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.

Myocardial ischemia/reperfusion injury(MIRI)occurs after cardiopulmonary bypass open heart surgery,cardiovascular intervention and thrombolytic therapy,which is the most important cause of cardiac insufficiency,heart fail-ure,and even death in patients after treatment.In recent years,studies have found that the release of endogenous active peptides can alleviate the production of MIRI,and regulating the function and action of endogenous peptides may be one of the most effective ways to treat MIRI.Dipeptidyl peptidase 4(DPP4)is an important serine protease in mammals,with enzymatic activity to hydrolyze endogenous peptides.Its primary physiological function is to metabolize short peptides,in-cluding growth factors,hormones,etc.This review aims to better understand and search for effective therapeutic targets by elucidating the impact of DPP4 on the hydrolysis of endogenous peptides in MIRI,and ultimately provide new ideas for the therapeutic effects of MIRI.

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.

Background and Aims:Severe and multiple complications significantly affect the survival of patients after pancreaticoduodenectomy(PD).Previous studies have primarily focused on improving anastomosis techniques to reduce postoperative fistulas,with limited research on anatomical approaches to decrease complications and improve patient outcomes.This article summarizes our team's experience in applying curettage and suction dissection method in PD and analyzes its safety and clinical efficacy. Methods:The clinical data from patients undergoing elective PD in the Department of Hepatobiliary Surgery of Inner Mongolia Medical University Hospital from January 2021 to June 2023 were retrospectively collected.Patients using the curettage and suction dissection method were designated as the observation group,while those using traditional anatomical techniques were served as the control group.The observation group utilized the Peng's multifunctional operational dissector(PMOD),whereas the control group used conventional electrotome and ultrasonic scalpel during operation.The main clinical variables between the two groups were compared,and factors affecting postoperative survival of patients were also analyzed. Results:A total of 169 patients were included,with 59 in the observation group and 110 in the control group.No significant differences in baseline characteristics were found between the groups(all P＞0.05).The observation group exhibited more nerve infiltration during surgery than the control group(64.41％vs.39.09％,P=0.002),but had significantly shorter operative time(236 min vs.330 min,P＜0.01).There were no significant differences in lymph node metastasis,blood loss,or vascular infiltration between the two groups(all P＞0.05).The incidence of postoperative pancreatic fistula was significantly lower in the observation group than that in the control group(16.9％vs.40.0％,P=0.002).No significant differences were noted between the groups in terms of reoperation rate within one month,postoperative hospitalization duration,bile leakage,bleeding,infection,delayed gastric emptying or survival(all P＞0.05).Multivariate Logistic regression analysis identified smoking,tumor nerve infiltration,and delayed gastric emptying as independent risk factors affecting survival(all P＜0.05). Conclusion:Using curettage and suction dissection method with PMOD in PD is safe and feasible.It is simpler,less invasive,and results in shorter operative time compared to traditional method,indirectly reducing postoperative complications.Its clinical efficacy is reliable,suggesting potential for broader application in clinical practice.

In recent years， with the increasing social aging， the incidence of Alzheimer's disease （AD）， a neurodegenerative disease， is increasing. Due to its complex pathogenesis， there have been no effective prevention and treatment methods at present. The main pathological feature of AD is the accumulation of hyperphosphorylated microtubule-associated protein （Tau） and amyloid β-protein （Aβ） in cells to form a large number of senile plaques. Autophagy is a protective mechanism in body that maintains homeostasis by removing abnormal proteins. Studies have shown that regulating autophagy pathway can affect Tau and Aβ in cells and achieve the purpose of treating AD. Traditional Chinese medicine （TCM） is characterized by multiple pathways， components and targets， which has unique advantages in the treatment of AD with unknown pathogenesis. At present， the prevention and treatment of AD by TCM has achieved initial success. Researchers have found that many single TCMs and TCM compounds treat AD by affecting autophagy-related pathways and regulating the autophagy activity. Therefore， this paper summarized the relevant research in recent years， described the active components of single TCMs and TCM compounds by classification， and discussed the generation and removal of phosphorylated Tau proteins and Aβ in cells regulated by different categories of active components and compounds via influencing tautophagy-related pathways to delay the process of AD， which facilitated the prevention and treatment of AD by TCM via influencing autophagy as the breakthrough point.

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 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.