferation, invasion, and metastasis through multiple mechanisms. However, existing studies are mostly single-center with small sample sizes, lacking systematic quantitative evaluation. This systematic review and meta-analysis aims to clarify the association between circRNA expression levels and prognosis as well as clinicopathological features in patients with cholangiocarcinoma (CCA). Two researchers independently searched Web of Science and PubMed databases to identify studies evaluating the relationship between circRNA expression and prognosis or pathological features of CCA, with the final search date of September 28, 2025. Literature screening was performed based on predefined inclusion criteria (cohort or case-control design; RT-qPCR detection of circRNA; available clinicopathological data) and exclusion criteria (duplicate data, reviews, non-human studies, non-English/Chinese publications). Risk of bias was assessed using the Newcastle-Ottawa Scale, and statistical analysis was conducted in StataSE 12.0 using the random-effects model for all primary meta-analyses.This study is registered on PROSPERO, number CRD420261352256. A total of 46 studies involving 3,416 CCA patients from China and a multinational cohort (France/Spain) were included. All studies used qRT-PCR; high-expression and low-expression groups were defined using various cut-off criteria including median, mean, X-tile, and Youden index derived from ROC analysis.The meta-analysis showes that high expression of oncogenic circRNAs is associated with poorer overall survival (HR = 2.27, 95
Introduction:Surgical resection is controversial in treating primary central nervous system lymphoma (PCNSL). This study aimed to elucidate the prognostic role of resection based on treatment- and survival-related tumor localizations. Methods:Magnetic resonance imaging (MRI) data of 122 untreated PCNSL patients from January 2007 to October 2021 were analyzed. Images were registered to a standard anatomical template, followed by lesion segmentation. Analysis of differential involvement (ADIFFI) identified statistically significant voxel-wise clusters using P-value heatmaps. Overall survival (OS) and progression-free survival (PFS) were evaluated via Kaplan-Meier analyses. Multivariate Cox regression was performed to identify independent prognostic factors. Results:Favorable but non-significant trends for OS and PFS were detected in patients receiving resection compared to biopsy. ADIFFI revealed that clusters in superficial frontal and parietal areas were more likely to receive resection, whereas deep-seated clusters were more inclined to be biopsied. Superficial localization also predominated in patients with OS > 2 years, suggesting the spatial confounding effect. Crucially, by controlling for the dual confounders of tumor location and age, significantly prognostic advantages for resection over biopsy were identified in patients with superficial PCNSLs aged ≤ 70 years. Further Cox regression in this subgroup demonstrated that surgical resection, particularly gross total resection, emerged as an independent protective factor for OS. Conclusions:The historically perceived limited benefit of resection in PCNSL may be confounded by tumor localization and patient age. For selected patients with superficial lesions aged ≤ 70 years, resection appears to provide survival advantages, offering a reference to refine surgical decision-making.
Background The impact of isolated small airway dysfunction (SAD) or preserved-ratio impaired spirometry (PRISm) on outcomes following laparoscopic hepatectomy remains unclear. Aims This study aimed to evaluate their association with postoperative pulmonary complications (PPCs). Method This single-center retrospective study included 771 patients. Multivariable analyses and propensity score matching (PSM) were employed to compare outcomes between patients with normal spirometry and those with SAD or PRISm. Results The PRISm group was associated with higher ICU admission rates (12.5% vs 5.0%, P = .001) and longer length of stay (LOS) (15.0 vs 12.0 days; P < .001). However, multivariable analysis identified operative duration as the sole independent risk factor for PPCs (OR = 1.200, P < .001). After 1:1 PSM, the matched cohorts (163 pairs vs. SAD; 101 pairs vs. PRISm) showed no significant differences in PPCs or other short-term outcomes. Surgical complexity (duration, transfusion), comorbidities (diabetes, age) and the occurrence of PPCs were the independent factors for prolonged LOS. Conclusion Preoperative SAD and PRISm were not associated with an increased risk of PPCs after laparoscopic hepatectomy. Prolonged LOS was significantly associated with surgical complexity, patient comorbidities, and the development of PPCs, but not with baseline spirometric anomalies.
