Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

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.

Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
Animals ; Ginsenosides/administration & dosage* ; Brain Edema/etiology* ; Male ; Benzofurans/administration & dosage* ; Glymphatic System/diagnostic imaging* ; Mice ; Infarction, Middle Cerebral Artery/drug therapy* ; Aquaporin 4/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Matrix Metalloproteinase 9/metabolism* ; Neuroprotective Agents/pharmacology* ; Depsides

In line with the rising global incidence of cancer,tumor metastasis has become the leading cause of mortality among cancer patients.Formation of the pre-metastatic niche(PMN)creates an optimal microenvironment for tumor cell colonization and metastasis,thus facilitating tumor dissemination.In this context,cancer-associated fibroblasts(CAFs)have garnered significant attention as a result of their multifaceted roles in tumor progression.CAFs enhance the formation of the PMN and promote the invasive behavior of tumor cells by remodeling the extracellular matrix,inducing epithelial-mesenchymal transition,stimulating angiogenesis and modulating the tumor immune microenvironment.These processes not only expedite metastasis but also enable tumor immune evasion.This paper reviews the fundamental mechanisms and functions of CAFs in tumor metastasis,examines their potential applications in cancer research and therapy,and offers new perspectives and directions for the development of anti-tumor metastasis strategies.

With rapid development of artificial intelligence(AI)technology,its application in basic medical teaching has become more and more extensive,bringing many changes and innovations to medical education.This paper attempts to apply AI to teaching of Medical Immunology,including preparation of teaching resources,teaching practice process,teaching evaluation and other teaching processes,aiming to improve work efficiency of teachers,optimize teaching strategies,improve teaching quality,stimu-late students'enthusiasm for learning,provide new ideas and methods for teaching reform of Medical Immunology,and promote deep integration of AI and basic medical education and teaching.

Objective To systematically evaluate and integrate qualitative studies on perception of exercise behaviors in community-dwelling older adults with frailty,and to provide references for clinical development of targeted exercise intervention strategies.Methods A systematic search of PubMed,Medline,Embase,PsycINFO,the Cochrane Library,SinoMed,Wanfang Database,CNKI,and VIP Database for qualitative studies on perception of exercise behaviors in older adults with frailty in the community was conducted from the inception of the databases to June 2024.Literature quality was evaluated using the Australian Joanna Briggs Institute Centre for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research(2016 edition),and Meta-synthesis was performed using the theme synthesis method.Results A total of 10 papers were included,grouped into 10 categories and integrated into the 3 domains of the capability,opportunity,and motivation-behavior model(COM-B model),i.e.Preparation for exercise behavior is influenced by capability factors(physical reserve,knowledge reserve,psychological preparation);stage-specific motivational evolution promotes the internalization of exercise behavior(guiding,focusing,stimulating,and maintaining);external conditions provide opportunities for exercise behavior(individual interaction,community environment,and social support).Conclusion Perceptions of exercise behavior among community-dwelling older adults with frailty or are complex and influenced by a variety of factors.Future exercise intervention strategies should consider modifiable factors,enhance knowledge education,stimulate intrinsic motivation,and solidify external conditions,while also accommodating individual differences and preferences,so as to promote exercise participation and health enhancement in this group.

OBJECTIVE To explorer the association between the clearance of serum procalcitonin(PCTc)and the risk of 28-day in-hospital mortality of the sepsis patients.METHODS A total of 270 patients who were diagnosed with sepsis in Huiya Hospital,the First Affiliated Hospital of Sun Yat-sen University from Jan.2022 to Jan.2025 were recruited as the research subjects and were divided into the low decline group with 76 cases,the moderate de-cline group with 74 cases and the high-level stability group with 120 cases according to the change of serum PCTc within 1 to 7 days after the admission.The association between the trajectory of change of PCTc and the risk of 28-day mortality of the sepsis patients was observed by Cox regression analysis method.The rough risk ratios(RRs)of complications of the different changing trajectories of PCTc were calculated by binary log-binomial regres-sion model.RESULTS The red blood cell(RBC)counts,white blood cell(WBC)counts,thrombin time(TT),prothrombin time(PT),activated partial thromboplastin time(APTT),D-dimer(D-D),C-reactive protein(CRP)and neutrophil to lymphocyte ratio(NLR)were higher in the low decline group than in the moderate de-cline and the high-level stability group(P＜0.05);while the levels of platelet(PLT)and fibrinogen(FIB)of the high-level stability group were higher than those of the low and moderate decline group(P＜0.05).Kaplan-meier survival curve analysis showed that the accumulative survival rate was 46.62％in the low decline group,64.31％in the moderate decline group and 81.24％in the high-level stability group,there was significant differ-ence(x2=25.479,P＜0.001).CONCLUSION The trajectory of change of PCTc can be served as an early-warn-ing index for the risk of in-hospital mortality and complications,which may provide important basis for develop-ment of individualized treatment program.

OBJECTIIVE:The positive role of exercise intervention in the prevention and treatment of sarcopenia has received widespread attention,but the optimal exercise dose for elderly sarcopenic patients still needs to be further determined.The article explored the dose-effect relationship between various elements of exercise prescription and the improvement of muscle mass,muscle strength and physical function in community-dwelling elderly patients with sarcopenia,aiming to provide scientific support for the development of exercise prescription for community-dwelling elderly patients with sarcopenia.METHODS:Literature published from the inception to October 9,2024 in PubMed,EMBASE,Scopus,Web of Science,CNKI,WanFang,VIP,and CBMdisc databases was systematically searched.Meta-analysis was performed using RevMan 5.3 software.Standardized mean difference(SMD)and its 95％CI were used as effect statistics.RESULTS:(1)A total of 11 randomized controlled trials were included,with 348 in the trial group and 304 in the control group.(2)Meta-analysis results showed that exercise improved appendicular skeletal muscle mass index,grip strength,and walking speed in elderly patients with sarcopenia(SMDs 0.46,0.63,0.67,P＜0.05).(3)When the frequency of exercise was 2-3 days/week,appendicular skeletal muscle mass index(SMD=0.57,95％CI:0.28-0.86,P＜0.001),grip strength(SMD=0.70,95％CI:0.37-1.02,P＜0.001),and walking speed(SMD=0.69,95％CI:0.20-1.18,P=0.006)were effectively improved in elderly patients with sarcopenia.(4)When the duration of exercise was 25-60 minutes per session,appendicular skeletal muscle mass index(SMD=0.28,95％CI:0.07-0.50,P=0.01),grip strength(SMD=0.37,95％CI:0.16-0.59,P＜0.001),and walking speed(SMD=0.39,95％CI:0.06-0.73,P=0.02)were effectively improved in elderly patients with sarcopenia.(5)When the exercise intensity was moderate,appendicular skeletal muscle mass index(SMD=0.69,95％CI:0.35-1.03,P＜0.001),and grip strength(SMD=0.36,95％CI:0.09-0.64,P=0.009),and walking speed(SMD=0.91,95％CI:0.34-1.47,P=0.002)were effectively improved in elderly patients with sarcopenia.(6)When the dose of exercise cycle was 8-12 weeks,appendicular skeletal muscle mass index(SMD=0.42,95％CI:0.20-0.64,P＜0.001),grip strength(SMD=0.45,95％CI:0.26-0.64,P＜0.001),and walking speed(SMD=0.76,95％CI:0.27-1.25,P=0.002)were effectively improved in elderly patients with sarcopenia.CONCLUSION:Active,regular exercise can improve muscle health in older adults with sarcopenia.It is recommended that older patients with sarcopenia exercise at least 2 to 3 days per week,25 to 60 minutes each time,lasting for 8 to 12 weeks of moderate intensity exercise to improve muscle health.

Objective:To investigate the feasibility and therapeutic efficacy of robot-assisted radical resection for hilar cholangiocarcinoma.Methods:This is a retrospective case series study. The clinical data of 29 patients who underwent robot-assisted radical resection for hilar cholangiocarcinoma at the Department of Minimally Invasive Hepatic Surgery,the First Affiliated Hospital of Harbin Medical University from July 2021 to February 2025 were retrospectively collected. There were 16 males and 13 females, aged ( M(IQR)) 68.0 (10.0) years (range:36 to 78 years), and body mass index (24.0±2.9) kg/m 2 (range:17.5 to 29.1 kg/m 2). Bismuth-Corlette classification: 12 cases type Ⅰ, 4 cases type Ⅱ, 6 cases type Ⅲb, and 7 cases type Ⅳ. Preoperative CA19-9 was 161.7(320.9) U/ml (range:7.1 to 1 000.0 U/ml), and carcinoembryonic antigen was 2.8(2.1)μg/L (range:0.3 to 203.1 μg/L). Preoperative total bilirubin was 134.2 (348.9) μmol/L (range:10.4 to 557.9 μmol/L), direct bilirubin was 90.8 (264.1) μmol/L (range:2.5 to 418.7 μmol/L), ALT was 136.4 (134.8) U/L (range:13.0 to 569.9 U/L), AST was 122.2 (119.9) U/L (range:16.0 to 384.0 U/L), and albumin was (34.5±6.3) g/L (range:21.7 to 41.3 g/L). Comparison of quantitative data at different time points using paired t-test or Mann-Whitney U test. Cox univariate analysis was performed for the relevant variables, and Cox multivariate regression analysis was used to screen the independent prognostic factors of patients after robot-assisted radical resection for hilar cholangiocarcinoma. Results:All the 29 patients successfully underwent robot-assisted radical resection of hilar cholangiocarcinoma, and the R0 resection rate was 93.1% (27/29) without conversion to laparotomy. The operation time was 295.0 (87.5) minutes (range:195 to 590 minutes), the intraoperative blood loss was 100.0 (150.0) ml (range:20 to 1 000 ml), the intraoperative blood transfusion rate was 20.1% (6/29), the number of lymph nodes dissected was 10.0 (7.0) pieces (range: 6 to 18 pieces), the first postoperative deflatus time was 3.0 (1.0) days (range:2 to 4 days), The oral feeding time was 5.0 (1.0) days (range: 4 to 7 days), the drainage tube removal time was 8.0 (2.0) days (range: 6 to 26 days), and the postoperative hospital stay time was 10.0 (6.0) days (range:7 to 27 days). The incidence of complications above grade Ⅱ of the Clavien-Dindo complication grading system was 24.1% (7/29), including 3 cases of gastrointestinal bleeding with recurrent high fever, 1 case of delayed gastric emptying, 1 case of bile leakage, and 5 cases of hypoalbuminemia. The total bilirubin was 42.8 (66.8) μmol/L (range:6.8 to 195.9 μmol/L), direct bilirubin was 28.1 (38.5) μmol/L (range:4.3 to 88.6 μmol/L), ALT was 55.8 (56.0) U/L (range:9.9 to 207.1 U/L), AST was 33.9 (17.9) U/L (range:10.6 to 122.7 U/L), and albumin was (32.1±3.8) g/L (range:22.8 to 37.7 g/L), the levels of transaminase and bilirubin in the postoperative liver function indexes were significantly improved compared with those before operation, and the differences were statistically significant (all P<0.05). The mortality rate of patients without perioperative death was 3.4% (1/29) at 90 days after surgery. The results of Cox multivariate regression analysis showed that R0 resection was an independent prognostic factor for survival at 1 year after surgery ( P<0.05). The follow-up time was 15.0 (12.0) months (range:6 to 30 months), 1 of the 29 patients died of intra-abdominal infection 1 week after discharge, and the remaining 28 patients were completely followed up, of which 20 patients had no recurrence and metastasis during the follow-up period, and the tumor-free survival was 15.0 (12.0) months (range:6 to 30 months), the tumor-free survival rate was 65.5% (19/29), the overall survival rate was 68.9% (20/29), and 8 patients with postoperative recurrence and metastasis. One patient with liver metastasis survived after reoperation, and one patient underwent postoperative chemoradiotherapy and died due to recurrence. There were 8 deaths during the follow-up, of which 7 died due to tumor recurrence and metastasis, and 1 died due to previous underlying diseases. Conclusion:Robot-assisted radical resection for hilar cholangiocarcinoma is feasible and effective.

[Objective] To investigate the factors influencing the detection of HLA-C expression by flow cytometry. [Methods] A total of 12 hematopoietic stem cell suspension samples from peripheral hematopoietic stem cell volunteer donors were randomly collected after CD34⁺ cell counting detection. The influence of detecting different number of nucleated cell (500 000, 50 000 and 5 000), sequential order of red blood cell lysis and antibody incubation, and the HLA-C antibody with varied remaining time from the expiration date on the detection results of HLA-C expression by flow cytometry were investigated, respectively. The significance of differences between different groups was analyzed through Student t test. [Results] There was no significant difference in the proportion of HLA-C positive cells and mean fluorescence intensity (MFI) among the three groups with different nucleated cell numbers detected (500 000, 50 000 and 5 000) (P>0.05). The sequential order of red blood cell lysis and antibody incubation had no influence on the proportion of HLA-C positive cells (P>0.05), but HLA-C MFI value was significantly lower when antibody incubation was performed after red blood cell lysis than that when antibody incubation was performed before red blood cell lysis (P<0.05). The proportion of HLA-C positive cells and MFI value detected by HLA-C antibody remaining 24 months from the expiration date were significantly higher than those detected by HLA-C antibody remaining only 5 months from the expiration date (P<0.05). [Conclusion] The present study has investigated the factors of influencing HLA-C expression level by flow cytometry, the results have important reference and application value for standardizing the experimental operation of HLA-C expression and improving the accuracy and comparability of detection results.