PurposeTo investigate the dynamic changes of frailty and its associated factors in patients with non-Hodgkin lymphoma during chemotherapy.MethodUsing a convenience sampling method, 266 patients with non-Hodgkin lymphoma hospitalized in the Department of Hematology at five tertiary hospitals in China were recruited from January to August 2025. General information, frailty, cognition, physical performance, nutrition, and anxiety were investigated before chemotherapy (T0), at the third cycle (T1), and at the end of chemotherapy (T2). Generalized Estimating Equations were utilized to analyze the factors related to frailty.ResultsFinally, 252 patients completed the longitudinal follow-up. The mean frailty scores were 4.31 ± 2.46 (T0), 5.22 ± 2.59 (T1), and 4.50 ± 2.65 (T2). Generalized estimating equations results indicated that factors significantly associated with frailty included sociodemographic factors (level of education), treatment-related variables (dose reduction, treatment delay), nutritional and inflammatory factors (appetite loss, lymphocyte count, hemoglobin, C-reactive protein, CONUT score), physical function factors (grip strength, SPPB score), cognitive function (MoCA-B score), and psychological status (GAD-7 score) (P < 0.05).ConclusionsA substantial proportion of patients with non-Hodgkin lymphoma meet criteria for frailty during chemotherapy, with prevalence peaking at 59.3% at the end of the third cycle, and the observed trajectory of initial increase followed by decrease warrants cautious interpretation given the observational design. Dynamic monitoring and individualized supportive care are recommended, though interventional studies are needed to confirm whether frailty can be genuinely modified.
BackgroundPiwi-interacting RNAs (piRNAs) are increasingly recognized as important regulators in tumor biology. However, which specific piRNAs actively suppress the progression and metastasis of lung adenocarcinoma (LUAD), and the mechanisms involved, remain largely undefined. This study aimed to identify tumor-suppressive piRNAs in LUAD and clarify their functional regulatory axis.MethodsSmall RNA sequencing was used to profile piRNA expression in LUAD tissues. Gain-of-function experiments were carried out by overexpressing piR-131582 in A549 and H1299 cell lines. Colony formation assays, flow cytometry, and Transwell assays were performed to evaluate cell proliferation, apoptosis, migration, and invasion, respectively. A mouse xenograft model was utilized to assess in vivo tumor growth. Bioinformatics prediction, combined with rescue experiments, was applied to identify and validate the downstream target of piR-131582.ResultsWe found that piR-131582 was significantly downregulated in LUAD tissues. Overexpression of piR-131582 suppressed colony formation, migration, and invasion in vitro, while promoting apoptosis. In parallel, it notably inhibited the growth of LUAD xenograft tumors in vivo. Mechanistically, piR-131582 directly targeted and degraded USP22. Re-introducing USP22 effectively reversed the anti-tumor effects induced by piR-131582, restoring the epithelial-mesenchymal transition (EMT) phenotype and reactivating EMT-related signaling pathways.ConclusionsOur results establish the piR-131582/USP22 axis as a critical tumor-suppressive node in LUAD. Restoring this natural inhibitory pathway may represent a promising direction for future therapeutic investigation in LUAD.
IntroductionPembrolizumab-based bladder preservation strategies are increasingly applied in invasive high-grade urothelial carcinoma, yet checkpoint inhibitor pneumonitis (CIP) remains an underrecognized, potentially fatal adverse event. Diagnosis can be markedly delayed when concurrent infection is present.Case presentationA 63-year-old man with invasive high-grade urothelial carcinoma developed complete tumor response after receiving disitamab vedotin plus pembrolizumab following chemotherapy intolerance. He subsequently presented with urinary tract infection and septic shock. Aggressive anti-infective and hemodynamic support promptly reversed shock and normalized systemic inflammatory markers. Nevertheless, follow-up chest computed tomography demonstrated persistent bilateral ground-glass opacities and consolidation without any improvement. Pre-treatment chest radiography had been normal, positron emission tomography–computed tomography showed marked bilateral pulmonary fluorodeoxyglucose uptake without bladder recurrence, and extensive microbiological workup excluded uncontrolled infection. The dissociation between well-controlled infection and stationary pulmonary lesions, together with typical imaging features, raised strong suspicion of pembrolizumab-induced CIP.ConclusionIn patients receiving PD-1 inhibitors, persistent pulmonary infiltrates despite effective anti-infective therapy should raise strong suspicion of checkpoint inhibitor pneumonitis and prompt dedicated diagnostic evaluation. This phenotype—the dissociation between resolving systemic infection and stationary lung lesions—may serve as a practical clue to consider CIP earlier, particularly when invasive diagnostic tools are unavailable; however, it is a suggestive rather than confirmatory finding and requires validation in larger cohorts.
Colorectal cancer with proficient mismatch repair (pMMR)/microsatellite stable (MSS) status is generally intrinsically resistant to immune checkpoint inhibitors; tumors with concomitant BRAF V600E mutations are highly aggressive, and conventional chemotherapy and targeted therapies have limited efficacy, resulting in a lack of effective personalized treatment options in clinical practice. This report describes a case of locally advanced right-sided colon adenocarcinoma that was pMMR/MSS, harbored a BRAF V600E mutation, and exhibited high programmed death-ligand 1 (PD-L1) expression (tumor proportion score [TPS] > 95%). The patient developed intestinal obstruction after failure of first-line conversion therapy. After undergoing palliative gastrojejunostomy and cecostomy, she developed gastroparesis and a liver abscess. Given the extremely high PD-L1 expression, tislelizumab monotherapy was initiated before the patient’s general condition had fully recovered. After three cycles, the patient’s performance status improved significantly. She then received a combination of tislelizumab and raltitrexed for two cycles; however, chemotherapy was discontinued due to raltitrexed-induced liver injury, and the patient continued maintenance therapy with tislelizumab monotherapy, achieving a partial response (PR) as the best outcome. After nine cycles of maintenance therapy, a new mass appeared in the right adnexal region, indicating disease progression; the overall progression-free survival (PFS) was 14 months. To the best of our knowledge, this is the first reported case of a patient with colorectal adenocarcinoma harboring a BRAF V600E mutation, characterized by extremely high PD-L1 expression and pMMR/MSS status, who achieved a PR with a regimen centered on programmed cell death protein 1 (PD-1) inhibitor monotherapy. This case suggests that for BRAF V600E-mutated colorectal cancer, assessment of PD-L1 expression levels should be considered regardless of mismatch repair status; if extremely high PD-L1 expression is present, even in the pMMR/MSS phenotype, PD-1 inhibitors may offer a potential personalized treatment option for these patients with poor prognosis and limited therapeutic choices.
