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.

This study aims to understand the epidemic distribution characteristics,antimicrobial resistance,virulence genes,and biofilm adhesion ability of Enterococcus in yaks on the Tibetan plateau.Three hundred and forty-six fresh yak fecal samples and 311 milk samples were collected from four provinces on the Tibetan plateau(Xizang,Sichuan,Gansu,Qinghai),totaling 657 sam-ples.Bacterial isolation and identification were conducted,followed by 16S rDNA gene detection and the construction of a systematic evolutionary tree.The isolated strains were tested for antimi-crobial resistance and virulence genes using PCR,and sensitivity tests were performed using 18 types of antibiotics.The biofilm adhesion ability of the isolated bacteria was determined using an improved semi-quantitative crystal violet staining method.The results showed that the total isola-tion rate of Enterococcus was 32.27％,with Sichuan having the highest at 60.23％,followed by Gansu,Qinghai,and Tibet autonomous region at 42.70％,23.47％,and 18.31％respectively.In terms of sample types,the isolation rate in fecal samples was 36.71％,and in milk samples,it was 27.33％.Through PCR amplification,bands of approximately 1 400 bp were obtained,and 5 strains were selected for evolutionary analysis,forming a separate cluster.Among the 212 isolated strains,a high resistance to clindamycin,quinupristin-dalfopristin,linezolid,levofloxacin,and erythromycin was observed,with various resistance phenomena,accounting for 60.85％.Only 5 out of 12 resist-ant genes were detected,namely erm(B),tet(L),tet(O),tet(M),and ant(6)-Ia.All 13 virulence genes were detected in Enterococcus,with detection rates in the range of 5.19％to 95.76％,where cpd was 95.75％,gelE was 91.98％,efaA was 86.79％,asal was 86.32％,and the rest ranged from 5.19％to 55.66％.The fsr virulence gene was not detected in Enterococcus from milk sources.Among the isolated strains,3.30％showed medium adhesive ability,48.58％showed weak adhesive ability,and 48.11％showed no adhesive ability.The above research revealed the preva-lence of yak derived Enterococcus,the carrying status of resistance and virulence genes,and the correlation between biofilm phenotypes,laying the foundation for mastering research data on yak-derived Enterococcus in the Tibetan plateau.

To investigate the role of the DPP4-nestin axis in liver fibrosis induced by alveolar cyst infection,a murine model was established using C57BL/6 mice via hepatic portal vein injection.Liver histopathological changes were assessed using HE staining,while immunohistochemistry and immunofluorescence were employed to evaluate the expression levels of nestin and DPP4 in infected mouse livers.In vitro,J S1 cell line was stimulated with recombinant DPP4 protein to es-tablish a cellular model,and qPCR,Western blot,and shRNA lentivirus interference techniques were utilized to examine the involvement of the DPP4-nestin axis in hepatic stellate cell activation.The findings demonstrated that compared to the Sham group,liver tissue structure disruption and collagen deposition were evident along with significantly increased expressions of nestin and DPP4(P＜0.050 0),which colocalized with nesin and α-SMA.Furthermore,stimulation with recombi-nant DPP4 protein significantly enhanced JS1 cell activation(P＜0.050 0)as well as upregulated nestin expression(P＜0.050 0)when compared to control group cells.Notably,shRNA lentivirus-mediated inhibition of nestin expression effectively suppressed the activating effects exerted by re-combinant DPP4 protein on JS1 cells(P＜0.050 0).Collectively,these results highlight the crucial regulatory role played by the DPP4-nestin axis in hepatic stellate cell activation triggered by alveo-lar infection;thus,targeting this axis may represent a novel therapeutic strategy for treating alveo-lar infection-induced liver fibrosis.

Objective:To prepare decellularized extracellular matrix (dECM)-gelatin methacryloyl (GelMA) composite hydrogels and to study their effects on hepatocyte proliferation.Methods:Hepatic dECM was prepared by elution, and GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels were prepared by pepsin solubilization. The morphology of normal liver and dECM liver was observed by eyes and scanning electron microscopy using hematoxylin-eosin, Sirius red and periodate-Schiff staining, respectively. The internal structure of the dECM-GelMA composite hydrogels was observed by scanning electron microscopy, and the pore diameter was measured. Liver HL-7702 cells were co-cultured with GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels, and the cell proliferation viability was determined by cell counting kit-8. The expression of proliferating cell nuclear antigen (PCNA), Wnt family protein 5a (Wnt5a), β-catenin, extracellular-regulated protein kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were detected by Western blotting. Comparisons were made using independent sample t-test or one-factor analysis of variance. Results:After decellularization, the hepatocyte morphology showed rounded depressions, and the extracellular matrix structure was intact. The GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels showed inernally porous structures. The pore diameter increased from (3.06±1.35) μm in the GelMA hydrogel to (16.01±4.02) μm in the 50% dECM-GelMA composite hydrogel. On the 3rd, 5th and 7th day, the relative cell proliferation was higher in the 50% dECM-GelMA composite hydrogel group than that in the GelMA hydrogel group (1.89±0.04 vs 1.53±0.01, 9.36±0.04 vs 3.89±0.09, 7.15±0.27 vs 4.89±0.15, all P<0.05). The relative expression levels of PCNA, Wnt5a, β-catenin, and p-ERK1/2/ERK1/2 proteins in the 50% dECM-GelMA composite hydrogel group were higher than those in the GelMA hydrogel group (2.14±0.04 vs 1.00±0.03, 2.36±0.09 vs 1.00±0.08, 1.45±0.03 vs 1.00±0.04, 1.43±0.04 vs 1.00±0.01, all P<0.05). Conclusions:A dECM-GelMA composite hydrogel can be prepared, which may promote hepatocyte proliferation by upregulating the phosphorylation of ERK1/2 and activating Wnt/β-catenin signaling pathway.

Objective:To investigate and analyze the relationship between genotype and phenotype in patients with early-onset high myopia (eoHM) associated with hereditary eye diseases.Methods:A family-based study was conducted among 30 families diagnosed with eoHM at Department of Ophthalmology of People's Hospital of Ningxia Hui Autonomous Region from January 2022 to June 2023. Seven families (23.3%, 7/30), all probands, and their 14 parents were included. These seven families were unrelated. Detailed patient and family histories were collected. All participants underwent comprehensive ophthalmic examinations, including best-corrected visual acuity, color vision testing, fundus color photography, optical coherence tomography, fluorescein fundus angiography, and fundus autofluorescence imaging. Full-field electroretinography was performed in four cases. Peripheral venous blood samples were collected from patients and their parents for whole-genome DNA extraction and whole-exome sequencing. Potential pathogenic variants were identified, and their pathogenicity was analyzed and confirmed by Sanger sequencing. The pathogenicity of newly discovered gene variants was evaluated according to the guidelines of the American College of Medical Genetics and Genomics (ACMG). Literature on previously reported eoHM associated with hereditary eye diseases was reviewed to analyze the relationship between variant genes and clinical phenotypes.Results:Among the seven families, three exhibited X-linked inheritance, two showed autosomal recessive inheritance, and two demonstrated autosomal dominant inheritance. All the patients were male. Among the seven patients, one case each was identified with congenital stationary night blindness (CSNB), Bornholm eye disease, X-linked retinitis pigmentosa (XL-RP), cone-rod dystrophy, Knobloch syndrome, familial exudative vitreoretinopathy (FEVR), and Stickler syndrome. Genetic testing revealed nine gene variants highly correlated with the observed phenotypes. The genetic testing results revealed that all patients were found to carry nine gene variants highly associated with the phenotype, including: a hemizygous missense variant NYX c.647A>T (p.N216I) (M1), an OPN1LW LIAVA haplotype variant (M2), a hemizygous frameshift variant RPGR c.3096_3097del (p.E1033RfsTer45) (M3), compound heterozygous variants TTLL5 c.1588_1589del (p.L531EfsTer24) and c.850G>C (p.D284H) (M4, M5), compound heterozygous variants COL18A1 c.2118dup (p.G707RfsTer23) and c.3523_3524del (p.L1175VfsTer72) (M6, M7), a heterozygous missense mutation FZD4 c.1499C>T (p.T500I) (M8), and a heterozygous frameshift variant COL11A2 c.966dup (p.T323HfsTer19) (M9). Among them, M2, M4, M5, M8 and M9 were newly discovered mutation sites, and M1, M3, M6 and M7 were known mutation sites. According to the classification standards and guidelines of genetic variation issued by ACMG, M2, M3, M4, M6, M7, and M9 were judged to be pathogenic variants, while M1, M5, and M8 were of unknown clinical significance. Through literature review, it was found that eoHM was more common among the clinical phenotypes of 4 types of hereditary retinal diseases, including CSNB, Stickler syndrome, FEVR and XL-RP. Conclusion:eoHM is intricately associated with inherited eye diseases and may serve as the earliest indicator of such conditions.

Objective:To investigate the effects and mechanism of metformin on the proliferation and expression of fibrotic proteins of human hypertrophic scar (HS) fibroblasts (Fbs).Methods:The study was an experimental study. From June 2021 to June 2022, 5 patients with HS were admitted to the Department of Burns and Cutaneous Surgery of the First Affiliated Hospital of Air Force Medical University, including 3 males and 2 females, aged from 21 to 36 years. HS tissue was collected, Fbs were isolated and cultured, and Fbs of passage 5 to 7 were used for experiment. Fbs were taken and cultured in their respective media supplemented with phosphate buffered solution (PBS) or metformin at final molarities of 5, 10, 20, and 40 mmol/L for 48 hours. The cell proliferation activity was detected using the cell counting kit-8 (CCK-8), and the proliferation inhibition rate of cells was calculated. The content of hydroxyproline in the cell culture supernatant was measured using a hydroxyproline assay kit. The phosphorylation levels of protein kinase B (Akt) and mammalian target of rapamycin (mTOR) in the cells were detected by Western blotting, and the ratios of phosphorylated Akt (p-Akt) to Akt and phosphorylated mTOR (p-mTOR) to mTOR were calculated. After 24 hours of culture, the mRNA expressions of type Ⅰ collagen, type Ⅲ collagen, and α-smooth muscle actin (α-SMA) in the cells were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. Another batch of Fbs were divided into control group (with conventional culture), LY294002 group, metformin group, and LY294002+metformin group. LY294002, metformin, and LY294002+metformin were added to the culture media of the last three groups, respectively, with the final molarities of LY294002 and metformin being 20 μmol/L and 10 mmol/L, respectively. CCK-8 was used to detect the cell proliferation activity at 0 (immediately), 24, and 48 hours of culture. After 48 hours of culture, Western blotting was used to detect the phosphorylation levels of Akt and mTOR in the cells, and the ratios of p-Akt to Akt and p-mTOR to mTOR were calculated. The sample size for the cell proliferation inhibition rate experiment was 4, and the sample size for the other experiments was 3.Results:After 48 hours of culture, compared with the cells treated with PBS, the proliferation inhibition rates of the cells treated with 5, 10, 20, and 40 mmol/L metformin were significantly increased (with t values of 10.69, 14.20, 19.73, and 52.54, respectively, P<0.05), the content of hydroxyproline in the culture supernatants of the cells treated with 10, 20, and 40 mmol/L metformin was significantly decreased (with t values of 8.06, 7.86, and 10.25, respectively, P<0.05), and the ratios of p-Akt to Akt in the cells treated with 10, 20, and 40 mmol/L metformin and the ratios of p-mTOR to mTOR in the cells treated with 20 and 40 mmol/L metformin were significantly decreased (with t values of 2.82, 4.28, 9.88, 5.66, and 9.08, respectively, P<0.05). After 24 hours of culture, compared with those treated with PBS, the mRNA expressions of type Ⅰ collagen and α-SMA in the cells treated with 5, 10, 20, and 40 mmol/L metformin and the mRNA expressions of type Ⅲ collagen in the cells treated with 10, 20, and 40 mmol/L metformin were significantly decreased (with t values of 4.35, 8.53, 9.57, 14.77, 4.14, 5.58, 7.89, 9.37, 5.18, 6.85, and 9.15, respectively, P<0.05). At 24 and 48 hours of culture, the proliferation activities of the cells in LY294002 group (with t values of 6.30 and 13.60, respectively) and metformin group (with t values of 6.47 and 10.69, respectively) were significantly lower than those in control group ( P<0.05). After 48 hours of culture, the ratios of p-Akt to Akt in the cells of LY294002 group and metformin group were 0.554±0.027 and 0.681±0.029, respectively, which were significantly lower than 1.053±0.193 in control group (with t values of 4.45 and 3.31, respectively, P<0.05). The ratio of p-Akt to Akt in the cells of LY294002+metformin group was 0.387±0.023, which was significantly lower than that in metformin group ( t=5.95, P<0.05). After 48 hours of culture, the ratio of p-mTOR to mTOR in the cells of LY294002 group was significantly lower than that in control group ( t=4.01, P<0.05), and the ratio of p-mTOR to mTOR in the cells of LY294002+metformin group was significantly lower than that in metformin group ( t=6.05, P<0.05). Conclusions:Metformin can inhibit the proliferation and expression of fibrotic proteins type Ⅰ collagen, type Ⅲ collagen, and α-SMA of human HS Fbs through phosphatidylinositol 3-kinase/Akt/mTOR signaling pathway.

Objective:To examine the influence of physical function status on supportive care needs (SCNS) in patients with primary liver cancer (PLC) and to explore the mediating roles of perceived social support and anxiety-depression, with the aim of providing evidence for nursing interventions to improve patients' care experience.Methods:A convenience sampling method was used to select PLC inpatients admitted to The First Affiliated Hospital of Jinan University between December 2022 and February 2024. Data were collected using a general information questionnaire, the 34-item Supportive Care Needs Survey-Short Form, the Hospital Anxiety and Depression Scale, the Perceived Social Support Scale, and the Karnofsky Performance Status Scale to conduct a cross-sectional survey. Pearson correlation analysis was performed to examine associations among SCNS, perceived social support, anxiety-depression, and physical function status. Structural equation modeling was used to assess the mediating effects of perceived social support and anxiety-depression on the relationship between physical function status and SCNS.Results:A total of 304 patients were enrolled, including 260 males and 44 females, 31 cases aged 18-40 years old, 160 cases aged 41 to 60 years old, and 113 cases over 60 years old. The mean total SCNS score was (98.32 ± 21.75) points, the mean anxiety-depression score was (23.31 ± 9.64) points, the mean perceived social support score was (56.62 ± 13.05) points, and the mean physical function status score was (66.28 ± 12.31) points. Pearson correlation analysis showed that physical function status was negatively correlated with SCNS and anxiety-depression ( r =-0.509, -0.447; both P<0.05) and positively correlated with perceived social support ( r =0.439, P<0.05). Physical function status had a direct effect of 60.74% on SCNS, with specific mediating effects of perceived social support and anxiety-depression accounting for 23.15% and 11.85%, respectively, and a chain mediating effect of 4.26%. Conclusions:Patients with PLC exhibited a moderately high level of supportive care needs. Physical function status not only exerted a direct negative effect on SCNS but also indirectly influenced SCNS through the chain mediation of perceived social support and anxiety-depression. Clinical medical staff should focus on enhancing patients' perception of social support and effectively alleviating anxiety and depressive symptoms, thereby reducing supportive care needs to some extent.

Objective:To construct and verify a risk prediction model for pulmonary infection in patients with aneurysmal subarachnoid hemorrhage (aSAH) after craniotomy and clipping, providing theoretical basis and practical guidance for improving the quality of postoperative care.Methods:Using the convenience sampling method, a retrospective selection was made of 397 patients with aSAH after craniotomy and clipping who were hospitalized in the Department of Neurosurgery of Shanxi Bethune Hospital (Shanxi Academy of Medical Sciences) from January 2019 to December 2023 as the modeling group. They were randomly divided into the training set and the test set at a ratio of 7:3, with 278 cases in the training set and 119 cases in the test set. Patients were divided into the infection group and the non-infection group based on whether they developed pulmonary infection. Univariate analysis was used to model the risk factors of pulmonary infection after aSAH craniotomy and clamping in the group, and Lasso regression was used to construct a predictive model. A total of 119 patients with aSAH admitted to the neurosurgery department of the same hospital from January to April 2024 were selected for the external validation of the model. The predictive effect of the model was evaluated through the receiver operating characteristic (ROC) curve.Results:In the modeling group, there were 216 male patients and 181 female patients. The incidence of pulmonary infection was 38.54% (153/397). Finally, five influencing factors, namely stroke, Hunt-Hess classification, mechanical ventilation, indwelling nasogastric tube and the timing of initiating enteral nutrition, were included to construct a predictive model. The areas under the ROC curves of the nomogram prediction models of this model in the training set, test set, and external validation group were 0.859(95% CI 0.791-0.928), 0.843(95% CI 0.796-0.890), and 0.800(95% CI 0.711-0.889), respectively. The calibration curve shows that the model's prediction fits well with the actual situation and has a high degree of calibration. Decision curve analysis indicates that this model has high clinical application value under different risk thresholds. Conclusions:The risk prediction model for pulmonary infection in patients after craniotomy and clipping with aSAH has good discrimination and calibration, which can provide reference for medical staff to identify high-risk patients at an early stage and take preventive intervention measures.

Objective:To examine the influence of physical function status on supportive care needs (SCNS) in patients with primary liver cancer (PLC) and to explore the mediating roles of perceived social support and anxiety-depression, with the aim of providing evidence for nursing interventions to improve patients' care experience.Methods:A convenience sampling method was used to select PLC inpatients admitted to The First Affiliated Hospital of Jinan University between December 2022 and February 2024. Data were collected using a general information questionnaire, the 34-item Supportive Care Needs Survey-Short Form, the Hospital Anxiety and Depression Scale, the Perceived Social Support Scale, and the Karnofsky Performance Status Scale to conduct a cross-sectional survey. Pearson correlation analysis was performed to examine associations among SCNS, perceived social support, anxiety-depression, and physical function status. Structural equation modeling was used to assess the mediating effects of perceived social support and anxiety-depression on the relationship between physical function status and SCNS.Results:A total of 304 patients were enrolled, including 260 males and 44 females, 31 cases aged 18-40 years old, 160 cases aged 41 to 60 years old, and 113 cases over 60 years old. The mean total SCNS score was (98.32 ± 21.75) points, the mean anxiety-depression score was (23.31 ± 9.64) points, the mean perceived social support score was (56.62 ± 13.05) points, and the mean physical function status score was (66.28 ± 12.31) points. Pearson correlation analysis showed that physical function status was negatively correlated with SCNS and anxiety-depression ( r =-0.509, -0.447; both P<0.05) and positively correlated with perceived social support ( r =0.439, P<0.05). Physical function status had a direct effect of 60.74% on SCNS, with specific mediating effects of perceived social support and anxiety-depression accounting for 23.15% and 11.85%, respectively, and a chain mediating effect of 4.26%. Conclusions:Patients with PLC exhibited a moderately high level of supportive care needs. Physical function status not only exerted a direct negative effect on SCNS but also indirectly influenced SCNS through the chain mediation of perceived social support and anxiety-depression. Clinical medical staff should focus on enhancing patients' perception of social support and effectively alleviating anxiety and depressive symptoms, thereby reducing supportive care needs to some extent.

Objective:To construct and verify a risk prediction model for pulmonary infection in patients with aneurysmal subarachnoid hemorrhage (aSAH) after craniotomy and clipping, providing theoretical basis and practical guidance for improving the quality of postoperative care.Methods:Using the convenience sampling method, a retrospective selection was made of 397 patients with aSAH after craniotomy and clipping who were hospitalized in the Department of Neurosurgery of Shanxi Bethune Hospital (Shanxi Academy of Medical Sciences) from January 2019 to December 2023 as the modeling group. They were randomly divided into the training set and the test set at a ratio of 7:3, with 278 cases in the training set and 119 cases in the test set. Patients were divided into the infection group and the non-infection group based on whether they developed pulmonary infection. Univariate analysis was used to model the risk factors of pulmonary infection after aSAH craniotomy and clamping in the group, and Lasso regression was used to construct a predictive model. A total of 119 patients with aSAH admitted to the neurosurgery department of the same hospital from January to April 2024 were selected for the external validation of the model. The predictive effect of the model was evaluated through the receiver operating characteristic (ROC) curve.Results:In the modeling group, there were 216 male patients and 181 female patients. The incidence of pulmonary infection was 38.54% (153/397). Finally, five influencing factors, namely stroke, Hunt-Hess classification, mechanical ventilation, indwelling nasogastric tube and the timing of initiating enteral nutrition, were included to construct a predictive model. The areas under the ROC curves of the nomogram prediction models of this model in the training set, test set, and external validation group were 0.859(95% CI 0.791-0.928), 0.843(95% CI 0.796-0.890), and 0.800(95% CI 0.711-0.889), respectively. The calibration curve shows that the model's prediction fits well with the actual situation and has a high degree of calibration. Decision curve analysis indicates that this model has high clinical application value under different risk thresholds. Conclusions:The risk prediction model for pulmonary infection in patients after craniotomy and clipping with aSAH has good discrimination and calibration, which can provide reference for medical staff to identify high-risk patients at an early stage and take preventive intervention measures.