ObjectiveProgrammed cell death protein-1 (PD-1) and cluster of differentiation (CD) 28 (CD28) are representative stimulatory and inhibitory signals that regulate T cell function. This retrospective study aimed to evaluate alterations in peripheral PD-1- and CD28-positive T cell populations in patients with benign pulmonary nodules and non-small cell lung cancer (NSCLC).MethodsKaplan-Meier plotter was used to analyze the prognostic value of PD-1 and CD28 expression in NSCLC. Flow cytometry was used to detect T cell subsets in peripheral blood. Serum tumor markers were detected using a chemiluminescent analyzer. Cytokine levels were detected by Cytometric Bead Array.ResultsA total of 526 patients with NSCLC (early stage: 251; advanced stage: 275), 55 patients with benign pulmonary nodules, and 33 healthy participants were included. Kaplan-Meier plotter analysis showed that higher PD-1 expression was correlated with poorer survival in patients with lung adenocarcinoma), whereas higher CD28 expression was correlated with favorable survival in patients with lung adenocarcinoma and lung squamous cell carcinoma. Compared with healthy controls, the proportion and number of peripheral PD-1+CD3+ T cells and PD-1+CD4+ T cells were significantly increased in patients with benign pulmonary nodules and NSCLS. The numbers of CD28+CD3+ T cells and CD28+CD4+ T cells were lower in patients with NSCLC than in healthy controls. Notably, there were no differences in PD-1+ or CD28+ T cells between patients with benign pulmonary nodules and NSCLC. The numbers of PD-1+ and CD28+ T cells were lower in patients with advanced NSCLC than in those with early NSCLC. Additionally, the levels of serum tumor markers (carcinoembryonic antigen, neuron-specific enolase, cancer antigen 125, cytokeratin 19 fragment antigen 21-1, and cancer antigen 50) were not different between patients with benign pulmonary nodules and early NSCLC but were higher in patients with advanced NSCLC. Moreover, serum interleukin 6 and interferon-γ levels were higher in patients with advanced NSCLC than in those with benign pulmonary nodules and early NSCLC.ConclusionIncreased PD-1 and decreased CD28 suggest potential T cell dysfunction in patients with benign pulmonary nodules and NSCLC. Patients with benign pulmonary nodules showed characteristics similar to those of patients with early NSCLC with respect to PD-1+/CD28+ T cells, tumor markers, and cytokines.

Advances in immunotherapy for acute myeloid leukemia (AML) have revealed critical gaps in selection of appropriate preclinical models. Conventional cytotoxic and targeted therapies could be tested in relatively straightforward systems. Immunotherapies are inherently distinct from conventional therapies, as their activity is shaped by dynamic, context-dependent interactions between leukemic cells, immune effectors, and the bone marrow microenvironment that are difficult to replicate outside the patient. Failure to recapitulate these interactions may limit the clinical translatability of promising results. Recognizing these shortcomings, the field has moved through several generations of modeling platforms. Existing platforms capture distinct but incomplete aspects of AML biology: in vitro systems offer control but lack immune context, syngeneic models provide intact immunity but limited human relevance, patient-derived xenograft (PDX) models preserve patient biology but lack immunity, and humanized models partially integrate both but remain constrained. In this review, we trace the development of these systems and use that trajectory to build a practical framework for model selection in AML immunotherapy research. Translational relevance depends on selecting preclinical models that align with the specific therapeutic question, rather than relying on availability or perceived complexity. To operationalize this, we propose a mechanism-driven framework that maps therapeutic mechanisms to the most appropriate biological contexts across preclinical platforms. This framework progresses sequentially from controlled mechanistic studies to in vivo validation, guiding model selection at each stage. Instead of prioritizing any single system, it emphasizes a complementary, question-driven approach that leverages the distinct strengths of each model while accounting for their limitations.

Neoadjuvant immunotherapy/targeted therapy combined with chemotherapy shows encouraging activity for oropharyngeal squamous cell carcinoma (OPSCC). However, evidence specific to tonsillar squamous cell carcinoma (TSCC) remains limited, particularly regarding the systematic relationships among radiological response, pathologic response, margin control, and voice and swallowing functional outcomes.

This single-arm, single-center study included patients with pathologically confirmed TSCC diagnosed between January 2024 and June 2025. Patients received triplet neoadjuvant therapy consisting of nimotuzumab, toripalimab, nab-paclitaxel, and carboplatin every 3 weeks for 2 cycles, followed by transoral radical tonsillectomy combined with radical cervical lymph node dissection. Radiologic response was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and volumetric magnetic resonance imaging (MRI). Pathologic response, margin status, perioperative safety, adjuvant treatment, and functional outcomes were evaluated.

Twenty patients achieved clinicopathologic downstaging after surgery. The primary-site pCR rate was 65.0%, nodal pCR was 60.0%, and overall ypT0N0 pCR was 45.0%. The objective radiological response (ORR) rate of the primary lesion was 100%, and 9 patients (45%) achieved a complete radiological response. Mean primary-tumor and dominant-node volume reductions were 76.18% and 72.59%, respectively. Both pre- and postneoadjuvant margins were negative in all patients, yielding R0 resection in all cases. Functional scores improved after neoadjuvant therapy, worsened transiently during radiotherapy, and generally recovered during follow-up.

Nimotuzumab plus toripalimab and chemotherapy produced high radiological and pathological response rates with reliable margin control in patients with locally advanced TSCC. Postneoadjuvant boundary assessment with intraoperative pathologic verification may support individualized resection planning, but routine resection of the primary lesion and cervical lymph node dissection remain necessary. Longer follow-up and prospective validation are required to confirm these results.

https://clinicaltrials.gov/study/, identifier NCT07353723.

Indeterminate thyroid cytology is among the most challenging bottlenecks in thyroid nodule management and continues to be a significant source of risk stratification ambiguity and potentially preventable diagnostic surgeries. While molecular analysis has helped refine preoperative risk stratification, especially among Bethesda III (AUS) and Bethesda IV (FN/SFN) thyroid nodules, issues remain regarding positive predictive value, availability, and subsequent malignancy risk, even among those having the "negative" molecular risk assessment. The field of artificial intelligence (AI) is presently experiencing an accelerated trajectory of expansion into thyroid diagnostic fields, extending initially from thyroid ultrasound into the realms of whole-slide cytology analysis and computational pathology. The purpose of this narrative review is to highlight the changing landscape of AI applications in the context of the workup of indeterminate thyroid nodules, focusing on thyroid cytology and decision support for indeterminate thyroid nodules. It is becoming clear from the evidence that AI has the potential to decrease subjectivity and variability in cytology/Whole-Slide Imaging (WSI) analysis, optimize the selection of candidates for biopsy in the upstream process, and optimize post-FNA evaluation by fusion of molecular analysis in the downstream process. Future application will depend upon validation, standardization, and prospectively conducted studies in patients.

The optimal timing of ruxolitinib initiation for acute graft-versus-host disease (aGVHD) prophylaxis after myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains undefined, particularly within anti-thymocyte globulin (ATG)-based platforms. This study compared immediate versus delayed short-course ruxolitinib initiation using a concurrent two-strategy design.

This single-center, retrospective, concurrent two-strategy cohort study enrolled 39 consecutive patients aged 15-65 years with hematologic malignancies who received standard "Beijing Protocol" backbone plus a 14-day short-course ruxolitinib. Patients were non-randomly assigned to immediate (day +1; n = 19) or delayed (at confirmed neutrophil engraftment; median day +13; n = 20) initiation. Haploidentical transplantation and ATG use were perfectly collinear in this cohort, complicating attribution of outcome differences. Co-primary endpoints were 100-day cumulative incidence of grade II-IV aGVHD and 2-year overall survival (OS). A 1:1 propensity score matching (PSM) analysis (12 pairs) served as a sensitivity analysis. Given the limited sample size, multivariable models were constructed as exploratory analyses and should be interpreted with caution.

Delayed initiation was associated with lower 100-day grade II-IV aGVHD (10.0% vs. 42.1%, P = 0.031), lower cytomegalovirus (CMV) reactivation (35.0% vs. 73.7%, P = 0.025), reduced grade ≥3 hematologic toxicity (35.0% vs. 68.4%, P = 0.043), and superior 2-year OS rate (90.0% vs. 57.9%, P = 0.012). PSM confirmed these findings (aGVHD: 8.3% vs. 41.7%, P = 0.039; OS: 91.7% vs. 58.3%, P = 0.028). In the exploratory haploidentical subgroup (n = 26), grade II-IV aGVHD was 11.8% vs. 55.6% (P = 0.028) and OS was 94.1% vs. 55.6% (P = 0.006). In exploratory multivariable models, immediate initiation was associated with higher aGVHD risk [adjusted subdistribution hazard ratio (sHR) 2.31, 95% CI 1.15-4.64, P = 0.019] and higher NRM (adjusted sHR 4.65, 95% CI 1.47-14.72, P = 0.009). Relapse risk was not significantly different (adjusted sHR 2.17, 95% CI 0.85-5.56, P = 0.095). Pre-transplant measurable residual disease (MRD) positivity was associated with inferior OS (adjusted hazard ratio [HR] 7.81, 95% CI 1.12-54.32, P = 0.038). Median follow-up was 42.1 months. Interpretation of the CMV reactivation difference is limited by the absence of donor and recipient CMV serostatus data.

Delaying short-course ruxolitinib until neutrophil engraftment was associated with reduced aGVHD and NRM and improved survival after myeloablative allo-HSCT. No statistically significant difference in relapse risk was observed, although a clinically meaningful difference cannot be excluded. These findings warrant confirmation in a multicenter randomized trial with adequate sample size, stratified by donor type and pre-transplant MRD.

To explore the lived experiences of social alienation among Chinese women with gynecologic malignancies and identify the meanings they attached to social withdrawal and reconnection.

This descriptive phenomenological study was conducted in a tertiary hospital in Hangzhou, China, in April 2025. Twelve women with histopathologically confirmed gynecologic malignancies were recruited through purposive sampling with maximum variation. Semi-structured face-to-face interviews were audio-recorded, transcribed verbatim, and analyzed using Colaizzi's seven-step phenomenological method.

Three themes and eight subthemes were identified. Participants described withdrawing from others to protect a threatened identity, including concealing the illness to avoid attention and restricting daily movement and social contact. They also described living in a body that feels changed and exposed, reflected in physical exhaustion and functional limits, changes in appearance and anticipated judgment, and concerns about family reputation and financial strain. Finally, they expressed a desire for understanding and a return to normal life, including feeling misunderstood in relationships and work and seeking work, normality, and meaningful connection. Across accounts, social alienation appeared to arise from the interaction of symptom burden, visible treatment effects, anticipated social judgment, practical constraints, and limited opportunities for understanding and support.

Social alienation among women with gynecologic malignancies is a multidimensional experience shaped by bodily change, social responses, and practical barriers to participation. Supportive care should include psychosocial assessment, family-informed communication, peer support, and individualized assistance with social and occupational reintegration.

Older adults with oral cavity squamous cell carcinoma (OCSCC) are underrepresented in clinical trials, and the comparative effectiveness of surgery versus definitive radiotherapy with or without chemotherapy (RT ± CT) remains uncertain.

To compare all-cause and OCSCC-specific mortality after curative-intent surgery versus definitive RT ± CT in older adults with newly diagnosed OCSCC.

Nationwide, population-based retrospective cohort study using linked registry and claims data. Propensity score fine stratification weighting (PS-FSW) and multivariable Cox proportional hazards models were used to reduce treatment selection bias.

Taiwan Cancer Registry, National Health Insurance Research Database, and Taiwan Death Registry.

Patients aged ≥65 years with newly diagnosed, nonmetastatic, pathologically confirmed OCSCC between January 1, 2009, and December 31, 2022.Intervention or Exposures:Curative-intent surgery, with or without adjuvant therapy, compared with definitive RT ± CT delivered with curative-intent.

All-cause mortality and OCSCC-specific mortality.

Among 1275 eligible patients, 492 underwent curative-intent surgery and 783 received definitive RT ± CT. After PS-FSW, baseline characteristics were well balanced. Surgery was associated with lower all-cause mortality (adjusted hazard ratio [aHR] 0.59; 95% confidence interval [CI] 0.51, 0.69; P < .0001) and lower OCSCC-specific mortality (aHR 0.63; 95% CI 0.51, 0.78; P < .0001) compared with definitive RT ± CT. The survival benefit persisted across age strata, including patients aged ≥85 years.

Curative-intent surgery was associated with superior all-cause and cancer-specific survival compared with definitive RT ± CT among older adults with OCSCC.

Chronological age alone should not preclude surgical consideration in older adults with OCSCC. Treatment decisions should incorporate physiologic fitness, comorbidity burden, geriatric assessment, and multidisciplinary evaluation; future studies should further evaluate treatment-related toxicity, functional outcomes, and quality-of-life.

To evaluate the feasibility, safety, and short-term oncological and functional outcomes of repeat robot-assisted partial nephrectomy (RAPN) for ipsilateral local recurrence of renal cell carcinoma after partial nephrectomy (PN) and describe the relevant surgical strategies.

We retrospectively evaluated eight consecutive patients who underwent repeat RAPN between April 2019 and January 2026. Patient characteristics, perioperative outcomes, renal function, pathological findings, and adhesion severity were analyzed. Intraoperative adhesions were graded as minor or severe based on the surgeon's assessment.

Eleven ipsilateral recurrent tumors were analyzed in eight patients. Repeat RAPN was successfully performed in all patients without conversion to open surgery or radical nephrectomy. The median operative time, warm ischemia time, and estimated blood loss were 157 min, 15 min, and 50 mL, respectively. No major (Clavien-Dindo grade ≥ III) complications occurred. All malignant tumors were pT1a with negative surgical margins. At the median follow-up of 17.5 months, no local recurrence or distant metastasis was observed. The median eGFR values at 1 and 3 months were 57.1 and 55.7 mL/min/1.73 m², respectively. Severe adhesions were more common among patients who did not receive anti-adhesion agents during initial surgery.

Repeat RAPN may be a feasible and safe salvage option for ipsilateral recurrence after PN, with acceptable early oncological and functional outcomes. Our findings suggest that anti-adhesion agent use during the initial PN may be associated with reduced adhesion-related difficulty during subsequent reoperations, although further validation is needed.

As population aging accelerates, patients aged ≥ 75 years represent a growing proportion of those diagnosed with ampullary tumors. Endoscopic papillectomy (EP) is an established minimally invasive treatment for ampullary adenoma; however, treatment selection in older patients requires careful consideration of oncologic benefit, procedural risk, geriatric vulnerability, and life expectancy. This review outlines key geriatric assessment tools and evaluates the safety, prognosis, and treatment selection of endoscopic and surgical approaches for ampullary tumors in older patients. With appropriate selection, short-term EP outcomes appear comparable between older and younger patients. However, EP can cause fatal adverse events and often requires long-term surveillance or retreatment. In older patients, long-term prognosis is strongly influenced by comorbidity burden and competing mortality, with a high age-adjusted Charlson Comorbidity Index associated with poorer overall survival. Natural history data from familial adenomatous polyposis and colorectal adenomas provide an indirect time-axis framework for considering surveillance in selected high-risk patients. Management of ampullary tumors in older patients should be guided by integrated assessment of oncologic and geriatric factors rather than chronological age alone. Standardized geriatric assessment may help identify patients best suited for intervention or surveillance. Prospective studies incorporating functional outcomes, quality of life, and treatment-related mortality are needed to support evidence-based decision-making.

Colorectal cancer (CRC) commonly evolves through precursor adenomatous polyps; however, reliable non-invasive biomarkers capable of distinguishing benign from malignant colorectal lesions remain limited. Circulating microRNAs have emerged as promising molecular indicators of tumour initiation and progression.

This study aimed to evaluate the diagnostic, prognostic, and mechanistic relevance of circulating miR-375 and miR-182 in patients with colorectal polyps and colorectal cancer. In addition, their performance was compared with conventional tumour markers and immunohistochemical staining of the tissues with caspase-3 was performed to assess apoptotic activity in malignant and adenomatous tissue.

A total of 450 participants were enrolled, including 150 patients with CRC, 150 patients with colorectal polyps, and 150 healthy controls. Clinical, anthropometric, biochemical, histopathological, and immunohistochemical data were collected. Circulating miRNA-375 and miRNA-182 expression levels were quantified and correlated with clinicopathological parameters. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) curve analysis, and logistic regression models were applied to identify independent predictors of CRC. Immunohistochemical staining for caspase-3 was performed on tissue samples.

miR-375 expression showed a progressive and significant downregulation from controls to polyps and CRC, whereas miR-182 demonstrated marked upregulation across the same spectrum (both p < 0.001). miR-375 and miR-182 exhibited excellent diagnostic performance for CRC detection. Logistic regression analysis identified miR-375 (OR = 0.003, p = 0.002) and miR-182 (OR = 8.254, p = 0.001) as independent predictors of CRC. Caspase positivity independently predicted lymph node metastasis (OR = 12.038, p = 0.004). miR-375 demonstrated significant inverse correlations with CEA and CA 19-9 levels.

The reciprocal dysregulation of miR-375 and miR-182 reflects a molecular transition from benign colorectal polyps to invasive CRC. These circulating miRNAs exhibit superior diagnostic accuracy compared with conventional tumour markers and may represent valuable non-invasive tools for early detection and risk stratification of colorectal cancer.