19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

INTRODUCTION: Obstructive sleep apnoea (OSA) is common in Singapore, with moderate to severe OSA affecting around 30% of residents. These consensus statements aim to provide scientifically grounded recommendations for the management of OSA, standar-dise the management of OSA in Singapore and promote multidisciplinary collaboration. METHOD: An expert panel, which was convened in 2024, identified several areas of OSA management that require guidance. The expert panel reviewed the current literature and developed consensus statements, which were later independently voted on using a 3-point Likert scale (agree, neutral or disagree). Consensus (total ratings of agree and neutral) was set a priori at ≥80% agreement. Any statement not reaching consensus was excluded. RESULTS: The final consensus included 49 statements that provide guidance on the screening, diagnosis and management of adults with OSA. Additionally, 23 statements on the screening, diagnosis and management of paediatric OSA achieved consensus. These 72 consensus statements considered not only the latest clinical evidence but also the benefits and harms, resource implications, feasibility, acceptability and equity impact of the recommendations. CONCLUSION The statements presented in this paper aim to guide clinicians based on the most updated evidence and collective expert opinion from sleep specialists in Singapore. These recommendations should augment clinical judgement rather than replace it. Management decisions should be individualised, taking into account the patient's clinical characteristics, as well as patient and caregiver concerns and preferences.
Humans ; Sleep Apnea, Obstructive/diagnosis* ; Singapore ; Consensus ; Adult

INTRODUCTION: Risk-based screening (RBS) has emerged as a promising alternative to age-based cancer screening. However, evidence regarding real-world implementation outcomes remains fragmented. Thus, a systematic review was conducted to evaluate the implementation metho-dologies and outcomes of RBS programmes across different cancer types. METHODS: MEDLINE, Embase, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials and Scopus were systematically searched from their respective dates of inception up to 8 July 2024. Prospective and rando-mised controlled trials (RCTs), which implement the RBS of cancer in an asymptomatic population, or studies retrospectively evaluating the outcomes of the same were included. Geographic distribution, population characteristics, RBS methodology, diagnostic accuracy and clinical outcomes were narratively synthesised. RESULTS: Among the 33 included studies (i.e. 21 prospective cohort, 8 RCTs, 3 retrospective and 1 non-RCT), sample sizes ranged from 102 to 1,429,890 participants. Most RBS trials were conducted in China (n=7, 21.2%), followed by the Netherlands (n=4, 12.1%) then the US, Australia and Sweden (n=3, 9.8%). Studies predominantly examined colorectal (27.3%), breast (21.2%) and prostate cancer (18.2%). Three main stratification approaches emerged: algorithmic (48.5%), validated risk models (39.4%) and physician assessment (9.1%). Implementation outcomes showed higher uptake in moderate-risk (75.4%) compared to high-risk (71.3%) and low-risk groups (67.9%). Five studies demonstrated cost-effectiveness with increased quality-adjusted life years, while 12 studies showed superior or non-inferior cancer detection rates compared to traditional screening. CONCLUSION The RBS of cancer has the potential to optimise healthcare resource allocation while minimising harm and increasing receptiveness for patients. More work is needed to evaluate long-term outcomes prior to the scaling of RBS programmes.
Humans ; Early Detection of Cancer/methods* ; Neoplasms/diagnosis* ; Risk Assessment ; Mass Screening/methods*

OBJECTIVE: To review the application and progress of unilateral biportal endoscopy (UBE) technology in the treatment of cervical degenerative diseases, and to provide reference for clinical treatment decisions. METHODS: The literature related to UBE technology in the treatment of cervical spondylotic radiculopathy (CSR) and cervical spondylotic myelopathy (CSM) at home and abroad was extensively reviewed, and the surgical methods, indications, effectiveness, and safety were analyzed and summarized. RESULTS: UBE technology is effective in the treatment of CSR and CSM, and has the advantages of good surgical field, reducing the injury of the posterior structure of the cervical spine, and protecting the facet joint process, but in general, the indications are relatively narrow, limited to single-segment or adjacent double-segment lesions, and the requirements for the operator are relatively high, and the learning curve is long. CONCLUSION UBE technology can be applied to the treatment of CSR and CSM, but it needs to be carried out by experienced UBE surgeons for specific cases.
Humans ; Cervical Vertebrae/surgery* ; Endoscopy/methods* ; Radiculopathy/surgery* ; Spondylosis/surgery* ; Decompression, Surgical/methods* ; Spinal Cord Diseases/surgery* ; Treatment Outcome

OBJECTIVE: To investigate the anti-inflammatory effect of rutaecarpine (RUT) on monosodium urate crystal (MSU)-induced murine peritonitis in mice and further explored the underlying mechanism of RUT in lipopolysaccharide (LPS)/MSU-induced gout model in vitro. METHODS: In MSU-induced mice, 36 male C57BL/6 mice were randomly divided into 6 groups of 8 mice each group, including the control group, model group, RUT low-, medium-, and high-doses groups, and prednisone acetate group. The mice in each group were orally administered the corresponding drugs or vehicle once a day for 7 consecutive days. The gout inflammation model was established by intraperitoneal injection of MSU to evaluate the anti-gout inflammatory effects of RUT. Then the proinflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and the proportions of infiltrating neutrophils cytokines were detected by flow cytometry. In LPS/MSU-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and proinflammatory cytokines were measured by ELISA. The percentage of pyroptotic cells were detected by flow cytometry. Respectively, the mRNA and protein levels were measured by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, the nuclear translocation of nuclear factor κB (NF-κB) p65 was observed by laser confocal imaging. Additionally, surface plasmon resonance (SPR) and molecular docking were applied to validate the binding ability of RUT components to tumor necrosis factor α (TNF-α) targets. RESULTS: RUT reduced the levels of infiltrating neutrophils and monocytes and decreased the levels of the proinflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 (IL-6, all P<0.01). In vitro, RUT reduced the production of IL-1β, IL-6 and TNF-α. In addition, RT-PCR revealed the inhibitory effects of RUT on the mRNA levels of IL-1β, IL-6, cyclooxygenase-2 and TNF-α (P<0.05 or P<0.01). Mechanistically, RUT markedly reduced protein expressions of tumor necrosis factor receptor (TNFR), phospho-mitogen-activated protein kinase (p-MAPK), phospho-extracellular signal-regulated kinase, phospho-c-Jun N-terminal kinase, phospho-NF-κB, phospho-kinase α/β, NOD-like receptor thermal protein domain associated protein 3 (NLRPS), cleaved-cysteinyl aspartate specific proteinase-1 and cleaved-gasdermin D in macrophages (P<0.05 or P<0.01). Molecularly, SPR revealed that RUT bound to TNF-α with a calculated equilibrium dissociation constant of 31.7 µmol/L. Molecular docking further confirmed that RUT could interact directly with the TNF-α protein via hydrogen bonding, van der Waals interactions, and carbon-hydrogen bonding. CONCLUSION RUT alleviated MSU-induced peritonitis and inhibited the TNFR1-MAPK/NF-κB and NLRP3 inflammasome signaling pathway to attenuate gouty inflammation induced by LPS/MSU in THP-1 macrophages, suggesting that RUT could be a potential therapeutic candidate for gout.
Animals ; NF-kappa B/metabolism* ; Male ; Indole Alkaloids/therapeutic use* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Inflammation/complications* ; Uric Acid ; Quinazolines/therapeutic use* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Gout/chemically induced* ; Inflammasomes/metabolism* ; Cytokines/metabolism* ; THP-1 Cells ; Mitogen-Activated Protein Kinases/metabolism* ; Mice ; Molecular Docking Simulation ; Lipopolysaccharides ; Quinazolinones

Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.

Objective To investigate the neuroprotective effects and mechanisms of abscisic acid(ABA)in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mouse models.Methods Eight-week-old C57BL/6J mice were randomly divided into three groups,control group(Ctrl),MPTP group,and MPTP+ABA group,12 mice in each group.Except for the control group,mice in the other groups were intraperitoneally injected with MPTP 25 mg/kg daily for 8 consecutive days to establish a subacute PD model.The MPTP+ABA group received intraperitoneal injections of ABA 25 mg/kg daily for 11 consecutive days,starting 3 days prior to MPTP administration.Behavioral tests were performed 24 hours after the last administration.On day 3,the expression of tyrosine hydroxylase(TH)and glial fibrillary acidic protein(GFAP)in the substantia nigra pars compacta(SNc)and striatum(STR)was analyzed by Western blotting,and mRNA levels of inflammatory factors were measured by Real-time PCR.Immunofluorescent staining was used to detect the expression of TH,GFAP,and ionized calcium-binding adapter molecule 1(Iba1).Results Compared with the control group,MPTP-treated mice exhibited impaired motor function,a reduced number of TH-positive dopaminergic neurons in the SNc,down-regulated TH protein expression in both the SNc and striatum,up-regulated GFAP protein expression,increased numbers of GFAP-and Iba1-positive cells,and elevated levels of pro-inflammatory factors.In contrast,the MPTP+ABA group showed improved motor function,increased TH-positive neurons in the SNc,up-regulated TH protein expression,down-regulated GFAP protein expression,reduced numbers of GFAP-and Iba1-positive cells,and decreased pro-inflammatory factor levels compared to the MPTP group.Conclusion ABA ameliorates motor dysfunction in MPTP-induced PD model mice,reduces degeneration and death of dopaminergic neurons in the SNc,suppresses the proliferation and activation of astrocytes and microglia in the SNc and striatum,and alleviates neuroinflammation.These results suggest that ABA exerts neuroprotective effects in MPTP-induced PD model mice.

Objective To establish a rapid detection method for Clostridium botulinum in food.Methods A rapid detection method based on RPA-CRISPR/Cas12a was developed by integrating recombinase polymerase amplification(RPA)with the CRISPR-Cas12a system.After the reaction conditions were optimized,the method's sensitivity,specificity,and usefulness were methodically confirmed.Results and Conclusion The optimized method achieved detection within 1 hour,with a limit of detection(LOD)of 1.91 copies/μL.No cross-reactivity was observed with non-target pathogens.The RPA-CRISPR/Cas12a-based detection method developed in this study exhibits high specificity,sensitivity,and operational simplicity and may provide a feasible solution for the rapid detection of foodborne pathogens.

Given the constraints imposed by the “14-day ethics” rule, numerous critical events occurring between the second and fourth weeks of embryonic development remain poorly understood. This underscores the necessity of a detailed understanding of embryonic development and regulation during this period, which is indispensable for preventing pregnancy failure, treating birth defects, and promoting human reproductive health.Rodents, characterized by their small size, rapid growth, strong reproductive capacity, and fully sequenced genomes, are widely used as crucial models for studying embryonic development. However, the substantial physiological differences between rodents and primates due to evolutionary divergence make it challenging to directly apply findings from rodent studies to primates. Besides, primates, our closest relatives in terms of evolutionary phylogenetics and physiological characteristics, share more than 95% genetic homology with humans, underscoring the urgent need for primate research. Furthermore, early-stage embryonic cells are both scarce and diverse, making their regulatory mechanisms and developmental pathways typically elucidated through single-cell sequencing. For instance, three significant articles published in Science in 2018 mapped the complete atlas of organ and tissue development from fertilization and captured dynamic gene expression profiles in zebrafish and frogs through single-cell transcriptomics. Unfortunately, relying solely on single-cell omics analysis falls short in effectively and comprehensively deciphering the intricate cellular network information. Single-cell multi-omics empower researchers to systematically decode cell heterogeneity and developmental trajectories at the individual cell level by combining transcriptomics, epigenomics, proteomics, and metabolomics analyses. These emerging technologies play a significant role in life sciences, enabling the elucidation of critical early primate embryonic development events from a multi-dimensional perspective, including zygotic genome activation (ZGA), X-chromosome dosage compensation, origins of primordial germ cells (PGCs), mechanisms of cell fate determination, and pivotal events in gastrulation and early organogenesis.This article chronicles the advancement of pivotal technologies, from single-cell histology to multi-omics, beginning with the single-cell transcriptome and culminating in a comprehensive analysis according to the central dogma of molecular biology. It highlights the transition from a singular to a holistic perspective in cellular analysis and reviews the application of multi-omics techniques in unveiling early primate embryonic development. Finally, it delves into the application of multi-omics technologies in enhancing our understanding of early primate embryonic development and explores future possibilities, directions, and challenges in this rapidly evolving field. In doing so, it emphasizes the critical role of interdisciplinary approaches, combining insights from genetics, molecular biology, and bioinformatics to foster innovations in reproductive medicine and developmental biology. The integration of such technologies offers the promise of breakthroughs in understanding complex biological processes, potentially leading to novel therapeutic strategies and advancements in reproductive health and medicine.