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.

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.

OBJECTIVE: To compare the effectiveness of lower extremity axial distractor (LEAD) and traction table assisted closed reduction and intramedullary nail fixation in treatment of femoral subtrochanteric fracture. METHODS: The clinical data of 117 patients with subtrochanteric fracture of femur treated by closed reduction and intramedullary nail fixation between May 2012 and May 2022 who met the selection criteria were retrospectively analyzed. According to the auxiliary reduction tools used during operation, the patients were divided into LEAD group (62 cases with LEAD reduction) and traction table group (55 cases with traction table reduction). There was no significant difference in baseline data, such as gender, age, injured side, cause of injury, fracture Seinsheimer classification, time from injury to operation, and preoperative visual analogue scale (VAS) score, between the two groups ( P>0.05). Total incision length, operation time, intraoperative blood loss, fluoroscopy frequency, closed reduction rate, fracture reduction quality, fracture healing time, weight-bearing activity time, and incidence of complications, as well as hip flexion and extension range of motion (ROM), Harris score, and VAS score at 1 month and 6 months after operation and last follow-up were recorded and compared between the two groups. RESULTS: There were 14 cases in the LEAD group from closed reduction to limited open reduction, and 43 cases in the traction table group. The incisions in the LEAD group healed by first intention, and no complication such as nerve and vascular injury occurred during operation. In the traction table group, 3 cases had perineal crush injury, which recovered spontaneously in 1 week. The total incision length, operation time, intraoperative blood loss, fluoroscopy frequency, and closed reduction rate in the LEAD group were significantly better than those in the traction table group ( P<0.05). There was no significant difference in the quality of fracture reduction between the two groups ( P>0.05). Patients in both groups were followed up 12-44 months, with an average of 15.8 months. In the LEAD group, 1 patient had delayed fracture union at 6 months after operation, 1 patient had nonunion at 3 years after operation, and 1 patient had incision sinus pus flow at 10 months after operation. In the traction table group, there was 1 patient with fracture nonunion at 15 months after operation. X-ray films of the other patients in the two groups showed that the internal fixator was fixed firmly without loosening and the fractures healed. There was no significant difference in fracture healing time, weight bearing activity time, incidence of complications, and postoperative hip flexion and extension ROM, Harris score, and VAS score at different time points between the two groups ( P>0.05). CONCLUSION For femoral subtrochanteric fracture treated by close reduction and intramedullary nail fixation, compared with traction table, LEAD assisted fracture reduction can significantly shorten the operation time, reduce intraoperative blood loss and fluoroscopy frequency, reduce incision length, effectively improve the success rate of closed reduction, and avoid complications related to traction table reduction. It provides a new method for good reduction of femoral subtrochanteric fracture.
Humans ; Fracture Fixation, Intramedullary ; Bone Nails ; Traction ; Blood Loss, Surgical/prevention & control* ; Retrospective Studies ; Treatment Outcome ; Femoral Fractures ; Hip Fractures/surgery* ; Lower Extremity ; Surgical Wound ; Fracture Fixation, Internal

Objective: To investigate the effect of H-uvulopalatopharyngoplasty(H-UPPP) combined with tongue base radiofrequency ablation in the treatment of obstructive sleep apnea hypopnea syndrome(OSAHS). Methods: Sixty-two patients with moderate or severe OSAHS, whose obstructive plane located in the oropharynx and tongue base were divided into two groups two groups according to the patient′s independent choice under the condition of fully informed before the operation. The control group of 30 cases underwent H-UPPP, while the experimental group of 32 patients underwent improved H-UPPP and tongue base radiofrequency. The clinical efficacy between the two groups was compared. Results: There was no significant difference between the two groups before operation. After the operation, the total effective rate of the experimental group was 71.9%, significantly higher than that of the control group (46.7%, χ²=4.09, P<0.05), the difference was statistically significant. After operation, in the control group, AHI was (19.4±8.1)/h, LSaO₂ was 0.767±0.052. In the experimental group, AHI was (17.8±7.8)/h, LSaO₂ was 0.790±0.059. There was significant difference in both groups before and after surgery (P<0.001), with statistical significance. In the experimental group, after operation, the minimum diameter of oropharyngeal cavity was (10.6±2.4) mm, there was obvious increase compared with the diameter of oropharyngeal cavity (9.9±2.2) mm before operation, the difference was statistically significant (t=2.64, P<0.05). In the control group, after operation, the minimum diameter of oropharyngeal cavity was(10.0±2.4) mm, there was no obvious increase compared with the diameter of oropharyngeal cavity (9.9±2.5) mm before operation, the difference was not statistically significant (P>0.05). Compared between control group and experimental group, the differences of AHI, LSaO₂, the minimum anteroposterior diameter of oropharyngeal cavity before and after operation were not statistically significant (P>0.05). Conclusion The effect of same time H-UPPP and radiofrequency ablation surgery is definitive.

Background & Objective: The calcitonin gene-related peptide (CGRP) has a central role in the pathogenesis of migraine, but variations in CGRP-related genes, including the calcitonin gene-related polypeptide-alpha (CALCA) gene and the receptor activity modifying 1 (RAMP1) gene, have not been found to link with migraine in Australian population. The goals of this study were to determine whether variants in the two genes are related to migraine in Chinese population. Methods: Using a case-control approach, rs3781719 and rs145837941 in the CALCA gene and rs3754701 and rs7590387 at the RAMP1 locus was analyzed in a cohort of 504 migraine cases and 529 ethnically matched controls. Genotyping was performed using Sequenom MALDI-TOF mass spectrometry iPLEX platform. Results: The CALCA gene rs145837941 variant was not found in migraine or control group. No significant difference in genotypic and allelic distribution was observed in the other three polymorphisms between migraine cases and controls. All the three SNPs were also not selected as significant factors that independently contributed to susceptibility to migraine in multivariate analysis. In the subgroup analysis, the CALCA rs3781719 seemed to be a significant risk for migraine with aura, but was not statistically significant after FDR correction. Moreover, there was no synergistic relationship between the three SNPs in the multifactor dimensionality reduction analysis for explore locus–locus interactions. Conclusion: Our data suggested that variants in CALCA gene and RAMP1 gene were not associated with migraine in the Han-Chinese population.
Calcitonin Gene-Related Peptide ; Migraine Disorders

OBJECTIVE: Acoustic rhinometry (AR) was performed to standardize the measurement techniques, result interpretation and reference values of nasal cavity volume (NV) in preschool children. METHOD: (1) Nasal cavity models were used to test the correlations between NV, minimal cross-sectional area (MCA), and nasal resistance. (2) There were 97 four-year-old and 137 five-year-old children underwent AR test. RESULT: (1) Model tests showed that resist the nce were better correlated with the change of volume than the MCA. (2) The average bilateral NV in preschool children was (2.03 +/- 0.4) ml. No significant gender and age difference were observed (P>0.05). CONCLUSION Volume measurement appears more sensitive and reliable than the MCA in assessing nasal patency. The AR result interpretation and normative NV values in preschool children are introduced.
Airway Resistance ; Child, Preschool ; Female ; Humans ; Male ; Nasal Cavity ; anatomy & histology ; physiology ; Reference Values ; Rhinometry, Acoustic ; methods