Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic liver disorder worldwide, characterized by complex molecular regulatory networks driving its pathogenesis. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), serve as critical regulators of gene expression and have been increasingly recognized for their pivotal roles in MASLD development. Rather than functioning in isolation, these ncRNAs form intricate regulatory networks that integrate and amplify disease signals across multiple cellular compartments and pathological stages. This review provides a comprehensive overview of how these ncRNA networks orchestrate MASLD progression, focusing on their roles in metabolic dysregulation, inflammation, and fibrosis. We further evaluate the diagnostic potential of circulating ncRNAs as stable, non-invasive biomarkers for disease stratification and monitoring, and discuss emerging therapeutic strategies targeting ncRNAs, including antisense oligonucleotides, synthetic mimics, and advanced delivery platforms such as lipid nanoparticles and engineered exosomes. Despite significant progress, challenges related to delivery efficiency, tissue specificity, and safety remain barriers to clinical translation. By synthesizing current knowledge of ncRNA networks in MASLD and highlighting opportunities for therapeutic intervention, this review provides a roadmap for translating ncRNAs into clinical applications for this increasingly prevalent metabolic liver disease.

Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

Metastasis is the leading cause of death from cutaneous melanoma. Identifying metastasis-related targets and developing corresponding therapeutic strategies are major areas of focus. While functional genomics strategies provide powerful tools for target discovery, investigations at the protein level can directly decode the bioactive epitopes on functional proteins. Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function. Herein, we developed a target and epitope discovery platform, termed functional aptamer evolution-enabled target identification (FAETI), by integrating affinity aptamer acquisition with phenotype screening and target protein identification. Utilizing the aptamer XH3C, which was screened for its migration-inhibitory function, we identified the Chondroitin Sulfate Proteoglycan 4 (CSPG4), as a potential target involved in melanoma migration. Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin α4. Taken together, our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery. Additionally, XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4, enabling the development of innovative therapeutic strategies.

Objective To investigate the utility of dual-energy CT combined with musculoskeletal ultraso-nography in differentiating between calcium pyrophosphate deposition disease and gouty arthritis.Methods A retro-spective analysis was conducted on the medical records of 102 patients diagnosed with gouty arthritis and 102 patients diagnosed with calcium pyrophosphate deposition disease.These patients were categorized into the Gout group and Calcium Deposition group,respectively,based on their respective diagnoses.All patients underwent dual-energy CT and musculoskeletal ultrasonography examinations,while joint fluid aspiration results or intra-articular crystal material served as the gold standard for diagnosis.The diagnostic efficacy of dual-energy CT and musculoskeletal ultrasonography in discriminating between calcium pyrophosphate deposition disease and gouty arthritis was evalu-ated.Results In the gout group,the proportion of male patients and serum uric acid levels were significantly higher compared to those in the calcium deposition group(P<0.05).The prevalence rates of knee joint,first metatarsopha-langeal joint,and ankle joint involvement were higher in the gout group,while knee joint,wrist joint,and shoulder joint involvement rates were higher in the calcium deposition group.The proportions of irregular bone cortex,carti-lage injury,and degenerative meniscus changes were lower in the gout group compared to the calcium deposition group(P<0.05).The proportions of double contour sign,tophus formation,hyperechoic band within ligaments or tendons,and bone erosion were higher in the gout group compared to the calcium deposition group(P<0.05),whereas cartilage calcification was lower in the gout group(P<0.05).The sensitivities for diagnosing calcium pyrophosphate deposition disease and gouty arthritis using dual-energy CT scan alone,musculoskeletal ultrasound alone,and their combined use were 86.27%,83.33%,and 94.12%respectively.The specificities for diagnosing these conditions using dual-energy CT scan alone,musculoskeletal ultrasound alone,and their combined use were 89.22%,88.24%,and 86.27%respectively.The positive predictive values were 88.89%,87.63%,and 87.27%,respectively.The negative predictive values were 86.67%,84.11%,and 93.63%,respectively.The accuracies were 87.75%,85.78%,and 90.20%respectively.The agreement Kappa values were 0.755,0.716,and 0.804 respectively.Conclusions The integration of dual-energy CT and musculoskeletal ultrasonography exhibits promising diagnostic efficacy in discriminating between calcium pyrophosphate deposition disease and gouty arthritis.This combined approach serves as a valuable adjunctive tool for the diagnosis of both conditions.

Objective:To systematically evaluate the experience of home-based hospice care from two different perspectives of professional caregivers and family caregivers, and summarize the barriers faced by caregivers.Methods:This study was Meta-synthesis. Qualitative studies on the barriers of home-based hospice care among professional caregivers or family caregivers were electronically searched on China National Knowledge Infrastructure, WanFang Data, VIP, PubMed, Web of Science, Cochrane Library, Embase, CINAHL and Medline. The search period was from database establishment to October 3, 2023. The quality evaluation of literature was conducted using the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center. The aggregation Meta-synthesis method was used to integrate the included article.Results:A total of ten articles were included, all had a quality evaluation level of B. Thirty-five results were extracted and summarized into eight new categories. Two integrated results were formed, including barriers to implementation of home-based hospice care by patients' family members (three categories) and barriers to implementation of home-based hospice care by professional caregivers (five categories) .Conclusions:Due to various factors such as external policies, organizations, and personnel, there are still many challenges in the practical development of home-based hospice care. Government and medical institutions can formulate or improve policies and service processes to address the obstacles to implementing home hospice care for different caregivers, and promote the development of home-based hospice care.

Objective This study utilizes bioinformatics methods to analyze differentially expressed genes(DEGs)between Alzheimer's disease(AD)and vascular dementia(VD)compared to normal controls.The aim is to identify key genes and validate their relevance to both types of dementia.Methods Gene chip dataset GSE122063 were obtained from the Gene Expression Omnibus(GEO)database.Using the GEO2R tool,DEGs in AD,VD,and normal control group were screened.We constructed a protein-protein interaction network using the STRING database and identified key genes through Cytoscape.Subsequently,DAVID database were used to analyze gene ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways associated with interconnected DEGs,predicting their biological functions.Finally,diagnostic performance were validated and assessed by using receiver operating characteristic curves.Results In the AD and VD groups,we identified 1099 and 505 DEGs,respectively,with 69 genes showing associations in the protein-protein interaction network.GO analysis revealed that DEGs are primarily located in the extracellular matrix,cell surface,and plasma membrane.They influence biological processes such as signal transduction and inflammatory responses,with functions related to receptor binding and signal receptor activity,collectively contributing to dementia development.KEGG analysis indicated significant enrichment of DEGs in immune-related signaling pathways,including microbial infections,rheumatoid arthritis,systemic lupus erythematosus,and inflammatory bowel disease.Four key genes—CCR5,CCL2,FCGR2A,and ITGB2—with significantly elevated expression in both AD and VD groups were indentifiied.The area under the curve suggests their potential diagnostic value for dementia.Conclusion Through bioinformatics analysis of AD and VD,the enriched signaling pathways and key genes associated with immunity and inflammation were discovered.These findings may play a crucial role in dementia progression and provide new insights for early diagnosis.

Objective:To systematically review the risk prediction models for diabetic retinopathy in patients with type 2 diabetes mellitus (T2DM) .Methods:Literature regarding the risk prediction models for diabetic retinopathy in T2DM were searched from CINAHL, PubMed, Web of Science, Cochrane Library, Embase, Wanfang, CNKI, VIP, and China Biology Medicine disc, with the search timeframe extending to October 1, 2022. Two researchers independently selected literature and extracted data, and the bias risk and applicability of the included literature were analyzed using the PROBAST tool for assessing risk of bias in prediction model studies.Results:A total of 14 articles were included. Age, duration of diabetes, glycated hemoglobin, proteinuria, blood pressure, and serum creatinine levels were the main predictive factors for diabetic retinopathy in T2DM; the Area Under the Receiver Operating Characteristic (ROC) curve of the predictive models ranged from 0.683 to 0.984, with calibration conducted in 6 models; 4 studies used external validation, while the rest used internal validation. All studies demonstrated good applicability, but all presented bias risk.Conclusions:The risk prediction models for diabetic retinopathy in T2DM demonstrate good predictive performance. However, high bias risk due to methodological flaws (such as improper handling of missing data, inappropriate methods for variable selection, lack of blinding, etc.) indicates they cannot be directly applied to clinical practice. Future work should either conduct extensive validation on existing models or undertake large-scale, diverse prospective studies to develop predictive models with superior performance and user-friendly application.

Objective To investigate the value of prenatal diagnosis in identifying the etiology and predicting the prognosis of fetal pleural effusion (FPE).Methods Forty-two cases of FPE were recruited in this study from January 2012 to September 2016.Ultrasound scan and genetic tests were performed on all fetuses.Seven fetuses with severe FPE were given pleurocentesis.Pregnancy outcomes of all the fetuses were followed up.Results FPE was commonly accompanied with other abnormalities,such as ascites,hydrops,hydramnion,hygroma colli,abnormal posturing,joint contractures,arrhythmia and micromandible.Chromosomal abnormality was detected in 11 fetuses (26.2％),of which ten were further confirmed by karyotype analysis,including six with 45,X,three trisomy 21 and one trisomy 18,and one was detected with a 9.83 Mb uniparental disomy (UPD) located at 12q24.21q24.31 by gene chip.One fetus was diagnosed with--SEA/--SEA thalassemia.All of the 12 families decided to terminate the pregnancies after genetic counseling.Among the other 30 fetuses,seven with severe FPE and normal karyotype underwent pleurocentesis.Five of the seven cases were with favorable outcomes,one with progressive hydrops was aborted and one neonate with severe hydrops died after birth.Spontaneous regression of FPE with good outcome was found in two cases.Parents of the other 21 fetuses chose to terminate the pregnancies.Conclusions Prenatal diagnosis is important to identify the etiology and predict the outcome of FPE.Chromosomal abnormality is a relatively common cause of FPE,and 45,X and trisomy 21 are the most common abnormalities.Intrauterine intervention is beneficial for FPE without chromosomal or other definite genetic abnormalities.Genetic test may be of great value for pregnant counseling.

Objective To discuss the operative strategies for cervical spine fracture combined with ankylosing spondylitis and the deformity of cervicothoracic kyphosis.Methods Retrospectively analyzed 21 cases of cervical spine fracture combined with ankylosing spondylitis and the deformity of cervicothoracic kyphosis,who underwent surgeries from January,2007 to August,2014.Twenty males and 1 female were included.Mean age was (48.6±7.5) years (range,36-65 years).The preoperative American Spine Injury Association (ASIA) classification distribution:2 cases of Grade A,6 cases of Grade B,7 cases of Grade C,5 cases of Grade D,and 1 case of of Grade E.The investigative surgical methods including posterior cervical open reduction,internal fixation and bone graft fusion;posterior cervical open reduction/decompression,internal fixation and bone graft fusion;or combined posterior and anterior cervical decompression,bone graft fusion and instrumentation.The operative time and blood loss were recorded,the clinical therapeutic effect was evaluated by visual analogue scale (VAS) score,ASIA grade improvement,cervical curvature (the angle between a line drawn parallel to the inferior endplate of C2 and a line drawn parallel to the inferior endplate of C7 in the lateral plane of an X-ray image) and radiological assessment (including bone graft fusion condition and internal fixation position).Results One case died from severe pulmonary infection and respiratory failure at the 45th day after operation.All the other 20 patients obtained complete follow-up with a mean time of (39.4±8.76) months (range,25-59 months).7 cases received posterior cervical open reduction,internal fixation and bone graft fusion,average operative time was (92.1±5.4) minutes and average blood loss was (96.1+23.7) ml.9 cases received the posterior cervical open reduction and decompression,internal fixation and bone graft fusion,mean operation time was (121.4± 14.0) minutes and blood loss was (250.0±38.9) ml.3 cases experienced combined posterior and anterior cervical decompression,bone graft fusion and fixation,average operative time was (222.4± 14.9) minutes and average blood loss was (354.3+46.7) ml.Mean of VAS scores at the 3th month postoperatively was 2.76±0.46,significantly lower than the preoperatively VAS scores (8.95±0.36).Mean of VAS scores at the 24th month postoperatively was 1.77±0.39,significantly lower than those at the 3th month postoperatively.The neurological function of spinal cord achieved significant improvement after operations and continued recovered gradually in the subsequent follow up.ASIA Classification distribution at the 24th month postoperatively was:0 case of Grade A,0 case of Grade B,3 cases of Grade C,8 cases of Grade D,9 case of Grade E.Mean of the cervical curvature after operation was-7.1°± 1.9°,significantly higher than preoperatively(-13.4°±3.3°) and did not have any loss of Cobb's angles at 24th month after operation.All the surviving cases achieved solid bone graft fusion.Mean bone graft fusion time was 5.8 months (range,4-9 months).There was no internal fixation loose,fracture and dislocation occurred during follow up.Conclusion All procedures can significantly relieve the painful symptoms,effectively restore the normal cervical alignment and stability,and remarkably improve the neural function of the patients suffering cervical spine fracture combined with ankylosing spondylitis and the deformity of cervicothoracic junction kyphosis.

Objective To evaluate the role of mitochondrial ATP-sensitive potassium (mito-KATP) channels in attenuation of renal ischemia-reperfusion (I/R) injury by lidocaine pretreatment in rats.Methods Sixty healthy male Wistar rats,weighing 300-350 g,were randomly assigned into 5 groups (n =12 each) using a random number table:sham operation group (group S); renal I/R group (group I/R); lidocaine pretreatment group (group L) ; 5-HD (a specific blocker of the mito-KATP channel) group and 5-HD + lidocaine pretreatment group (group 5-HD + L).Renal ischemia was induced by occlusion of bilateral renal arteries for 60 min with atraumatic microclips followed by 4 h reperfusion.At 60 min before renal ischemia,lidocaine 5 mg/kg was intravenously injected followed by continuous infusion at 2 mg· kg-1 · h-1 in group L.5-HD 10 mg/kg was injected intraperitoneally at 65 min before ischemia in group 5-HD.In 5-HD + L groups,5-HD 10 mg/kg was injected intraperitoneally at 65 min before ischemia and the other procedures were similar to those previously described in group L.In S and I/R groups,the animals received equal volumes of normal saline instead of lidocaine.Blood samples were obtained at 6 h of reperfusion for determination of serum creatinine (Cr) and urea mitrogen (BUN) concentrations.Bilateral kidneys were removed for determination of mitochondrial membrane potential in the renal tubular epidural cells,malondialdehyde (MDA) content,and superoxide dismutase (SOD) activity and for microscopic examination.Results Compared with group S,the serum Cr and BUN concentrations and MDA content were significantly increased,and SOD activity and mitochondrial membrane potential were decreased in I/R,L,5-HD and 5-HD + L groups (P ＜ 0.05).Compared with group I/R,the serum Cr and BUN concentrations and MDA content were significantly decreased,and SOD activity and mitochondrial membrane potential were increased in L and 5-HD + L groups (P ＜ 0.05),and no significant changes were found in the serum Cr and BUN concentrations,MDA content,SOD activity and mitochondrial membrane potential in group 5-HD (P ＞ 0.05).Compared with group L,the serum Cr and BUN concentrations and MDA content were significantly increased,and SOD activity and mitochondrial membrane potential were decreased in 5-HD + L group (P ＜ 0.05).The pathological changes were significantly reduced in group L as compared with I/R and 5-HD + L groups.Conclusion Mito-KATp channels are involved in reduction of I/R-induced renal injury by lidocaine pretreatment in rats.