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.

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

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.

Objective To analyze changes in sleep,mood state,and brain function in healthy populations living in near-sea-level environments before and after exposure to high-altitude environment,and to explore the correlations between regional brain functional changes and variations in sleep and mood states.Methods A total of 45 healthy volunteers were enrolled.The participants came from regions of near-sea-level altitudes and were exposed to the high-altitude environment for a short period of time.The Pittsburgh Sleep Quality Index(PSQI),Zung Self-Rating Depression Scale(SDS),Patient Health Questionnaire-9(PHQ-9),Zung Self-Rating Anxiety Scale(SAS),and Generalized Anxiety Disorder-7(GAD-7)were administered to assess sleep quality as well as depressive and anxiety symptoms at 4 time points—prior to high-altitude exposure,immediately after exposure,one month after returning to low-altitude regions,and three months after returning to low-altitude regions.Resting-state functional magnetic resonance imaging(rs-fMRI)data were collected before and after high-altitude exposure,and regional brain functional parameters,including the amplitude of low-frequency fluctuations(ALFF)and functional connectivity strength,were analyzed.Statistical analyses were performed,including a linear mixed-effects model to evaluate longitudinal changes in scale scores,paired-sample t-tests to compare brain function differences before and after exposure,and Pearson correlation analyses to examine the relationship between brain functional changes and alterations in sleep and mood states.Results Compared with the pre-exposure findings,the participants exhibited significantly increased PSQI scores(8.89±4.41 vs.5.08±2.69,P<0.05)and PHQ-9 scores(3.60±4.19 vs.1.54±2.30,P<0.05)immediately after high-altitude exposure.One month after returning to the low-altitude environment,both sleep and depression scores decreased relative to the findings immediately after exposure(PSQI:3.88±2.13 vs.8.89±4.41,P<0.05;PHQ-9:1.50±2.25 vs.3.60±4.19,P<0.05)and showed no statistically significant difference compared with the pre-exposure findings(P>0.05).Three months after returning to near-sea-level environment,sleep,depression,and anxiety scores were all reduced compared with the findings immediately after exposure(PSQI:3.76±2.31 vs.8.89±4.41,P<0.05;PHQ-9:1.24±2.13 vs.3.60±4.19,P<0.05;SAS:23.84±5.93 vs.27.93±7.05,P<0.05),also showing no significant difference compared with the pre-exposure levels(P>0.05).Brain function analysis revealed that,relative to the pre-exposure levels,ALFF in the bilateral superior temporal gyrus,insula,and dorsolateral prefrontal cortex(DLPFC)increased after high-altitude exposure(P<0.05),and that functional connectivity strength in the DLPFC was also elevated(P<0.05).Furthermore,changes in DLPFC functional connectivity strength were positively correlated with changes in sleep and mood scores(P<0.05).Conclusion High-altitude exposure has a significant impact on the sleep,mood states,and brain function of populations from near-sea-level regions,and DLPFC,in particular,is closely associated with changes in sleep and mood states.The findings of this study provide a theoretical basis for health management and intervention strategies in high-altitude environments.

Objective To evaluate the influencing factors of aspiration in neurological critically ill patients by Meta-analysis.Methods PubMed,Embase,Web of Science,CNKI,and Wanfang Data were searched from inception to 1 October,2023,to obtain relevant studies on influencing fac-tors of aspiration in neurological critically ill patients.The literature screening,data extraction and quality evaluation were completed by two researchers.RevMan 5.4 and Stata 13.0 software were ap-plied for pooled Meta-analysisand assessed publication bias,respectively.Results A total of 8 arti-cles,including 1,315 neurocritical care patients,were included in this study.Nine influencing factors related to aspiration were extracted for Meta-analysis.The Meta-analysis results showed that the three influencing factors that caused aspiration in neurocritical care patients were stroke history(OR=5.03,95％CI,2.71 to 9.32,P＜0.000 01),National Institutes of Health Stroke Scale(NIHSS)score＞10(OR=3.35,95％CI,1.75 to 6.42,P=0.000 3),and gastric residual volume＞150mL(OR=7.13,95％CI,2.55 to 9.96,P=0.001).Conclusion This study provides a scientific basis for clinical healthcare professionals to early identify high-risk patients for aspiration,take targeted inter-vention measures,and prevent the occurrence of aspiration.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To compare the clinical efficacy of endoscopic posterior transforaminal lumbar interbody fusion (Endo-PTLIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of single-segment lumbar degenerative diseases.Methods:A retrospective analysis was conducted on the clinical data of 56 patients with single-segment lumbar degenerative diseases treated at Xiuzhou District People's Hospital between September 2020 and March 2023. Patients were divided into two groups based on the surgical approach: the Endo-PTLIF group (24 cases, 11 males and 13 females; mean age: 56.5±8.4 years, range: 43-72 years) and the MIS-TLIF group (32 cases, 10 males and 22 females; mean age: 54.5±10.4 years, range: 37-73 years). Perioperative parameters, visual analog scale (VAS) scores for pain, Oswestry disability index (ODI), lumbar lordosis (LL), disc height (DH), and dural sac cross-sectional area (DSCA) were compared between the two groups.Results:No significant differences were observed between the two groups in baseline characteristics, preoperative VAS, ODI, LL, DH, or DSCA ( P>0.05). However, the operative time in the Endo-PTLIF group (173.9±12.3 minutes) was significantly longer than in the MIS-TLIF group (136.5±19.5 minutes, P<0.05). Similarly, the Endo-PTLIF group required more fluoroscopy exposures (15.9±1.8) than the MIS-TLIF group (13.0±1.6, P<0.05). In contrast, intraoperative blood loss in the Endo-PTLIF group (68.9± 12.9 ml) was significantly lower than in the MIS-TLIF group (126.7±35.4 ml, P<0.05). Additionally, the Endo-PTLIF group had a shorter hospital stay [7.00 (6.25, 7.75) days] compared to the MIS-TLIF group [10.00 (9.25, 11.00) days, P<0.05]. At one week and one month postoperatively, the Endo-PTLIF group had significantly lower back pain VAS scores [2.00 (2.00, 3.00) and 2.00 (2.00, 2.00), respectively] and a lower ODI (25.83%±3.83%) compared to the MIS-TLIF group [3.00 (2.25, 4.00), 2.50 (2.00, 3.00), and 30.09%±4.02%, respectively; P<0.05]. Beyond one month postoperatively, there were no significant differences in leg pain VAS scores between the groups, and back pain VAS and ODI showed no significant differences after six months ( P>0.05). At the final follow-up, the excellent and good rates, according to MacNab criteria, were 95.8% in the Endo-PTLIF group and 93.8% in the MIS-TLIF group, with no significant difference ( P>0.05). At 12 months postoperatively, both groups showed significant improvements in LL, DH, and DSCA compared to preoperative values ( P<0.05), but there were no significant differences between the two groups ( P>0.05). The fusion rates were 96% in the Endo-PTLIF group and 94% in the MIS-TLIF group, with no significant difference ( P>0.05). Complications included one case of dural tear in the Endo-PTLIF group, and one case of dural tear and one case of incision infection in the MIS-TLIF group. Conclusion:Endo-PTLIF achieves comparable clinical efficacy to MIS-TLIF in the treatment of single-segment lumbar degenerative diseases, with the added advantages of reduced intraoperative blood loss and faster postoperative recovery.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Objective:To compare the differences in the maximum stress distribution between bone-only and osteochondral composite distal humeral hemiarthroplasty prostheses under various physiological motion states using a finite element analysis.Methods:High-resolution CT scan data from 7 fresh-frozen cadaveric elbow specimens [5 males, 2 females; 4 left and 3 right sides; age: (40.4±5.9) years] were used to reconstruct three-dimensional models of bony structures and cartilage. Two types of distal humeral hemiarthroplasty prostheses were designed using reverse engineering techniques: bone-only (bone prosthesis group) and osteochondral composite (osteochondral prosthesis group). At 4 flexion-extension angles (0°, 30°, 90°, 130°) and 3 rotational positions (neutral, pronation, supination), the maximum stress distributions in the native bones and 2 types of prostheses were systematically evaluated and compared using finite element analysis to investigate the differences in mechanical performance under physiological motion conditions.Results:Under a 200 N axial load and at 0°, 30°, 90°, and 130°, respectively, the maximum von Mises stress in the elbow joint model was (11.64±1.12) MPa, (12.62±1.15) MPa, (11.73±0.99) MPa, and (11.67±1.08) MPa in the native bone group, (13.60±1.75) MPa, (14.97±2.09) MPa, (13.62±1.84) MPa, and (13.70±1.91) MPa in the bone prosthesis group, and (12.45±1.57) MPa, (13.79±1.56) MPa, (12.44±1.55) MPa, and (12.72±1.29) MPa in the osteochondral prosthesis group. In neutral position, pronation and supination, the maximum von Mises stress in the elbow joint model was, respectively, (11.72±1.17) MPa, (11.68±1.22) MPa, and (12.36±0.94) MPa in the native bone group, (13.69±1.72) MPa, (13.07±1.26) MPa, and (15.15±2.20) MPa in the bone prosthesis group, and (13.02±1.32) MPa, (13.39±1.92) MPa, and (12.15±1.13) MPa in the osteochondral prosthesis group. Two way ANOVA showed that the main effects of flexion-extension angles and of rotation states were significantly different in the 3 groups of models ( P<0.05). The interaction effects between flexion-extension angle and prosthesis was significantly different( P<0.05), but interaction effects between rotational position and prosthesis is not significantly different ( P>0.05). The maximum stresses at the prosthesis in all the flexion-extension angles in the bone prosthesis group were significantly higher than those in the other 2 groups ( P<0.05). In neutral position and pronation, the maximum stresses in the bone prosthesis group and osteochondral prosthesis group were significantly higher than that in the native bone group ( P<0.05). In supination, the maximum stress in the bone prosthesis group was significantly higher than that in the osteochondral prosthesis group and in the native bone group ( P<0.05), but there was no such a significant difference between the latter 2 groups ( P>0.05). Conclusions:Preservation of the cartilaginous structure effectively reduces stress concentration in distal humeral hemiarthroplasty prostheses. The osteochondral composite design demonstrates significantly better mechanical performance than the bone-only prosthesis design, suggesting its distinct advantages in replicating the natural mechanical environment of a joint.

Background and Aims:Papillary thyroid carcinoma(PTC)is the most common endocrine malignancy in China,with cervical lymph node metastasis being a frequent and critical clinical feature that directly affects patient prognosis and recurrence risk.In recent years,with the rapid increase in the prevalence of overweight and obesity in China,the role of body mass index(BMI)in various tumors has attracted growing attention.This study aimed to investigate the association between overweight and cervical LNM in PTC,analyze sex-specific differences and influencing factors,and provide evidence for precise clinical management.Methods:A retrospective analysis was conducted on the clinicopathologic data of 1 445 patients with classical PTC treated at Xiangya Hospital of Central South University between August 2021 and June 2022.Patients were divided into groups based on the presence or absence of lymph node metastasis.Restricted cubic spline analysis explored the nonlinear relationship between BMI and lymph node metastasis risk.Univariate and multivariate Logistic regression analyses were applied to identify independent risk factors.Furthermore,sex-stratified analysis was performed among overweight patients(BMI≥24 kg/m2)to determine sex-specific risk factors for lymph node metastasis.Results:Among all patients,716(49.6%)had lymph node metastasis.Univariate analysis showed that BMI,sex,age,tumor diameter,multifocality,and extrathyroidal extension were significantly associated with cervical lymph node metastasis in PTC patients(all P<0.05).A nonlinear positive correlation was observed between BMI and lymph node metastasis risk,which was more pronounced in male patients.Additionally,BMI was positively correlated with triglyceride levels and negatively correlated with high-density lipoprotein cholesterol.Sex-stratified analysis revealed that in overweight male patients,younger age(OR=0.954),larger tumor diameter(OR=1.085),and multifocality(OR=2.776)were independent risk factors for LNM;in overweight female patients,younger age(OR=0.943)and larger tumor diameter(OR=1.074)were the main influencing factors.Conclusion:Overweight is closely associated with cervical lymph node metastasis in PTC,and the high-risk factors for LNM differ between male and female overweight patients.Young age,larger tumor size,and multifocality in overweight males,and young age and larger tumors in overweight females indicate a higher risk of metastasis.It is recommended that high-risk populations receive enhanced preoperative evaluation and individualized lymph node dissection strategies to achieve precise treatment and improved risk control.