The presence of physiological barriers in the eye （both external and internal） makes conventional ophthalmic medications （eye drops， ointments， gels， etc.） less bioavailable and difficult to reach the posterior segment of the eye. Although intravitreal injection can deliver drugs to the posterior segment of the eye， it has disadvantages such as infection， injury， and poor tolerance. Ophthalmic microneedle breaks through the intra- and extra-ocular barriers， enabling the drug to reach the target site accurately and to be released continuously greatly avoiding intraocular infections and injuries， and improving the bioavailability of the drug， which has obvious advantages as an ophthalmic drug delivery tool. Ophthalmic microneedle can be classified into hollow microneedle， dissolving microneedle， and coated microneedle according to the usage methods. Each type of microneedle has its own advantages and has shown satisfactory performance in the treatment of diseases such as bacterial and fungal keratitis， glaucoma， exudative age-related macular degeneration， diabetic macular edema， non-infectious uveitis， corneal neovascularization， and even choroidal melanoma.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence, in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.
Humans ; Immunoconjugates/adverse effects* ; Neoplasms/immunology* ; Animals ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/therapeutic use*

OBJECTIVES: This study aimed to explore the clinical efficacy of severe early childhood caries (SECC) treatment combined with local anesthesia under general anesthesia. METHODS: A total of 108 children under 6 years old who underwent SECC dental treatment under general anesthesia at the Department of Pediatric Dentistry, Third Affiliated Hospital of Air Force Medical University from March to December 2023 were selected as the study subjects, with American Society of Anesthesiologists (ASA) classification of classⅠor Ⅱ. The study subjects were divided into a control group (n=54) and an experimental group (n=54) by retrieving intraoperative cases and postoperative follow-up records. The control group was given general anesthesia through inhalation combined with nasotracheal intubation, whereas the experimental group was given local anesthesia with 2% lidocaine on each treated tooth on the basis of general anesthesia. The basic information, preoperative anesthesia depth, hemodynamic changes during different surgical procedures, postoperative pain, and adverse reactions in the two groups were recorded and analyzed. RESULTS: No statistically significant difference was found in the basic information and preoperative anesthesia depth between the two groups (P>0.05). Among the three procedures (pulpotomy, root canal treatment, and tooth extraction), the three observed indicators in the experimental group were significantly lower than those in the control group (P<0.05). The proportion of patients in the experimental group who needed to take analgesic measures in accordance with the modified facial pain scale (FPS-R) score was significantly lower than that in the control group at postoperative wakefulness and 2 h after surgery (P<0.05). Meanwhile, no statistically significant difference was observed between the groups at 24 h after surgery (P>0.05). The proportion of patients in the experimental group who needed to take analgesic measures on the basis of the parent posto-perative pain measurement (PPPM) score was significantly lower than that in the control group when they were awake after surgery (P<0.05). No statistically significant difference was found between the groups at 2 and 24 h after surgery (P>0.05). Moreover, no statistically significant difference was observed in the incidence of adverse reactions between the two groups at 24 h after surgery (P>0.05). CONCLUSIONS The combination of local anesthesia during SECC dental treatment under general anesthesia results in minimal changes in intraoperative hemodynamics and mild postoperative pain response, hence worthy of clinical promotion.
Humans ; Anesthesia, General ; Child, Preschool ; Dental Caries/therapy* ; Pain, Postoperative/prevention & control* ; Anesthesia, Local/methods* ; Male ; Hemodynamics ; Female ; Lidocaine/administration & dosage* ; Child ; Anesthetics, Local/administration & dosage* ; Anesthesia, Dental/methods*

Objective:To design and evaluate a cell membrane vaccine strategy based on dendritic cell membrane microbubbles(DCM@MBs),and to explore its potential application in tumor immunotherapy,especially the immune-specific killing of tumor cells through the activation of T cells.Methods:At first,tumor cell membrane proteins were extracted and dendritic cells(DCs)were acti-vated to confirm that tumor antigens could effectively stimulate the maturation of immature DCs.Mature DC membranes were then mixed with lipids to prepare DCM@MBs,which were characterized for morphology,size,and protein composition by confocal laser scanning microscopy and sodium dodecyl sulfate-polyacrylamide gel electrophoresis.Finally,in vitro co-culture experiments were con-ducted to assess the effect of DCM@MBs on the activation of T cells and their ability for specific killing of tumor cells.Results:In the in vitro DC activation experiment,after stimulation with tumor cell membrane proteins,the 25 μg/mL group had a significant increase in the expression level of MHC class Ⅱ molecule(25.167%±1.203%)on the surface of immature DCs compared with the control group(P<0.001),and DCM@MBs presented with microbubbles encapsulated by red cell membranes,with uniform dispersion and a size of 1-5 μm.In the in vitro co-culture experiment,the amount of breast cancer cells(9.893±0.341)%.Conclusion:The DCM@MBs strategy proposed in this study shows significant potential in tu-mor immunotherapy and can effectively activate T cells and specifically kill and eliminate tumor cells,which provides new ideas for tu-mor immunotherapy.

Objective To investigate the temporal and spatial relationship between autophagosome formation during spermatid deformation and lipid droplet distribution in seminiferous tubules,thereby providing insights into the en-ergy sources underlying spermiogenesis.Methods Healthy adult wild-type male mice were used in this study.The expression profile of the autophagy marker microtubule-associated protein light chain 3(LC3)in the testis was ex-amined using immunohistochemical staining and Western blot.The ultrastructural features of autophagosomes were observed via transmission electron microscopy.Lipid droplets in the seminiferous tubules were visualized by Oil Red O staining,and the relationship between lipid metabolism and energy dynamics was assessed by measuring ATP content and ATPase activity.Results Autophagosomes were detected in deforming spermatids and Sertoli cells.LC3 was predominantly expressed in the cytoplasm of elongating spermatids,with increasing levels found from stages Ⅱ to Ⅳ.Concurrently,lipid droplets within these cells also increased,peaking in spermatids and residual bodies during stagesⅦ-Ⅷ,followed by a decline.In contrast,lipid droplets in Sertoli cells remained markedly in-creased during stages Ⅸ-Ⅰ and low during stages Ⅱ-Ⅷ.The change of ATP levels in the seminiferous tubules showed a similar pattern as Sertoli cell lipid content,whereas ATPase activity showed an inverse trend.All these changes displayed a clear stage-dependent manner.Conclusions During spermatid elongation in mice LC3 expres-sion,autophagosome formation,lipid droplet accumulation in both spermatozoa and Sertoli cells,as well as ATP and ATPase levels in seminiferous tubules exhibit a tightly coordinated spatiotemporal relationship.These findings suggest that autophagy and lipid metabolism synergistically contribute to the energy supply required for the extensive cellular remodeling that occurs during spermiogenesis.