INTRODUCTION: Adverse childhood experiences (ACEs) are associated with significant long-term impacts, yet few interventions specifically target ACE exposure, especially in Asian populations. Anchor, Singapore's first home visitation programme, addresses maltreat-ment among preschool children. This study evaluated Anchor's impact on children's developmental and behavioural outcomes. METHOD: We conducted a prospective evaluation of children under 4 years assessed for maltreatment from November 2019 to July 2023. Developmental and behavioural progress was measured every 6 months using the Ages and Stages Questionnaires (ASQ-3) and ASQ:Social-Emotional (ASQ:SE-2), and annually using the Child Behaviour Checklist (CBCL). RESULTS: The results of 125 children (mean age 20.0 months, 48% female) were analysed. The mean length of stay in programme was 21.2 (7.3) months. At baseline, 92 (73.6%) children were at risk of develop-mental delay and 25 (31.7%) children aged ≥18 months had behavioural concerns. The programme was associated with significant improvements in gross motor (P=0.002) and fine motor (P=0.001) domains of the ASQ-3 and internalising problem scale (P=0.001) of the CBCL. CONCLUSION Anchor effectively enhances develop-mental and behavioural outcomes for children exposed to maltreatment. Targeted early intervention through such programmes can mitigate adverse impacts, optimising developmental trajectories and potentially reducing the long-term clinical and economic burdens associated with ACEs.
Humans ; Female ; Male ; Child Abuse/therapy* ; Child, Preschool ; Singapore ; House Calls ; Infant ; Prospective Studies ; Child Development ; Developmental Disabilities/epidemiology* ; Program Evaluation ; Child Behavior Disorders ; Child Behavior

Erectile dysfunction (ED) is prevalent among men, but its relationship with dietary habits is uncertain. The aim of our study was to assess whether dietary patterns enhance erectile function by reviewing the literature published before August 1, 2022, via PubMed, Web of Science, and EMBASE databases. The data compiled included author details; publication dates, countries, treatments, patient numbers, ages, follow-ups, and clinical trial outcomes, such as ED cases, odds ratios (ORs), confidence intervals (CIs), and International Index of Erectile Function-5 (IIEF-5) scores with means and standard deviations. An analysis of 14 studies with 27 389 participants revealed that plant-based diets (OR = 0.71, 95% CI: 0.66-0.75; P < 0.00001), low-fat diets (OR = 0.27, 95% CI: 0.13-0.53; P = 0.0002), and alternative diets such as intermittent fasting and organic diets (OR = 0.54, 95% CI: 0.36-0.80; P = 0.002) significantly reduced ED risk. High-protein low-fat diets (hazard ratio [HR] = 1.38, 95% CI: 1.12-1.64; P < 0.00001) and high-carb low-fat diets (HR = 0.79, 95% CI: 0.55-1.04; P < 0.00001) improved IIEF-5 scores. Combined diet and exercise interventions decreased the likelihood of ED (OR = 0.49, 95% CI: 0.28-0.85; P = 0.01) and increased the IIEF-5 score (OR = 3.40, 95% CI: 1.69-5.11; P < 0.0001). Diets abundant in fruits and vegetables (OR = 0.97, 95% CI: 0.96-0.98; P < 0.00001) and nuts (OR = 0.54, 95% CI: 0.37-0.80; P = 0.002) were also correlated with lower ED risk. Our meta-analysis underscores a strong dietary-ED association, suggesting that low-fat/Mediterranean diets rich in produce and nuts could benefit ED management.
Humans ; Male ; Erectile Dysfunction/epidemiology* ; Diet ; Diet, Fat-Restricted ; Feeding Behavior ; Penile Erection/physiology* ; Diet, Vegetarian

Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

OBJECTIVE: To investigate the biomechanical characteristics of retrograde tibial nailing (RTN) and distal tibial L-shaped plating in the internal fixation of distal tibial fractures. METHODS: Fourteen fresh adult tibia specimens were selected, comprising 7 males and 7 females aged from 34 to 55 years old. The specimens were randomly divided into experimental group and control group by numerical table method with 7 specimens in each group. RTN was used for internal fixation of distal tibial fractures in the experimental group, and L-shaped plate was used for internal fixation of distal tibial fractures in the control group. The axial compression properties of the two groups of specimens were tested under the pressure of 100, 200, 300, 400, and 500 N after operation, and torsional resistance at torque levels of 1.0, 2.0, 3.0, 4.0, 5.0 N·m. The anti-fatigue performance of the specimens was tested at 500 N pressure for 3 000 and 10 000 cycles. X-ray fluoroscopy was performed to observe whether the the internal fixator was deformed and whether the screw was loosened or broken. RESULTS: When the pressure was 400 N and 500 N, the axial compression displacement of the experimental group was (1.11±0.06) mm and (1.24±0.05) mm, which were smaller than those of the control group (1.21±0.08) mm and (1.37±0.11) mm, and the differences were statistically signific (P<0.05). Under the pressure of 500 N, the axial compression stiffness of the experimental group was (389.24±17.79) N·mm^-1, which was significantly higher than that of the control group (362.37±14.44) N·mm^-1(P<0.05). When the torque was 4 and 5 N·m, the torsion angles of the experimental group were (2.97±0.23) ° and (3.41±0.17) °, which were smaller than those of the control group (3.31±0.28) ° and (3.76±0.20) °, and the differences were statistically significant (P<0.05). When the torque was 5 N·m, the torsional stiffness of the experimental group was (1.48±0.07) N·m per degree, which was higher than that of the control group (1.36±0.06) N·m per degree, and the difference was statistically significant (P<0.05). For the intragroup comparison of fatigue resistance, the differences in axial compression displacement between the two groups were not statistically significant at 3 000 and 10 000 cycles (all P>0.05). When 3 000 times and 10 000 times of compression, the axial compression displacement of the experimental group was (1.38±0.08), (1.43±0.07) mm, which was smaller than that of the control group (1.51±0.10), (1.54±0.08) mm, the differences were statistically significant (P<0.05). In the experimental group, no screw loosening, fracture or internal fixation deformation was found, while in the control group, locking screw loosening occurred in 2 models after 10 000 pressures. CONCLUSION The biomechanical performance of RTN is obviously better than that of the distal tibial L-shaped plate, which provides biomechanical data support for the clinical application of RTN.
Humans ; Female ; Male ; Adult ; Tibial Fractures/physiopathology* ; Middle Aged ; Biomechanical Phenomena ; Bone Plates ; Fracture Fixation, Internal/instrumentation* ; Bone Nails ; Tibia/surgery*

This study aims to isolate and culture primary rabbit spinal cord microvascular endothelial cells in vitro,providing a practical source of test cells for spinal cord injury research.Spinal cord tissue was aseptically extracted from one-month-old rabbits and processed sequentially through mincing,bovine serum albumin density gradient centrifugation,mesh filtration,and type Ⅱ collagenase digestion to ob-tain purified spinal cord microvascular segments.The microvascular segments were homogeneously mixed with an apprapriate volume of M199 complete culture medium and seeded into a culture dish for primary culture.Throughout the culture period,cell growth performance were continuously observed and recor-ded.Additionally,immunocytochemical staining was performed to evaluate the expression of factor Ⅷ-re-lated antigen.The results showed that after 24 hours of inoculation,a small amount of endothelial-like cells were observed to emerge from the spinal cord microvascular segments.Within 36～60 hours,the cell colonies gradually expanded and fused.After 72 hours,the cells spread across the base of the dish,forming a"cobblestone-like"monolayer.Immunocytochemical staining showed that more than 99％of the cells showed brown-red cytoplasm and were positive for factor Ⅷ-related antigen.It is these results that suggest this study has successfully established a convenient and stable primary rabbit spinal cord micro-vascular endothelial cells culture method.

This study aims to isolate and culture primary rabbit spinal cord microvascular endothelial cells in vitro,providing a practical source of test cells for spinal cord injury research.Spinal cord tissue was aseptically extracted from one-month-old rabbits and processed sequentially through mincing,bovine serum albumin density gradient centrifugation,mesh filtration,and type Ⅱ collagenase digestion to ob-tain purified spinal cord microvascular segments.The microvascular segments were homogeneously mixed with an apprapriate volume of M199 complete culture medium and seeded into a culture dish for primary culture.Throughout the culture period,cell growth performance were continuously observed and recor-ded.Additionally,immunocytochemical staining was performed to evaluate the expression of factor Ⅷ-re-lated antigen.The results showed that after 24 hours of inoculation,a small amount of endothelial-like cells were observed to emerge from the spinal cord microvascular segments.Within 36～60 hours,the cell colonies gradually expanded and fused.After 72 hours,the cells spread across the base of the dish,forming a"cobblestone-like"monolayer.Immunocytochemical staining showed that more than 99％of the cells showed brown-red cytoplasm and were positive for factor Ⅷ-related antigen.It is these results that suggest this study has successfully established a convenient and stable primary rabbit spinal cord micro-vascular endothelial cells culture method.

Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid decline in renal function. Renal ischemia-reperfusion injury (RIRI) is one of the main causes of AKI with the underlying mechanism incompletely clarified. The liver X receptors (LXRs), including LXRα and LXRβ, are members of the nuclear receptor superfamily. It has been shown that LXRs play an important role in regulating glucose and lipid metabolism, cholesterol efflux, and inflammation. The purpose of this study was to explore the role and mechanism of LXRs in RIRI. We determined the effects of LXR activation on renal function and histological changes in a mouse RIRI model and a cellular model of hypoxia/reoxygenation (H/R). In vivo results showed that LXRs agonist GW3965 significantly inhibited the increase of serum creatinine and urea nitrogen levels induced by RIRI. Both HE and PAS staining of kidney tissues revealed that GW3965 alleviated the morphological damages caused by RIRI. Immunohistochemical staining showed that GW3965 mitigated 4-HNE and GRP78 levels induced by RIRI. Furthermore, TUNEL assay indicated that GW3965 reduced RIRI-induced renal cell apoptosis. Quantitative real-time PCR (qPCR) analysis revealed that GW3965 attenuated RIRI-induced IL-6 and IL-1β mRNA expression. Compared with wild-type group, LXRα gene deficiency had little effect on RIRI-associated renal functional decline and morphological damages. Additionally, in vitro study demonstrated that GW3965 alleviated H/R-induced decrease of HK-2 human renal proximal tubule cell viability and restored the activity of superoxide dismutase (SOD) after H/R. Western blot results showed that GW3965 mitigated the increase of 4-HNE and GRP78 protein expression levels after H/R; However, knockdown of LXRβ using the small interfering RNA (siRNA) technique reduced cell viability compared to GW3965-treated group. Taken together, the LXRs agonist GW3965 significantly alleviates RIRI in mice possibly by reducing apoptosis, oxidative stress, endoplasmic reticulum stress and inflammation. These results also preliminarily confirm that the renal protective effects of LXRs agonists are dependent on LXRβ.
Animals ; Liver X Receptors/genetics* ; Reperfusion Injury/prevention & control* ; Mice ; Benzoates/pharmacology* ; Benzylamines/pharmacology* ; Male ; Endoplasmic Reticulum Chaperone BiP ; Mice, Inbred C57BL ; Apoptosis ; Acute Kidney Injury/prevention & control* ; Kidney/pathology* ; Humans

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*