As the application of immune checkpoint inhibitors(ICIs)in the perioperative treatment of melanoma is increasingly introduced at earlier stages,it presents a critical opportunity for the development and clinical translation of neoadjuvant therapy.The results of phaseⅠ/Ⅱ clinical trials on neoadjuvant ICI therapy for melanoma demonstrate that neoadjuvant ICIs effectively improve the pathologic re-sponse rate in melanoma patients.Recent studies have shown that combining ICIs with other treatment modalities,including radiotherapy,chemotherapy,and targeted therapies,can enhance antitumor efficacy of neoadjuvant treatment for patients with melanoma.Optimizing treatment regimens,managing adverse events,identifying and addressing pseudoprogression,and handling cases of oligoprogression have become key areas of research in incorporating ICI regimens into neoadjuvant treatment for patients with melanoma.The search for bio-markers to monitor immunotherapy efficacy is expected to become a major focus of future research.This article provides a review of the re-search progress,controversies,and challenges in the application of ICIs in the neoadjuvant treatment of melanoma,and discusses future re-search directions,aiming to offer insights into the clinical application and development of ICIs in melanoma neoadjuvant therapy.

Metastatic castration-resistant prostate cancer (mCRPC) is often resistant to conventional therapies, and prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy has emerged as a promising therapeutic strategy. Ligands such as 177Lu-PSMA and 225Ac-PSMA have demonstrated clinical benefits in ongoing studies and show potential when combined with endocrine therapy, chemotherapy, immunotherapy, and radiotherapy. Additionally, novel therapeutic approaches, including PSMA-targeted antibody-drug conjugates (ADCs), chimeric antigen receptor T-cell (CAR-T) therapy, and bispecific T-cell engagers (BiTEs), are being actively explored. This review summarizes the recent advancements in PSMA-targeted treatment and their clinical applications.

Metastatic castration-resistant prostate cancer (mCRPC) is often resistant to conventional therapies, and prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy has emerged as a promising therapeutic strategy. Ligands such as 177Lu-PSMA and 225Ac-PSMA have demonstrated clinical benefits in ongoing studies and show potential when combined with endocrine therapy, chemotherapy, immunotherapy, and radiotherapy. Additionally, novel therapeutic approaches, including PSMA-targeted antibody-drug conjugates (ADCs), chimeric antigen receptor T-cell (CAR-T) therapy, and bispecific T-cell engagers (BiTEs), are being actively explored. This review summarizes the recent advancements in PSMA-targeted treatment and their clinical applications.

Objective To investigate the growth, development and health status of primary and secondary school students in Xinzhou District of Wuhan, and analyze the detection and change trend of common diseases in primary and secondary school students, and to provide a basis for relevant departments to formulate prevention and control measures of common diseases in students. Methods The monitoring data of common diseases and health influencing factors of primary and secondary school students in Xinzhou District from 2019 to 2022 were analyzed and compared according to different genders, different grades and ages. SPSS 20.0 software was used to analyze the data of detection rates of myopia, dental caries, obesity, malnutrition and abnormal spinal curvature. Results The overall detection rates of myopia, dental caries, malnutrition, obesity and abnormal spinal curvature were 57.00%, 58.45%, 4.60%, 14.91%, and 6.33%, respectively, in Xinzhou District from 2019 to 2022. The annual change rates were 7.22%, 15.10%, -2.72%, 13.29%, and 4.91%, respectively. The detection rates of myopia, dental caries, obesity and abnormal spinal curvature showed an increasing trend in each year (χ² ≥17.22, P<0.001). The detection rates of myopia and malnutrition increased with the increase of age and school level (both χ²≥42.37, P<0.001), while the opposite was true for the detection rates of dental caries and obesity (both χ²≥14.26, P<0.001). The detection rates of myopia and dental caries were higher in girls than in boys (both χ²≥33.66, P<0.001), while the detection rates of obesity and abnormal spinal curvature were higher in boys than in girls (both χ²≥8.22, P<0.005). The detection rates of myopia, dental caries, obesity and abnormal spinal curvature in 2019 were lower than those in 2020-2022 (χ²≥4.11, P<0.05), while the detection rates of malnutrition had decreased. Conclusion The growth, development and health status of primary and secondary school students in Xinzhou District are serious. The detection rate of common diseases such as myopia, dental caries, obesity and abnormal curvature of the spine is on the rise, which should be the focus of the surveillance work of common diseases in primary and secondary school students in the future, and comprehensive intervention measures are urgently needed to prevent and control these common diseases.

Occupational health technical service (OHTS) is one of the core contents in the technical support system of occupational disease prevention and control, and efficient management of OHTS institutions is necessary for improving the service ability. At present, OHTS institutions in China face several issues, such as uneven distribution in terms of quantity, function, unclear area coverage and roles and overlapping responsibilities among different types of institutions, and insufficient service capabilities with inconsistent service levels in some institutions. With the implementation of the national reform like the “separating permits from business license” and “delegate power, streamline administration and optimize government services"”policies, the management mode and operational approach of OHTS institutions have been profoundly changed. In light of this, five key recommendations are proposed to improve the management of OHTS institutions and enhance their management effectiveness, ensuring the sustainable development of national OHTS services. Firstly, it is necessary to clarify the relationship between national and provincial administrative levels in managing OHTS institutions to ensure their healthy and orderly development. Secondly, multiple measurements are taken to strengthen OHTS institutional capacity building to address regional disparities in technical capabilities and service quality. Thirdly, both technical capabilities and service quality should be focused on strengthening the supervision and management of OHTS institutions, preventing the decline of key conditions such as staffing, laboratories, equipment, and quality management after obtaining qualifications. Fourthly, “dual randomized- inspections and one open” and “internet+supervision” methods are used as basic tools for managing OHTS institutions operating across multiple provincial regions and enforcing cross-regional law. Fifthly, professional integrity of radiological health service institutions should be restored to effectively apply their technical advantages in their specialized fields.

This study explores the role and underlying molecular mechanisms of fucoidan sulfate(FPS) in regulating heme oxygenase-1(Hmox1)-mediated ferroptosis to ameliorate myocardial injury in diabetic cardiomyopathy(DCM) through in vivo and in vitro experiments and network pharmacology analysis. In vivo, a DCM rat model was established using a combination of "high-fat diet feeding + two low-dose streptozotocin(STZ) intraperitoneal injections". The rats were randomly divided into four groups: normal, model, FPS, and dapagliflozin(Dapa) groups. In vitro, a cellular model was created by inducing rat cardiomyocytes(H9c2 cells) with high glucose(HG), using zinc protoporphyrin(ZnPP), an Hmox1 inhibitor, as the positive control. An automatic biochemical analyzer was used to measure blood glucose(BG), serum aspartate aminotransferase(AST), serum lactate dehydrogenase(LDH), and serum creatine kinase-MB(CK-MB) levels. Echocardiography was used to assess rat cardiac function, including ejection fraction(EF) and fractional shortening(FS). Pathological staining was performed to observe myocardial morphology and fibrotic characteristics. DCFH-DA fluorescence probe was used to detect reactive oxygen species(ROS) levels in myocardial tissue. Specific assay kits were used to measure serum brain natriuretic peptide(BNP), myocardial Fe~(2+), and malondialdehyde(MDA) levels. Western blot(WB) was used to detect the expression levels of myosin heavy chain 7B(MYH7B), natriuretic peptide A(NPPA), collagens type Ⅰ(Col-Ⅰ), α-smooth muscle actin(α-SMA), ferritin heavy chain 1(FTH1), solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), 4-hydroxy-2-nonenal(4-HNE), and Hmox1. Immunohistochemistry(IHC) was used to examine Hmox1 protein expression patterns. FerroOrange and Highly Sensitive DCFH-DA fluorescence probes were used to detect intracellular Fe~(2+) and ROS levels. Transmission electron microscopy was used to observe changes in mitochondrial morphology. In network pharmacology, FPS targets were identified through the PubChem database and PharmMapper platform. DCM-related targets were integrated from OMIM, GeneCards, and DisGeNET databases, while ferroptosis-related targets were obtained from the FerrDb database. A protein-protein interaction(PPI) network was constructed for the intersection of these targets using STRING 11.0, and core targets were screened with Cytoscape 3.9.0. Molecular docking analysis was conducted using AutoDock and PyMOL 2.5. In vivo results showed that FPS significantly reduced AST, LDH, CK-MB, and BNP levels in DCM model rats, improved cardiac function, decreased the expression of myocardial injury proteins(MYH7B, NPPA, Col-Ⅰ, and α-SMA), alleviated myocardial hypertrophy and fibrosis, and reduced Fe~(2+), ROS, and MDA levels in myocardial tissue. Furthermore, FPS regulated the expression of ferroptosis-related markers(Hmox1, FTH1, SLC7A11, GPX4, and 4-HNE) to varying degrees. Network pharmacology results revealed 313 potential targets for FPS, 1 125 targets for DCM, and 14 common targets among FPS, DCM, and FerrDb. Hmox1 was identified as a key target, with FPS showing high docking activity with Hmox1. In vitro results demonstrated that FPS restored the expression levels of ferroptosis-related proteins, reduced intracellular Fe~(2+) and ROS levels, and alleviated mitochondrial structural damage in cardiomyocytes. In conclusion, FPS improves myocardial injury in DCM, with its underlying mechanism potentially involving the regulation of Hmox1 to inhibit ferroptosis. This study provides pharmacological evidence supporting the therapeutic potential of FPS for DCM-induced myocardial injury.
Animals ; Ferroptosis/drug effects* ; Rats ; Diabetic Cardiomyopathies/physiopathology* ; Male ; Rats, Sprague-Dawley ; Polysaccharides/pharmacology* ; Heme Oxygenase-1/genetics* ; Myocytes, Cardiac/metabolism* ; Myocardium/pathology* ; Humans ; Cell Line ; Heme Oxygenase (Decyclizing)

Objective:To investigate the association between social support and subjective and objective cognitive functions among the middle-aged and elderly population in Pingyin County, Jinan City, Shandong Province.Methods:Employing a multi-stage cluster random sampling method, a cross-sectional study was conducted in 2023 by selecting people aged 45-70 years from seven villages in three towns within Pingyin County, Jinan City, as survey respondents. Social Support Rating Scale (SSRS), Subjective Cognitive Decline-Questionnaire 9 (SCD-Q9) and Montreal Cognitive Assessment-Basic (MoCA-B) were used to assess the social support and cognitive status of interviewees, and a self-developed questionnaire was used to collect other basic information. Pearson correlation analysis, multiple linear regression and multifactorial logistic regression were used to explore the relationship between social support and subjective and objective cognitive functions.Results:A total of 1 891 subjects were finally included in the study, with 45.52±6.99 for the SSRS total score, an abnormal rate of 43.68% (826/1 891) for the SCD-Q9 score and an abnormal rate of 60.02% (1 135/1 891) for the MoCA-B score. The SSRS total score, subjective support score, objective support score and support utilization score were negatively correlated with SCD-Q9 scores and positively correlated with MoCA-B scores (all P<0.05). An increase in SSRS total score ( β=-0.034, 95% CI: -0.051--0.017, P<0.001) and objective support score ( β=-0.074, 95% CI: -0.121--0.027, P=0.002) can lower SCD-Q9 scores. Compared to those who had only 1 source of financial support or help with practical problems when experiencing an acute situation, those with 2-4 ( OR=0.53, 95% CI: 0.34-0.82), 5 ( OR=0.46, 95% CI: 0.27-0.79), or 6-7 ( OR=0.42, 95% CI: 0.22-0.81) sources of help were more likely to have normal SCD-Q9 scores. Compared to individuals with ≤2 close friends who provided support and help, those with 3-5 ( OR=0.67, 95% CI: 0.50-0.91) or ≥6 friends ( OR=0.72, 95% CI: 0.54-0.97) were more likely to have normal MoCA-B scores. Moreover, compared to individuals who never participated in group activities, those who actively participated ( OR=0.59, 95% CI: 0.42-0.81) were more likely to have normal MoCA-B scores. Conclusions:Social support has protective effects on subjective and objective cognitive functions, and various social support conditions have different protective effects on subjective and objective cognitive functions among middle-aged and older people. Improving social support conditions for middle-aged and elderly individuals may delay the process of cognitive decline.

As the application of immune checkpoint inhibitors(ICIs)in the perioperative treatment of melanoma is increasingly introduced at earlier stages,it presents a critical opportunity for the development and clinical translation of neoadjuvant therapy.The results of phaseⅠ/Ⅱ clinical trials on neoadjuvant ICI therapy for melanoma demonstrate that neoadjuvant ICIs effectively improve the pathologic re-sponse rate in melanoma patients.Recent studies have shown that combining ICIs with other treatment modalities,including radiotherapy,chemotherapy,and targeted therapies,can enhance antitumor efficacy of neoadjuvant treatment for patients with melanoma.Optimizing treatment regimens,managing adverse events,identifying and addressing pseudoprogression,and handling cases of oligoprogression have become key areas of research in incorporating ICI regimens into neoadjuvant treatment for patients with melanoma.The search for bio-markers to monitor immunotherapy efficacy is expected to become a major focus of future research.This article provides a review of the re-search progress,controversies,and challenges in the application of ICIs in the neoadjuvant treatment of melanoma,and discusses future re-search directions,aiming to offer insights into the clinical application and development of ICIs in melanoma neoadjuvant therapy.

Objective:To investigate the association between social support and subjective and objective cognitive functions among the middle-aged and elderly population in Pingyin County, Jinan City, Shandong Province.Methods:Employing a multi-stage cluster random sampling method, a cross-sectional study was conducted in 2023 by selecting people aged 45-70 years from seven villages in three towns within Pingyin County, Jinan City, as survey respondents. Social Support Rating Scale (SSRS), Subjective Cognitive Decline-Questionnaire 9 (SCD-Q9) and Montreal Cognitive Assessment-Basic (MoCA-B) were used to assess the social support and cognitive status of interviewees, and a self-developed questionnaire was used to collect other basic information. Pearson correlation analysis, multiple linear regression and multifactorial logistic regression were used to explore the relationship between social support and subjective and objective cognitive functions.Results:A total of 1 891 subjects were finally included in the study, with 45.52±6.99 for the SSRS total score, an abnormal rate of 43.68% (826/1 891) for the SCD-Q9 score and an abnormal rate of 60.02% (1 135/1 891) for the MoCA-B score. The SSRS total score, subjective support score, objective support score and support utilization score were negatively correlated with SCD-Q9 scores and positively correlated with MoCA-B scores (all P<0.05). An increase in SSRS total score ( β=-0.034, 95% CI: -0.051--0.017, P<0.001) and objective support score ( β=-0.074, 95% CI: -0.121--0.027, P=0.002) can lower SCD-Q9 scores. Compared to those who had only 1 source of financial support or help with practical problems when experiencing an acute situation, those with 2-4 ( OR=0.53, 95% CI: 0.34-0.82), 5 ( OR=0.46, 95% CI: 0.27-0.79), or 6-7 ( OR=0.42, 95% CI: 0.22-0.81) sources of help were more likely to have normal SCD-Q9 scores. Compared to individuals with ≤2 close friends who provided support and help, those with 3-5 ( OR=0.67, 95% CI: 0.50-0.91) or ≥6 friends ( OR=0.72, 95% CI: 0.54-0.97) were more likely to have normal MoCA-B scores. Moreover, compared to individuals who never participated in group activities, those who actively participated ( OR=0.59, 95% CI: 0.42-0.81) were more likely to have normal MoCA-B scores. Conclusions:Social support has protective effects on subjective and objective cognitive functions, and various social support conditions have different protective effects on subjective and objective cognitive functions among middle-aged and older people. Improving social support conditions for middle-aged and elderly individuals may delay the process of cognitive decline.

Objective:To investigate the effect of capsaicin on lipopolysaccharide(LPS)-induced microglial inflammatory response by modulating silent mating type information regulation 2 homolog 1(SIRT1)/high mobility group box-1 protein(HMGB1)/nuclear factor κB(NF-κB)signaling pathway.Methods:BV2 mouse microglia were cultured in vitro,and pretreated with capsaicin(10 μmol/L),SIRT1 inhibitor EX527(100 μmol/L),capsaicin+EX527(10 μmol/L capsaicin+100 μmol/L EX527)for 3 hours,and then treated with LPS(1 μg/ml)for 24 hours,the corresponding groups were LPS group,LPS+capsaicin group,LPS+EX527 group,and LPS+capsaicin+EX527 group,a normal cultured control group(Control)was also set up.Morphological changes of BV2 cells in each group were observed under a microscope;CCK-8 method was used to detect the viability of BV2 cells in each group;immunofluo-rescence staining was applied to detect the positive expressions of ionic calcium adaptor protein(Iba-1)and the polarization of M1(positive for CD16/32)/M2(positive for CD206)subtypes in BV2 cells in each group;ELISA was applied to detect levels of inflamma-tory factors in BV2 cells in each group;Western blot and co-immunoprecipitation were applied to detect expression of SIRT1/HMGB1/NF-κB signaling pathway-related proteins in each group.Results:Compared with Control group,BV2 cells in LPS group were atro-phied,with shortened processes,the cell viability,and levels of IL-1β,TNF-α and IL-6 were increased,Iba-1 positive expression of BV2 cells and M1 type BV2 cells were increased,while expression of SIRT1 protein was decreased,expressions of acetylated(ace)-HMGB1 protein,cytoplasmic HMGB1 protein and nuclear NF-κB protein were increased(P<0.05);after capsaicin pretreatment,the above conditions were improved,and the M2 type BV2 cells were increased;adding EX527 pretreatment on the basis of capsaicin pre-treatment,the above conditions were all aggravated.Conclusion:Capsaicin can inhibit the inflammatory response induced by LPS-in-duced BV2 cell activation,which may be achieved by modulating the SIRT1/HMGB1/NF-κB signaling pathway.