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.

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.

Non-small cell lung cancer(NSCLC)is a prevalent and aggressive global malignancy.Conventional sur-gical treatments,radiotherapy,chemotherapy,and targeted therapies often fall short in halting disease progression due to inher-ent limitations,resulting in suboptimal prognosis.Despite the advent of immunotherapy drugs offering new hope for NSCLC treatment,current efficacy remains insufficient to meet all patient needs.Therefore,actively exploring novel immunotherapeu-tic approaches to further reduce mortality rates in NSCLC patients has become a crucial focus of NSCLC research.This article aims to systematically review the anti-tumor effects ofinterleukin-21 and follicular helper T cells in NSCLC immunotherapy by summarizing and analyzing relevant literatures from both domestic and international sources,as well as exploring the potential for enhancing NSCLC treatment prospects through immune checkpoint regulation via immunotherapeutic means.

OBJECTIVE To predict the in vivo bioequivalence of lenvatinib mesilate capsules and reference preparation by using the parallel artificial membrane permeability analysis. METHODS Based on the biopharmaceutics classification system classification of lenvatinib mesilate and the parallel artificial membrane permeation model, the in vitro dissolution permeation rate test model of lenvatinib mesilate capsules was established, through real-time monitoring of the dissolution and penetration of lenvartinib mesylate capsules and reference preparations in fasting gastric juice, intestinal fluid and postprandial intestinal fluid, the flux and total penetration of drugs through the membrane were calculated. RESULTS In fasting state and fed state, the 90% confidence interval of geometric mean ratio of two key quality parameters (permeation flux and permeation amount) of the preparation A all were in the range of 80.00%−125.00%, the preparation B did not fall into this interval. CONCLUSION This research method can predict the bioequivalence of renvartinib mesylate capsule and reference preparation, and has a certain correlation in vivo and in vitro.

Objective To evaluate the differences in efficacy,safety and economics of vancomycin hydrochloride for injection between two manufacturers based on real-world data.Methods A total of 6 757 cases of intravenous use of vancomycin hydrochloride for injection from different manufacturers between January 1,2013 and December 31,2019 in the Affiliated Drum Tower Hospital of Nanjing University Medical School were retrospectively analyzed,and 5308 cases were matched by 1∶1 propensity score method,including 2 654 cases in the group A(domestic drug group)and 2 654 cases in group B(the innovator drug group).The differences in efficacy and safety between the two groups were compared.Cost-effectiveness analysis was used to compare the drug economics of the two groups.Results There were no significant differences in clinical cure rate,bacterial clearance rate,and incidence of adverse events between the two groups(P>0.05).In terms of economics,the average cost of vancomycin per capita,average daily cost of vancomycin and average cost of antibiotics per capita were significantly different between the two groups(P<0.05),and the cost of group B was higher than that of group A.Conclusion The efficacy and safety of vancomycin hydrochloride for injection were consistent between the two manufacturers.

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

Abstract: Objective To investigate the prevalence and influencing factors of depressive symptoms among primary and middle school students in Xihu District, Hangzhou City, so as to provide insights into depression control among primary and middle school students. Methods: Students were sampled from two primary schools, two junior high schools, two ordinary high schools and one vocational high school in Xihu District using a stratified cluster random sampling method from September to November, 2021. Participants' demographics, diet, exercise, sleep and campus bullying were collected using questionnaire surveys. The depressive symptoms were evaluated using the Chinese version of the Center for Epidemiologic Studies-Depression Scale (CES-D), and factors affecting the depressive symptoms were identified among primary and middle school students using a multivariable logistic regression model. Results: A total of 1 518 students were investigated, including 518 primary school students (34.12%), 363 junior high school students (23.91%), 463 ordinary high school students (30.50%) and 174 vocational high school students (11.46%). Of all participants, there were 805 males (53.03%). The prevalence of depressive symptoms was 38.87% among the participants, and was 36.10%, 42.42%, 42.33% and 30.46% among primary school, junior high school, ordinary high school and vocational high school students, respectively. The multivariable logistic regression analysis showed that gender (OR=1.601, 95%CI: 1.289-1.989), type of school (junior high school, OR=1.299, 95%CI: 0.974-1.734; ordinary high school, OR=1.351, 95%CI: 1.025-1.780; vocational high school, OR=0.862, 95%CI: 0.585-1.272), frequency of fresh vegetable intake (less than once daily, OR=0.454, 95%CI: 0.304-0.679; once and more daily, OR=0.359, 95%CI: 0.235-0.548), duration spent on the internet (0.5 to 1 h daily, OR=1.447, 95%CI: 1.044-2.006; 1 h and longer daily, OR=1.456, 95%CI: 1.072-1.978), sufficient sleep (OR=0.525, 95%CI: 0.371-0.744), suffering from campus bullying (OR=1.992, 95%CI: 1.491-2.661) were associated with the development of depressive symptoms. Conclusions The prevalence of depressive symptoms is high among primary and middle school students in Xihu District. Gender, type of school, dietary behaviors, sleep duration and campus bullying are factors affecting the development of depressive symptoms.

Objective:To investigate the clinical effect of esophagofundostomy combined with pericardial devascularization in the treatment of upper gastrointestinal hemorrhage caused by portal hypertension.Methods:The clinical data of 108 patients with portal hypertension admitted to the Affiliated Hospital of Inner Mongolia Medical University from Feb 2009 to Feb 2015 were analyzed. Among them 42 patients underwent esophagofundostomy combined with pericardial devascularization as the study group, and 66 patients underwent pericardial devascularization only as the control group. All patients presented with splenomegaly or hypersplenism; the spleen was routinely removed during the operation.Results:The difference of operation time between the study group and the control group was statistically significant [(157±41) min vs. (143±27) min, t=2.81, P<0.05]. The improvement in the esophagogastric varices in the study group within 6 months was significantly better than that in the control group( Z=2.47, P<0.05). In addition, the rebleeding rates of varicose veins within 1, 3 and 5 years in the study group was 2%, 5% and 10%, while that in the control group was 15%, 21% and 26% (χ 2=5.49, 4.27, 4.31, all P<0.05). Conclusions:Esophagofundostomy combined with pericardia devascularization achieves complete devascularization and low rebleeding rate.

Objective: To evaluate the significance of double pancreatico-jejunostomy in preventing pancreatic fistula after central pancreatectomy (CP) . Methods: The clinical data of 10 patients who were admitted to the Affiliated Hospital of Inner Mongolia Medical University from Feb. 2012 to Dec. 2018 were analyzed retrospectively. Results: All the 10 patients underwent CP, closure of the proximal pancreatic stump, and end-to-side invaginated pancreaticojejunostomy; At the same time, invaginated pancreaticojejunal anastomosis or duct-to-mucosa pancreaticojejunostomy was performed to the distal pancreatic remnant. The duration of the operation was (240±60) min, and the average intraoperative blood loss was 300 ml. Incidence of pancreatic fistulas was 30% (3/10) . There were no grade B or C pancreatic fistulas, or perioperative deaths. The duration of postoperative hospital stay varied from 9 to 25 days. Endocrine and exocrine functions were well maintained during the follow-ups of 7 months to 5 years, and no tumors recurred. Conclusions Although operation time and technical difficulty increase, central pancreatectomy using double pancreaticojejunostomy is safe, feasible, and appears to be associated with a low rate of postoperative pancreatic fistulas.