Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Public hospitals have formed a relatively perfect working foundation in the introduction and training of young talents,but the evaluation system of young talents is not perfect.Based on the requirements of high-quality development,grasp the principle of party management of talents,combine the talents development situation in Jiading District Maternal and Child Health Care Hospital,takes the special training of young talents in administration as the starting point,comprehensively uses the literature method,interview method and Delphi method to establish the index database,uses the exploratory factor analysis meth-od to calculate the index weight,and constructs the evaluation model of young talents in hospital administrative management,so as to help hospitals better screen and evaluate talents and give full play to the value and role of talents as the first resource.

Objective To systematically summarize medication patterns and explore the potential mechanisms of core herbal combinations in treating chronic glomerulonephritis(CGN)based on data mining and network pharmacology,and to provide a reference for clinical treatment strategies.Methods Electronic book databases were searched to screen the CGN prescription from the works of contemporary Xin'an medical practitioners.Frequency statistics,association rule analysis,and clustering algorithms via the traditional Chinese medicine(TCM)Inheritance Support Platform V3.5 were applied to identify high-frequency herbs(frequency of use>10%)and core combinations.Active ingredients and potential targets were predicted using TCMSP,PubChem,and SwissTargetPrediction databases.Disease-related targets were retrieved from OMIM and GeneCards,after obtaining the intersecting targets,followed by protein-protein interaction(PPI)network construction(STRING platform),Cytoscape topological analysis,and GO and KEGG pathway enrichment(DAVID).Results A total of 151 prescriptions related to the treatment of CGN were included,involving 213 flavours of TCM,including 42 varites of high frequency drugs,mainly in the categories of supplementing deficiency,eliminating dampness and diuresis and clearing heat.Theherb properties were mainly cold,warm,and neutral,with flavors of sweet,bitter,and pungent.Herbs primarily targeted the liver,lung,kidney,and spleen meridians.Thecore combination"Astragali Radix,Dioscorea Rhizome,Atractylodis Macrocephalae Rhizoma,Imperata Rhizome,Pyrrosiae Folium,Poria"was identified,with key active ingredients including quercetin,stigmasterol,and β-sitosterol.Core targets involved IL6,EGFR,TNF,AKT1,and PIK3CA,while enriched pathways included PI3K-Akt and AGE-RAGE signaling.Conclusion Contemporary Xin'an practitioners primarily treat CGN by tonifying the spleen,nourishing the kidney,and clearing damp-heat.Thecore herbal combination exerts synergistic effects through multi-target intervention in immune-inflammatory pathways,oxidative stress,and fibrotic pathways,highlighting the holistic therapeutic advantages of TCM formulas via multi-component synergistic regulation and multi-target interactions.This study provides a theoretical foundation for further experimental validation and clinical applications.

Objective To investigate the current situation of off-label use of immune checkpoint inhibitors(ICIs)in China and the cognition of medical staff.Methods From August 31 to September 9,2022,a nationwide survey questionnaire was sent to medical staff in the form of electronic questionnaire.The questionnaire included 13 questions,covering four dimensions:Drug allocation,current situation of medication beyond the instructions,cognition of medication beyond the instructions and current situation of medication beyond the instructions.Results A total of 745 questionnaires were collected.75.70％of respondents reported off-label use of ICIs in their hospitals,with the most common type being off-label indications.The primary reasons for such practices included support from authoritative domestic and international guidelines,clinical research data validation,and approved indications in foreign regulatory documents.85.37％of respondents believed off-label use could offer new hope for patients,while 68.86％considered it unlikely to increase adverse reactions.44.97％of respondents' hospitals had not established off-label use registration systems for ICIs.88.86％of respondents emphasized the need for stricter regulations governing off-label use of immunotherapeutic agents.Conclusion Off-label use of ICIs is common,and there is a lack of unified guidance in clinical practice.It is urgent to form norms and consensus on the management of off-label use of ICIs.

Objective:To investigate the clinicopathological characteristics and prognostic influencing factors in young breast cancer patients.Methods:A retrospective case series study was conducted. The clinical data of 408 young patients with breast cancer in the Fifth Medical Center of Chinese PLA General Hospital from January 2005 to December 2020 were retrospectively analyzed. The clinical characteristics and prognostic influencing factors of patients were observed. The Kaplan-Meier method was used to analyze overall survival (OS) and disease-free survival (DFS) of patients. Univariate analysis of prognostic factors was conducted by using the log-rank test, and multivariate analysis was performed by using Cox proportional risk model.Results:The median age [ M ( Q1, Q3)] of 408 young female patients with breast cancer was 36 (33, 39) years; the 5-year OS and 5-year DFS rates were 89.9%, 84.0% of 387 breast cancer patients in early and middle stage (except for stage Ⅳ). There were statistically significant differences in the 5-year OS and 5-year DFS rates (excluding stage Ⅳ of DFS) of patients with different clinical staging and molecular subtypes (all P < 0.05). The differences were statistically significant in the 5-year DFS rate of patients with different pathological types and histological grades (all P < 0.05). There were no statistically significant differences in the 5-year OS and DFS rates between the patients receiving breast-conserving surgery or mastectomy (all P > 0.05). The results of multivariate Cox regression analysis indicated that clinical staging ( HR = 3.121, 95% CI: 2.301-4.233, P < 0.001) and molecular classification ( HR = 1.441, 95% CI: 1.126-1.845, P = 0.004) were independent prognostic factors for OS. Additionally, clinical staging ( HR = 3.001, 95% CI: 2.174-4.141, P < 0.001) was identified as an independent prognostic factor for DFS. Conclusions:The prognosis of young breast cancer patients is closely related to clinical staging and molecular subtype. The later the clinical stage is, the poorer prognosis is. Luminal-type breast cancer has a better prognosis than other subtypes. For early-stage breast cancer patients who meet the criteria for breast-conserving surgery, breast-conserving surgery is the first-choice alternative.

Objective To study the effect of esketamine on postoperative inflammatory celluar cyto-kines and mental state in the patients with total hysterectomy.Methods A total of 162 patients with elective laparoscopic total hysterectomy in Wenzhou municipal Hospital of Integrated Traditional Chinese and Western Medicine from August 2020 to June 2024 were selected as the study subjects and randomly divided into the control group(n=54),low-dose group(n=53)and high-dose group(n=55).The three groups routinely conducted the general anesthesia.The low-dose group and high dose group were intravenously injected by 0.2 mg/kg and 0.4 mg/kg esketamine once at preoperative 10 min respectively,and the same amount of normal saline in the control group was injected.The general condition and operation time in the three groups,occur-rence of nausea and vomiting,hallucinations,nightmares,agitation,drowsiness and dizziness on postoperative 1 d as well as the VAS scores in 3 groups were recorded.Venous blood on preoperative 1 d(T0),postoperative 1 d(T1)and 3 d(T2)was collected,the levels of the nucleotide-binding oligomerization domain-like receptor pyrin domain protein 3(NLRP3),interleukin(IL)-6,IL-1β,tumor necrosis factor-α(TNF-α),brain-derived neurotrophic factor(BDNF)and neuropeptide Y(NPY)were measured.The Hamilton Anxiety Scale(HA-MA)and Hamilton Depression Rating Scale(HAMD)were used to evaluate the anxiety and depression of the patients.The difference in the HAMA scores generated based on general data at T2 among various the sub-groups between the low-dose group and the control group was analyzed.Results Compared with the control group,the incidence rate of nausea and vomiting and VAS score in the low-dose group and high-dose group were lower,and the difference was statistically significant(P＜0.05).Compared with the control group,the levels of NLRP3,IL-6,IL-1β and TNF-α at T1 and T2 in the low-dose group and high-dose group were lower,and the differences were statistically significant(P＜0.05).Compared with the control group,the BDNF level at T1 and T2 in the low dose group and high dose group was higher,the NPY level was lower,and the differ-ences were statistically significant(P＜0.05).Compared with at T0,the HAMA and HAMD scores of T1 and T2 in the low-dose group and high-dose group were decraesed,and the differences were statistically significant(P＞0.05).Compared with the control group,the HAMA and HAMD scores at T1 and T2 time points the low-dose group and high-dose group were lower,and the differences were statistically significant(P＜0.05).Conclusion Esketamine could improve the anxiety and depression condition and reduce the inflammation level in the patients.

Oral inflammatory diseases caused by odontogenic infections cover a wide range and have a high incidence rate,which can affect the morphology and function of the maxillofacial area and seriously en-danger oral health.Macrophages are important immunoactive cells in oral tissues,which can be polarized into M1/M2 type in different microenvironments,and then exert pro-inflammatory or anti-inflammatory effects,and are widely involved in the progression of odontogenic infectious diseases.In infections caused by oral mi-crobial factors such as bacteria,the distribution characteristics and polarization direction of macrophages in tis-sues are specific.At present,the research on macrophage polarization-related inflammatory diseases has attrac-ted more and more attention,and the regulation of macrophage M1/M2 polarization is gradually being used in the treatment of related diseases,and many research progress has been made in the diagnosis and treatment of odontogenic infectious diseases.In this paper,we elaborate on the distribution characteristics,polarization trends and related applications of macrophage polarization in common oral inflammatory diseases such as pul-pitis,apical periodontitis,periodontitis and peri-implantitis which are mainly caused by dental infections.The aim is to provide new ideas and targets for the diagnosis and treatment of oral inflammatory diseases.

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Objective This study investigated feasible cases and their significance in promoting the"generalized"development of inspection through digital-intelligent equipment.Methods A qualitative research approach was used,involving interviews conducted between February 2025 and March 2025 with experts in traditional Chinese medicine diagnostics,clinical research methodology,medical engineering integration,and related disciplines,using both online and offline methods.In accordance with the Consolidated Criteria for Reporting Qualitative Research,feasible cases involving the specific application of digital equipment in various parts of observation were collected through item enrichment.The significance of extending observation capabilities via these cases was analyzed,along with the overall implications of integrating digital technologies with traditional inspection method.Results Interviews were completed with 11 experts from domestic universities and research institutes in the fields of traditional Chinese medicine diagnosis,medical engineering integration,and related disciplines.A total of 78 feasible cases of digital-intelligent inspection were identified,along with 69 insights regarding the significance of enhancing the inspection capabilities.These insights were synthesized into two dimensions and 23 holistic meanings.The first dimension is to expand the scope of inspection,including obtaining internal environmental characteristics,observing external environmental characteristics,expanding thermodynamic characteristic data,and crossing time and space.The second dimension is to improve the quality of observation and diagnosis information collection and analysis,including 19 specific meanings,such as standardized collection environment,objective quantification,and refined observation.Conclusion Digital-intelligent equipment plays a significant role in expanding the scope of inspection content and achieving high-quality acquisition and analysis of extensive inspection information.These advancements extend and enrich the capabilities of traditional inspection method in traditional Chinese medicine.