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.

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.

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 analyze TCM master Yan Zhenghua's medication rules of ascending,descending,floating and sinking properties for the treatment of respiratory diseases,inherit his valuable academic experience.Methods Using four books edited by Professor Yan Zhenghua's disciples as the main source,Professor Yan Zhenghua's prescriptions for clinical treatment of respiratory diseases were systematically collected and analyzed.Statistical analysis was conducted on the patients'gender and age,differentiation of diseases and syndrome types of the prescriptions,as well as the properties of ascending,descending,floating and sinking,dosage,and commonly used pairs of Chinese materia medica.Results Totally 208 prescriptions were included in this study,involving 178 kinds of Chinese materia medica and 64 kinds of monarch drug,most of them were descending and sinking drug,and the whole prescription was mainly descending and sinking.On average,each prescription used 13.2 kinds of Chinese materia medica,and most dosage points were within the range of conventional dosage.Among later adding medicines,Houttuyniae Herba had the highest frequency of use.The medicinal pairs of Asteris Radix et Rhizoma-Cynanchi Stauntonii Rhizoma et Radix,Cynanchi Stauntonii Rhizoma et Radix-Stemonae Radix and Asteris Radix et Rhizoma-Stemonae Radix were often used.Armeniacae Semen Amarum,Fritillariae Thunbergii Bulbus,and Asteris Radix et Rhizoma were commonly used in those descending and sinking prescriptions.Conclusion In the treatment of respiratory diseases,Professor Yan Zhenghua prefers to use descending and sinking drugs with ascending and floating drugs and dual trend drugs to regulate qi activity,and has the characteristics of Menghe medical school,which is"mild and flexible medication".

Rosacea is a chronic recurrent inflammatory skin disease, and correct assessment of clinical symptoms and severity may facilitate treatment options. This review summarizes a range of subjective, semi-subjective and objective methods currently used in the assessment of rosacea severity, in order to provide useful tools for clinical assessment of rosacea severity and give guidance on treatment modification according to the therapeutic effect.

Objective:To investigate the recognition of the post competency index system among rural general practice assistant physicians and its influencing factors.Methods:This study was a cross-sectional survey. A questionnaire survey on the recognition of post competency index system was conducted from October 2020 to September 2021 among rural general practice assistant physicians from 10 provinces/municipalities selected by stratified cluster sampling method. The recognition of rural general practice assistant physicians at all levels of indexs and the factors influencing recognition were analyzed.Results:A total of 1 123 questionnaires were distributed and 1 024 valid ones were collected with a recovery rate of 91.18%. Of the 1 024 respondents, 529 were male(51.7%) and 435 were aged 40-49 years(42.5%), which was the highest proportion by age group. The average overall recognition score of the index system was 4.41, and the scores of the primary indexes were 4.32-4.45. Three primary indexes had the highest recognition scores: professional competence, basic health care services, and interpersonal communication and teamwork. The recognition scores on the second level index were 4.18-4.61, and the proportion of recognition scores greater than 4 was over 80%. There were significant differences in the recognition scores of the index system among assistant physicians with different working years, educational background, professional title and work unit ( F/H=6.41, 14.83, 12.45, 7.53, P<0.01). Educational background(associate degree: B=0.091, P=0.015; bachelor degree and above: B=0.196, P<0.001) and professional title(intermediate professional title and above: B=-0.234, P<0.001) were the independent factors influencing the recognition degree of the index system for rural general practice assistant physicians. Conclusions:The post competency index system is generally recognized by rural general practice assistant physician, and academic qualifications and professional title status may influence its recognition.