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 investigate the status quo of mobile phone addiction, social anxiety, sleep quality, safe behavior and the influence of mobile phone addiction on safe behavior of nursing students in practice, so as to provide evidence for improving the safety behavior of nursing students in practice.Methods:A total of 700 nursing students from The First Affiliated Hospital of Zhengzhou University from March 1 to 20, 2023 were selected by cluster sampling method. A cross-sectional investigation was conducted using the general data questionnaire, the Smartphone Addiction Scale-Short Version, the Nurse Safety Behavior Scale, the Social Anxiety Scale and the Pittsburgh Sleep Quality Index.Results:A total of 678 valid questionnaires were collected, with an effective recovery rate of 96.9%. Among the 678 nursing students in practice, 87 were male and 591 were female, aged (21.25±1.16) years old. The scores of safety behavior, mobile phone addiction, social anxiety and sleep quality of 678 nursing students were (52.33±7.31), (28.21±9.86), (41.92±7.64) and (4.56±2.79) respectively. Mobile phone addiction had a statistically significant effect on the prediction of safety behavior ( β = - 0.178, P<0.01). Social anxiety had an intermediate effect between mobile phone addiction and safety behavior, and the indirect effect accounted for 25.5%. Sleep quality could buffer the influence of social anxiety on safety behavior ( β = 0.022, P<0.05). Conclusions:The safety behaviors of student nurses are good, and there are phenomena of mobile phone addiction and social anxiety. Nursing managers and educators can effectively manage the mobile phones of nursing studentsin practice, reduce their social anxiety and improve their sleep quality, so as to improve the safety behaviors of nursing students in practice and ensure the safety of patients.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.