The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

OBJECTIVES: To investigate the role of ferroptosis in diquat-induced acute kidney injury (AKI) and its molecular mechanisms. METHODS: Transgenic zebrafish models with Tg (Eco.Tshb:EGFP) labeling of the renal tubules and Tg (lyz:dsRed2) labeling of the neutrophils were both divided into control group, gentamicin (positive control) group, diquat poisoning group, ferroptosis inhibitor group. The indicators of kidney injury, inflammatory response, and ferroptosis were examined in the zebrafish, and the changes in expressions of voltage-dependent anion-selective channel protein 1 (VDAC1) and mitochondrial ferritin (FTMT) were detected using Western blotting. RESULTS: AKI induced by diquat exhibited a significant dose-effect relationship, and the severity of injury was proportional to the exposure concentration. Diquat also caused marked oxidative stress and inflammatory responses in the zebrafish models. Rhodamine metabolism assay and HE staining revealed significantly declined glomerular filtration function of the zebrafish as diquat exposure concentration increased. Immunofluorescence staining highlighted significant changes in the expressions of ferroptosis markers GPX4 and FTH1 in zebrafish renal tissues following diquat exposure. In diquat-exposed zebrafish, treatment with ferrostatin-1, a ferroptosis inhibitor, obviously upregulated GPX4 and downregulated FTH1 expressions and improved the metabolic rate of glucan labeled with rhodamine B. Diquat exposure significantly upregulated the expression of VDAC1 and FTMT in zebrafish, and the application of ferrostatin-1 and VBIT-12 (a VDAC1 inhibitor) both caused pronounced downregulation of FTMT expression. CONCLUSIONS Ferroptosis is a critical mechanism underlying diquat-induced AKI, in which VDAC1 and FTMT play important regulatory roles, suggesting their potential as therapeutic target for AKI caused by diquat.
Animals ; Zebrafish ; Ferroptosis/drug effects* ; Acute Kidney Injury/chemically induced* ; Diquat/toxicity* ; Animals, Genetically Modified ; Voltage-Dependent Anion Channel 1/metabolism* ; Ferritins/metabolism* ; Oxidative Stress

Image 1.

Objective:To analyze the current status and trends in the clinical management and outcomes of respiratory distress syndrome (RDS) in preterm infants <32 weeks′ gestation admitted to the Chinese Neonatal Network (CHNN) from 2019 to 2023.Methods:A cross-sectional study was conducted from November 2024 to January 2025 using the CHNN cohort of very preterm and extremely preterm infants. A total of 30 869 RDS infants with gestational age <32 weeks were admitted within 1 day after birth to CHNN centers from 2019 to 2023. Data on demographics, perinatal management, early complications within 7 days of age, and in-hospital outcomes were collected. Yearly groups were defined by admission year. Trends by year were evaluated by Cochran-Armitage trend test, linear regression model and median regression model.Results:The gestational age at birth of 30 869 RDS infant was 28.9 (27.1, 30.7) weeks and the birth weight was 1 259 (932, 1 586) g. Males account for 56.5% (17 363/30 757). From 2019 to 2023, the prevalence of RDS was 73.8% (5 503/7 461), 74.5% (5 490/7 368), 79.8% (5 884/7 372), 81.6% (6 435/7 889), and 86.0% (7 557/8 789), respectively, showing an increasing trend year by year ( P<0.001). The overall rate of pulmonary surfactant administration was 72.4% (22 359/30 869), fluctuating between 71.2% (5 381/7 557) and 74.3% (4 089/5 503) over the 5-year period. Antenatal corticosteroids were administered to 82.3% (24 357/29 597) mothers of RDS infants and 23.6% (7 218/30 565) RDS infants received noninvasive positive end-expiratory pressure support in the delivery room, both showing a increasing trend over the 5 years (both P<0.001). The incidence of pneumothorax and the use rate of inhaled nitric oxide within 7 days of age were 1.3% (393/30 846) and 1.4% (436/30 869), respectively, both showing increasing trends over the 5 years (both P<0.001). The rate of complete course of antenatal corticosteroids administration was 64.6% (14 458/22 382), the rates of discharge against medical advice and mortality within 7 days of age were 5.3% (1 635/30 869) and 2.7% (724/26 803), respectively, all showing a decreasing trend over time (all P<0.05). Regarding in-hospital outcomes, mortality rate of RDS infants was 4.6% (1 228/26 803), showing a downward trend year by year ( P=0.005). The incidence of bronchopulmonary dysplasia (BPD) was 35.0% (9 417/26 919), and the combined incidence of death or BPD was 36.4% (9 763/26 803), both showing an increasing trend year by year (both P<0.001). Conclusions:RDS prevalence increased annually in preterm infants <32 weeks′ gestation from 2019 to 2023, with declining mortality but rising BPD rates. While antenatal steroid use and noninvasive positive end-expiratory pressure support application improved, full-course antenatal steroid compliance decreased. These findings highlight the need for standardized perinatal management protocols to improve the clinical management of RDS.

Objective To analyze the acupoint selection law in acupuncture treatment for sinusitis using data mining techniques.Methods Relevant literature on acupuncture treatment for sinusitis was retrieved from CNKI,Wanfang Data,VIP and CBM from January 1,2000 to December 20,2024.Descriptive statistics were performed on the frequency of acupoint usage,meridian tropism,and regional distribution.SPSS Modeler 18.0,Cytoscape 3.10.3 and Origin Pro were employed to conduct association rule mining,co-occurrence network analysis,and systematic cluster analysis on the acupoints.Results A total of 69 articles were included,yielding 114 acupoint prescriptions involving 65 distinct acupoints.The most frequently used acupoints were Yingxiang,Yintang and Hegu,etc.;the most commonly used meridians were large intestine meridian,Governor Vessel,gallbladder meridian and bladder meridian.Acupoint selection was predominantly concentrated in the head/neck region,lower limbs and upper limbs.Among the specific acupoint categories,Jiaohui acupoint,Wushu acupoint and Yuan acupoint were used most frequently.The acupoint combinations with the strongest associations were Hegu-Yingxiang,Hegu-Yintang-Yingxiang and Fengchi-Yingxiang.The top 22 high-frequency acupoints could be grouped into 5 clusters.Conclusion Acupuncture treatment for sinusitis can exert the functions to disperse wind and unblock the orifices,drain heat and resolve turbidity,expel pathogens and alleviate pain,tonify deficiency and dissipate cold,as well as harmonize qi and blood.The characteristics of acupoint combination include a primary focus on local points supplemented by distal points,pattern differentiation-based selection,and a propensity for unblocking yang qi.The core acupuncture formula is Yingxiang-Yintang-Hegu-Fengchi.

OBJECTIVE To analyze the risk factors for multidrug-resistant organism （MDRO） infection in patients with prolonged invasive mechanical ventilation （IMV） complicated by ventilator-associated pneumonia （VAP） in the intensive care unit （ICU）， thus providing a reference for improving the clinical effect of VAP treatment in this region. METHODS A retrospective analysis was performed on the clinical data of patients who were admitted to the ICU in Shexian Branch of the Second Affiliated Hospital of Zhejiang University School of Medicine （hereinafter referred to as “our hospital”） from October 2022 to February 2025， received prolonged IMV， and developed VAP. The distribution and drug resistance of pathogens were statistically analyzed. Patients were divided into the MDRO group and the non-MDRO group according to whether an MDRO infection occurred. Univariate analysis and multivariate Logistic regression analysis were used to screen independent risk factors for MDRO infection. RESULTS A total of 281 pathogenic strains were cultured from 97 patients， including 262 Gram-negative bacteria （93.24%）， 9 Gram-positive bacteria （3.20%）， and 10 fungi （3.56%）. The main Gram-negative bacteria were Pseudomonas aeruginosa， Klebsiella pneumoniae subspecies pneumoniae， and Acinetobacter baumannii. The former two showed high resistance rates （all≥25%） to common antibiotics such as imipenem， while A. mail：64375689@qq.com baumannii demonstrated high resistance to most antimicrobial agents. The main Gram-positive bacteria were Staphylococcus aureus subspecies aureus and S. haemolyticus， which were resistant to multiple antibiotics such as clindamycin （resistance rates all＞30%）. Among 281 pathogenic strains， 121 were MDRO， 62 were resistant to carbapenems， and 33 produced extended-spectrum β-lactamases. The serum albumin＜28 g/L， ICU stay≥14 days， and use of benzodiazepines were independent risk factors for MDRO infection in patients with prolonged IMV and VAP in our hospital’s ICU （odds ratios were 3.289， 2.991 and 2.680， 95% confidence intervals were 1.183-9.144， 1.021-8.765， and 1.012- 7.094， respectively， P＜0.05）. CONCLUSIONS Pathogens infecting patients with prolonged IMV and VAP in the ICU are mainly Gram-negative bacteria， with P. aeruginosa， K. pneumoniae subspecies pneumoniae and A. baumannii， accounting for a high proportion， and the drug resistance situation is severe. Serum albumin＜28 g/L， ICU stay≥14 days， and use of benzodiazepines are independent risk factors for MDRO infection in such patients.

Objective: To investigate the effects of blood component transfusion on the prognosis of patients with varying severity of traumatic brain injury (TBI). Methods: A retrospective analysis was conducted on clinical data from 621 TBI patients admitted between January 2012 and December 2022. The patients in the blood transfusion group were categorized into three groups based on Glasgow Coma Scale (GCS) scores: severe impairment (GCS 3-8, n=302), moderate impairment (GCS 9-12, n=186), and mild impairment (GCS 13-14, n=133). General clinical data and laboratory test indexes were analyzed. Patients were further divided into two subgroups based on in-hospital mortality: death group (n=72) vs survival group (n=549). Univariate and multivariate logistic regression analysis was used to analyze the effects of different blood component transfusion volumes on the prognosis of TBI patients. ROC curve was used to evaluate the prognostic value of red blood cell transfusion volume. Results: Patients with GCS scores 3-8 had significantly longer hospital stays (21.73±15.89 vs 20.83±11.54 vs 15.5±7.76) and higher RBC transfusion volumes (6.16±6.79 vs 4.67±2.81 vs 3.67±3.20) than the other two groups (P<0.05). NLR, PCT, CRP, PT, Fib, FDP and DDI after the last transfusion showed significant differences from pre-transfusion values (P<0.05). The death group exhibited higher transfusion volumes of RBCs, plasma, platelets, and cryoprecipitate compared with the survival group (P<0.05). Univariate (OR: 1.541, 95%CI: 1.412-1.682) and multivariate (OR: 1.522, 95%CI: 1.362-1.700) logistic regression analyses showed that the RBC transfusion volume was a risk factor affecting the prognostic factors of TBI patients after infusion of blood components. ROC curve analysis showed that RBC transfusion volume could serve as a prognostic marker (sensitivity: 0.708, specificity: 0.812). Conclusion: Blood component transfusion alters inflammatory and coagulation markers in patients with different degrees of TBI, and RBC transfusion volume is a viable prognostic indicator for TBI outcomes.

Objective:To evaluate the safety and efficacy of accelerator-based boron neutron capture therapy (AB-BNCT) in the treatment of recurrent and refractory malignant tumors.Methods:The data of 14 patients admitted to Xiamen Humanity Hospital from September 2022 to April 2023 were prospectively collected, including 7 patients with primary brain malignancies and 7 patients with locally recurrent inoperable head and neck malignancies. All patients received intravenous infusion of boron drug (NBB-001, p-dihydroxyborylphe nylalanine, a patented freeze-dried formulation) at a total nominal dosage of 500 mg/kg (11 patients) or 750 mg/kg (3 patients), and were irradiated with neutrons (operating with NeuPex system). Adverse events after treatment were recorded and assessed. The primary efficacy endpoint was the 90 d objective response rate (ORR), while the secondary endpoints included progression-free survival (PFS) and complete response rate (CRR). Data were compiled and analyzed by SAS 9.4 software. The rate and 95% CI were calculated using Clopper-Pearson method. Results:The median dose delivered to 80% of the target volume (D 80%) was 16.80 GyE (range: 8.93-23.79 GyE). The most common adverse reactions were hyperamylasemia, alopecia, and hyperprolactinemia. Five patients experienced 8 cases of grade 3 or above adverse events, including 1 case of grade 4 acute kidney injury and 7 cases of grade 3 adverse events. All adverse events were recovered after observation or treatment. At 90 d after treatment, the ORR of all patients was 9/14 (64%, 95% CI: 35%-87%), disease control rate (DCR) was 10/14 (71%, 95% CI: 42%-92%), CRR was 2/14 (14%, 95% CI: 2%-42%); and the best overall response during the entire course included an ORR of 10/14 (71% ,95% CI: 42%-92%), DCR of 13/14 (93%, 95% CI: 66%-100%), and CRR of 3/14 (21% ,95% CI: 5%-51%). The 1-year survival rate for head and neck malignancies was 71.4%, and the 2-year survival rate was 42.8%. The 1-year survival rate for recurrent brain malignancies was 42.8%. Conclusion:AB-BNCT demonstrates favorable safety and promising efficacy in treating primary brain malignancies and recurrent/refractory head and neck malignancies, representing a potential therapeutic option.

Objective This study aims to explore the efficacy and complication rates of the transcranial approach(TCA)and extended endoscopic endonasal approach(EEEA)for the treatment of craniopharyngiomas based on the QST classification,providing a scientific reference for clinical decision-making on surgical approach.Methods A total of 151 patients who underwent craniopharyngioma surgery at our center from January 2018 to December 2023 were enrolled.The patients were categorized into Q-CP(suprasellar type),S-CP(infundibular type),and T-CP(tuberal type)according to the QST classification.Systematic collection and analysis were performed on the outcomes of TCA and EEEA treatments,respectively.The differences in effectiveness between the two approaches were evaluated based on the QST classification.Results The improvement rate of visual symptoms was overall higher in the EEEA group than in the TCA group(59.1%vs.36.5%,P=0.006),and the visual deterioration rate was lower(3.0%vs.14.1%,P=0.006).However,the incidence of cerebrospinal fluid leakage was higher in the EEEA group(15.2%vs.3.5%,χ2=4.986,P=0.026).The incidence of postoperative seizures(8.2%vs.0,P=0.019),brain contusions(10.6%vs.0,P=0.005),and subdural hematoma(9.4%vs.0%,P=0.01)was higher in the TCA group.For patients with Q-CP type,the EEEA group had a higher rate of total tumor resection(92.9%vs.65.2%,P=0.025)and a lower recurrence rate(3.6%vs.21.7%,P=0.047),with shorter hospital stays and lower postoperative costs.The TCA group had higher intraoperative blood loss in this type(300 mL vs.200 mL,Z=-2.261,P=0.024).For S-CP type patients,the EEEA group showed a higher rate of total tumor resection(91.3%vs.74.2%)and a lower recurrence rate(0 vs.12.9%,P=0.031),with lower postoperative hospital costs.In T-CP type,due to the deeper location,EEEA showed limitations in protecting hypothalamic function and the TCA group had a better postoperative hypothalamic function score(P=0.035).Conclusion Based on QST classification,EEEA has advantages in Q-CP and S-CP types and is recommended as the preferred surgical procedure;In the T-CP type,TCA surgery is more helpful in protecting hypothalamic function.

Objectives:To preliminarily investigate the safety and efficacy of same-day discharge(SDD)following radiofrequency catheter ablation for arrhythmia.Methods:A total of 50 consecutive patients who underwent radiofrequency catheter ablation for arrhythmia in the SDD strategy at Fuwai Hospital from 8 July 2024 to 18 September 2024 were included in this analysis.The study evaluated the immediate success rate of the ablation,the rate of all-cause and arrhythmia-related readmission,outpatient or emergency visits and incidence of complications within 30 days post ablation,and recurrence rate of arrhythmias over a 3-month follow-up period.Results:The average age of the 50 patients was(47.2±16.1)years old,32 patients(64.0%)were male.Radiofrequency catheter ablation was performed in 47 patients(94.0%),including 18(36.0%)atrial fibrillation(AF)ablation.Three patients(6.0%)underwent electrophysiological study only.The immediate success rate for ablation patients was 100%(47/47).None of the patients developed vascular puncture-related or ablation-related complications.The average hospital stay and postoperative observation time were(6.84±1.13)hours and(3.40±1.12)hours,respectively.The all-cause and arrhythmia-related readmission,outpatient or emergency visits rates within 30 days were 12.0%(6/50)and 2.0%(1/50),respectively.Two patients(4.0%)post ablation experienced AF recurrence during the 3-months follow-up period.Conclusions:Radiofrequency catheter ablation for arrhythmias in SDD strategy is safe,effective,and feasible.