Patient-derived organoids (PDOs) have been demonstrated not only to predict the response to neoadjuvant chemotherapy but also to tailor the treatment options for advanced breast cancer to improve prognosis. Here, we first reported a case of breast cancer liver metastasis that obtained clinical complete response (cCR) after treatment with eribulin and capecitabine, which showed sensitivity in the organoid drug sensitivity testing, and we conducted a systematic literature review. Our case report further provides a scientific basis for the PDOs as a powerful preclinical model to predict individual treatment sensitivity and improve the treatment outcomes of patients with advanced breast cancer, especially those with refractory or heavily treated breast cancer.

This study aimed to verify whether the Down-staging Depth Score (DDS), a novel prognostic indicator, could serve as a robust early predictor of long-term outcomes in patients with locally advanced breast cancer (LABC) after neoadjuvant chemotherapy(NAC). A total of 783 eligible patients with LABC from four tertiary cancer centres were retrospectively enrolled between January 2017 and December 2023. All patients received standard NAC followed by curative surgery. Individualized postoperative radiotherapy, targeted therapy, and endocrine therapy were administered in accordance with clinical guidelines. DDS was calculated as the discrepancy between pre-treatment clinical TNM staging score and post-treatment pathological staging score. The primary endpoint was 5-year disease-free survival (DFS); secondary endpoints included overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS). Survival outcomes were estimated using the Kaplan-Meier method. Univariate analysis and multivariate Cox regression models were applied to identify independent prognostic factors. All patients were randomly assigned to a 70% training cohort and a 30% validation cohort. Receiver operating characteristic (ROC) curve analysis with 1000 bootstrap resamples and decision curve analysis (DCA) were performed to systematically compare the predictive efficacy and net clinical benefit of DDS, pathological complete response (pCR), and Miller-Payne (MP) grading system. The median follow-up duration was 58 months. The overall 5-year DFS, OS, LRFS, and DMFS rates were 73.7%, 92.6%, 85.7%, and 78.7%, respectively. Kaplan-Meier analysis revealed that patients with DDS ≥ 4 exhibited significantly superior 5-year DFS (89.2% vs. 59.7%), LRFS (94.3% vs. 77.9%), DMFS (91.1% vs. 67.6%), and OS (98.1% vs. 87.6%) compared with those with DDS < 4 (all P < 0.001). Multivariate Cox regression confirmed that lymphovascular invasion and DDS were independent prognostic factors for DFS and OS. ROC analysis demonstrated that DDS yielded higher area under the curve (AUC) values than pCR and MP grading in both training (0.733 vs. 0.550 vs. 0.607) and validation cohorts (0.711). Bootstrap validation verified its stable predictive performance. DCA further validated that DDS provided superior net clinical benefit across a broad threshold range compared with conventional prognostic markers. As a novel, objective, and reproducible prognostic indicator and risk-stratification tool, DDS exhibits robust and superior performance in predicting long-term survival outcomes among LABC patients treated with NAC, outperforming conventional pCR and MP grading systems. DDS can reliably stratify prognostic risk and assist clinicians in formulating individualized postoperative adjuvant strategies and surveillance schedules. Further large-sample multicentre external validation is warranted to standardize the optimal DDS cutoff and promote its widespread application in the precise management of breast cancer.

Background: Transmural healing (TH) is an emerging therapeutic target in Crohn’s disease (CD). Visceral adipose tissue (VAT) is associated with the prognosis of CD, but few studies investigate the ability of VAT in predicting TH. Objectives: We aimed to quantitatively assess VAT by magnetic resonance enterography (MRE) and evaluate the prediction of baseline VAT volume for TH in CD patients with Ustekinumab (UST) treatment. Design: This is an observational study. Methods: We retrospectively included CD patients receiving UST treatment, with bowel wall thickness (BWT) >3 mm assessed by MRE at baseline. Clinical characteristics, laboratory, endoscopic, and MRE indicators were evaluated at baseline, week 26 (W26), and week 78 (W78) of the therapy. Quantification of VAT volume was assessed by MRE at baseline, and adjusted by body mass index (BMI). The TH was defined as BWT ⩽3 mm without any signs of inflammation at W26 and W78. Results: Sixty-two patients were included in our study. After UST treatment for W26 and W78, 8 (13.1%) and 13 (21.0%) patients achieved TH. Compared with baseline, laboratory indicators such as C-reactive protein and erythrocyte sedimentation rate, simple endoscopic score for CD, and BWT were significantly improved at W26 and W78. We divided patients into the TH and non-TH groups at both W26 and W78, and found that adjusted VAT volume at baseline was significantly lower in the W26-TH and W78-TH groups. Adjusted VAT volume was then categorized into four scores by quartiles, and multivariable analysis showed that baseline VAT score could negatively predict W26-TH (odds ratio (OR) = 0.296, p = 0.018) and W78-TH (OR = 0.419, p = 0.012). Conclusion: Our study demonstrated that baseline VAT was an independent risk factor for predicting both short- and long-term TH in CD patients receiving UST. Patients with lower VAT volume at baseline were more likely to achieve TH after UST treatment.

Selecting first-line treatments for advanced hepatocellular carcinoma (HCC) requires carefully balancing the survival benefits against the risk of serious adverse events (SAEs). However, conventional evaluation methods often fail to incorporate multiple clinical endpoints into a single unified framework. To address this limitation, we developed the Efficacy-Safety Integrated Ranking Algorithm (ESIRA), a quantitative framework that generates composite treatment rankings by assigning adjustable weights to efficacy and safety outcomes and calculating the Euclidean distance of each regimen to an ideal efficacy-safety profile. In a training cohort comprising 4,179 patients from eight randomized trials, treatment rankings varied markedly depending on the weighting scheme. Nivolumab plus ipilimumab ranked highest when the safety weight exceeded 0.7, whereas sintilimab plus bevacizumab and camrelizumab plus apatinib rose sharply in ranking when the efficacy weight exceeded 0.8. Sensitivity analysis identified 0.7:0.3 as the optimal efficacy-to-safety weight ratio, under which nivolumab plus ipilimumab achieved the highest composite Q-value (Q is the ranking function with higher values indicating higher ranks) (Q 0.60, 95

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma and is characterized by substantial heterogeneity. This study aimed to develop a liquid-liquid phase separation (LLPS)-related prognostic model to improve risk stratification. Transcriptomic and clinical data from four cohorts (n = 768) were analysed. Multiple machine learning algorithms were applied to identify prognostic LLPS-related genes (LRGs) and construct a 6-LRG model. Model performance was assessed using survival analysis, time-dependent receiver operating characteristic curves and multivariable modelling. Additional analyses were conducted to explore potential biological and microenvironmental differences between risk groups. The 6-LRG model stratified patients into groups with significantly different overall survival across datasets, with 1-year area under curve (AUCs) ranging from 0.661 to 0.820, 3-year AUCs from 0.683 to 0.779 and 5-year AUCs from 0.711 to 0.807. The 6-LRG model remained independent of established clinical variables and improved risk prediction when integrated into a nomogram. Distinct biological and immune characteristics were observed between groups. The 6-LRG model may provide additional prognostic information in DLBCL and generates hypotheses regarding underlying biological mechanisms. However, prospective validation in larger populations is essential before any implementation.

BACKGROUND:Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma, and previous studies have indicated the potential of zanubrutinib in the treatment of DLBCL. This meta-analysis aims to evaluate the efficacy of zanubrutinib in DLBCL patients and further explore potential differences in treatment effects across diverse patient subgroups. METHODS:A systematic literature search was conducted using two major databases (PubMed and Embase) and four key conference websites to ensure comprehensive coverage of relevant studies. Key outcomes included overall response rate (ORR), complete response rate (CRR), progression-free survival (PFS) and overall survival (OS). RESULTS:A total of 47 studies involving 1346 patients were included in the meta-analysis. Zanubrutinib in previously untreated patients with DLBCL showed a pooled CRR of 79.7% (95% CI 72.7%-86.7%) and a pooled ORR of 95.0% (95% CI 92.6%-97.4%), while the pooled CRR was 44.7% (95% CI 32.4%-56.9%) and the pooled ORR was 67.5% (95% CI 58.0%-77.0%) for the relapsed/refractory patients. For patients with extranodal involvement and elderly patients, the pooled ORRs were 82.3% (95% CI 75.7%-88.9%) and 90.7% (95% CI 85.7%-95.7%), respectively. Pooled analysis of survival curves showed that among previously untreated patients, the median PFS was 31.2 months and median OS was not reached, while the median PFS and OS were 5.9 months and 21.8 months among relapsed/refractory patients, respectively. CONCLUSIONS:Zanubrutinib-based regimen achieved encouraging treatment response, especially in specific subtypes of DLBCL, including double expressor, elderly, extranodal involvement, and non-GCB DLBCL.

BACKGROUND:Primary intestinal (PI) diffuse large B-cell lymphoma (DLBCL) represents a biologically and clinically heterogeneous subtype of extranodal lymphoma. The international prognostic index (IPI) was originally developed for predominantly nodal DLBCL (N-DLBCL) and inadequately reflected site-specific risk within the intestine. Prompted by colorectal carcinoma where primary tumor laterality (left vs right of the splenic flexure) is prognostically relevant, we raised the question of whether analogous intestinal laterality might influence survival in PI-DLBCL. AIM:To investigate whether intestinal laterality influences survival in PI-DLBCL and construct a location-integrated prognostic nomogram. METHODS:We retrospectively analyzed 3832 PI-DLBCL patients (SEER 2002-2021) and externally validated in 107 patients (Sun Yat-sen University Cancer Center 2014-2024). A prognostic nomogram integrating age, Ann Arbor stage, chemotherapy, surgery, and tumor sidedness (left vs right of the splenic flexure) was constructed. To mitigate treatment-selection bias, we additionally performed propensity score matching (PSM) for left- vs right-sided PI-DLBCL. RESULTS:Left-sided PI-DLBCL was independently associated with inferior overall survival (OS) (hazard ratio = 1.15, P = 0.035) and the association persisted after PSM. When compared with intra-abdominal N-DLBCL, right-sided PI-DLBCL showed superior OS, whereas left-sided PI-DLBCL had worse OS. The nomogram achieved superior discrimination vs the IPI (C-index: 0.749 vs 0.710) and higher time-dependent area under the curves (1-year: 0.865 vs 0.753; 2-year: 0.792 vs 0.731; 3-year: 0.786 vs 0.727) in the external validation cohort. The nomogram stratified patients into low-, median-, and high-risk groups with clear OS separation in both the training and external cohorts. CONCLUSION:Intestinal laterality is an independent, clinically actionable determinant of survival in PI-DLBCL. The proposed nomogram provides individualized survival prediction and risk stratification and showed higher discrimination than the IPI, supporting the incorporation of tumor anatomical location into prognostic assessment and risk-adapted management.

BACKGROUND:Adult sacrococcygeal teratoma (SCT) is extremely rare in clinical practice, with most cases manifesting as mature cystic types. Given the scarcity of clinical studies and literature on this topic, standardized surgical guidelines for adults are notably absent, and current treatment strategies are predominantly derived from pediatric surgical practices. Furthermore, data on surgical outcomes and risk factors for postoperative dysfunction or recurrence in adult patients remain limited. Continued research on tumor treatment modalities and risk factors is still warranted. AIM:To assess surgical outcomes and identify risk factors for dysfunction and recurrence in adult mature cystic SCTs. METHODS:We conducted a retrospective analysis of 64 adult patients with mature cystic SCT who received surgical treatment at Shandong Provincial Hospital Affiliated to Shandong First Medical University, from January 2005 to December 2020, ensuring all had complete clinical and follow-up data. We compared the clinical outcomes of three different surgical approaches: Laparoscopic-assisted anterior (Type A), posterior (Type B), and combined laparoscopic-posterior (Type C), evaluating them through perioperative indicators. Univariate and multivariate logistic regression analyses were performed to determine risk factors for postoperative dysfunction and tumor recurrence. RESULTS:The study incorporated 64 patients, all of whom had been pathologically confirmed to have mature cystic SCTs. The clinical efficacy in adult mature cystic SCTs was not significantly impacted by the various surgical approaches employed. Maximum tumor diameter of 10 cm or more, Altman classification of type III/IV, and intraoperative blood loss of 400 mL or greater were risk factors for postoperative dysfunction (anorectal dysfunction, urinary dysfunction and lower extremity motor dysfunction). The sacrococcyx being left unresected was determined to be an independent risk factor for tumor recurrence. CONCLUSION:Surgical approach does not affect outcomes; larger tumors, advanced Altman type, blood loss, and unresected sacrococcyx increase risks of dysfunction and recurrence.

Background: Well-differentiated Grade 3 neuroendocrine tumors (G3 NETs) represent a heterogeneous entity with limited therapeutic standards. Surufatinib, a small-molecule inhibitor, has shown efficacy in G1/G2 NETs, but its specific role in the G3 subpopulation and optimal patient selection strategies remain to be elucidated. Objectives: This study aimed to evaluate the real-world efficacy of surufatinib in G3 NETs and identify the factors that influenced progression-free survival (PFS). Design: A national, multicenter, retrospective observational study. Methods: We analyzed data from 77 patients with unresectable or metastatic G3 NETs (Ki-67 > 20%) treated with surufatinib across 15 centers in China between January 2021 and April 2024. The reporting of this study conforms to the STROBE statement. The primary endpoint was PFS. A multivariable Cox proportional hazards model was used to explore prognostic factors. Results: The median Ki-67 index was 30% (range: 22%−70%), and 49 patients were of pancreatic origin. A total of 11 patients were treatment-naïve, and 27 patients received surufatinib-based combination therapy. The overall median PFS was 9.4 months (95% confidence interval: 8.5–13.0), and the objective response rate (ORR) was 22.1%. Patients with a Ki-67 index ⩽ 30% had longer PFS than the Ki-67 > 30% group (12.6 vs 9.0 months, hazard ratio = 0.270, p = 0.003). Combined treatment showed a numerical trend toward improved ORR (33.3% vs 16.0%, p = 0.08), but did not significantly prolong PFS compared to surufatinib monotherapy (9.7 vs 9.4 months, p = 0.64). Conclusion: Surufatinib was a promising therapeutic option for G3 NETs. Prospective, larger-scale cohorts are warranted to confirm the efficacy and address the predictive markers for better patient selection.

Abstract Background: Patients with neuroendocrine carcinomas (NECs) have limited treatment options after front-line therapy, and have a high unmet clinical need for new effective therapies. Delta-like ligand 3 (DLL3) is broadly expressed in NECs. ZL-1310 is a novel antibody-drug conjugate (ADC) that employs the TMALIN® (Tumor Microenvironment Activable LINker-payload) platform, an anti-DLL3 monoclonal antibody linked to a topoisomerase I inhibitor payload via a stable protease-cleavable linker. We report initial safety and efficacy data from Phase 1b of the ZL-1310-002 (NCT06885281) trial assessing ZL-1310 monotherapy in patients (pts) with NECs. Methods: Patients had advanced/metastatic de novo NECs (excluding small cell lung cancer) and had progressed on or after platinum-based chemotherapy. ZL-1310 was given via IV at a starting dose of 1.6 mg/kg every 3 weeks until disease progression or unacceptable toxicity. Antitumor activity was assessed by RECIST v1.1 (investigator-assessed). Results: As of 11 Nov 2025, 28 pts with NECs were treated (GastroEnteroPancreatic (GEP)-NEC: 50%, cervical/uterine: 14%, unknown primary 14%, neuroendocrine prostate carcinoma (NEPC) 7%, bladder 7%, large cell neuroendocrine carcinoma of the lung (LCNEC-L) 4%, mediastinal 4%); median age was 53 years (range: 27, 76), ECOG PS: 0/1 (32%/68%); male: 18 (64%); Asian: 64%; 5 (18%) of the pts had 2 lines of prior therapy. DLL3 expression by immunohistochemistry was performed retrospectively in central laboratory and was available for 26 pts and 80% (21/26) patients were positive (cutoff: H-score ≥ 1). The median H-score was 123 (range: 0-288). Median follow-up was 2.9 months (range: 0.2-6.0); pts received a median of 3.2 treatment cycles (range: 1, 9). Seventeen (61%) of pts remain on treatment; disease progression was the most common reason for treatment discontinuation. A total of 25 pts (89%) had treatment-emergent adverse events (TEAEs), and 4 (14.3%) had Grade 3+ TEAEs. Most common TEAEs (>20%, all grade) include anemia (39%), nausea (36%) and vomiting (29%). One pt (3.6%) decreased the dose of ZL-1310 due to AE (G3 neutrophil count decreased); one pt (3.6%) experienced G2 interstitial lung disease leading to treatment discontinuation. No Grade 5 AE was reported. Objective response rate (ORR) was 48% with 8 confirmed and 2 unconfirmed responses in 21 evaluable pts, including one pt with prior DLL3-targeted bispecific antibody treatment who achieved confirmed PR. Conclusions: ZL-1310 dosed at 1.6mg/kg Q3W is well tolerated. The AE profile observed in pts with NEC is generally consistent with that of SCLC from a larger study. The preliminary efficacy results are encouraging in this patient population with a high unmet need following platinum-based chemotherapy. Phase 2 expansion in NEC is ongoing to further evaluate the safety and efficacy of ZL-1310 and updated data will be presented. Citation Format: Rohit Thummalapalli, Ming Lu, Alexander Spira, Amr Mohamed, Rahul Aggarwal, Yu Wang, Namrata Vijayvergia, Jordi Rodon, Andrew Scott Paulson, Pingkuan Zhang, Hui Yang, Yuan Xin, Jingmin Wen, Jie Chen. Preliminary results from the phase 1b/2, open-label, multi-center study of ZL-1310, a DLL3-targeted ADC, in patients with neuroendocrine carcinomas and other selected solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT189.

Precise regulation of the activating H3K4me3 and repressive H3K27me3 histone modifications at bivalent promoters is essential for normal development but is frequently disrupted in cancer. Among the polycomb group (PCGF) family members, which are key components of polycomb repressive complex 1 (PRC1), PCGF1 emerged as the factor most strongly associated with poor prognosis in non-small cell lung cancer (NSCLC) based on analyses of The Cancer Genome Atlas (TCGA) cohort. In lung cancer cells, PCGF1 upregulation enhanced the deposition of H2AK119ub and H3K27me3 at chromatin. These depositions inhibit the cytokine-cytokine receptor interaction pathway, especially CCL5, CXCL10, CD40, and FAS. Single-cell RNA sequencing further indicated that PCGF1 acts as a negative regulator of natural killer (NK) cell effector function. When NK cell-derived cytokines attempted to activate the cytokine-cytokine receptor interaction pathway in tumor cells, this repressive chromatin state attenuated pathway activation. Consequently, reduced expression of these genes weakened NK cell recruitment and cytotoxic responses. Collectively, this study uncovers a previously unrecognized mechanism by which PCGF1-driven disruption of bivalent promoter balance silences immune signaling cascades, enabling tumor cells to evade NK cell-mediated immunity in NSCLC. These findings highlight bivalent chromatin as a critical regulatory node in tumor immune escape and establish PCGF1 as a promising epigenetic target for immunotherapeutic intervention.PCGF1 promotes immune evasion in NSCLC by suppressing cytokine-cytokine receptor interaction pathway. Upregulation of PCGF1 in NSCLC cells enhances the deposition of the repressive histone modifications H2AK119ub and H3K27me3 while reducing the enrichment of the transcriptionally active histone modification H3K4me3 at target chromatin regions, thereby suppressing cytokine-cytokine receptor interaction pathway. This epigenetic repression reduces the expression of immune-related genes, including CCL5, CXCL10, CD40, and FAS. Consequently, tumor-cell responses to NK cell-derived cytokines are attenuated, leading to impaired NK cell recruitment and cytotoxicity. The schematic diagram was created using BioRender.

Patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who experience disease progression following anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy face poor prognoses and limited therapeutic options. Bispecific antibodies (BsAbs) have emerged as a promising salvage strategy. This meta-analysis was conducted to evaluate the efficacy and safety of CD3×CD20 BsAbs in R/R LBCL patients after CAR-T failure. Clinical studies published between 2021 and 2025 were systematically reviewed, and a random-effects model was applied for pooled and subgroup analyses. A total of fifteen studies involving 1,169 patients were included. The pooled overall response rate (ORR) was 45

ABSTRACT Background Secondary primary solid malignancies (SPSMs) significantly impact long‐term outcomes in lymphoma patients. However, subtype‐specific differences remain unclear, such as diffuse large B‐cell lymphoma (DLBCL) and follicular lymphoma (FL). Methods This study collected 1,377 DLBCL and 489 FL patients, identifying 50 DLBCL and 31 FL cases with SPSMs. Clinical characteristics, SPSM types, and survival were compared in these 81 patients. Demographic, clinical, treatment‐related variables (including radiotherapy for primary lymphoma, recorded as yes/no), and survival outcomes were collected. Overall survival (OS) was analyzed using Kaplan–Meier estimates and Cox proportional hazards models. The cumulative incidence of SPSMs was evaluated with competing risk analysis (death as a competing event), and group comparisons were performed with Gray's test. Prognostic factors identified in univariable analysis (p < 0.05) were included in a multivariable Cox model. A nomogram was developed, with discriminative ability assessed by the area under the receiver operating characteristic curve (ROC). Statistical significance was set at p < 0.05. Results SPSMs were observed more frequently in FL (6.34%) than DLBCL (3.63%). Thyroid cancer predominated (22.2%, 18/81). DLBCL patients developed SPSMs earlier than FL patients (median 28.47 vs. 41.77 months, p = 0.031), though cumulative incidence accounting for competing risks did not differ significantly (Gray's test p = 0.34). DLBCL patients with SPSMs had inferior OS compared to FL patients (p = 0.04). Non‐GCB DLBCL showed greater SPSM diversity and survival disadvantage. Multivariable analysis identified FL (vs. DLBCL) subtype (HR = 0.328, p = 0.018), bone marrow infiltration (HR = 2.815, p = 0.014), initial radiotherapy before SPSM diagnosis (HR = 3.475, p = 0.005), and shorter time to SPSM development (HR = 0.973 per month, p = 0.021) as independent prognostic factors for worse OS. The nomogram model showed acceptable discrimination, with an AUC of 0.761 in the time‐dependent ROC analysis. Conclusion This study provides novel insights into SPSM characteristics and prognostic differences in DLBCL and FL patients within a Chinese cohort. SPSMs in FL patients were observed more frequently, while DLBCL patients, particularly those with non‐GCB subtypes, experience earlier SPSM onset and poorer survival. The validated nomogram, incorporating lymphoma‐related factors, enables personalized risk stratification. However, the single‐center design, small sample size (n = 81), and lack of SPSM‐specific data limit generalizability, necessitating multi‐center studies with comprehensive SPSM characterization for validation.

BACKGROUND:Crohn disease (CD) is frequently complicated by intestinal strictures, which require early recognition and management. This study aimed to identify biomarkers associated with CD-related strictures by use of serum and intestinal proteomics and to develop diagnostic and predictive models for potential clinical application. METHODS:Serum samples from treatment-naive CD patients and paired intestinal samples from stricturing intestine were subjected to proteomic analysis. Machine learning approaches were employed to select stricture-related biomarkers and develop models. The candidate protein was validated using external cohorts and molecular experiments. RESULTS:The discovery cohort included 62 patients. A diagnostic model for intestinal stricture was developed using serum levels of 5 proteins from 30 nonstricturing, nonpenetrating (B1) phenotype and 20 stricturing (B2) phenotype patients, achieving an area under the curve of 0.754. A predictive model for stricture progression, based on another set of 5 proteins in 10 B1 progressors, achieved an AUC of 0.947 internally. Serum enzyme-linked immunoassay (ELISA) validation in the First Affiliated Hospital of Sun Yat-sen University (FAH-SYSU) and Sir Run Run Shaw Hospital (SRRSH) cohorts (n = 62) confirmed elevated glypican-6 (GPC6) levels in the stricturing (B2) group, with a similar trend observed in intestinal tissue in the progression group of the RISK cohort (n = 237). Single-cell transcriptomic analysis and immunofluorescence staining further confirmed higher GPC6 expression and protein levels in the fibrostenotic mucosa and submucosa, particularly in fibroblasts. CONCLUSIONS:We developed serum-based diagnostic and predictive models for intestinal strictures in CD, which may be suitable for clinical use once externally adequately validated. GPC6 emerged as a candidate biomarker closely associated with intestinal fibrosis, offering promising implications for its diagnosis and prognosis.

This study evaluated the efficacy and safety of camrelizumab combined with platinum-based chemotherapy (taxanes [T] or fluorouracil agents [F] plus platinum [P] drugs) as the first-line treatment in advanced esophageal squamous cell carcinoma (ESCC), using immune repertoire sequencing (IRS) to explore treatment response mechanism. In this multi-center, prospective cohort study, 88 patients received camrelizumab plus TP or FP, achieving a 1-year progression-free survival of 56.8% and overall survival of 68.2%. The objective response rate (ORR) was 64.8%, with a disease control rate of 91.1%. While most treatment-related adverse events were mild, 12.5% of patients experienced grade ≥3 toxicities. IRS showed significant differences in T-cell receptor (TCR) β-chain and immunoglobulin heavy chain between patients with (ORR group) or without ORR (non-ORR group), particularly in the distribution and expression of some genes. Specifically, we found the significant differences in the amino acid composition of complementarity determining region 3 (CDR3) polypeptide sequences in TCR and B-cell receptor (BCR) between the ORR and non-ORR groups. For TCR, we observed substantial oligoclonal enrichment and differences in the abundance of specific V and J genes. Similarly, for BCR, we detected differences in the clonotype abundance of CDR3 polypeptide segments and identified several differential V genes. Camrelizumab combined with platinum-based chemotherapy is effective and well-tolerated as the first-line treatment for ESCC, and IRS may reveal mechanism influencing treatment response.

Metastatic liver tumor burden (LTB) is a prognostic factor affecting the survival of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), but evaluation of the LTB usually depends on radiologic and functional imaging. This study aimed to develop a clinical model based on easily accessible clinicopathological markers to predict LTB level in GEP-NET patients. LTB was quantified based on 68Ga-DOTANOC PET/CT scan. The optimal cut-off value for high and low-LTB was determined based on our previous study. Serum levels of liver enzymes and tumor biomarkers were obtained within one week before PET/CT scan. The whole dataset was divided into training set and validation set. LASSO regression method was used to select predictors, and multivariate logistic regression was used to develop a clinical model which was further visualized by constructing a nomogram. Area under the curve (AUC) was applied to assess the accuracy of the constructed model. We retrospectively enrolled 200 patients with well-differentiated GEP-NETs. Ki-67 index, GGT (gamma-glutamyltransferase), LDH (lactate dehydrogenase), and NSE (neuron-specific enolase) were selected through the LASSO regression method, and a nomogram was built based on these variables. The predictive model yielded an AUC of 0.785 (95