Objective: To investigate the incidence, characteristics, and influencing factors of resolution discrepancies within the minipool (MP) testing model across Chinese blood station laboratories in 2024. Methods: A nationwide, multicenter, cross-sectional study was conducted, including 334 blood station laboratories that reported nucleic acid reactive data among enzyme immunoassay non-reactive samples. Of these, 296 laboratories adopted the pool resolution model, with a total of 12 536 273 samples tested. Systematic analysis was performed on resolution data, focusing on the MP-NAT reactivity rate, the pool resolution concordance rate, and the resolution discrepancy rate. Subgroup analyses were conducted based on reagent types, viral targets, and Ct values. Potential causes were further explored through laboratory surveys and re-examination of raw amplification curves. Results: In 2024, the national average MP-NAT reactivity rate was 0.15%. The overall pool resolution concordance rate was 57.86%, which showed a gradual decline as Ct values increased across all reagents. The national average resolution discrepancy rate was 0.081‱(102/12 536 273), with 17.91%(53/296) of laboratories reporting at least one discrepancy. Nine reagent types were associated with these events, exhibiting reagent-specific patterns. For Reagent A2, the predominant discrepancy was HBV reactive pools resolving as HIV (36.36%); for Reagent D1, HBV pools frequently resolved as HCV (38.89%); and for Reagent E, the most common pattern was HIV pools resolving as HBV (48.00%). These resolution discrepancies were strongly associated with high Ct values: the median pool Ct for HBV exceeded 38, while those for HCV and HIV both exceeded 40. Investigations across 16 laboratories revealed that most discrepant samples exhibited “tailing” amplification curves, with some cases linked to cross-contamination or reagent batch-specific issues. Conclusion: While the incidence of resolution discrepancies in the MP-NAT model remains low in China, variations exist across different reagents and laboratories. These discrepancies are closely associated with low viral load, reagent performance, and laboratory operational practices.

ObjectiveTo investigate the effects of Anmei Dan （AMD） on the expression of proteins in the C-X3-C motif chemokine ligand 1 （CX3CL1）/C-X3-C chemokine receptor 1 （CX3CR1） signaling pathway， hippocampal inflammation， and learning and memory in an aged sleep-deprived model. MethodsSixty aged C57 mice were randomly assigned into a control group， a model group， a melatonin group （1.3 mg·kg^-1·d^-1）， and high-， medium-， and low-dose AMD groups （26.26， 13.13， 6.565 g·kg^-1·d^-1， respectively）， with 10 mice per group. Continuous sleep deprivation was administered for 4 weeks through a custom-built sleep deprivation chamber. The cognitive function of mice was assessed via the Y-maze test. Histomorphological alterations in pyramidal cells of the hippocampal CA1 and DG regions were examined by hematoxylin-eosin （HE） and Nissl staining. Synaptic morphology in the hippocampus was visualized with Golgi staining. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of inflammatory cytokines interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the hippocampal tissue as well as the level of interleukin-10 （IL-10） in the prefrontal cortex. Real-time PCR was performed to detect markers of M1-type ［cluster of differentiation （CD） 86 and inducible nitric oxide synthase （iNOS）］ and M2-type ［CD206 and arginase 1 （Arg1）］ macrophages. Western blot was employed to quantify the protein levels of CX3CL1， CX3CR1， phosphorylated nuclear factor κB p65 subunit （p-NF-κB p65）， and phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK） in the hippocampus. Immunofluorescence double staining was performed to co-label CX3CR1 with ionized calcium-binding adapter molecule 1 （Iba-1） for observation of the co-localization of target proteins with microglia. ResultsCompared with the control group， the model group exhibited disrupted daily activity patterns with reduced spontaneous alternation rates （P<0.01）， disorganized morphology and arrangement of hippocampal neurons， accompanied by reduced numbers of Nissl bodies and dendritic spines （P<0.01）， upregulated protein levels of IL-6， IL-10， IL-1β， TNF-α， CX3CL1， CX3CR1， p-NF-κB p65， p-p38 MAPK， and Iba-1 and mRNA levels of CD86 and iNOS （P<0.01）， and downregulated mRNA levels of CD206 and Arg1 （P<0.05，P<0.01）. Compared with the model group， the melatonin group and medium- and high-dose AMD groups showed increased spontaneous alternation rates （P<0.01）， improved neuronal morphology， number， and spine density in the hippocampal CA1 and DG regions （P<0.01）， declined levels of IL-6， IL-10， IL-1β， and TNF-α （P<0.05， P<0.01）， downregulated protein levels of CX3CL1， CX3CR1， p-NF-κB p65， p-p38 MAPK， and Iba-1 and mRNA levels of CD86 and iNOS， and upregulated mRNA levels of CD206 and Arg1 （P<0.01）. ConclusionAMD may improve the learning and memory in aged sleep-deprived mice by mediating neuroinflammation through the CX3CL1/CX3CR1 signaling pathway.

Patients with inflammatory bowel disease (IBD) require long-term pharmacotherapy. Due to the wide variety of clinically available drugs, medication safety has become increasingly concerning. As an indispensable component of pharmaceutical formulations, drug excipients may induce various adverse reactions, including rash, allergic responses, and gastrointestinal discomfort, and may even lead to severe organic injury. However, they are often overlooked in clinical practice. Therefore, identifying and managing excipient-related adverse reactions is crucial for ensuring medication safety. To address this issue, this article systematically reviews common excipients in IBD therapeutics, the underlying mechanisms of excipient-induced adverse reactions, and corresponding management strategies, aiming to enhance clinicians' awareness of excipient-related issues, improve their ability to recognize and manage such reactions, and ultimately ensure patient safety.

Metabolic dysfunction-associated fatty liver disease （MAFLD） is a chronic liver disease closely related to metabolic dysfunction. Its global prevalence is increasing year by year and shows a trend toward younger onset. It is closely associated with cardiovascular and cerebrovascular diseases， chronic kidney disease， and extrahepatic malignant tumors， and has become a major public health problem affecting the health of the Chinese population. At present， the treatment of MAFLD mainly focuses on lifestyle intervention. When metabolic cardiovascular risk factors and liver injury are present， pharmacological intervention is required. However， there is still no specific drug therapy for MAFLD. In recent years， many studies have found that the pathogenesis of MAFLD involves interactions among multiple factors， including insulin resistance， oxidative stress， endoplasmic reticulum stress， programmed cell death， immune dysregulation， inflammasomes， gut microbiota imbalance， and bile acid metabolism. Traditional Chinese medicine （TCM） has advantages in integrated regulation with multiple components and multiple targets， and shows significant efficacy in the treatment of MAFLD. Active components of Chinese medicinal herbs and Chinese medicine compound formulas exert definite therapeutic effects by regulating multiple signaling pathways to improve lipid metabolism disorders， inhibit inflammatory responses， and regulate the gut microbiota， thereby effectively improving clinical symptoms and delaying the occurrence and development of MAFLD. Therefore， strengthening research on the mechanisms of action of TCM in MAFLD is of crucial importance and significance for its treatment. This article summarizes the mechanisms by which Chinese medicine monomers and compound formulas intervene in MAFLD through the regulation of related signaling pathways， based on the retrieval and analysis of relevant literature from multiple databases， with the aim of providing theoretical support and a reference basis for the clinical application of TCM in the treatment of MAFLD.

Objective To observe the effects of Yixintai on lipid metabolism and the protein expressions of CPT-1 and CD36 in rats with heart failure;To explore the mechanism of its treatment of heart failure.Methods 106 out of 120 SD rats were selected to establish the heart failure model induced by myocardial infarction by ligating the left anterior descending coronary artery,and 14 rats were selected as the sham-operation group.The successful model rats were randomly divided into model group,trimetazidine group and Yixintai low-,medium-and high-dosage groups,with 14 rats in each group.The administration group was given corresponding drugs by gavage once a day for 4 weeks.LVEF,LVFS,LVIDd and LVIDs were measured by color doppler ultrasonography,the contents of ANP,BNP,LA and FFA in serum were detected by ELISA,the contents of TG,TC,LDL and HDL were detected by automatic biochemical analyzer,HE and Masson staining were used to observe the morphology of myocardial tissue,the expressions of CPT-1 and CD36 protein in myocardial tissue were detected by Western blot.Results Compared with the sham-operation group,LVEF and LVFS in the model group decreased(P<0.05),the LVIDs and LVIDd increased(P<0.05);the contents of serum ANP,BNP,LA,FFA,TG,TC and LDL increased(P<0.05),while the content of HDL decreased(P<0.05),with myocardial edema,irregular arrangement of myocardial fibers,increased inflammatory cell infiltration and collagen fiber deposition;the protein expressions of CPT-1 and CD36 in myocardial tissue decreased(P<0.05).Compared with the model group,the LVEF and LVFS in Yixintai each dosage groups and trimetazidine group increased(P<0.05),LVIDs and LVIDd decreased(P<0.05);the contents of ANP,BNP,LA,FFA,TG,TC and LDL in serum of Yixintai medium-and high-dosage groups and trimetazidine group decreased(P<0.05),the content of HDL increased(P<0.05);myocardial edema was improved,inflammatory cell infiltration was reduced,collagen fiber deposition was reduced,and the protein expressions of CPT-1 and CD36 in myocardial tissue increased(P<0.05).Conclusion Yixintai may improve myocardial energy metabolism and treat heart failure by increasing the expression of CPT-1 and CD36 protein in myocardial tissue and promoting fatty acid β oxidation.

Objective:To develop a novel fibroblast activation protein (FAP) cyclic peptide imaging agent, Al 18F-FAP-NOX, evaluate its in vitro and in vivo properties, and explore its feasibility of PET/CT imaging in tumors with FAP positive expression. Methods:Al 18F-FAP-NOX was manually synthesized. The in vitro stability of Al 18F-FAP-NOX was determined using radio high performance liquid chromatography (HPLC). The lipid water partition coefficient log P, in vitro cell uptake experiments, microPET/CT imaging and biodistribution in 293T-FAP tumor-bearing mice were conducted to preliminarily evaluate the pharmacokinetics and biological efficacy of Al 18F-FAP-NOX. Afterwards, a patient (male, 65 years old) with lung cancer underwent Al 18F-FAP-NOX PET/CT imaging. Results:Al 18F-FAP-NOX was successfully synthesized with a yield of (26.28±2.31)% without attenuation correction ( n=4), and the radiochemical purity was more than 95%. Al 18F-FAP-NOX exhibited good stability and hydrophilicity (log P=-3.02±0.08, n=5). In cell assays, the uptake of Al 18F-FAP-NOX in HT1080-FAP cells reached the plateau phase at 15 min ((7.31±0.53) percentage activity of injection dose per million cells (%ID/mio cells)), exhibiting high cellular uptake. The uptake of Al 18F-FAP-NOX could be significantly inhibited by 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-FAP-2286. The microPET/CT results of 293T-FAP tumor-bearing mice in vivo showed that Al 18F-FAP-NOX was highly uptaken in FAP-positive tumor tissues (60 min: (12.47±1.66) percentage activity of injection dose per gram of tissue (%ID/g)), while the uptake was very low in FAP-negative tumors. The biodistribution results were similar to the microPET/CT imaging results of tumor-bearing mice. The human clinical imaging showed an abnormal increase in Al 18F-FAP-NOX uptake (SUV max 5.5) of the lung cancer lesions. Conclusions:A novel cyclic peptide radiopharmaceutical, Al 18F-FAP-NOX, demonstrates good stability and hydrophilicity. It can be quickly distributed to tumor tissue in vivo. The human clinical PET/CT imaging shows certain diagnostic ability of Al 18F-FAP-NOX for lung cancer lesions. It is a promising cyclic peptide agent for PET imaging.

Objective:To systematically evaluate the safety and efficacy of the novel fibroblast activation protein (FAP)-targeted tracer 64Cu-FAP inhibitor (FAPI)-XT117 in patients with malignant solid tumors, and to compare with 18F-FDG. Methods:This self-controlled study was conducted on fifteen patients (8 males, 7 females; age (60 ±9) years) with malignant solid tumors from the First Affiliated Hospital of Guangzhou Medical University between July 2023 and December 2023. Each subject underwent 64Cu-FAPI-XT117 PET/CT at 30, 60, and 120min post-injection and was assigned to three dose cohorts (111MBq, 148MBq, and 185MBq; 5 patients in each cohort), and safety assessments were conducted within 24h after injection. In addition, all patients underwent 18F-FDG PET/CT at 60min post-injection. Time-activity curves were generated for 64Cu-FAPI-XT117, and the dosimetry was calculated. Image quality was evaluated using a 5-point Likert scale, and the optimal injected activity and imaging time point were determined. The paired t test was used to compare differences of the lesion detection count and SUV max between 64Cu-FAPI-XT117 and 18F-FDG PET/CT. Results:64Cu-FAPI-XT117 was well tolerated, with no adverse events reported. Time-activity curves of 68Ga-FAPI-XT117 revealed prominent uptake in the uterus, while the background activity in other organs remained low, with the whole-body effective dose of (0.0084±0.0021)mSv/MBq. The optimal imaging time point for 64Cu-FAPI-XT117 PET/CT was 60min post-injection, with an optimal administered activity of 111MBq. Compared with 18F-FDG, 64Cu-FAPI-XT117 demonstrated significantly higher uptake and more lesions in lymph-node metastases (SUV max: 8.6±3.8 vs 15.3±6.8, t=2.33, P=0.048; number of lesions: 8.3±5.4 vs 15.0±6.4; t=4.21, P=0.003) and distant metastases (SUV max: 11.8±3.7 vs 20.9±7.2, t=3.66, P=0.022; number of lesions: 7.0±3.2 vs 12.4±3.7, t=2.86, P=0.046). Conclusions:64Cu-FAPI-XT117 PET/CT is well tolerated in patients with solid tumors, with a controllable radiation risk. Moreover, it outperforms 18F-FDG PET/CT in the assessment of metastases.

Over the past decade, the field of bone tumor pathology in China has made remarkable progress. These achievements are reflected not only in the innovation and standardization of diagnostic techniques, which have significantly improved diagnostic accuracy, but also in the in-depth exploration of tumor pathogenesis and the continuous refinement of treatment protocols. More than one hundred research papers on bone tumor pathology published in the Chinese Journal of Pathology stand as a testament to the relentless efforts and practical contributions of Chinese pathologists in this field. On the occasion of the Chinese Journal of Pathology′s 70th anniversary, we summarize the progress in bone tumor pathology while also looking forward to the future, aiming to promote greater advancements in this field.

Objective:To analyze the clinical characteristics and genetic profile of patients with 46, XY Disorders of sex development (DSD) and a female phenotype in order to provide insights for the diagnosis and management of similar cases.Methods:A retrospective analysis was conducted on 36 children with 46, XY DSD and a female phenotype who were treated at the Department of Endocrinology, Genetics and Metabolism of Henan Children′s Hospital between March 1, 2016, and June 30, 2024. The evaluations included external genitalia scoring using the Prader scale and External Masculinization Score (EMS), imaging studies to assess gonadal development, and assessments of adrenal and gonadal function via adrenal hormone levels, sex hormone levels, and human chorionic gonadotropin (hCG) stimulation testing. Gender role behavior was assessed using gender role scales and sandplay therapy. Whole exome sequencing and Sanger sequencing were used to identify and validate genetic variants. A multidisciplinary team (MDT) comprehensively determined gender rearing based on molecular genetic diagnosis. This study was approved by the Medical Ethics Committee of Henan Children′s Hospital (Ethics No.: 2024-K-105).Results:The median age at initial consultation was 3 years and 1 month (range: 7 days to 16 years). Common symptoms included primary amenorrhea, clitoromegaly, and inguinal hernia. Fully feminized external genitalia were observed in 52.7% of the cases, and 80.5% had absence of the uterus. Internal gonads included absent gonads (5.6%), ovotestes (8.3%), streak gonads (5.6%), cryptorchidism (75.0%), and normally positioned testes (5.6%). At initial diagnosis, median luteinizing hormone (LH) was 1.305 IU/L, with elevated LH in 14 cases. Median follicle-stimulating hormone (FSH) was 4.87 IU/L, with elevated FSH in 17 cases. Median testosterone was 0.025 ng/mL. Median dihydrotestosterone (DHT) was 36.90 pg/mL. After hCG stimulation, median testosterone was 0.984 ng/mL and median DHT was 71.69 pg/mL. The testosterone/DHT ratio was elevated in one case (35.7). Testosterone levels remained below 1 ng/mL after hCG stimulation in 18 cases. Anti-Müllerian hormone (AMH) was decreased in 15 cases and increased in 3 cases. Inhibin B (InhB) was increased in 7 cases and decreased in 4 cases. Pathogenic variants were detected in 88.9% of the patients, involving AR (11 cases), CYP17A1 (4 cases), GATA4 (1 case), NR0B1 (1 case), NR5A1 (7 cases), SRD5A2 (1 case), WT1 (2 cases), STAR (4 cases), and LHCGR (1 case), totaling 34 variant sites. Among these, 9 variants were de novo, and 23 were inherited from parents. Sixteen variant sites were previously unreported. Gender assignment was male in 11 cases (30.6%) and female in 25 cases (69.4%). Conclusion:Common symptoms in 46, XY DSD patients with a female phenotype include primary amenorrhea, clitoromegaly, and inguinal hernia. Elevated FSH, androgen deficiency, and decreased AMH and InhB may indicate testicular dysgenesis or impaired androgen synthesis. Adrenal insufficiency should raise suspicion for defects in steroid hormone synthesis pathway enzymes.

As the volume of medical research using large language models (LLM) surges, the need for standardized and transparent reporting standards becomes increasingly critical. In January 2025, Nature Medicine published statement titled by TRIPOD-LLM reporting guideline for studies using large language models. This represents the first comprehensive reporting framework specifically tailored for studies that develop prediction models based on LLM. It comprises a checklist with 19 main items (encompassing 50 sub-items), a flowchart, and an abstract checklist (containing 12 items). This article provides an interpretation of TRIPOD-LLM’s development methods, primary content, scope, and the specific details of its items. The goal is to help researchers, clinicians, editors, and healthcare decision-makers to deeply understand and correctly apply TRIPOD-LLM, thereby improving the quality and transparency of LLM medical research reporting and promoting the standardized and ethical integration of LLM into healthcare.