Background Liver cancer is the sixth most common malignancy and the third leading cause of cancer-related death worldwide. In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated great potential and promising prospects in cancer treatment. However, CAR-T cell infusion is associated with various severe side effects. There is a paucity of reports describing serial monitoring of laboratory biomarkers in complications. Case presentation Here we report a patient with relapsed hepatocellular carcinoma who developed grade-3 cytokine-release syndrome and moderate capillary-leak syndrome after infusion of CAR-T cells. Following CAR-T infusion, the serum cytokine profile and liver enzyme levels were significantly elevated, accompanied by pancytopenia and coagulopathy. Conclusion After CAR-T-cell administration, laboratory parameters should be closely monitored and complications such as CRS and CLS managed promptly and effectively, which will improve the safety of CAR-T therapy.

BACKGROUND:Hemolysis is a major cause of sample rejection in blood gas analysis. We aimed to develop a low-cost spectrometer for hemolysis detection in emergency laboratories. METHODS:The spectrometer was developed using a complementary metal-oxide-semiconductor (CMOS) sensor and DVD-ROM grating. We evaluated the linearity, precision, and interference resistance of the instrument in accordance with CLSI and China National Accreditation Service for Conformity Assessment (CNAS) guidelines. In 51 clinical blood gas samples subjected to mechanically simulated hemolysis, the correlation between absorbance at 540 nm (A540 nm) and the hemolysis index (H index) determined by the Cobas c701 biochemical analyzer was evaluated. We utilized the hemolysis absorbance value that causes a maximum ±10% deviation in potassium (K+) and calcium ion (Ca2+) results as a reference to establish the rejection criteria for hemolysis in blood gas samples. RESULTS:The detection range of the spectrometer spanned 0.160< A540 nm <2.67, exhibiting a highly significant correlation with the H index (P < 0.01). The between-run coefficient of variation (CV) for the device was below 5%, while the within-laboratory CV remained below 10%. At interfering substance levels of 8.0 mg/dL (136.8 μmol/L) for unconjugated bilirubin, 13.3 mg/dL (226.7 μmol/L) for conjugated bilirubin, and 431.4 mg/dL (4.87 mmol/L) for triglycerides, detection bias stayed within 10%. Hemolysis significantly altered pH, partial pressure of oxygen (pO2), K+, and Ca2+ (P < 0.05). By calculating the bias caused by hemolysis on the test results, rejection criteria were established: A540nm >0.671 hemolysis will affect K+ results and A540nm >0.960 hemolysis will affect Ca2+ results. CONCLUSION:This low-cost spectrometer enables reliable pre-analysis hemolysis detection, improving accuracy in blood gas testing.

BACKGROUND:Current tumour-node-metastasis (TNM) staging for hepatocellular carcinoma (HCC) relies primarily on anatomical factors without incorporating tumour biological characteristics, limiting prognostic precision. This study aimed to develop and validate a novel staging system integrating serum biomarkers alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) with conventional TNM classification to enhance prognostic stratification following hepatectomy. METHODS:This multicentre cohort study included patients undergoing curative hepatectomy for HCC at six hospitals in China. The APTNM staging system was constructed by combining preoperative AFP (≥200 μg/L = 1 point), PIVKA-II (≥400 mAU/mL = 1 point), and AJCC 8th edition TNM stage (stages I-III = 1-3 points). Patients were classified as APTNM stage I (1 point), stage II (2-3 points), or stage III (4-5 points). Prognostic performance was evaluated using Kaplan-Meier analysis, multivariate Cox-regression, net reclassification improvement (NRI), and time-dependent receiver operating characteristic (ROC) curves. RESULTS:Among 660 HCC patients, the APTNM staging system demonstrated clear stratification for 5-year overall survival (OS) [stage I (n = 195), 47.7 %; stage II (n = 316), 28.1 %; stage III (n = 149), 15.3 %; P < 0.001] and recurrence-free survival (RFS) (stage I, 29.4 %; stage II, 12.7 %; stage III, 0.0 %; P < 0.001). Multivariate analysis confirmed APTNM staging as an independent predictor of both OS (stage II: HR 1.592, 95 % CI 1.209-2.096; stage III: HR 2.314, 1.668-3.211; both P < 0.001) and RFS (stage II: 1.556, 1.230-1.969; stage III: 2.159, 1.623-2.872; both P < 0.001). Time-dependent NRI values ranged from 0.20 to 0.26 for OS and 0.18-0.31 for RFS across 5-year follow-up, demonstrating substantial improvement over conventional TNM staging. Time-dependent ROC analysis consistently showed superior performance for the APTNM staging. CONCLUSIONS:The APTNM staging system successfully integrates tumour biomarkers with anatomical factors, providing significantly enhanced prognostic stratification compared with conventional TNM staging. This biologically informed approach may facilitate more precise risk stratification and guide individualised postoperative surveillance and adjuvant therapy decisions for patients with HCC.

OBJECTIVE:To develop artificial intelligence (AI)-based intelligent review rules to accurately screen samples that require retests or blood smear microscopy examinations, thereby reducing the review rate, improving the work efficiency of haematology laboratories, and ensuring the quality of whole blood analysis. METHODS:A total of 10,212 EDTA-K2 venous blood samples from the clinical laboratories of 4 hospitals from May 2022 to April 2025 were collected. Among them, 9000 samples from the First People's Hospital of Foshan, the Zhongda Hospital affiliated to Southeast University, and the First Affiliated Hospital of Sun Yat-sen University were used to establish the rules, and 1212 samples from the Zhongshan Hospital affiliated to Fudan University were used for rule validation. The obtained rules were compared with the 41 review rules set by the International Consensus Group for Haematology Review (ICGHR). All samples were tested using a haematology analyser under the customized dilution ratio (CDR) mode and smear microscopy, if the microscopic examination results trigger the 10 microscopic anomalous rules established by the ICGHR, then the sample is deemed to be an anomalous sample. Intelligent review rules were established using the gradient boosting decision tree (GBDT) algorithm. Moreover, the false negative rate, false positive rate, and review rate of the validation set were statistically analysed. RESULTS:(1) Among the 9000 samples in the establishment set, 4493 anomalous samples were identified by microscopic examination, and 26 intelligent review rules were established using the GBDT algorithm. (2) For the external validation set, 180 anomalous samples were identified by microscopic examination. Compared with those of the 41 international review rules, the false positive rate (14.60%) and review rate (27.55%) of the intelligent review rules were significantly lower (false positive rate: 30.19%, review rate: 44.14%). The false negative rate of the intelligent review rules (1.89%) was comparable to that of the 41 international review rules (0.90%) and met the ICGHR requirement of a false negative rate < 5%, with no critical hematologic cells missed. CONCLUSION:Intelligent review rules generated using AI techniques effectively reduce the false positive rate and review rate and prevent missed diagnoses of hematologic cells while ensuring test quality. The review rules generated by AI methods significantly increase laboratory efficiency and are especially suitable for medical institutions.

ABSTRACT Emerging evidence highlights the tumor microenvironment's (TME) role in hepatocellular carcinoma (HCC), yet how tumor‐infiltrating myeloid cells drive relapse is unclear. Using full‐length single‐cell RNA sequencing (scRNA‐seq) on samples from primary and early‐relapse HCC patients, we identified a dendritic cell subset DC3, which in relapsed tumor exhibited features of mature DCs enriched in immunoregulatory molecules (mregDCs). Mechanistically, mregDCs recruit dysfunctional CD161 + CD8 + T cells, which secrete TNF‐α, thereby activating the non‐canonical NF‐κB pathway to promote the differentiation of mature DCs into mregDCs via tumor necrosis factor receptor 2 (TNFR2). Our results from in vivo mouse models demonstrated that dual blockade of TNFR2 and PD‐L1 reduced tumor burden more effectively than anti‐PD‐L1 monotherapy in mregDC‐rich HCC. We also found strong interactions between mregDCs and FCN1+ monocytes, a myeloid‐derived suppressor cell (MDSC)‐like population. Our study characterizes an mregDC‐mediated immunosuppressive network in relapse HCC, nominating TNFR2 as a therapeutic target for myeloid‐focused HCC immunotherapy.

Liver fibrosis can arise from diverse etiologies, including metabolic stress and nutritional deficiencies. The methionine- and choline-deficient (MCD) diet induces liver fibrosis independent of metabolic syndrome, offering a model to study non-metabolic drivers of hepatic fibrogenesis. SUMO-specific protease 2 (SENP2) has been implicated in metabolic liver disease, but its role in nutritionally induced fibrosis remains unknown. Here, we investigated how hepatic Senp2 regulates MCD-induced liver fibrosis, with a focus on vascular remodeling. Liver-specific Senp2 knockout mice and wild-type littermates were fed an MCD diet to establish fibrosis. Liver injury, fibrosis, inflammation, and angiogenesis were assessed. Hepatic Senp2 deficiency markedly attenuated MCD-induced liver injury, fibrosis, and inflammation. Notably, Senp2 loss triggered a distinct hepatic vascular remodeling pattern: it promoted portal angiogenesis while suppressing hepatic sinusoidal capillarization, as evidenced by altered Cd31 expression and vascular architecture. Mechanistically, Senp2 ablation significantly reduced leukocyte cell-derived chemotaxin 2 (LEC2) expression and secretion, alongside downregulation of both active non-phospho-β-catenin and total β-catenin. In the MCD-induced fibrosis model, hepatic Senp2 drives pathological vascular remodeling through a β-catenin/Lect2 axis. Loss of Senp2 restrains this pathway, rebalances hepatic angiogenesis, and ultimately mitigates fibrosis progression. This reveals a nutrition-specific, pro-fibrotic mechanism of Senp2 centered on vascular regulation, highlighting a potential therapeutic target for non-metabolic fibrotic liver diseases.

The mechanisms underlying the interactions between disseminated tumor cells (DTCs) and their tissue microenvironment during metastatic colonization are currently poorly understood. We integrated multimodal single-cell and spatial profiling from liver cancer mouse models and human metastases to track the spatiotemporal dynamics of DTCs and their microenvironments from single-cell seeding to overt lung metastasis. We identified a residual population of quiescent Phgdhhigh DTCs that survived initial innate immune clearance and became transiently enriched in micrometastases. These cells shaped an immune-scarce microenvironment through PHGDH-dependent, H3K27me3-mediated epigenetic silencing of chemokine transcription, thereby promoting metastatic expansion. Cx3cr1high interstitial macrophages were also transiently enriched before DTC expansion, creating an immune-privileged niche for metastatic outgrowth by recruiting immunosuppressive cells. Inactivating the PHGDH-H3K27me3 axis in DTCs or depleting interstitial macrophages restored immune surveillance and inhibited metastatic colonization. These findings provide insights into the development of micrometastasis-targeting regimens.

Background: Sitosterolemia is an autosomal recessive genetic disorder characterized by hypercholesterolemia and tendon/hip xanthomas, primarily caused by pathogenic mutations in the ABCG5 or ABCG8 gene. Case presentation: We report the clinical features and therapeutic outcomes of a 29-year-old Chinese male patient diagnosed with sitosterolemia. The patient first presented with xanthomas in childhood and subsequently developed recurrent hypercholesterolemia in adulthood. Genetic sequencing identified two distinct compound heterozygous mutations in the ABCG5 gene: c.1256G>A (p.Arg419His) and c.751C>T (p.Gln251*). Lipoprotein profiling, including targeted analysis of plant sterols (xenosterols), was performed using gas chromatography-mass spectrometry. Following poor response to statin therapy, the patient was initiated on a low-plant-sterol and low-cholesterol diet, combined with ezetimibe (an NPC1L1 inhibitor). Serum total cholesterol and low-density lipoprotein cholesterol levels normalized within 2 months of this intervention. Conclusion: This case expands the mutational spectrum of sitosterolemia and provides valuable insights for the diagnosis and clinical management of this rare disorder.

Hemophilia B (HB), an X-linked recessive disorder, results from variants in the coagulation factor IX gene (F9). The F9 c.520 + 13 A > G variant is a recurrent intronic variant in HB patients, accounting for 15.05

Abstract Background The global burden of metabolic diseases is increasingly severe, with a continuous rise in prevalence among younger populations. There is an urgent need to explore the long‐term trends of metabolic risk factors across generations. This study aimed to investigate birth cohort effects on metabolic profiles among Chinese adults to provide a basis for precision prevention and control. Methods This retrospective longitudinal study analysed real‐world clinical laboratory data (2010–2024) from Fudan University Zhongshan Hospital in China including five metabolic indicators—fasting glucose (FG), total cholesterol (TC), triglycerides (TG), low‐density lipoprotein cholesterol (LDL‐C) and high‐density lipoprotein cholesterol (HDL‐C). The study included 3 888 861 adults born between 1930 and 1999, with 9059 individuals forming a fixed cohort for annual testing. Birth cohorts were defined in 10‐year intervals from the 1930s to the 1990s. Linear regression (overall population) and mixed‐effects models (fixed cohort) were used to assess cohort trends, adjusting for age and sex. Results In the overall population, compared with earlier birth cohorts, later cohorts had significantly higher levels of FG (1990s vs. 1930s: +.438 mmol/L; p < .001). Lipid changes were more complex: TC and LDL‐C decreased in earlier cohorts (1930s‒1970s) but rebounded in the 1980s‒1990s (LDL‐C [1990s vs. 1930s]: +.034 mmol/L; p < .001), while HDL‐C and TG continued to decline (HDL‐C [1990s vs. 1930s]: ‒.075 mmol/L; TG [1990s vs. 1930s]: ‒.218 mmol/L; p < .001). Additionally, a fixed cohort with repeated annual measurements was established to provide longitudinal validation, enhancing the robustness of findings against population variability. Conclusions The significant birth cohort effects on metabolic indicators suggest that younger generations, particularly those 1980s‒1990s cohorts, face greater metabolic risks than 1930s‒1970s cohorts. These findings support intensifying early screening of blood glucose and lipid profiles and encourage prompt dietary and lifestyle modifications to counter the rising metabolic trends in the 1980s–1990s cohorts. Key points Younger generations (1980s–1990s) exhibit higher fasting glucose and rebounding total cholesterol and low‐density lipoprotein cholesterol, alongside declining high‐density lipoprotein cholesterol and triglycerides compared to 1930s–1970s cohorts. A large fixed cohort with longitudinal follow‐up robustly confirms the accelerated metabolic risk accumulation in younger Chinese generations. Findings underscore the critical need for early screening and preventive strategies targeting the 1980s–1990s birth cohorts.

Oocyte maturation defect (OMD) is a rare cause of female infertility characterized by the persistent arrest of oocytes at immature stages. While biallelic PATL2 variants have been associated with OMD, the underlying molecular mechanisms remain unclear. This study aimed to identify novel PATL2 variants in OMD patients and investigate their functional consequences using a Patl2 knockout (KO) mouse model. We recruited two unrelated OMD patients and performed whole-exome sequencing (WES), followed by sanger validation of candidate variants. A CRISPR/Cas9-generated Patl2 KO mouse model was established, and transcriptomic profiling of oocytes from wild-type (WT) and Patl2−/− mice was conducted to identify differentially expressed genes (DEGs) and signaling pathways. We identified three PATL2 variants in the patients: a novel frameshift variant (c.99delA, p.Glu35fs), a novel synonymous variant (c.930G > A, p.K310K) confirmed by mini-gene assay to disrupt splicing and a recurrent splicing variant (c.223 − 14_223-2delCCCTCCTGTTCCA, p.R75Vfs*21). Sequence variant analysis classified these variants as pathogenic/likely pathogenic according to the ACMG/AMP guidelines. Transcriptome sequencing of Patl2−/−oocytes revealed dysregulation of key follicular development genes (Zfp36, Cited1, Fgf8, Id1, Efna1/4). KEGG pathway analysis highlighted significant upregulation of the hypoxia-inducible factor-1(HIF-1) signaling pathway and transforming growth factor-beta(TGF-beta) signaling pathway and mitogen activated protein kinase (MAPK) signaling pathway, suggesting impaired oocyte energy metabolism and disrupted granulosa-oocyte communication. We identified the first likely pathogenic synonymous PATL2 variant causing aberrant splicing and a novel frameshift variant in OMD, broadening the PATL2 mutational spectrum. These findings provide direct evidence for PATL2’s critical role in female reproduction, where it regulates mRNA expression of proteins essential for oocyte meiotic progression and early embryonic development.

Pseudomonas aeruginosa is a prevalent nosocomial pathogen causing respiratory tract infections, and its biofilm formation poses challenges to treatment and influences prognosis. However, the data on strong biofilm-forming strains in Chinese respiratory tract infection patients and their independent prognostic value remain unclear. This retrospective study included 362 inpatients with Pseudomonas aeruginosa-induced respiratory tract infections (Jan 2021–Jun 2023). Strains were subjected to crystal violet staining for biofilm quantification and Vitek2 Compact system for antimicrobial susceptibility testing. Global Optimal Matching and Logistic regression were used for analysis. 54.7

Tumor-associated macrophages (TAMs) are key regulators of the metastatic immune microenvironment, yet the specific TAM subsets that drive immune suppression and tumor progression in colorectal cancer liver metastasis (CRLM) remain poorly defined. Here, we integrated CyTOF, single-cell and spatial transcriptomics, bulk RNA sequencing, and lipidomics to identify a distinct population of lipid-laden, immunosuppressive TREM2+ TAMs enriched in CRLM. These cells exhibited high expression of lipid metabolism-related genes, including APOE, LIPA, and GPNMB, and accumulated abundant intracellular lipid droplets. Spatial analyses revealed their preferential localization at the invasive margins and within intratumoral colonic lumen-like structures-regions characterized by the buildup of APOE protein, mucinous material, and apoptotic tumor debris. Transcriptional analyses suggest these macrophages follow a Kupffer cell-related differentiation trajectory and acquire an immunoregulatory phenotype via uptake of tumor-derived lipids. Functionally, TREM2+ TAMs produced leukotrienes via the ALOX5/ALOX5AP pathway, which in turn sustained chronic inflammatory signaling. This inflammatory milieu potentiated neutrophil recruitment and fostered tumor cell stemness, thereby reinforcing an immunosuppressive metastatic niche and correlating with poor patient prognosis. In vivo murine depletion model and ex vivo organotypic tumor models confirmed that either selective ablation of TREM2+ TAMs or pharmacological inhibition of leukotriene synthesis alleviated immunosuppression and potentiated the efficacy of anti-PD-1 therapy. Our study defines a conserved lipid-associated TREM2+ TAM population as an essential contributor of immune evasion and microenvironment remodeling in liver metastasis, and suggest it as a potential therapeutic target in metastatic colorectal cancer.

The mortality of hepatocellular carcinoma (HCC) is high. Plant-derived bioactive compounds have emerged as potential therapies for HCC. Procyanidin (PAC) has been shown to possess immune-modulating and anti-tumor properties. However, the role and mechanism of total PAC in treating HCC remain unclear. We established subcutaneous and orthotopic HCC mouse models to assess the effect of PAC on tumor growth. Multi-omics analyses and in vitro experiments were conducted to investigate the changes in the gut microbiota, related-metabolites, and the tumor microenvironment (TME). 16S rDNA sequencing revealed that PAC could reshape the gut microbiota, notably increasing Lactobacillus murinus abundance. Furthermore, transplantation of Lactobacillus murinus reduced tumor volumes in mice. Single-cell RNA sequencing showed upregulation of the MAPK pathway in B cells within the TME. Metabolomic analysis suggests that 5-Hydroxytryptophan (5-HTP) derived from Lactobacillus murinus was significantly increased in B cells from mesenteric lymph nodes (MLNs) in the PAC-treated group. In vitro experiments revealed that 5-HTP could significantly upregulate the MAPK pathway in B cells. Additionally, 5-HTP-educated B cells could activate IFN-γ+CD8+T cells through B cell-T cell interactions, indicating that 5-HTP is a key metabolite in the therapeutic effect of PAC. Finally, feeding 5-HTP to HCC mice reduced tumor volume, upregulated the MAPK pathway in B cells from MLNs, and activated IFN-γ+CD8+T cells in the TME. PAC reshapes the gut microbiota and metabolites, upregulates the MAPK pathway in B cells from MLNs, and activates CD8+T cells in the TME through the gut-liver axis, thereby inhibiting HCC progression.

Accurate medical diagnosis often relies on both textual self-reported symptoms and structured medical examination results of patients. However, these examinations vary significantly in cost—measured in time, money, or patient discomfort---creating a challenging trade-off between diagnostic accuracy and resource efficiency. To address this issue, we propose a dynamic diagnostic framework that incrementally selects medical examinations based on individual characteristics of each patient. Starting with textual self-reported symptoms and basic demographic, the system determines follow-up examinations step-by-step, improving accuracy while minimizing additional costs. Specifically, we introduce Dynamic feature selection with Instance-Specific Cost sensitivity (DISC). DISC treats each examination as a feature and learns to acquire them sequentially to optimize predictive performance under personalized cost constraints. To support richer clinical understanding, we further develop a multimodal framework that integrates unstructured self-reported symptom text with structured medical examination data. We conduct experiments on 680,000 patients with 43 million medical examination records, demonstrating that DISC high diagnostic accuracy even when accounting for examination costs. Our work provides substantial momentum for the advancement of AI in healthcare, offering both methodological and practical foundations that can significantly accelerate the deployment of intelligent, cost-aware diagnostic systems in real-world clinical settings.

Pancreatic ductal adenocarcinoma is a highly aggressive gastrointestinal malignancy with an extremely poor prognosis. Metabolic reprogramming serves as a key driver of its growth and invasion. Substantial evidence indicates that lactate, a product of glucose metabolic reprogramming, plays a crucial role in tumorigenesis and progression. Beyond its traditional view as a waste product, lactate functions as a metabolic fuel, signaling molecule, and epigenetic modification substrate, exhibiting pleiotropic roles in tumor proliferation, invasion, and immune suppression. Notably, lactate-mediated histone and non-histone lactylation exerts crucial regulatory effects across tumor cells, immune cells, and stromal cells within the cancer microenvironment. Inhibitors targeting key lactate-metabolizing enzymes and transporters, along with combinatorial therapeutic strategies, represent potential avenues for the future precision treatment of pancreatic ductal adenocarcinoma. This systematic review summarizes research advances on lactate metabolism and lactylation modification in pancreatic ductal adenocarcinoma, aiming to provide insights for the future exploration of lactate regulatory networks and the development of precision targeted therapies.

Pretargeting strategies, which decouple the delivery of the targeting vector from the injection of the radioactive ligand, represent a major advancement in cancer nuclear imaging and radionuclide therapy. This approach effectively overcomes the high background signal and radiotoxicity associated with traditional direct targeting methods, which arise from the slow clearance of the carriers. This review systematically summarizes recent advances in pretargeting technologies for cancer. First, we provide a detailed comparison of noncovalent pretargeting strategies and bioorthogonal reaction-based covalent pretargeting strategies. Subsequently, various targeting vectors used in bioorthogonal nuclear imaging, such as antibodies, peptides, nanoparticles, and cell surface engineering are reviewed, and the potential of pretargeting strategies to enhance the efficacy of radionuclide therapy is discussed. Furthermore, the current status of clinical translation is outlined, together with the major challenges related to reaction kinetics, in vivo stability, and immunogenicity. Finally, future perspectives are presented, emphasizing the critical role of multidisciplinary integration among chemistry, materials science, biology, and clinical medicine in advancing the clinical application of pretargeting strategies.

Rationale: Trophoblast cell-surface antigen 2 (Trop2) is an essential therapeutic target in breast cancer, yet non-invasive methods for assessing its expression and predicting response to Trop2-directed antibody-drug conjugates (ADCs) remain limited. We aimed to evaluate the diagnostic accuracy of 68Ga-MY6349 positron emission tomography/computed tomography (PET/CT) in patients with breast cancer and assess its impact on clinical decision-making. Methods: We prospectively enrolled 73 patients with suspected or confirmed breast cancer who underwent both 68Ga-MY6349 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT from December 2024 to April 2025. Lesion-based diagnostic performance was compared using histopathology and follow-up imaging as reference standards. Treatment decisions were recorded before and after 68Ga-MY6349 PET/CT. Serial 68Ga-MY6349 PET/CT was performed to assess the early metabolic response in three patients with triple-negative breast cancer receiving sacituzumab tirumotecan. Results: 68Ga-MY6349 PET/CT identified more malignant lesions (564 vs. 436) and fewer false positives (2 vs. 40) than 18F-FDG PET/CT. In the initial-staging cohort (n = 30), 68Ga-MY6349 PET/CT led to TNM stage upgrades in 6/30 patients (20%) and treatment modifications in 4/30. In the restaging cohort (n = 43), clinical management was altered in 5/43 patients (12%) owing to the identification of additional metastatic lesions or rectification of false-positive findings via 68Ga-MY6349 PET/CT. 68Ga-MY6349 PET/CT yielded higher overall tumor uptake (median maximum standardized uptake value (SUVmax), 5.9 vs. 4.1; P < 0.001) and improved lesion conspicuity, particularly in lymph node and metastatic lesions. Exploratory analysis in three patients receiving Trop2-ADC therapy showed that early changes in 68Ga-MY6349 uptake after two treatment cycles were concordant with the subsequent clinical response. Conclusions: 68Ga-MY6349 PET/CT demonstrated superior diagnostic performance to 18F-FDG PET/CT in breast cancer staging and diagnosis, directly influencing therapeutic strategies. Preliminary findings from the triple-negative breast cancer cases suggest that early changes in SUVmax may be associated with the treatment response to Trop2-targeted ADC therapy, warranting further prospective validation in larger patient populations.

OBJECTIVE:To explore the applicability of the laboratory-specific sFLC reference intervals in patients with CKD and to define new sFLC reference intervals on N-Latex platform in Chinese CKD patients. METHODS:We retrospectively analyzed clinical data from 1,700 patients at all stages of CKD who attended Zhongshan Hospital, Fudan University, between 1 January 2023 and 31 December 2025; the cohort comprised 1,066 males and 538 females with 60 (IQR49-69) years. sFLC concentrations and κ/λ ratio were characterized, and stage-specific 95% reference intervals were derived from 1,135 randomly selected CKD patients and validated in other 565 patients. The clinical utility of these intervals was further validated with 36 patients initially diagnosed with LC-monoclonal gammopathy and eGFR < 60 mL/min/1.73 m2. RESULTS:The laboratory-specific reference intervals (κFLC 9.6-23.2 mg/L, λFLC 11.6-37.5 mg/L, κ/λ ratio 0.540-1.150) showed limitations in CKD patients, with 96.2%, 85.0% and 12.2% of individuals falling outside these intervals, respectively. We derived CKD-stage-specific 95% reference intervals stratified by eGFR: eGFR 30-59 mL/min/1.73 m2: κFLC 17.9-103.0 mg/L, λFLC 20.7-112.3 mg/L, κ/λ ratio 0.489-1.401; eGFR < 30 mL/min/1.73 m2: κFLC 42.5-297.8 mg/L, λFLC 49.7-338.8 mg/L, κ/λ ratio 0.518-1.245. The novel CKD-specific reference intervals led a reduction of 11.3% and 3.9% in abnormal κ/λ ratio rates among patients with eGFR 30-59 mL/min/1.73 m2 and eGFR < 30 mL/min/1.73 m2, respectively. All 36 LC-monoclonal gammopathy patients with eGFR < 60 mL/min/1.73 m2 exhibited an abnormal κ/λ ratio ;none fell within the novel κ/λ ratio reference interval. CONCLUSION:The CKD-specific sFLC reference intervals on N-Latex platform significantly reduce the proportion of abnormal sFLC results and enhance the application value of sFLC in CKD patients.