Objective To investigate the role and potential mechanism of secreted phosphoprotein 1 (SPP1)⁺ macrophages in the formation of chronic renal allograft fibrosis. Methods The expression features of SPP1⁺ macrophages in renal allografts of chronic allograft dysfunction (CAD) patients were analyzed based on single-cell transcriptome data of renal tissues from patients with CAD. Transcription factor VIPER analysis and DoRothEA transcription factor activity analysis were performed on the single-cell transcriptome data. Renal tissue samples were collected from kidney transplant recipients, including the CAD group (n=5) and the non-renal allograft fibrosis group (CTL group, n=5). A mouse model of chronic allograft rejection was established and divided into the allogeneic kidney transplantation group (CAD group, n=3) and the syngeneic kidney transplantation group (SYN group, n=3). Hematoxylin-eosin staining was used to detect renal tissue injury in mice, and Masson staining was used to detect renal tissue fibrosis. Immunofluorescence staining was performed to detect SPP1 expression in renal tissues of transplant recipients and mouse renal allografts. Bone marrow-derived macrophages (BMDMs) were extracted from mice and subjected to hypoxia stimulation. The expression of hypoxia-inducible factor (HIF)-1α and SPP1 was detected by Western blot, and SPP1 expression was detected by flow cytometry. BMDMs were transfected with HIF-1α overexpression plasmid and HIF-1α small interfering RNA (siRNA) followed by hypoxia intervention, and the expression of HIF-1α and SPP1 was detected by Western blot. Mouse aortic endothelial cells (MAECs) were co-cultured with the supernatant of BMDMs, and the expression of endothelial-mesenchymal transition (EndMT)-related markers was detected by Western blot and immunofluorescence. Results Single-cell transcriptome analysis showed that the proportion of SPP1⁺ macrophages in renal allograft tissues was significantly higher in the CAD group than in the CTL group (P<0.05). The renal injury score and the percentage of interstitial fibrotic area in the CAD group were significantly higher than those in the SYN group (both P<0.05). Immunofluorescence staining showed that the proportion of SPP1⁺ macrophages was increased in the CAD group compared with the CTL group, and also increased in the CAD group compared with the SYN group (both P<0.05). VIPER analysis and DoRothEA transcription factor activity analysis revealed activation of the hypoxia pathway and upregulated expression of transcription factors such as HIF-1α in SPP1⁺ macrophages. SPP1 expression was elevated in BMDMs under hypoxic conditions. Knockdown of HIF-1α inhibited hypoxia-induced SPP1 protein expression, whereas overexpression of HIF-1α upregulated SPP1 protein levels. After co-culture of hypoxia-induced BMDMs with MAECs, the expression levels of EndMT-related markers were increased. Conclusions SPP1⁺ macrophages differentiated under hypoxia are significantly infiltrated in the formation of chronic renal allograft fibrosis, and may promote renal allograft fibrosis by inducing EndMT in renal vascular endothelial cells.

Recently， the American College of Gastroenterology （ACG） released the clinical guidelines on perioperative risk assessment and management of patients with cirrhosis， proposing a comprehensive approach for perioperative risk assessment and management in these patients. The guidelines mainly focus on the severity of liver diseases， extrahepatic comorbidities， and surgery-specific factors， with an emphasis on individualized risk stratification using validated risk assessment tools （such as the VOCAL-Penn score） for patients with cirrhosis. This article gives an excerpt of the key statements in the guidelines.

Objective To investigate the association of serum total testosterone(TT),free testosterone(FT),sex hormone-binding globulin(SHBG),and estradiol(E_2)with all-cause mortality rate(AMR)in males and to evaluate their predictive value. Methods Based on data from the National Health and Nutrition Examination Survey(NHANES)cycles(1999—2004 and 2013—2016),the relationships between different sex hormones and AMR was analyzed with Cox proportional hazards regression models. The dose-response relationships between different sex hormones and male AMR were assessed with restricted cubic splines(RCS). The predictive performances of different sex hormones for male AMR were compared with receiver operating characteristic(ROC)curves and the area under the curve(AUC). The survival differences across varying sex hormone levels were evaluated with Kaplan-Meier survival curves and log-rank tests. Results This study involved 3632 adult male participants with a median follow-up of 6.5 years,during which 320 AMR occurred(8.8%). Cox univariate analysis indicated that TT,FT and SHBG were risk factors for AMR(P＜0.001). Cox multivariate analysis revealed that FT and SHBG were independent risk factors for AMR(FT:HR=0.90,95%CI:0.86-0.94; SHBG:HR=1.01,95%CI:1.01-1.02). RCS revealed a U-shaped nonlinear relationship between TT,FT and AMR(P＜0.001); SHBG showed a positive dose-response relationship with AMR(P＜0.001). The AUCs of FT predicting the 5-year,10-year,and 15-year AMR were 0.78(95%CI:0.73-0.82),0.80(95%CI:0.76-0.84),and 0.84(95%CI: 0.80-0.88),respectively,significantly outperforming other indicators. Subgroup analysis revealed that FT was negatively correlated with male AMR,but this association was modulated by age,race,smoking status and diabetes status(P_(interaction)＜0.05). Kaplan-Meier survival analysis showed that different levels of TT and FT(Q1-Q4)were significantly positively correlated with survival rate(P＜0.001),while different levels of SHBG were significantly negatively correlated with survival rate,with patients in the Q4 group having the highest risk of death(P＜0.001). Conclusion Based on US NHANES,studies have shown that the FT and SHBG are independent risk factors for male AMR,and FT demonstrates greater predictive value for male AMR than TT.

This review systematically summarizes the unique metabolic mechanisms of breast cancer,their interac-tions with the tumor microenvironment(TME),and the latest advances in targeted therapies.The interplay between metabolic reprogramming and the TME underpins malignant progression and therapeutic resistance.Breast cancer cells reshape energy supply through the Warburg effect,aberrant fatty acid synthesis,and amino acid metabolism,while immune cells,fibroblasts,and the acidic milieu within the TME promote immune evasion and drug resistance via metabolic coupling.Although traditional strategies targeting key metabolic enzymes remain valuable,they are often insufficient to overcome metabolic adaptability.In recent years,combined metabolic and immunotherapeutic approaches have emerged as promising strategies:by reducing lactate accumulation,restoring T-cell function,and reprogramming tumor-associated macrophages and cancer-associated fibroblasts,these therapies can remodel the immunosuppressive microenvironment and enhance immunotherapy efficacy.The application of metabolomics and single-cell sequencing further elucidates breast cancer heterogeneity,providing a basis for individualized precision treatment.Future challenges include deciphering resistance mechanisms,developing highly selective metabolic in-hibitors,and designing integrated multi-omics-based therapeutic regimens.

ObjectiveTo investigate the ability of chimeric antigen receptor T-cell with programmed cell death-1 （PD-1） knockdown （si-PD-1 CAR-T） targeting folate receptor alpha （FRα） to eliminate hepatoma cells. MethodsThe bioinformatics database TCGA was used to analyze the expression level of FRα antigen in liver cancer tissue and normal liver tissue and the association between FRα expression and the survival of liver cancer patients. The mRNA encoding the CAR structure targeting FRα antigen and the small interfering RNA （siRNA） targeting the PD-1 gene were transduced into T cells using an electroporator to prepare FRα-CAR-T and si-PD-1-CAR-T cells. Flow cytometry was used to analyze the expression efficiency of FRα-CAR and the knockdown efficiency of PD-1. Hepatoma cell lines JHH-1 and Hep-G2 were cultured in vitro， and flow cytometry was used to analyze the expression of FRα on the surface of tumor cells. With FRα-CAR-T， si-PD-1 CAR-T， and mock vector-transduced T cells （Mock T） used as effector cells and with JHH-1 and Hep-G2 cells as target cells， CCK-8 assay was used to measure the killing efficiency of effector cells against target cells at different effector-to-target ratios （1∶1， 2.5∶1，5∶1，10∶1，20∶1）. ELISA was used to measure the secretion of interferon gamma （IFN-γ） and interleukin-2 （IL-2） in the supernatants from co-cultures of effector and target cells （10∶1）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， while a one-way analysis of variance was used for comparison between multiple groups， and the SNK test was used for further comparison between two groups. The Kaplan-Meier method was used for comparison of survival differences. ResultsThe analysis of the TCGA database showed that there was a significant increase in the expression level of FOLR1 in liver cancer tissue， and liver cancer patients with high expression of FOLR1 had a significantly shorter overall survival than those with low expression （P=0.013）. After transduction of mRNA into T cells， the expression rate of FRα-CAR reached 89.8% in CAR-T and 84.7% in si-PD-1 CAR-T cells， and co-transfection with mRNA and siRNA could downregulate PD-1 in T cells and maintain a low expression state for at least 7 days. The expression rate of FRα antigen was 100% in JHH-1 cells， while it showed negative expression in Hep-G2 cells. CCK-8 assay showed that the killing efficiency of si-PD-1-CAR-T against JHH-1 cells was significantly higher than that against FRα-CAR-T cells （P<0.05）. ELISA showed that compared with Mock T cells， FRα-CAR-T cells co-cultured with JHH-1 cells showed significant increases in the secretion of IL-2 （1 032.50±135.90 pg/mL vs 50.26±7.87 pg/mL，P<0.001） and IFN-γ （1 430.56±184.20 pg/mL vs 89.05±11.26 pg/mL，P<0.001）， and in addition， the release levels of IFN-γ and IL-2 after co-culture of si-PD-1-CAR-T and JHH-1 cells were significantly higher than the release level of FRα-CAR-T （P<0.05）. ConclusionFRα is a potential target for liver cancer treatment， and PD-1 knockdown in T cells can significantly enhance the in vitro killing activity of FRα-CAR-T cells.

Antimicrobial resistance (AMR) has emerged as a major global public health challenge, with traditional prevention and control methods exhibiting significant limitations in detection efficiency, data processing, and clinical decision-making. Leveraging its robust capabilities in data analysis and pattern recognition, artificial intelligence (AI) technology has been widely applied across multiple critical aspects of AMR containment. Current evidence demonstrates that AI technologies can significantly enhance the efficiency of resistancediagnosis, optimize personalized treatment strategies, and improve real-time monitoring of resistant pathogen transmission. Despite persistent challenges such as data heterogeneity, model interpretability, and ethical compliance in practical applications, AI holds immense promise in supporting precision infection management and addressing the growing crisis of antimicrobial resistance.This article systematically reviews the clinical applications of AI in AMR prevention and control, including resistance detection and prediction based on mass spectrometry and genomic data, the use of clinical decision support systems in anti-infective therapy, as well as the role of AI in epidemiological surveillance, pathogen tracking, early warning systems, and novel antimicrobial drug discovery aiming to provide reference for clinical practice.

Objective:To analyze the efficacy and safety of different surgical approaches for the treatment of anterior skull base malignancies involving the orbit.Methods:Retrospective analysis was conducted on patients with anterior skull base malignancies involving orbit who attended Xuanwu Hospital of Capital Medical University from April 2013 to July 2021. They were divided into endoscopic endonasal approach(EEA), lateral orbital approach(ELOA), and sublabial transmaxillary approach(ESTMA) groups according to the primary surgical approach. One-way analysis of variance and χ 2 test were used to compare the clinical characteristics, degree of tumour resection, rate of postoperative cranial nerve palsy and improvement of visual acuity; Log-rank test was applied to assess the difference in overall survival (OS). Results:One hundred and ninety-eight patients were enrolled, including 107 males and 91 females, aged (48.5±15.3) years. There were 153, 33, and 12 patients in the EEA, ESTMA, and ELOA groups, respectively. There were no significant differences among the three groups in age, gender, and history of radiotherapy, chemotherapy or surgery ( P>0.05 for all). All patients in ELOA group had preoperative visual impairment (12/12), with a significantly higher percentage than EEA group (56/153) and ESTMA group (14/33) ( χ2=19.72, P<0.001). There was no significant difference between three groups in the degree of tumor resection (gross total resection: 84.97% vs. 81.82% vs. 58.33%, χ2=5.58, P>0.05), postoperative cranial nerve palsy rate (13.07% vs. 30.30% vs. 16.67%, χ2=5.95, P>0.05), visual improvement rate (58.93% vs. 57.14% vs. 58.33%, χ2=0.04, P>0.05) and 5-year OS (60.69% vs. 42.66% vs. 50.00%, χ2=3.22, P>0.05). Conclusion:All three surgical approaches were safe, effective and feasible treatment modalities.

Objective To investigate the effect of lung lobe surface projection localization combined with lung segment drainage sputum technique on airway clearance in patients with aspiration pneumonia,providing a reference for clinical nursing practice.Methods A convenience sampling method was used to select 62 patients with perioperative aspiration pneumonia secondary to brain diseases admitted to a tertiary A hospital in Beijing from May 2022 to October 2024 as the research subjects.A total of 31 patients admitted from August 2023 to October 2024 were assigned to a control group,and 31 patients admitted from May 2022 to July 2023 were assigned to an experimental group.The experimental group received lung lobe surface projection positioning combined with lung segment drainage sputum technique on top of conventional back percussion sputum clearance technique,while the control group received conventional back percussion sputum clearance technique.After the intervention,the differences in oxygenation state,inflammatory test indicators,treatment efficiency,vital signs and frequency of suction coughing between 2 groups were compared.Results After the intervention,the experimental group showed better oxygenation index,frequency of suction coughing,white blood cell count,percentage of neutrophils,procalcitonin levels,interleukin-6 levels,and treatment efficiency compared to those in the control group(P＜0.05).There was no statistically significant difference in heart rate,respiratory rate,and C-reactive protein levels between 2 groups(P＞0.05).Conclusion Lung lobe surface projection positioning combined can effectively promote the patients with aspiration pneumonia of loosening of sputum in the lungs,improve airway clearance efficiency,enhance the patient's pulmonary ventilation and gas exchange capacity,improve oxygenation levels,and reduce systemic inflammatory levels.

Objective:To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province.Methods:A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Approval Number: 2019 Medical Ethics Review No. 67). Results:Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c. 1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c. 467G>A (p.Gly156Asp) and c. 1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c. 1297G>C (p.Ala433Pro) and c. 1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and may affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. Conclusion:The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c. 1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.

Objective To investigate the post-intervention experiences in elderly stroke patients who received the group-based acceptance and commitment therapy(ACT)and to provide a reference to improve the group-based ACT intervention strategies for the patients.Methods With the descriptive phenomenological research,the semi-structured in-depth interviews were conducted with 15 elderly stroke patients who had received the group-based ACT intervention for 6 months in a Tier-IIIA hospital in Hunan Province between May and July 2023.The data acquired from the interviews were analysed using the Colaizzi method.Results The experiences in elderly stroke patients with the group-based ACT intervention were categorised into three main themes and ten sub-themes:(1)The impact of intervention on the psychology and spirit(change cognition and accept oneself;enhance awareness and reflect on oneself;clarify values and adapt to oneself;disengage from suffering and achieve dissociation;understand suffering and discover a sense of meaning in life);(2)Behavioural changes brought by the intervention(change approaches to improve health;engage in rehabilitation exercises and build confidence;enhance social interactions and integrate into life);(3)Suggestions for the intervention program(tailor to the physiological characteristics of the elderly;adapt to the psychological characteristics of the elderly).Conclusion The group-based ACT intervention has a beneficial effect on the psychological,spiritual and behavioural changes in the elderly stroke patients.The intervention programs should be improved according to the physical and mental characteristics therefore to improve the mental health of elderly stroke patients.