Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

Objective:To investigate the clinical characteristics of children with Chikungunya fever.Methods:This retrospective cohort study analyzed clinical data of 91 children with Chikungunya fever at the Department of Pediatrics, Foshan women and Children Hospital between July 2025 and August 2025. The patients were divided into four groups based on onset-age: 0-<1 year, 1-<3 years, 3-<6 years, and 6-14 years. One-way ANOVA and chi-square tests were used to compare the clinical features of children with Chikungunya fever at different ages.Results:Among the 91 children with chikungunya fever, 55 were male and 36 were female, with an onset age of 6 (2, 11) years, age groups comprised 0-<1 year (10 cases), 1-<3 years (13 cases), 3-<6 years (17 cases) and 6-14 years (51 cases). Fever occurred in 87 cases (96%), with 50 cases (57%) had high fever. Skin rash was observed in 89 cases (98%), and 60 cases (67%) had a generalized rash. Joint pain was reported in 57 cases (63%), among which 35 cases (61%) had pain in two or more locations, with the knee involved in 21 cases (37%), the ankle in 15 cases (26%), and the wrist in 6 cases (11%).The knee was the most commonly affected joint 21 cases (37%), followed by the ankle 15 cases (26%) and wrist 6 cases (10%). Joint ultrasound was performed in 31 cases (34%), all showed joint effusion, including 8 cases (26%) without complaints of joint pain. The incidence of high fever was significantly lower in the 3-<6 years and 6-14 years groups compared to the 0-<1 year group (both P<0.05). The 6-14 years group also had a lower incidence of high fever than the 1-<3 years group ( P<0.05). The 1-<3 years group had longer duration of fever than the 3-<6 years and 6-14 years groups (both P<0.05). The incidence of joint pain was higher in the 3-<6 years and 6-14 years groups compared to the 1-<3 years group (both P<0.05), and higher in the 6-14 years group than in the 3-<6 years group ( P=0.007). Among all 91 children, 22 cases (24%) had abnormal liver function, 49 cases (54%) showed elevated lactate dehydrogenase (LDH), and 2 cases (2%) had elevated creatine kinase. The proportions of elevated aspartate aminotransferase (AST) and LDH were higher in the 0-<1 year and 1-<3 years groups compared to the 3-<6 years and 6-14 years groups (all P<0.05). Conclusions:The clinical characteristics of children with Chikungunya fever vary among children of different ages. Children in the 0-<3 years are more prone to high fever with longer duration and generalized maculopapular rash, while the children in the 6-14 years have have a higher proportion of joint pain, and joint ultrasound revealed effusion in all examined children. AST and LDH levels are elevated in the 0-<3 years groups.

Objective:To evaluate the sample preparation proficiency and storage proficiency of 11 clinical biobanks in Beijing through simulated experiments, and to establish an assessment method for the quality comparability of biological samples.Methods:An exploratory research design was adopted. In November 2023, artificial composite serum quality control materials containing six recombinant human protein markers—recombinant human alanine aminotransferase (rhALT), recombinant human aspartate aminotransferase (rhAST), recombinant human creatine kinase (rhCK), recombinant human creatine kinase-MB (rhCK-MB), recombinant human B-type natriuretic peptide (rhBNP), and recombinant human troponin I (rhTNI)—were distributed to 11 clinical biobanks in Beijing City. Sample preparation and storage followed the standardized operating procedures. Proficiency differences were assessed through statistical analysis.Results:Three-way repeated measures ANOVA revealed all six protein markers showed a declining trend over storage time in ultra-low-temperature environments ( F values 11.68-4 179.66, all P<0.01). However, neither long-term/temporary refrigerator types ( F values 0.01-1.23, all P>0.05)nor placement locations within refrigerators significantly affected the stability of these six proteins ( F valus 0.03-1.47, all P>0.05). The biases in detection results for rhALT, rhAST, rhTNI, and rhBNP at different storage time points were within the allowable bias limits for each item, supporting their use as markers for protein stability in biobank samples. All 11 institutions passed the storage proficiency assessment. In the preparation proficiency assessment, deviations were observed in post-preparation sample results, with a notably high out-of-control rate for rhCK (36.36%). Conclusion:Sample preparation proficiency can serve as a quality control metric for clinical biobanks. Future external quality assessment systems for biobanks should focus on sample preparation rather than storage processes.

Objective: To investigate the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF) on histone H3 lysine 18 lactylation (H3K18la) in the hippocampus of rats with diabetes mellitus complicated with depression (DD) and predict the regulatory genes of H3K18la. Methods: Male Sprague-Dawley rats were divided into control, model, and positive drug (metformin [0.18 g/kg] and fluoxetine [1.8 mg/kg]) groups, and the three groups were treated with high, medium, and low ZGJTJYF doses (20.52, 10.26, and 5.13 g/kg, respectively), with 10 rats per group. After treatment, the forced swimming and water maze tests were performed to assess depressive-like behaviors and cognitive function. An enzyme-linked immunosorbent assay was used to measure blood insulin, glycosylated hemoglobin, lactate levels, and lactate content in the hippocampus. Western blotting was used to detect H3K18la expression in the hippocampus. Cleavage Under Targets and lagmentation(CUT&Tag) experiments targeted hippocampal H3K18la epigenetic modification regions to analyze the transcription factors bound by H3K18la. Kyoto Encyclopedia of Genes and Genomes and Protein-Protein Interaction networks were constructed to identify key pathways and target genes regulated by H3K18la. Results: Compared with the normal group, the model group rats showed prolonged immobility time in the forced swim test, increased escape latency in the water maze experiment, decreased target quadrant distance ratio (P<0.01), increased serum lactate content, and decreased lactate content in hippocampal homogenate (P<0.01), as well as decreased H3K18la protein expression in the hippocampus (P<0.01). Compared with the model group, ZGJTJYF reduced the immobility time in the forced swim test and the escape latency in the water maze test (P<0.01), while the distance ratio in the target quadrant increased (P<0.01) in model rats. Lowered fasting blood glucose, insulin, and glycosylated hemoglobin levels (P<0.05, P<0.01) were also observed. ZGJTJYF also increased the lactate content and H3K18la protein expression in hippocampal homogenate (P<0.05, P<0.01). The DNA sequences bound by H3K18la were predominantly enriched at the transcription start sites. ZGJTJYF modulated H3K18la-associated pathways, including cell adhesion junctions, tumor growth factor-beta (TGF-β) signaling, stem cell pluripotency regulation, mitogen-activated protein kinase(MAPK) signaling pathway, and insulin resistance, leading to the identification of 12 target genes. Conclusion ZGJTJYF enhances hippocampal lactate levels and H3K18la modification in DD rats, which may regulate neural cell interactions, neurogenic stem cell function, TGF-β signaling, MAPK signaling, and insulin resistance pathways.

Objective:To deconstruct the overall medical expense and analyze systemic characteristics of cost structure dynamics in China from the perspective of optimizing healthcare resource allocation.Methods:Utilizing hospitalization records in a sample city from 2022-2023 as the research literature,the linear regression models for different cost components was established over the two-year period within each DRG-based case group to identify statistically significant temporal trends and directional changes in cost structures.Results:Most DRG groups exhibited significant trends in at least one cost component.Notable concentration patterns emerged in medication,comprehensive care and therapeutic service costs.When evaluating structure improvement,most achieved optimized allocation in at least one major cost component.Conclusion:The sample city demonstrates continuous optimization in healthcare cost structures,yet specific cost categories and DRG groups deviated from resource allocation optimization goals.Policy interventions should prioritize granular,DRG-specific adjustments to address heterogeneous structural dynamics.

Objective:To evaluate the sample preparation proficiency and storage proficiency of 11 clinical biobanks in Beijing through simulated experiments, and to establish an assessment method for the quality comparability of biological samples.Methods:An exploratory research design was adopted. In November 2023, artificial composite serum quality control materials containing six recombinant human protein markers—recombinant human alanine aminotransferase (rhALT), recombinant human aspartate aminotransferase (rhAST), recombinant human creatine kinase (rhCK), recombinant human creatine kinase-MB (rhCK-MB), recombinant human B-type natriuretic peptide (rhBNP), and recombinant human troponin I (rhTNI)—were distributed to 11 clinical biobanks in Beijing City. Sample preparation and storage followed the standardized operating procedures. Proficiency differences were assessed through statistical analysis.Results:Three-way repeated measures ANOVA revealed all six protein markers showed a declining trend over storage time in ultra-low-temperature environments ( F values 11.68-4 179.66, all P<0.01). However, neither long-term/temporary refrigerator types ( F values 0.01-1.23, all P>0.05)nor placement locations within refrigerators significantly affected the stability of these six proteins ( F valus 0.03-1.47, all P>0.05). The biases in detection results for rhALT, rhAST, rhTNI, and rhBNP at different storage time points were within the allowable bias limits for each item, supporting their use as markers for protein stability in biobank samples. All 11 institutions passed the storage proficiency assessment. In the preparation proficiency assessment, deviations were observed in post-preparation sample results, with a notably high out-of-control rate for rhCK (36.36%). Conclusion:Sample preparation proficiency can serve as a quality control metric for clinical biobanks. Future external quality assessment systems for biobanks should focus on sample preparation rather than storage processes.

Objective:To deconstruct the overall medical expense and analyze systemic characteristics of cost structure dynamics in China from the perspective of optimizing healthcare resource allocation.Methods:Utilizing hospitalization records in a sample city from 2022-2023 as the research literature,the linear regression models for different cost components was established over the two-year period within each DRG-based case group to identify statistically significant temporal trends and directional changes in cost structures.Results:Most DRG groups exhibited significant trends in at least one cost component.Notable concentration patterns emerged in medication,comprehensive care and therapeutic service costs.When evaluating structure improvement,most achieved optimized allocation in at least one major cost component.Conclusion:The sample city demonstrates continuous optimization in healthcare cost structures,yet specific cost categories and DRG groups deviated from resource allocation optimization goals.Policy interventions should prioritize granular,DRG-specific adjustments to address heterogeneous structural dynamics.

Objective:To investigate the clinical characteristics of children with Chikungunya fever.Methods:This retrospective cohort study analyzed clinical data of 91 children with Chikungunya fever at the Department of Pediatrics, Foshan women and Children Hospital between July 2025 and August 2025. The patients were divided into four groups based on onset-age: 0-<1 year, 1-<3 years, 3-<6 years, and 6-14 years. One-way ANOVA and chi-square tests were used to compare the clinical features of children with Chikungunya fever at different ages.Results:Among the 91 children with chikungunya fever, 55 were male and 36 were female, with an onset age of 6 (2, 11) years, age groups comprised 0-<1 year (10 cases), 1-<3 years (13 cases), 3-<6 years (17 cases) and 6-14 years (51 cases). Fever occurred in 87 cases (96%), with 50 cases (57%) had high fever. Skin rash was observed in 89 cases (98%), and 60 cases (67%) had a generalized rash. Joint pain was reported in 57 cases (63%), among which 35 cases (61%) had pain in two or more locations, with the knee involved in 21 cases (37%), the ankle in 15 cases (26%), and the wrist in 6 cases (11%).The knee was the most commonly affected joint 21 cases (37%), followed by the ankle 15 cases (26%) and wrist 6 cases (10%). Joint ultrasound was performed in 31 cases (34%), all showed joint effusion, including 8 cases (26%) without complaints of joint pain. The incidence of high fever was significantly lower in the 3-<6 years and 6-14 years groups compared to the 0-<1 year group (both P<0.05). The 6-14 years group also had a lower incidence of high fever than the 1-<3 years group ( P<0.05). The 1-<3 years group had longer duration of fever than the 3-<6 years and 6-14 years groups (both P<0.05). The incidence of joint pain was higher in the 3-<6 years and 6-14 years groups compared to the 1-<3 years group (both P<0.05), and higher in the 6-14 years group than in the 3-<6 years group ( P=0.007). Among all 91 children, 22 cases (24%) had abnormal liver function, 49 cases (54%) showed elevated lactate dehydrogenase (LDH), and 2 cases (2%) had elevated creatine kinase. The proportions of elevated aspartate aminotransferase (AST) and LDH were higher in the 0-<1 year and 1-<3 years groups compared to the 3-<6 years and 6-14 years groups (all P<0.05). Conclusions:The clinical characteristics of children with Chikungunya fever vary among children of different ages. Children in the 0-<3 years are more prone to high fever with longer duration and generalized maculopapular rash, while the children in the 6-14 years have have a higher proportion of joint pain, and joint ultrasound revealed effusion in all examined children. AST and LDH levels are elevated in the 0-<3 years groups.

Background: and Purpose Non-high-density lipoprotein cholesterol (non-HDL-C), which represents the total cholesterol content of all pro-atherogenic lipoproteins, has recently been included as a new target for lipid-lowering therapy in high-risk atherosclerotic patients in multiple guidelines. Herein, we aimed to explore the relationship between non-HDL-C level and the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing stroke recurrence. Methods: This study comprised a post hoc analysis of the CHANCE-2 (Ticagrelor or Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II) trial, from which 5,901 patients with complete data on non-HDL-C were included and categorized by median non-HDL-C levels, using a cutoff of 3.5 mmol/L. The primary efficacy and safety outcomes were recurrent stroke and severe or moderate bleeding within 90 days. Results: Ticagrelor-aspirin significantly reduced the risk of recurrent stroke in patients with low non-HDL-C (71 [4.8%] vs. 119 [7.7%]; adjusted hazard ratio [HR] 0.54; 95% confidence interval [CI], 0.40–0.74), but not in those with high non-HDL-C (107 [7.3%] vs. 108 [7.6%]; adjusted HR, 0.88; 95% CI, 0.67–1.16), compared with clopidogrel-aspirin (P for interaction=0.010). When analyzed as a continuous variable, the benefit of ticagrelor-aspirin for recurrent stroke decreased as non-HDL-C levels increased. No significant differences in the treatment assignments across the non-HDL-C groups were observed in terms of the rate of severe or moderate bleeding (5 [0.3%] vs. 8 [0.5%] in the low non-HDL-C group; 4 [0.3%] vs. 2 [0.1%] in the high non-HDL-C group; P for interaction=0.425). Conclusion CHANCE-2 participants with low non-HDL-C levels received more clinical benefit from ticagrelor-aspirin versus clopidogrel-aspirin compared to those with high non-HDL-C, following minor ischemic stroke or transient ischemic attack.

Objective We aimed to study the protective effect of total glucosides of paeony (TGP) on chemical liver injury with pattern of liver yin deficiency in rats and determine whether it exerts these effects through the phosphoinositide 3-kinase(PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway.Methods Forty male Sprague-Dawley rats were randomly divided into the following four groups: (i) the blank group, (ii) the model group, (iii) the Yiguan Jian group, and (iv) the TGP group (10 rats per group). For 6 weeks, rats in all groups except for the blank group were injected intraperitoneally with 20％ carbon tetrachloride olive oil solution and were given thyroid tablets (30mg/kg) by gavage in order to establish the model of chemical liver injury with pattern of liver yin deficiency. During the modeling period, rats in the blank and model groups were gavaged daily with distilled water, while rats in the Yiguan Jian group and the TGP group were gavaged with 635mg/kg of Yiguan Jian decoction and 50mg/kg of TGP suspension, respectively. During the administration period, the body weight and rectal temperature of rats were measured every 2 weeks. After the administration, 24-hour food intake, 24-hour water intake, and moisture capacity in tongue surface were recorded. Serum cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and interleukin-1 receptor antagonist (IL-1Ra) contents were measured by ELISA and the cAMP/cGMP ratio was calculated. Changes in the serum levels of alanine aminotransferase (ALT), alanine transaminase (AST), gamma-glutamyl transpeptidase (γ-GT), alkaline phosphatase (ALP), total bilirubin (TBIL), and total bile acids (TBA) were detected using colorimetric method. Masson staining was performed to observe the degree of liver fibrosis and to calculate the relative collagen area. Real-time PCR and Western blotting were conducted to determine the PI3K, AKT, and mTOR mRNA and protein expression levels in rat liver.Results Compared with the blank group, rats in the model group had a lower body weight at weeks 2, 4, and 6, a higher rectal temperature at weeks 2, 4, and 6, and a higher 24-hour food intake; the cAMP level was elevated, the cGMP level was decreased, and the cAMP/cGMP ratio was elevated; the contents of IL-1, IL-6, and TNF-α were elevated, and the contents of IL-10 and IL-1Ra were decreased; ALT, AST, γ-GT, ALP, TBIL, and TBA levels were elevated; the percentage of collagen area in the liver was increased; and the mRNA and protein phosphorylation levels of PI3K, AKT, and mTOR were elevated ( P<0.05). Compared with the model group, rats in the TGP group showed a decrease in rectal temperature at weeks 2, 4, and 6, a decrease in 24-hour food intake and water intake, and an increase in the moisture capacity in tongue surface; rats in the Yiguan Jian and TGP groups showed a decrease in cAMP, an increase in cGMP, and a decrease in the cAMP/cGMP, the contents of IL-1, IL-6, and TNF-α were decreased and the content of IL-10 was increased, the percentage of collagen area in the liver was decreased; ALT, AST, γ-GT, ALP, and TBIL levels were decreased in the TGP group, and PI3K, AKT, and mTOR were downregulated at the mRNA and protein levels(P<0.05).Conclusion TGP has a good protective effect on chemical liver injury with pattern of liver yin deficiency in rats. TGP may regulate the balance of yin and yang by inhibiting the PI3K/AKT/mTOR pathway, reducing the secretion of pro-inflammatory cytokines, and increasing the release of anti-inflammatory cytokines.