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 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.

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.

Bone Transplantation/adverse effects* ; Transplantation, Autologous/adverse effects*

Bladder cancer （BCa） is the most common malignant tumor of the urinary system， and its incidence is increasing year by year. At present， for all patients with resectable non-metastatic muscle-invasive BCa， radical cystectomy + bilateral pelvic lymph node dissection is strongly recommended， but they still face the risk of recurrence， metastasis and death. In recent years， the proportion of patients with advanced and metastatic BCa is increasing among patients with newly diagnosed BCa. Although current treatment models are diverse， they often struggle to achieve significant efficacy due to their low effectiveness and adverse effects， resulting in low survival rates for patients with advanced and metastatic BCa. Therefore， the treatment of BCa still faces great challenges， and there is an urgent need to discover an effective new antitumor drug. With the improvement of medical standards， traditional Chinese medicine has shown great advantages in the treatment of BCa. Traditional Chinese medicine is mild and easy to accept， and can inhibit tumor progression through a multi-pathway， multi-way and multi-target manner， so as to exert its anticancer effect. Taraxaci Herba is a medicinal and food homologous plant， which has many biological activities， such as antibacterial， anti-inflammatory， anti-oxidation， anti-tumor， protecting liver and gallbladder， reducing blood sugar and enhancing immunity， and it has shown a clear anticancer effect in breast cancer， liver cancer， gastric cancer， tongue cancer and lung cancer. By reviewing previous studies worldwide， this article summarizes the mechanism of Taraxaci Herba extract in inducing autophagy and apoptosis， inhibiting cell migration and invasion， regulating cell cycle and proliferation， regulating cell metabolism， inhibiting tumor angiogenesis， combining the effects of chemotherapeutic drugs， and regulating the transduction of related signal pathways. On this basis， this study systematically elaborates on the potential mechanism of Taraxaci Herba against BCa， in order to provide a theoretical basis for the research and treatment of BCa.

Objective:To explore the causal relationship between human immune cells and hypertrophic scar (HS) using two-sample bidirectional Mendelian randomization (MR) method.Methods:This study was based on two-sample MR method, and the datasets of 731 immune cells and HS were obtained from the genome-wide association study (GWAS) catalog database and Finngen database, respectively. A significance threshold was established to discern single nucleotide polymorphism (SNP) significantly correlated with immune cells or HS, thereby eliminating the impact of weak instrumental variable bias. The inverse variance weighted (IVW) method (meanwhile, the Benjamini-Hochberg (BH) procedure of false discovery rate (FDR) to adjust P values) was used for preliminary detection of the causal relationship between immune cells and HS and screen the immune cells that had a significant causal relationship with HS. Further, the causal relationship between the selected immune cells and HS was detected through five two-sample MR methods: IVW method, weighted median method, simple mode method, weighted mode method, and MR-Egger method, and the scatter plot was drawn. SNPs conformed to the hypothesis were subjected to Cochran Q test for heterogeneity assessment, MR-Egger regression coupled with MR-PRESSO to eliminate horizontal pleiotropic effects, and a leave-one-out analysis was also conducted to determine if significant results were driven by individual SNP. Finally, the IVW method contained in the two-sample MR analysis was utilized to inversely examine the causal relationship between HS and immune cells. Results:The number of SNPs in 731 immune cells reaching the significance threshold varied from 7 to 1 786, while in HS, 119 SNPs met the significance threshold, with the F values of all SNPs being greater than 10, suggesting a low likelihood of bias from weak instrumental variables. The IVW method revealed that 60 types of immune cells potentially had a causal relationship with HS (with all P values <0.05), and after adjustment using the BH method, only CD45RA and CD39 positive regulatory T cell (Treg) maintained a potentially strong causal relationship with HS ( PFDR<0.05). The IVW method (with odds ratio of 1.16 and 95% confidence interval of 1.08-1.24, P<0.05, PFDR<0.05), weighted median method (with odds ratio of 1.16 and 95% confidence interval of 1.05-1.28, P<0.05), weighted mode method (with odds ratio of 1.14 and 95% confidence interval of 1.02-1.27, P<0.05), and MR-Egger method (with odds ratio of 1.18 and 95% confidence interval of 1.07-1.30, P<0.05) of scatter plot all suggested a causal relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS, only simple mode method of scatter plot suggested a not obvious relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS ( P>0.05). Cochran Q test indicated no heterogeneity in the causal relationship between CD45RA on CD39 positive Treg and HS ( P>0.05). MR-Egger regression and MR-PRESSO analyses showed that there was no horizontal pleiotropy in the significant causal relationship between CD45RA and CD39 positive Treg and HS ( P>0.05). Leave-one-out analysis confirmed that the significant causal relationship between CD45RA and CD39 positive Treg and HS remained stable after sequentially removing individual SNP. Reverse two-sample MR analysis showed that HS had no potential causal relationship with any of the 731 types of immune cells ( P>0.05). Conclusions:From the perspective of genetics, it is revealed that immune cells CD45RA and CD39 positive Treg may increase the risk of HS.

Objective:To evaluate the mechanical performance of customized metal prosthesis with tibia stems of varying lengths for tibial bone defects reconstruction.Methods:Morphologically matched postoperative finite element models of bone defect revision were developed, with three gradients (15 mm, 30 mm, and 45 mm) according to the degree of bone defect and were reconstructed with 3D printed tantalum metal prosthesis using three tibial stem lengths (80 mm, 120 mm, and 150 mm), respectively. Conventional static and dynamic (walking gait) loading was performed to analyze the peak tibial stress distribution and accumulated sliding distance at the prosthetic interface, and to assess the effects of the three tibial stems of different lengths on the stability of the customized tibial defect restorations and the internal tibial stress state.Results:The peak accumulated sliding distance of the dynamically loaded morphologically matched restorations ranged from 17.94 to 21.31 mm with static loading, which were 68% to 84.3% higher than those of 10.26 to 11.69 mm with static loading. The peak tibial stresses in the dynamically loaded model were greater than those in the statically loaded model, with an increase of 28%-49.2%, including 132.94-143.88 MPa in the statically loaded model and 170.41-200.14 MPa in the dynamically loaded model. The overall accumulated sliding distance of the tibia prosthetic model gradually decreased from the tibial osteotomy surface, and the accumulated peak sliding distances ranged from 10.26 to 11.69 mm for static loading, and from 17.94 to 21.31 mm for dynamic loading. The bone tissue stresses in the anterolateral and medial-posterior tibia increased gradually from top to bottom, and the maximum stress value in each section was in the posterior medial tibia (the maximum value was 200.14 MPa). The highest bone tissue stress in the lateral tibia was affected by the tibial stem length, which resulted in a different location, and it was the area most affected by stress shielding (maximum value of 170.65 MPa).Conclusion:For stability assessment of morphologically matched tantalum customized prosthesis, physiological gait dynamic loading studies are more reliable than static loading; the choice of tibial stem length depends on a combination of accumulated peak sliding distances and tibial bone stress distribution factors.

Objective:To evaluated the safety and feasibility of dissection of lymph nodes posterior to right recurrent laryngeal nerve (ⅥB compartment) in endoscopic thyroidectomy through gasless axillary posterior approach.Methods:A total of 350 cases with right lobe papillary thyroid carcinoma (PTC) who underwent endoscopic lobectomy, isthmusectomy and central compartment neck dissection via gasless axillary posterior approach based at the Department of General Surgery, Nanfang Hospital, Southern Medical University from June 2020 to December 2022 were retrospectively analyzed. Summarize the clinical, pathological characteristics, and postoperative complications of the patients. SPSS 25.0 was used for statistical analysis of the data.Results:All 350 patients underwent endoscopic surgery successfully, with no conversion to open surgery. There were 303 females and 47 males, with an average age of (36.3±9.2) years. Of those, 287 patients were in pT1a stage, 62 in pT1b stage, and one patient in pT2 stage. There was no T3 or T4 stage patient. The mean numbers of yielded lymph nodes in right central compartment and ⅥB compartment were 8.11±4.65 (range, 1-31) and 2.62±1.86 (range, 1-12), respectively. ⅥB compartment metastasis was detected in 52 (14.86%) of 350 patients. The incidence of transient recurrent laryngeal nerve injury was 0.86%(3/350). Postoperative hematoma occurred in three patients (0.86%).Conclusion:The dissection of ⅥB compartment in endoscopic thyroidectomy through gasless axillary posterior approach is safe and feasible in selected PTC patients