Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Bispecific antibodies （BsAbs）， as an important recent innovation in the field of tumor immunotherapy in recent years， can simultaneously or sequentially target different antigens or two different epitopes of the same antigen. Compared with traditional monoclonal antibodies， they can produce superior therapeutic effects. This article reviews the progress in clinical applications and safety research of BsAbs in cancer therapy， revealing that they （such as blinatumomab， glofitamab， teclistamab， amivantamab， etc.） exhibit significant therapeutic efficacy against hematological malignancies， lung cancer， cervical cancer， melanoma， and other cancers. For cytokine release syndrome （CRS） induced by BsAbs， prophylactic or pre-emptive medication is commonly administered in clinical practice； for neurotoxicity and infections triggered by BsAbs， clinical practice necessitates rigorous monitoring of patients’ vital signs and the provision of essential treatments. In addition， different BsAbs exhibit variations in escalation dose， infusion rate， storage duration， and equipment requirements. Therefore， strict adherence to the instructions in the drug package inserts is essential during clinical operations to ensure safety and therapeutic efficacy. In the future， more multicenter trials need to be conducted to validate the efficacy and safety of BsAbs across different tumor types and patient populations， and long-term follow-up data should be accumulated to optimize treatment cycles and dosage regimens.

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Human naïve pluripotent stem cells (PSCs) hold great promise for embryonic development studies. Existing induction and culture strategies for these cells, heavily dependent on MEK inhibitors, lead to widespread DNA hypomethylation, aberrant imprinting loss, and genomic instability during extended culture. Here, employing high-content analysis alongside a bifluorescence reporter system indicative of human naïve pluripotency, we screened over 1,600 chemicals and identified seven promising candidates. From these, we developed four optimized media-LAY, LADY, LUDY, and LKPY-that effectively induce and sustain PSCs in the naïve state. Notably, cells reset or cultured in these media, especially in the LAY system, demonstrate improved genome-wide DNA methylation status closely resembling that of pre-implantation counterparts, with partially restored imprinting and significantly enhanced genomic stability. Overall, our study contributes advancements to naïve pluripotency induction and long-term maintenance, providing insights for further applications of naïve PSCs.
Humans ; DNA Methylation/drug effects* ; Genomic Instability ; Pluripotent Stem Cells/metabolism* ; Cell Culture Techniques/methods* ; Cells, Cultured

Lipids play an important role in the regulation of cell life processes. Although there are various lipid detection methods, Raman spectroscopy, a non-invasive technique, provides the detailed chemical composition of lipid profiles without a complex sample preparation procedure and possesses greater potential in basic biology, clinical diagnosis and disease therapy. In this review, we summarized the characteristics and advantages of Raman-based techniques and their primary contribution to illustrating cellular lipid metabolism.

Objective:To discuss the clinical efficacy of microwave ablation(MWA)and surgical treatment in the patients with Hashimoto thyroiditis(HT)complicated with T1aN0M0 stage papillary thyroid carcinoma(PTC),and to clarify the feasibility and advantages of MWA as a minimally invasive treatment modality.Methods:A retrospective cohort study was used.A total of 165 patients diagnosed with HT complicated with T1aN0M0 stage PTC from January 2018 to December 2020 were selected and divided into MWA group(82 cases)and surgery group(83 cases).The patients in MWA group underwent MWA treatment under ultrasound guidance,and the patients in surgery group underwent unilateral thyroid lobectomy+unilateral lymph node dissection.The median follow-up time was(65.98±7.32)months.The indicators such as age,preoperative tumor volume,operation time,intraoperative blood loss,hospital stay,hospitalization cost,tumor progression,incidence of postoperative complications,changes in thyroid function,tumor recurrence rate,and life quality score of the patients in two groups were recorded and analyzed.Results:There were no significant differences in the baseline sample data including age,gender,preoperative tumor volume,margin,shape,aspect ratio,calcification,and preoperative thyroid function between two groups(P>0.05).Compared with surgery group,the operation time,intraoperative blood loss,hospital stay,and hospitalization cost of the patients in MWA group were significantly decreased(P<0.01),and there was no significant difference in the incidence of postoperative complications(P>0.05).All nodules in the patients in MWA group achieved complete ablation within 18 months.The functional thyroid parenchyma in the patients in MWA group was well preserved after operation,and the thyroid function was maintained within the normal physiological range during the follow-up period.The Thyroid Cancer-specific Quality of Life Questionnaire(THYCA-QoL)results showed that compared with MWA group,the scores of voice,sympathetic nerve symptoms,throat/mouth problems,psychological,sensory problems,scar,and chills of the patients in surgery group were significantly inecreased(P<0.05).There was no significant difference in the tumor progression rate between two groups(P>0.05).Conclusion:During the median follow-up period,both MWA and surgical treatment achieve satisfactory clinical efficacy in the patients with HT complicated with T1aN0M0 stage PTC.MWA treatment has significant advantages in operation time,intraoperative blood loss,hospital stay,hospitalization cost,quality of life,and preservation of thyroid function,and it can be used as a minimally invasive treatment option for such patients,but its long-term oncological safety needs to be further evaluated by extending the follow-up.

Objective It evaluates the high-quality development policies of public hospitals at the provincial level in China,and provides theoretical basis and countermeasures for formulating and optimizing the high-quality develop-ment policies of public hospitals.Methods The ROST CM 6.0 software was used to conduct text mining for 11 sample policies,and the Policy Modeling Consistency(PMC)index model was constructed to evaluate the sample policies quantitatively.Results The average PMC index of 11 sample policies included in the study was 7.16 points,of which 8 were excellent grades and 3 were qualified grades.The first-level variables X5 service system(0.82),X8 Party leadership(0.91)and X6 organization and operation(0.94)scored higher;X2 policy timeliness(0.52),X7 cultural construction(0.68)and X4 service capability(0.71)scored low.Conclusion The content of the high-quality develop-ment policy of public hospitals at the provincial level is basically in line with the national policy,and is relatively excel-lent in the aspects of organization and operation,service system and party leadership,etc.,but there are some weaknesses in the aspects of policy timeliness,cultural construction and service capacity,etc.,which can be op-timized and improved from the aspects of improving service capacity,supplementing long-term policies and strengthening hospital cultural construction.

Objective To explore the high-quality development path of tertiary public hospitals and provide scientific reference for deepening the reform of public hospitals.Methods Based on SPO theory,it constructed an analytical framework for the high-quality development of tertiary public hospitals,collected data of a quarterly monitoring in-dex for the performance assessment and high-quality development of tertiary public hospitals in a certain province in 2023,and analysed 73 tertiary public hospitals participating in the performance assessment as the object of analy-sis,and adopted the fuzzy-set Qualitative Comparative Analysis to explore different condition sets of high-quality de-velopment of tertiary public hospitals and reveal the path of high-quality development of public hospitals.Results High-quality development is the result of multi-factor interaction.Four configurations were identified to promote the high-quality development of tertiary public hospitals:service quality-technology-driven path,service quality-driven path,comprehensive service-driven path,and service quality-benefit-driven path.Quality safety and functional orientation were found to be the core elements in promoting high-quality development of public hospitals.Conclusion Hospitals at all levels should strengthen the guidance of party building,combine with the actual functional positioning,take quality and safety as the core,and optimize the combination conditions of technical level,personnel structure,service process,and cost control.It is essential to clarify the development strategy of hospitals,implement the dynamic concept,and realize the high-quality development of public hospitals.