Hepatocellular carcinoma (HCC) develops in a chronically injured liver where metabolic adaptation, oxidative stress, innate immune signalling, and immune tolerance are already intertwined. Mitochondria connect these processes: they sustain tumour-cell fitness, yet damaged organelles expose mitochondrial DNA (mtDNA) as an intracellular and intercellular danger signal. Persistent reactive oxygen species, altered mitochondrial dynamics, nucleoid instability, and incomplete mitophagy-lysosomal clearance can oxidise, fragment, and displace mtDNA. The resulting material may remain in the cytosol, circulate freely or in protein-associated complexes, or be transferred within extracellular vesicles. These forms are not immunologically equivalent. Cytosolic mtDNA favours cGAS-STING access; endocytosed material can engage endolysosomal TLR9; and oxidised mtDNA can cooperate with mitochondrial reactive oxygen species, ATP, cardiolipin, and ionic perturbation in NLRP3 inflammasome-associated signalling. Redox remodelling also alters interferon responsiveness, inflammasome competence, and myeloid-cell metabolism, allowing recipient cells to assign different meanings to a similar mitochondrial signal. We integrate these mechanisms into an acute immune activation-chronic immune adaptation continuum. Transient, spatially restricted, and efficiently cleared danger can support antigen presentation and effector recruitment, whereas recurrent or poorly cleared signalling can become embedded in suppressive myeloid remodelling, lymphocyte dysfunction, and spatial immune escape. Direct HCC studies support treatment-induced mtDNA-STING activation, hypoxic extracellular-vesicle-mediated mtDNA transfer, macrophage TLR9 signalling, and TFAM-mtDNA-NLRP3 coupling. The transition between immune states remains a testable synthesis, not an established linear pathway. Therapeutic intervention should be matched to signal form, recipient-cell competence, timing, spatial context, and hepatic reserve; pathway activation alone is an inadequate guide.

Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of several hematological malignancies, but its broader application remains constrained by the complexity, cost, and time required for conventional ex vivo manufacturing. In vivo CAR T-cell therapy has emerged as a promising next-generation strategy that aims to generate CAR T cells directly within the patient through targeted delivery of CAR-encoding genetic information to endogenous T cells. This approach has the potential to simplify treatment workflows, shorten manufacturing timelines, reduce production costs, and improve the accessibility of CAR-based immunotherapy. In this review, we summarize the conceptual evolution from ex vivo to in vivo CAR T-cell therapy and discuss major delivery platforms for in vivo CAR T-cell generation, including engineered lentiviral vectors (LVs), adeno-associated viral vectors, lipid nanoparticles, polymeric nanoparticles, extracellular vesicles, and fusogenic nanovesicles. We further examine key translational challenges and corresponding optimization strategies, including approaches to improve T-cell targeting specificity and delivery controllability, reduce vector immunogenicity, enhance CAR expression persistence, mitigate safety concerns associated with ectopic transduction or genomic integration, and potentially overcome the physical, antigenic, and immunosuppressive barriers encountered in solid tumors. Finally, we summarize early clinical trial progress and discuss future directions for improving the safety, efficacy, and translational potential of in vivo CAR T-cell therapy. Overall, in vivo CAR T-cell therapy represents an important extension of adoptive cell therapy and may reshape the development and clinical implementation of cell-based immunotherapies.

The optimal choice of chemotherapy regimen for resectable colorectal liver metastases (CRLM) is still undetermined. The study aimed to estimate the impact of perioperative or adjuvant chemotherapy on disease-free survival (DFS), and explore the underlying mechanisms which influence chemotherapy efficacy.

Eight hundred twenty-two patients undergoing curative resection of CRLM were retrospectively collected from May 2018 to December 2023. Treatment effects between perioperative and adjuvant chemotherapy were compared in full subgroup analyses by Kaplan-Meier and Cox proportional hazards methods. Single-cell RNA sequencing and tumor derived organoids were used to explore the molecular mechanisms.

After propensity score matching, 630 patients were enrolled with ratio 1:1 in adjuvant and perioperative chemotherapy group. The median DFS in adjuvant and perioperative group was comparable with 28 and 32.5 months, respectively (HR = 0.99, P = 0.945). Perioperative chemotherapy was associated with improved DFS (25 vs. 13 months, P = 0.039) in patients with a clinical risk score (CRS) of 5. Notably, within the high-risk CRS 4-5 population receiving perioperative chemotherapy, patients with chronic hepatitis B (CHB) had significantly worse DFS (HR = 4.31, 95% CI 1.93-9.64; P < 0.001). Single-cell analyses revealed TSPAN8⁺ stem-like epithelial cells were enriched in sample with CHB. TSPAN8 knockdown sensitized colorectal cancer cells to 5-fluorouracil, and anti-TSPAN8 antibody showed synergistic efficacy with 5-fluorouracil in patient-derived liver metastasis organoids. In addition, the enhanced SPP1-CD44 signaling between TSPAN8⁺ epithelial cells and SPP1⁺ macrophages also contributed to 5-fluorouracil resistance.

Higher CRS identify a subgroup of CRLM patients who may derive greater benefit from perioperative chemotherapy. HBV-related serological profiles is a potential predictor of chemotherapy resistance. The exploratory findings warrants further validation.

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms of the gastrointestinal tract. They most often arise in the stomach, followed by the small intestine. Small bowel GISTs usually present with gastrointestinal bleeding, anemia, abdominal pain, or nonspecific symptoms, whereas intestinal obstruction is uncommon because these tumors typically grow outward from the bowel wall. We report the case of a 58-year-old woman with no previous abdominal surgery who presented with one month of abdominal pain, constipation, and vomiting, which progressed to complete absence of stool and flatus for 48 hours. CT and MRI showed a 4.5-cm exophytic distal ileal mass with multiple peritoneal nodules and no liver lesions or lymphadenopathy. Because of the obstructive presentation, exploratory laparoscopy was performed. Intraoperative findings showed a stenosing ileal tumor and diffuse peritoneal implants. Frozen-section analysis of two nodules suggested metastatic GIST, and segmental ileal resection with primary anastomosis was performed to relieve the obstruction and establish a definitive diagnosis. Histology showed a spindle-cell GIST positive for KIT (CD117) and DOG1, with a mitotic rate of 4/50 high-power fields. The peritoneal nodules were metastatic implants. The postoperative course was uneventful, and imatinib 400 mg daily was started one week later. After nearly two years of clinical and radiological follow-up, the patient remained stable without disease progression. This report highlights that ileal GIST should be considered in cases of unexplained small bowel obstruction, especially when imaging shows an exophytic mass without lymphadenopathy.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder, often beginning in adolescence and associated with reproductive, metabolic, and psychological complications. The present study evaluated whether adolescent patients meeting the 2023 adolescent-specific PCOS criteria (Rotterdam phenotypes A and B) exhibit poorer mental health or lower quality of life (QoL) in adulthood compared with those with Rotterdam PCOS phenotypes C and D.

A retrospective analysis was conducted among women previously hospitalized in pediatric endocrinology wards and diagnosed with PCOS during adolescence. Clinical data, hormonal profiles, and comorbidities were extracted from medical records. The study group [SG] comprised patients with Rotterdam PCOS phenotypes A and B, while the comparison group [CG] included phenotypes C and D and adolescents at risk of PCOS. In adulthood, participants completed a 66-item survey including self-reported BMI, menstrual symptoms, Ferriman-Gallwey scoring, comorbidity assessment, the Patient Health Questionnaire-9 (PHQ-9), and the WHOQOL-BREF.

A total of 46 individuals completed the survey, including 32 participants in the SG and 14 in the CG. The median age was 22.5 years in the SG and 21.5 years in the CG. All participants were Polish. During adolescence, SG and CG differed in testosterone levels (p = 0.0007) and number of patients with menstrual irregularities (p = 0.006). In adulthood, no significant between-group differences were observed in BMI, Ferriman-Gallwey scores, PHQ-9 outcomes, or WHOQOL-BREF domain scores. The distribution of depressive symptom severity did not differ significantly. Moreover, no correlations were found between QoL or depressive symptoms and BMI change, disease duration or hirsutism. However, mean PHQ-9 scores in both groups indicated clinically relevant depressive symptoms.

Adult women diagnosed with PCOS (Rotterdam phenotypes A and B) in adolescence did not exhibit poorer quality of life or increased depressive symptoms compared with women presenting Rotterdam PCOS phenotypes C and D or adolescents previously classified as being at risk of PCOS. No significant differences were observed between groups in PHQ-9 or WHOQOL-BREF scores, nor were these outcomes related to BMI, hyperandrogenism, or disease duration. Both groups demonstrated elevated depressive symptom levels, highlighting the need for longitudinal studies on long-term psychological outcomes in PCOS.

Acute appendicitis remains a common surgical emergency. The COVID-19 pandemic severely impacted all the health systems globally including surgical emergencies management. This study aimed to assess changes in diagnosis and treatment of acute appendicitis in a tertiary emergency hospital serving an urban population before, during, and after the COVID-19 years.

This was a population-based cohort study including consecutive ≥ 18-year-old residents of a metropolitan area presenting with acute appendicitis at the tertiary emergency hospital. The study period between January 2018 and December 2023 was divided into: 2018-2019 (pre-COVID-19); 2020-2021 (COVID-19); 2022-2023 (post-COVID-19). Comparisons among the three periods were performed using one-way ANOVA and the Chi-square or Fisher's exact test as appropriate.

The breakdown of 1,721 patients included was: 662 in 2018-2019, 422 in 2020-2021, and 637 in 2022-2023. Although the catchment area population (1,817 vs. 1,799 vs. 1,781 MM; p = 0.2), 27 surgeons (27 vs. 27 vs. 27), and 107,202 CT scans (32,048 vs. 38,806 vs. 36,348; p = 0.716) were stable, colonoscopies significantly decreased in 2020-2021 (4,588 vs. 2,457 vs. 4,204; p = 0.012). The number of patients presenting with acute appendicitis decreased during the pandemic, with a relative increase in complicated cases. However, complication and mortality rates did not differ. The postoperative length of stay did not change significantly, despite the increased laparoscopic access rates. The appendiceal neoplasm rates were 2.4% in the COVID-19 and 1.9% in the post-COVID-19 year groups.

This six-year population-based study found a decreased number of patients presenting with acute appendicitis during the pandemic years, with a relative increase in complicated cases but no difference in mortality rates. The rates of appendiceal neoplasms raise concerns regarding the offering of conservative treatment.

Acute lymphoblastic leukemia (ALL) is a common type of acute leukemia and is essentially a malignant clonal proliferative disorder of hematopoietic stem cells. Currently, the widespread application of high-dose chemotherapy combined with allogeneic hematopoietic stem cell transplantation (allo-HSCT) has significantly improved patient survival and has become the most effective therapeutic strategy for ALL. However, relapse remains a major challenge after transplantation. Most relapses occur in the bone marrow, whereas extramedullary relapse is relatively uncommon, and relapse involving the female reproductive system is extremely rare. Herein, we report a case of ALL with uterine and ovarian relapse after allo-HSCT. Extramedullary relapse was confirmed by pelvic mass biopsy. The patient subsequently received combined treatment with chemotherapy, radiotherapy, and chimeric antigen receptor T‑cell (CAR‑T) immunotherapy, resulting in complete regression of the uterine and ovarian lesions and achieving clinical remission. It should be noted that relapse of acute leukemia in the reproductive system after transplantation can be easily misdiagnosed as a primary malignancy of the reproductive system. Therefore, accurate differentiation between primary and secondary tumors and early initiation of effective treatment are essential. In clinical practice, diagnostic accuracy should be improved by integrating the patient's clinical history with magnetic resonance imaging (MRI) findings, thereby avoiding unnecessary surgical trauma and improving long‑term prognosis.

Dysregulation of mitophagy contributes to the initiation and progression of hepatocellular carcinoma (HCC). Nuclear protein localization 4 homolog (NPLOC4) is an essential protein involved in various cellular processes and has been implicated in multiple cancers. Recent studies have suggested that NPLOC4 participates in the regulation of mitophagy; however, its role in HCC remains unclear. This study aims to investigate the role of NPLOC4 in mitophagy and its underlying regulatory mechanisms in HCC.

RNA sequencing data from the GSE277232 and GSE251942 datasets obtained from the Gene Expression Omnibus (GEO) database were analyzed together with mitophagy-related genes collected from the GeneCards database to identify differentially expressed mitophagy-related genes in HCC. NPLOC4 expression was further analyzed and validated by Western blotting. Small interfering RNA (siRNA)-mediated knockdown of NPLOC4 was performed in HCC cells for functional loss-of-function assays. Mitophagy levels were evaluated by analyzing the expression of mitophagy-related proteins, transmission electron microscopy, and immunofluorescence staining.

Bioinformatics analysis identified NPLOC4 as a key differentially expressed mitophagy-related gene. NPLOC4 was significantly upregulated in HCC tissues and was associated with poor clinical prognosis (all P<0.05). Knockdown of NPLOC4 inhibited HCC cell proliferation, migration, and invasion, while promoting apoptosis (all P<0.05). In addition, NPLOC4 knockdown suppressed mitophagy and the Wnt/β-catenin signaling pathway in HCC cells (all P<0.05). Treatment with the Wnt agonist BML-284 abolished the inhibitory effect of NPLOC4 knockdown on mitophagy (P<0.05), indicating that NPLOC4 regulates mitophagy through activation of the Wnt/β-catenin pathway. Furthermore, treatment with the mitophagy inducer carbonyl cyanide m-chlorophenyl hydrazone (CCCP) reversed the inhibitory effects of NPLOC4 knockdown on HCC cell proliferation, migration, and invasion (all P<0.05), suggesting that NPLOC4 silencing suppresses HCC progression by regulating mitophagy.

NPLOC4 is highly expressed in HCC. Downregulation of NPLOC4 inhibits activation of the Wnt/β-catenin signaling pathway, thereby inhibiting mitophagy and ultimately inhibiting HCC cell proliferation, migration, and invasion. These findings suggest that NPLOC4 may serve as a potential biomarker and therapeutic target for HCC.

Recent trials support omitting axillary lymph node dissection (ALND) in selected sentinel node-positive patients, but those with preoperative biopsy-proven nodal metastasis remain underrepresented. We characterized axillary nodal burden and its preoperative predictors.

We retrospectively studied patients with cT1-3 breast cancer and biopsy-proven axillary metastasis who underwent upfront ALND between 2008 and 2023 with at least one positive node. Nodal burden was classified as limited (1-2 positive nodes) or extensive (≥3). Multivariable logistic regression identified predictors.

Among 1671 patients (median 21 nodes retrieved), 662 (39.6%) had limited and 1009 (60.4%) had extensive nodal burden. Suspicious node count on axillary ultrasound (AUS) was independently associated with extensive burden (two nodes: OR 2.26, 95% CI 1.64-3.12; ≥3 nodes: OR 2.08, 1.67-2.59; both p < 0.001), as was higher clinical T stage (cT2: OR 1.35, p = 0.009; cT3: OR 1.57, p = 0.008). Extensive burden ranged from 41.0% (cT1, one suspicious node) to 75.0% (cT3, two suspicious nodes). The AUS ≥3 and AUS 2 groups did not differ for ≥3 positive nodes but differed for ≥10 positive nodes (24.8% vs. 14.0%). Among 574 patients with a non-palpable axilla, AUS remained associated with extensive burden whereas clinical T stage did not.

Extensive nodal burden was common yet heterogeneous. AUS suspicious node count and clinical T stage were associated with extensive disease, but discrimination was modest. These findings do not support uniform omission of ALND and require prospective validation.

This study aimed to examine sexual quality of life (SQoL) and its associated factors among women with endometrial cancer, including menopausal symptoms, body image, sexual knowledge, and sexual function.

A cross-sectional observational study was conducted. A total of 113 women with endometrial cancer were recruited using convenience sampling. Data were collected through electronic questionnaires assessing demographic and clinical characteristics and key study variables. Hierarchical multiple regression analysis was performed to identify significant predictors of SQoL. The study was reported in accordance with the STROBE checklist for cross-sectional studies.

The mean SQoL score was 68.86 (SD = 20.59), with 37.2% of participants reporting low to moderate levels. Significant factors associated with SQoL included body mass index (β = -0.17), receipt of radiotherapy (β = -0.28), menopausal symptoms (β = -0.20), body image distress (β = -0.26), and sexual function (β = 0.38). The final model explained 46% of the variance (p < 0.001), with sexual function emerging as the strongest predictor.

SQoL among endometrial cancer survivors was associated with physiological, psychological, and functional factors. Sexual function showed the strongest association with SQoL, whereas receipt of radiotherapy and greater body image distress were associated with poorer SQoL. These findings highlight the importance of comprehensive survivorship care that includes routine assessment of sexual function, symptom management, body image support, and sexual rehabilitation. An integrated, multidisciplinary approach may help address the complex physical, psychological, and relational factors associated with sexual quality of life among endometrial cancer survivors.