BACKGROUND: Platinum resistance is a major determinant of poor outcome in advanced epithelial ovarian cancer, yet reliable predictors available before treatment initiation remain scarce. Ascitic fluid is commonly obtained during diagnostic work-up and directly reflects the peritoneal tumour microenvironment, but its cytomorphological information has not been systematically exploited for treatment-response prediction. METHODS: We present OVCAP, a multi-scale deep-learning framework that analyses pretreatment ascites cytology whole-slide images to estimate platinum-resistance risk. The study included 438 patients with FIGO stage IIIB-IV epithelial ovarian cancer. Model performance was evaluated in one internal and two independent external validation cohorts. Attention-guided cytopathology review was performed to identify high-risk morphologic patterns, and integrated single-cell RNA sequencing analyses were used to characterise the underlying biological features. RESULTS: OVCAP achieved area under the receiver operating characteristic curve (ROC-AUC) values of 0.894, 0.863, and 0.828 in the internal and two independent external validation cohorts, respectively, and outperformed the KELIM score (AUC 0.619). Attention-guided cytopathology review identified recurrent high-risk morphologic patterns in resistant disease: epithelial cytoplasmic vacuolization and interaction-rich malignant aggregates accompanied by immune and mesothelial cells. Integrated single-cell analyses linked these phenotypes to membrane remodelling, lipid reprogramming, hypoxia-associated stress signalling, and reinforced adhesion and immunoregulatory networks. CONCLUSION: These findings support pretreatment ascites cytology as a clinically accessible substrate for early risk stratification before first-line platinum-based therapy.

Ovarian cancer is the gynecological malignancy with the highest mortality rate. Platinum resistance remains a major clinical challenge, severely limiting the therapeutic efficacy of cisplatin-based chemotherapy. In recent years, nanomedicine delivery systems have emerged as a promising strategy to enhance the efficacy of conventional cancer treatments. Herein, we constructed a multifunctional graphene oxide-based nanoplatform by functionalizing graphene oxide with hyaluronic acid, gold nanorods, and indocyanine green, followed by loading of cisplatin to form GO-HA-GNRs-ICG@Pt. This nanoplatform exhibits remarkable photothermal and photodynamic conversion efficiency, active tumor-targeting capability, and pH/near-infrared light dual-responsive cisplatin release. More importantly, in vitro and in vivo studies demonstrate that GO-HA-GNRs-ICG@Pt achieves significantly higher therapeutic efficacy and better biosafety compared to cisplatin monotherapy in A2780 ovarian cancer cells. Mechanistically, we discovered that GO-HA-GNRs-ICG@Pt activates the ROS-PINK1/Parkin-mediated mitophagy signaling axis, ultimately enhancing the cisplatin sensitivity of ovarian cancer cells. This work not only provides a theoretical foundation for the development of targeted multifunctional nanoplatforms for integrated cancer therapy but also offers a new synergistic treatment strategy with potential for addressing drug resistance in clinical ovarian cancer.

Multiscale tissue ecosystems are governed by coupled intracellular decision-making, cell-cell interactions, and spatially structured microenvironmental signals, yet these scales are often studied separately. Here we present MISSTE, a modular framework that integrates Boolean intracellular state logic, agent-based modeling, and partial differential equation fields within a unified spatial simulation architecture. As a proof of concept, we applied MISSTE to CAR-T therapy in a solid tumor microenvironment. The model recapitulated emergent features of CAR-T behavior, including limited tumor penetration, stromal suppression, localized cytokine remodeling, hypoxia-associated constraint, and progressive functional exhaustion. Comparison of baseline and optimized conditions showed that coordinated enhancement of interaction range, migration, and cytotoxic function improved immune persistence and partial tumor control. Systematic parameter scans further identified effective immune-tumor contact as a stronger determinant of outcome than killing strength alone, highlighting spatial access as the dominant bottleneck. Guided by these results, we designed sequential intervention strategies and found that time-ordered enhancement of infiltration, killing, and late functional protection outperformed a static optimized regime. Together, these results establish MISSTE as a generalizable multiscale methodology for dissecting tissue ecosystems and for generating mechanistically grounded strategies for engineered cellular therapy design.

OBJECTIVE: To evaluate the comparative efficacy and safety of quetiapine versus haloperidol for delirium treatment in hospitalized adults. DATA SOURCES: Systematic search in MEDLINE (via PubMed), Embase, and Cochrane Central Register of Controlled Trials from inception through February 19, 2026. STUDY SELECTION: RCTs directly comparing quetiapine and haloperidol for delirium treatment in adult inpatients. DATA EXTRACTION: Two reviewers independently extracted data and assessed risk of bias using the Cochrane RoB 2 tool. Primary outcome was change in delirium severity (DRS-R-98). Secondary outcomes included ICU and hospital length of stay (LOS), mortality, sleep duration, and extrapyramidal symptoms (EPS). DATA SYNTHESIS: Four RCTs comprising 292 patients were included. No significant difference was found in delirium severity reduction (MD, -1.99; 95% CI, -4.70 to 0.72; p = 0.15; I = 73.6%), ICU LOS (MD, -0.84 days; 95% CI, -2.30 to 0.62), hospital LOS (MD, -0.06 days; 95% CI, -2.32 to 2.19), or mortality (RR, 0.68; 95% CI, 0.35 to 1.34). Quetiapine showed non-significant trends toward fewer EPS (RR, 0.14; 95% CI, 0.02 to 1.06) and increased sleep duration (MD, 1.59 h; 95% CI, -0.45 to 3.63). TSA indicated the required information size was not reached. CONCLUSIONS: Quetiapine and haloperidol show no statistically significant differences in efficacy or safety for delirium management. GRADE certainty was very low for all outcomes, and TSA confirmed the evidence is inconclusive due to sparse data and imprecision. The absence of statistical significance should not be interpreted as equivalence. Selection should be individualized based on individual patient risk profiles and adverse-effect susceptibility until adequately powered trials are available.

BACKGROUND: Significant liver fibrosis is often clinically silent but predicts adverse outcomes. We developed and externally validated an interpretable machine-learning (ML) framework using readily obtainable demographic, anthropometric, and clinical variables for population-level pre-screening of significant liver fibrosis. METHODS: We included 9424 European participants from the UK Biobank, of whom 1678 were classified as high risk using the Fibrosis-4 Index (FIB-4) ≥ 1.45 or NAFLD Fibrosis Score (NFS) ≥ -1.455. Ten ML algorithms were trained and internally evaluated using a stratified training, validation, and test design. XGBoost was further validated in the 2017-2023 National Health and Nutrition Examination Survey (NHANES; n = 15,270) and an independent real-world cohort (n = 694), in which significant fibrosis was defined as liver stiffness measurement ≥ 8.0 kPa. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC), interpretability by Shapley additive explanations and local interpretable model-agnostic explanations, and prognostic relevance by all-cause mortality. RESULTS: XGBoost achieved AUCs of 0.818 (95% CI, 0.796-0.841) and 0.816 (95% CI, 0.786-0.846) in the internal validation and test cohorts, respectively. In external validation, AUCs were 0.746 (95% CI, 0.735-0.757) in NHANES and 0.793 (95% CI, 0.750-0.836) in the real-world cohort. Interpretation analyses highlighted weight, age, height, hypertension, and waist circumference, with consistent support for anthropometric predictors. Model-defined high-risk status was associated with higher all-cause mortality (log-rank P < 0.001) and remained independently associated with mortality in the internal validation and test cohorts. CONCLUSION: This XGBoost model, based on readily accessible demographic and clinical variables, shows good potential for accurately identifying individuals at high risk of significant liver fibrosis in primary care settings. This approach serves as a valuable tool for improving early detection strategies and facilitating timely interventions for significant liver fibrosis.

BACKGROUND: Bone is the most common metastatic site in Breast cancer, where osteoclast activation contributes to osteolytic destruction. Bufalin (BU) has shown anti-tumor activity in several cancers, but its effects on breast cancer bone metastasis remain unclear. PURPOSE: This study aimed to investigate whether BU suppresses breast cancer-induced osteoclast differentiation and osteolytic bone metastasis, and to explore its underlying mechanism. METHODS: In vivo murine models of breast cancer bone metastasis were used to evaluate the effects of BU on metastatic progression. Osteoclast differentiation and resorptive function were assessed using in vitro and in vivo assays. Biochemical, biophysical, and genetic approaches were employed to identify and validate the direct molecular target of Bu, and downstream signaling pathways regulating osteoclastogenesis were investigated. The clinical relevance of SEC13 (SEC13 homolog, nuclear pore and COPII coat complex component) was analyzed using breast cancer tissue specimens and patient outcome data. Potential combinatorial effects of BU with the RANKL inhibitor denosumab were also briefly evaluated. RESULTS: BU markedly suppressed bone metastasis and inhibited tumor-induced osteoclastogenesis. SEC13 was identified as a molecular target associated with BU treatment and was highly expressed in breast cancer tissues, correlating with poor clinical outcomes. Genetic ablation or pharmacological inhibition of SEC13 in tumor cells significantly reduced osteoclast differentiation and metastatic burden. Mechanistically, SEC13 promoted osteoclastogenesis via HMGB1 release and subsequent activation of the TLR4/NF-κB signaling axis in the bone microenvironment, a process effectively disrupted by BU. Notably, combined treatment with BU further strengthened the suppressive effects of denosumab on osteoclast differentiation and bone metastasis. CONCLUSIONS: BU demonstrates potent pharmacological activity against breast cancer bone metastasis by targeting SEC13 and suppressing tumor-induced osteoclast differentiation. This effect is mediated through inhibition of HMGB1 release and blockade of the TLR4/NF-κB signaling axis, leading to reduced osteoclast formation and inhibition of metastatic progression.

BACKGROUND: The adaptive upregulation of the immune-checkpoint PD-L1 in response to interferon-γ (IFNγ) protects solid tumors from cytotoxic lymphocytes and undermines adoptive cell immunotherapies. Currently, pharmacologically interrupting the trafficking of nascent PD-L1 to the surface of cancer cells is not feasible in a clinical setting. HYPOTHESIS/PURPOSE: We investigated whether silibinin (SBN), the primary bioactive flavonolignan found in Silybum marianum (milk thistle) seeds, could impede the post-translational glycomaturation of PD-L1 and enhance T-cell-mediated antitumor cytotoxicity. METHODS: We assessed the effects of SBN on PD-L1 glycomaturation by integrating electrophoretic mobility shifts, Endo-H/PNGase-F glycosidase sensitivity mapping, transcript-level glyco-enzyme arrays, computational molecular dynamics (MD), biochemical cross-linking, AlphaLISA binding, and flow cytometry. Co-cultures of cancer cells with cytokine-activated T cells were performed using SBN as a single agent or in combination with the small-molecule PD-L1 inhibitor BMS-1166. RESULTS: SBN converted nascent PD-L1 into an Endo H-sensitive, 43 kDa, high-mannose species that becomes trapped in the endoplasmic reticulum (ER), regardless of STAT3 status. SBN did not alter CD274/PD-L1 transcription or global N-glycosylation. MD predicted, and BS3 cross-linking confirmed, weak but significant SBN-induced PD-L1 dimerization which diminished PD-1 binding. SBN increased the ability of BMS-1166, which also induces PD-L1 dimerization and ER retention of underglycosylated PD-L1, to block PD-1/PD-L1 interaction and to eradicate IFNγ-elicited plasma-membrane PD-L1. SBN was synthetically lethal with BMS-1166, causing multiple cancer types to become highly responsive to the immunocytolytic activity of T cells. CONCLUSION: SBN is a plant-derived molecular glue that intercepts PD-L1 glycomaturation co-translationally in the ER. When combined with canonical PD-L1 dimerizers, SBN collapses adaptive PD-L1 expression and renders cancer cells exquisitely susceptible to the cytolytic insults of T cells. Due to its favorable safety profile and oral bioavailability, SBN is a promising "glycotherapeutic" phytochemical for T-cell-based immunotherapy, particularly in IFN-rich tumors with reactive PD-L1 expression programs.

BACKGROUND: Acute pancreatitis (AP), a common gastrointestinal emergency, lacks specific treatments. β-elemene (ELE), a sesquiterpene derived from Curcuma phaeocaulis, has attracted attention for its anti-inflammatory and immunomodulatory properties beyond its known antitumor effects. However, its potential protective role in AP and the underlying mechanisms remain incompletely elucidated. PURPOSE: In this study, we investigated the protective effect of ELE against AP and elucidated its potential mechanism of action. METHODS: Ceruletide and L-arginine-induced AP mice were used to evaluate the protective effect of ELE on the pancreas of mice. In the mechanism study, RNA sequencing was used to identify potential signaling pathways in pancreatic tissues from AP mice. Subsequently, pull-down, SPR, and DARTS experiments were performed to identify the binding sites between ELE and IL-17RA. Ixekizumab, a clinically available IL‑17RA monoclonal antibody, was used to confirm IL‑17RA as ELE's key target in the AP mouse model. RESULTS: Our research revealed that ELE effectively alleviated pancreatic damage in AP mice. Pancreatic tissue RNA sequencing revealed a pronounced association with the IL-17 signaling pathway following ELE administration. Further in vivo and in vitro studies revealed that ELE mitigated the inflammatory response in mouse pancreas and bone marrow-derived macrophages by inhibiting the IL-17RA signaling and subsequent NF-κΒ activation. Mechanistically, ELE directly targeted the F534 of the IL-17RA protein. The IL-17RA-neutralizing antibody, ixekizumab, and ELE alleviated AP with comparable efficacy, without a significant difference, suggesting that ELE exerts its protective effects, at least in part, through the IL‑17RA receptor. CONCLUSION: Our research revealed that ELE effectively alleviates AP by modulating the IL-17RA-NF-κΒ signaling axis-mediated inflammatory response. These findings suggest that ELE may be a potential therapeutic approach for the anti-inflammatory treatment of AP.

Ovarian cancer treatment has long been challenged by clinical obstacles including platinum resistance recurrence and incomplete eradication of micrometastatic lesions. This study presents a platinum(II)-based compound AP-604 through the "Targeted Drug Conjugate (TDC)" strategy to overcome the limitations inherent in conventional chemotherapy. Research indicated that AP-604 preserved potent PIKfyve targeting capability (IC = 15.4 ± 1.3 nM) while also exhibiting pronounced cytotoxicity against A2780 (IC = 2.2 ± 0.4 μM). Mechanistic investigations revealed a multi-mode antitumor action involving concurrent activation of the BCL-2/caspase-dependent apoptotic pathway and S phase specific cell cycle arrest, complemented by enhanced platinum accumulation that exacerbated DNA damage. In vivo tests showed that AP-604 at a high dose achieved stronger tumor suppression than Cisplatin, Apilimod, and their combination without inducing significant histopathological damage. These findings proved that AP-604 has potential as a promising drug candidate with enhanced efficacy and favorable safety profiles in treatment of ovarian cancer.

CLDN18.2, a tight junction protein aberrantly overexpressed in gastric, pancreatic, and other cancers but minimally expressed in normal tissues, is a promising target for antibody-drug conjugate (ADC)-based therapies. This study describes the development and preclinical characterization of h1D6-ADC-5, a novel ADC composed of a proprietary humanized anti-CLDN18.2 monoclonal antibody (h1D6) and the cytotoxic payload DUO-5, conjugated via site-specific technology. h1D6 was generated by immunizing CLDN18.2 knockout mice followed by humanization; it exhibited high specificity for CLDN18.2 (no cross-reactivity with CLDN18.1) and improved binding affinity and in vivo efficacy vs. existing antibodies (e.g., IMAB362). Using C-Lock site-directed conjugation, h1D6 was linked to DUO-5 (a tubulin polymerization inhibitor) to yield h1D6-ADC-5 with a controlled average drug-to-antibody ratio of 4.3. In vitro, h1D6-ADC-5 selectively bound CLDN18.2-positive cells (AGS-CLDN18.2, NUGC4), were efficiently internalized, and induced apoptosis by downregulating anti-apoptotic proteins and upregulating pro-apoptotic markers. It also exerted a "bystander effect," killing adjacent CLDN18.2-negative cells via released DUO-5. In vivo, Zr-labeled h1D6-ADC-5 showed prolonged tumor accumulation in CLDN18.2-positive xenograft, with significant tumor regression (nearly complete regression at 10 mg/kg) while no overt toxicity was observed based on body weight and histology. These preclinical data demonstrate that h1D6-ADC-5 is a promising candidate for treating CLDN18.2-positive cancers.

BACKGROUND AND AIMS: Helicobacter pylori (H. pylori) eradication is crucial for gastric cancer (GC) prevention. However, increasing clarithromycin (CLR) resistance (CLRR) poses significant challenges. This study aimed to investigate CLRR patterns across different gastric diseases in Uzbekistan. METHODS: We retrospectively analyzed 279 H. pylori-infected patients with chronic non-atrophic gastritis (CNAG), chronic atrophic gastritis (CAG), gastric ulcer (GU), mucosa-associated lymphoid tissue lymphoma (MALT-L), or GC between 2020-2022. Among 194 cagA-positive patients who received eradication therapy, CLRR was defined by 23S rRNA mutations (A2142G, A2142C, A2143G) or treatment failure with CLR-based regimens. Logistic regression identified factors associated with CLRR, evaluated by univariate and multivariate analysis, and predicted probability models were generated based on disease type and patient characteristics. RESULTS: The overall CLRR rate was 44.8% (87/194), with 41.2% showing genotypic resistance. CLRR rates increased with disease severity: CNAG (33.3%), CAG (31.7%), GU (59.3%), MALT-L (54.1%), and GC (69.6%). Multivariate analysis identified older age (OR=2.27, 95%CI: 1.05-5.10), GU (OR=2.65, 95%CI: 1.04-6.96), and GC (OR=3.73, 95%CI: 1.34-11.2) as independent CLRR predictors. Disease-specific patterns emerged: GU and GC showed positive associations between age / body mass index and CLRR probability, while MALT-L demonstrated inverse relationships. CONCLUSIONS: High CLRR rates in Uzbekistan correlate with gastric disease severity. The disease-specific CLRR probability patterns identified in our study provide a practical framework for optimizing empirical therapy selection when comprehensive resistance testing is unavailable.

BACKGROUND AND AIMS: The use of opioids has expanded significantly worldwide in patients with cancer-related pain. Therefore, opioid-induced constipation (OIC) is emerging as one of the most frequent and distressing gastrointestinal side effects. Despite the high prevalence, OIC is frequently underdiagnosed and inadequately managed, with critical effects on the quality of life of patients. METHODS: The present study assessed the real-life prevalence of opioid use and OIC in 316 consecutive cancer patients hospitalized in an Internal Medicine ward and evaluated the outcomes following PEG or naldemedine during hospitalization. When OIC was diagnosed (Rome IV criteria), all patients underwent polyethylene glycol (PEG). Naldemedine was subsequently administered in refractory OIC. RESULTS: A total of 82 patients (26% of admissions) were assuming opioids for cancer pain, with constipation diagnosed in 62% and 24% of patients with or without opioid treatment, respectively. The risk of OIC was higher during combined opioids than in monotherapy, and fentanyl was associated with the highest OIC prevalence. Among patients with OIC, 47% responded to polyethylene glycol (PEG), whereas 52.9% started naldemedine 200 micrograms/day for a refractory OIC, with subsequent improvement in 59.3% of cases. CONCLUSIONS: The prevalence of opioid use and OIC is relevant among hospitalized cancer patients. The systematic adoption of standardized diagnostic tools can improve recognition and the clinical management in patients with OIC, in particular in case of refractory OIC. It is essential to increase awareness on this condition and to implement management pathways based on existing guidelines.

BACKGROUND AND AIMS: This study aimed to characterize the dynamic changes in inflammation and T-lymphocyte subsets for early gastrointestinal cancer before and after endoscopic submucosal dissection (ESD) (pre-ESD; postoperative days 1, 7, and 30). METHODS: A total of 189 patients with early gastrointestinal cancer who underwent ESD and achieved en bloc resection were enrolled, including 53 cases of early esophageal cancer, 55 cases of early gastric cancer, and 81 cases of early colorectal cancer. Patients were categorized into a non-R0 en bloc resection group (n=32), a non-curative R0 resection group (n=62), and a curative resection group (n=95). Clinical characteristics, T-lymphocyte subsets, inflammatory markers, and postoperative complications were analyzed. RESULTS: ESD significantly ameliorated T-lymphocyte subsets and inflammatory cytokines, with the most pronounced improvement observed in the curative resection group. Pre- and post-ESD levels of these markers were significantly correlated with lesion size, tumor morphology, and depth of invasion. The non-R0 en bloc resection group had a markedly higher complication rate than the other groups, whereas the curative resection group showed the lowest rate. Improvements in immune and inflammatory indices after ESD did not differ significantly among early cancers of different sites. The postoperative complication incidence was not associated with tumor sites. CONCLUSIONS: ESD markedly ameliorates the imbalance between T-lymphocyte subsets and inflammatory cytokine levels in early gastrointestinal cancer, with these indicators showing strong correlations with lesion size, tumor morphology, and depth of invasion. Curative resection demonstrates the greatest therapeutic benefit and the lowest postoperative complication rate.

Hepatocrinology is an emerging interdisciplinary field that examines the bidirectional interactions between the liver and the endocrine system, emphasizing how hepatic dysfunction influences hormonal regulation and how endocrine disorders, in turn, shape liver metabolism, inflammation, and disease progression. This review summarizes current theoretical frameworks, including hepato-endocrine axes, hepatokine signaling, and multi-organ communication models, highlighting the liver's role as a central endocrine hub. Key hepatic hormones, transport proteins, and hepatokines such as fetuin-A, fibroblast growth factor 21, and selenoprotein P are discussed in relation to metabolic disorders including metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction-associated steatohepatitis, polycystic ovary syndrome, diabetes, and advanced chronic liver disease. The review further explores hormonal axes involving the thyroid, pancreas, adrenal glands, parathyroids, and gonads, illustrating their complex interplay with hepatic physiology. Current challenges, such as limited long-term studies and therapeutic controversies, are examined alongside emerging directions involving hepatokine-targeted therapies, precision medicine, and microbiome-driven modulation. Understanding these interconnected pathways is essential for improving diagnostic accuracy, risk stratification, and therapeutic strategies in hepato-endocrine disorders.

INTRODUCTION: Rising cancer incidence disproportionately affects low- and middle-income countries (LMICs). Brachytherapy (BT), a form of radiotherapy (RT), is an important modality in the treatment of cervical cancer and prostate cancer. Given its unique resource requirements, barriers to the use of BT are present, especially in LMIC settings. AREAS COVERED: This nonsystematic review aims to describe the role of BT in the treatment of cervical and prostate cancer, discuss barriers in the implementation and use of BT in LMIC settings, share suggested solutions, and highlight cases from global settings. Barriers are discussed in categories including infrastructure, financial, geographic, and human resources and training. Cases presented highlight barriers and facilitators to implementing BT. EXPERT OPINION: With BT a required component of treatment for locally advanced cervical cancer, and an important treatment modality in prostate cancer, understanding the barriers present to BT and the impact on real-world outcomes, is crucial. A critical part of ongoing research will be the continued study of resource-stratified guidelines for brachytherapy and particularly image guidance. The cases presented here may serve as models for other settings, with the goal of increasing access to this essential treatment modality for patients around the globe.

Mucinous cystic neoplasms are rare benign tumours of the liver, accounting for less than 5% of all liver cysts. The exact etiology of mucinous cystic neoplasms is unclear, but female dominance and estrogen receptor positivity of ovarian type stromal cells suggest a role of hormonal factors in their development. The diagnosis is challenging as there are no specific laboratory or imaging characteristics, and the final diagnosis is often based on histological examination. A 27-year-old female patient was admitted to hospital with jaundice and abdominal pain. Laboratory results showed elevated levels of bilirubin and obstructive liver enzymes, while abdominal ultrasound revealed a septate cystic lesion in the liver. Further investigations - including ERCP, cholangioscopy assisted and percutaneous biopsy - did not provide clear diagnosis. Histological examination after surgical resection ultimately revealed a mucinous cystic neoplasm with low-grade dysplasia. Mucinous cystic neoplasms are rare liver tumours, and due to diagnostic difficulties, surgical intervention is often required. This case emphasizes that various non-surgical diagnostic methods might not be sufficient for establishing a final diagnosis. Orv Hetil. 2026; 167(26): 1041-1045.

INTRODUCTION: One of the most serious potential complications of thyroid surgery is temporary or permanent dysfunction of the recurrent laryngeal nerve. According to the literature, the development of nerve injury is influenced by several predictive factors, including demographic, surgical and pathological factors. OBJECTIVE: The aim of our research was to determine the prevalence of temporary and permanent vocal cord paralysis following thyroid surgery in our patient population, and to identify preoperative factors that may be associated with the development of paralysis. METHOD: We retrospectively analyzed the data of patients who underwent thyroid surgery between January 1, 2022 and March 31, 2024. In addition to demographic data, we examined the surgical indication, interventional procedure and postoperative histological results. Fisher's exact test and multivariate regression analysis were used to analyze whether age 65 years or older, malignant indication, and total thyroidectomy had prognostic significance for recurrent laryngeal nerve injury. RESULTS: During the study period, a total of 155 operations were performed on 153 patients (125 women, 30 men; mean age: 53.7 years) (nerve at risk: 227). Of these, 143 were primary operations, 11 were completion thyroidectomies and 1 was reoperation; 83 cases were lobectomy, 72 cases were total thyroidectomy. The surgical indication was benign in 123 cases (category II-IV according to The Bethesda System for Reporting Thyroid Cytopathology [2023], drug-resistant hyperthyroidism, compression symptoms), and malignant in 32 cases (category V-VI, contralateral malignancy, cold nodule). Histological examination confirmed 128 benign and 27 malignant lesions. Immediate postoperative laryngeal dysmotility occurred in 18 cases (nerve at risk: 19; 8.4%). 4 patients were lost to follow-up, so 11 cases (5.0% of 220 nerve at risk) proved to be temporary and 3 cases (1.4% of 220 nerve at risk) proved to be permanent paralysis. Statistical analysis did not confirm any of the examined factors as independent predictors. CONCLUSION: The incidence of postoperative laryngeal paralysis was in line with international data, and none of the examined potential risk factors were able to prove their prognostic significance, so the personalized risk assessment still relies primarily on literature data in our practice. Orv Hetil. 2026; 167(26): 1034-1040.

The stable modulation of the local charge distribution behavior induced by unsaturation sites within photocatalysts continues to pose a significant challenge in the quest to achieve notable enhancements in photocatalytic activity. Herein, we harnessed the hydrogen annealing reduction technique to deliberately introduce oxygen vacancies (OVs) into the BiOCl lattice for constructing the OVs-Bi-O structure, which decreases the valence state of Bi, and diminishes the Bi─O coordination, further establishing a charge asymmetric region within the material. This distinctive structural arrangement facilitates the sufficient migration of electrons to adjacent Bi sites that are closely linked to the OVs, significantly promoting the capture capability of electrons, leading to more adsorption and activation of water and oxygen as well as the conversion of reactive oxygen radicals. The engineered OVs-BiOCl variant showcases potential photocatalytic prowess, boasting a satisfactory photocatalytic application than that of its unmodified BiOCl counterpart. Under low-light conditions, this variant impressively achieves a ∼98.1% removal efficiency for RhB, while concurrently achieving an almost complete elimination of E. coli. This finding presents an insightful approach for manipulating unsaturation coordination active sites through the strategic introduction of controllable defects and elucidates the impact of unsaturation coordination on photocatalytic efficiency.

Colorectal cancer (CRC) remains among the most prevalent and deadliest malignancies worldwide, with limited survival outcomes, particularly in patients with metastatic disease. Despite advances in immunotherapy, immune checkpoint inhibitors (ICIs) have shown efficacy mainly in mismatch repair-deficient (dMMR) CRC, while responses in mismatch repair-proficient (pMMR) microsatellite-stable (MSS) cases remain limited. Emerging evidence highlights the gut microbiome as a critical factor influencing CRC development, progression, and therapeutic response. In particular, the gut microbiota has been shown to affect the efficacy of ICIs, with dysbiosis contributing to treatment resistance and specific microbial taxa enhancing antitumor immune responses. Preclinical and clinical studies have demonstrated that microbiome-based interventions, including probiotics, fecal microbiota transplantation (FMT), dietary modulation, and traditional medicines, can restore immune function by modulating immune cell populations and producing immunoregulatory metabolites. These effects may enhance responsiveness to ICIs and contribute to the suppression of tumor growth. However, we also address key limitations in this field, including inconsistent findings and safety concerns, such as infection risks, to guide future translational efforts. Overall, while microbiome-based interventions represent a promising adjunct to CRC immunotherapy, rigorous clinical trials and mechanistic validation are required before their routine clinical implementation.

Liver hepatocellular carcinoma (LIHC) remains a critical health challenge with limited treatments. This study employed network toxicology and molecular docking to investigate how polycyclic aromatic hydrocarbons (PAHs), as environmental carcinogens, promote LIHC. By analyzing TCGA LIHC data and screening genes via the Comparative Toxicogenomics Database, 1,817 key PAH-LIHC-related genes were identified. Enrichment analyses revealed associated biological pathways, and a protein-protein interaction network pinpointed 321 MCODE-derived functional module genes. A prognostic risk model based on 14 model genes was developed, demonstrating high accuracy in predicting 1 year survival for LIHC patients. Immune infiltration analysis showed distinct profiles between high- and low-risk groups. Molecular docking showed favorable docking scores and potential binding conformations of PAHs to key genes (ANXA5, LOX, HSP90AA1). Among these, the ANXA5-805-PAH complex was further subjected to a 50 ns molecular dynamics simulation to describe its short-term dynamic behavior. The results provide exploratory computational clues for PAH-related candidate targets, but further confirmation is required through rigorous docking protocol validation, repeated simulations, and experimental studies. This research provides a PAH-related prognostic model and elucidates molecular mechanisms of environmental toxin-driven liver cancer.

INTRODUCTION: Ciltacabtagene autoleucel (cilta-cel) has demonstrated deep and durable responses in patients with relapsed/refractory multiple myeloma (RRMM), supporting the goal of sustained minimal residual disease (MRD) negativity as a marker for potential functional cure, characterized by prolonged treatment-free disease control. Initially, cilta-cel was approved in the US for RRMM after ≥ 4 prior lines of therapy (LOT), and after 1-3 prior LOT in April 2024. This study describes real-world clinical outcomes, including MRD negativity, of cilta-cel after 1-3 prior LOT. METHODS: Electronic medical records from Loopback Analytics (April 2024-May 2025) were used, supplemented with physician notes. Adults with RRMM treated with cilta-cel after 1-3 prior LOT were included. Post-infusion outcomes (cilta-cel response, MRD negativity, disease progression, and overall survival) were assessed overall and by bridging therapy (BT) regimen. RESULTS: Overall, 120 patients were included (median age 67 years, 43.3% female). Prior to infusion, 87.5% received BT, including alkylator-based (28.6%), IMiD ± mAb-based (25.7%), PI-based (20.0%), talquetamab (14.3%), and other regimens (11.4%). Over a median follow-up of 5.8 months, among patients with a response assessment (81.7%), the overall response rate (ORR) to cilta-cel was 98.0%, including 72.4% with complete response. Among 36 MRD-evaluable patients, MRD negativity (10) was achieved in 35 (97.2%), with a median time to MRD negativity of 80.0 days. At last follow-up, 94.2% of patients remained progression-free, 95.8% had not initiated subsequent treatment, and 99.2% remained alive. Across BT regimens, ORR to cilta-cel was 95-100% and MRD negativity was achieved in 80-100%. CONCLUSIONS: This real-world study demonstrates the effectiveness of cilta-cel in RRMM after 1-3 prior LOT. High rates of response and MRD negativity were reported overall and across BT regimens, including talquetamab. Longer follow-up with repeated MRD measurements may provide further insights into response durability and survival outcomes, helping to contextualize the potential for a functional cure.

Philadelphia-negative myeloproliferative neoplasms (MPNs) carry a disproportionate thrombotic burden that cannot be explained by conventional cardiovascular risk factors or blood count parameters alone. This review synthesizes emerging evidence positioning MPN-associated thrombosis as a distinct pathobiologic entity, clonal thrombo-inflammation, driven by the convergence of somatic mutations and innate immune activation. We examine the continuum from clonal hematopoiesis of indeterminate potential (CHIP) to overt MPN, highlighting how Janus kinase 2 (JAK2)V617F and other driver mutations reprogram myeloid cells toward hyperinflammatory phenotypes. A recurring mechanistic theme is NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and interleukin-1 family signaling, which may create a feed-forward loop in which mutant clones amplify inflammatory circuits that, in turn, may enhance clonal fitness and contribute to thrombogenicity across multiple cellular compartments. We propose the 'thrombotic niche' as a conceptual, multi-compartment model encompassing mutant hematopoietic stem cells, hyperinflammatory myeloid effectors, hyperreactive platelets, platelet-leukocyte aggregates, and activated endothelium, but it remains a hypothesis-generating framework that lacks direct prospective clinical validation. Current cytoreductive strategies inadequately address this underlying biology, leaving substantial residual vascular risk. Emerging anti-inflammatory and anti-clonal strategies targeting interleukin-1 beta (IL-1β) (canakinumab), mutant-selective JAK2 inhibition, NLRP3 inflammasome blockade, and P-selectin-mediated adhesion are biologically plausible, but their ability to reduce thrombotic events in MPN remains unproven and should be viewed as hypothesis-generating rather than established clinical benefit. We conclude by outlining a translational research agenda integrating inflammation-aware risk stratification, niche-directed imaging, and spatial multi-omics to guide precision anti-inflammatory interventions in MPN.

Spontaneous regression of colorectal liver metastasis (CRLM) is an extremely rare phenomenon with only a few reported cases. However, the underlying mechanism remains unclear. Infection-triggered immune reactivation and inflammation have also been proposed to be potential contributors. IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition characterized by IgG4-positive plasma cell infiltration and fibrosis, and rarely manifests in the liver as an inflammatory pseudotumor (IPT). We herein report a rare case of a 71-year-old man with possible spontaneous regression of CRLM accompanied by coexisting IgG4-rich IPT-like changes. Eight months after the laparoscopic Hartmann's operation for rectal cancer, imaging revealed hepatic lesions in segments S5 and S7, which were diagnosed as CRLM. Partial hepatectomy revealed necrotic adenocarcinoma in the S7 lesion, with IgG4-rich IPT-like inflammatory changes. Postoperative evaluation revealed markedly elevated serum IgG4 levels and IgG4-positive plasma cell infiltration in the mediastinal lymph nodes, fulfilling the diagnostic criteria for systemic IgG4-RD. Twenty months postoperatively, the patient remained recurrence-free without adjuvant chemotherapy or steroid therapy. This case report describes the coexistence of spontaneous tumor regression and IgG4-related hepatic IPT within the same lesion and provides insight into the clinicopathological spectrum linking tumor regression and IgG4-RD.

Small non-functioning pancreatic neuroendocrine tumors (pNETs) measuring under 10 mm are considered eligible for observation and follow-up, although a minority of small NETs may exhibit show an aggressive behavior. We report a case of small G2-NET that was surgically removed and later developed metastatic recurrence in multiple organs. The patient, a woman in her sixties with a pancreatic body cyst, had been under follow-up for more than a decade. Several years later, a hypoechoic area appeared in the pancreatic body. Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) was performed twice; however, a definitive diagnosis was not obtained. Subsequent EUS revealed extension of the lesion into the main pancreatic duct, which was diagnosed as a pancreatic body tumor with intraductal extension. Distal pancreatectomy was performed, and histology revealed a small G2-NET, measuring 8 × 7 mm in diameter. Multiple metastatic tumors were detected 4.5 years after surgery, and the patient is currently undergoing treatment with everolimus and lanreotide. This case supports the viewpoint that small G2-NETs, even those measuring less than 10 mm, may have a risk of metastasis, highlighting the need for careful follow-up and appropriate therapeutic interventions.