Objective To investigate the effect and mechanism of Efferocytosis Relatived LncRNA (EFRL) on homocysteine-induced atherosclerosis in macrophage efferocytosis. Methods RAW264.7 cells were cultured in vitro, and the Control group (0 μmol/L Hcy) and Hcy intervention group (100 μmol/L Hcy) were set up. After GapmeR transfection of macrophages with Hcy intervention, EFRL knockdown negative control group (Hcy combined with LNA-NC) and EFRL knockdown group (Hcy combined with LNA-EFRL) were set up. High-throughput sequencing was applied for different expression of LncRNA MSTRG. 88917.16 (EFRL), UCSC was used to analyze its conservation, CPC and CPAT were used to analyze its ability to encode proteins, and GO and KEGG were used to analyze related biological functions. The localization of LncRNA EFRL in macrophages was analyzed by nucleoplasmic separation and RNA-FISH. Quantitative real-time PCR was used to detect the expression levels of LncRNA EFRL and its target gene SPAST in Hcy-treated macrophages. The apoptosis rate of Jurkat cells induced by UV was detected by flow cytometry. In vitro efferocytosis assay combined with immunofluorescence technique was used to analyze macrophage efferocytosis. ELISA was used to detect the levels of interleukin 1β(IL-1β) and IL-18. Results The new LncRNA MSTRG.88917.16 was identified and named EFRL(Efferocytosis Relatived LncRNA). UCSC, CPC and CPAT analyses showed that LncEFRL is highly conserved and does not have the ability to encode proteins. GO and KEGG analyses suggested that LncEFRL may be involved in macrophage efferocytosis. LncRNA EFRL was localized in the nucleus of macrophages as determined by nucleoplasmic separation and RNA-FISH. In comparison to the Control group, the expression levels of LncRNA EFRL and its target gene SPAST in the Hcy group were increased. In comparison to the Control group (0 min), the apoptosis rate of the experimental group (15, 30 min) Annexin V is more than 85%. Compared with Hcy combined with LNA-NC group, Hcy combined with LNA-EFRL group had enhanced macrophage efferocytosis and reduced levels of inflammatory factors. Compared with Hcy combined with LNA-NC group, the expression level of SPAST in Hcy combined with LNA-EFRL group was decreased. Conclusion Inhibition of EFRL expression can alleviate the process of Hcy inhibiting macrophage efferocytosis, and the mechanism is related to the regulation of the downstream target gene SPAST by EFRL.
RNA, Long Noncoding/physiology* ; Animals ; Homocysteine ; Mice ; Macrophages/drug effects* ; Humans ; RAW 264.7 Cells ; Atherosclerosis/chemically induced* ; Apoptosis/genetics* ; Phagocytosis/genetics* ; Jurkat Cells ; Interleukin-1beta/genetics* ; Efferocytosis

Neurodegenerative disorders (NDDs) are prevalent chronic conditions characterized by progressive synaptic loss and pathological protein alterations. Increasing evidence suggested that mitochondrial quality control (MQC) serves as the key cellular process responsible for clearing misfolded proteins and impaired mitochondria. Herein, we provided a comprehensive analysis of the mechanisms through which MQC mediates the onset and progression of NDDs, emphasizing mitochondrial dynamic stability, the clearance of damaged mitochondria, and the generation of new mitochondria. In addition, traditional Chinese medicines (TCMs) and their active monomers targeting MQC in NDD treatment have been demonstrated. Consequently, we compiled the TCMs that show great potential in the treatment of NDDs by targeting MQC, aiming to offer novel insights and a scientific foundation for the use of MQC stabilizers in NDD prevention and treatment.

The identification and optimization of mutations in nanobodies are crucial for enhancing their therapeutic potential in disease prevention and control. However, this process is often complex and time-consuming, which limit its widespread application in practice. In this study, we developed a workflow, named Evolutionary-Nanobody (EvoNB), to predict key mutation sites of nanobodies by combining protein language models (PLMs) and molecular dynamic (MD) simulations. By fine-tuning the ESM2 model on a large-scale nanobody dataset, the ability of EvoNB to capture specific sequence features of nanobodies was significantly enhanced. The fine-tuned EvoNB model demonstrated higher predictive accuracy in the conserved framework and highly variable complementarity-determining regions of nanobodies. Additionally, we selected four widely representative nanobody-antigen complexes to verify the predicted effects of mutations. MD simulations analyzed the energy changes caused by these mutations to predict their impact on binding affinity to the targets. The results showed that multiple mutations screened by EvoNB significantly enhanced the binding affinity between nanobody and its target, further validating the potential of this workflow for designing and optimizing nanobody mutations. Additionally, sequence-based predictions are generally less dependent on structural absence, allowing them to be more easily integrated with tools for structural predictions, such as AlphaFold 3. Through mutation prediction and systematic analysis of key sites, we can quickly predict the most promising variants for experimental validation without relying on traditional evolutionary or selection processes. The EvoNB workflow provides an effective tool for the rapid optimization of nanobodies and facilitates the application of PLMs in the biomedical field.

Background: Normalized creatinine-to-cystatin C ratio (NCCR) was reported to approximate relative skeletal muscle mass and diabetes risk. However, the association between NCCR and cardiometabolic multimorbidity (CMM) remains elusive. This study aimed to explore their relationship in a large-scale prospective cohort. Methods: This study included 5,849 middle-age and older participants from the China Health and Retirement Longitudinal Study (CHARLS) enrolled between 2011 and 2012. The baseline NCCR was determined as creatinine (mg/dL)/cystatin C (mg/L)×10/body mass (kg). CMM was defined as the simultaneous occurrence of two or more of the following conditions: heart disease, stroke, and type 2 diabetes mellitus. Logistic regression analysis and Cox regression analysis were employed to estimate the relationship between NCCR and CMM. The joint effect of body mass index and NCCR on the risk of CMM were further analyzed. Results: During a median 4-year follow-up, 227 (3.9%) participants developed CMM. The risk of CMM was significantly decreased with per standard deviation increase of NCCR (odds ratio, 0.72; 95% confidence interval, 0.62 to 0.85) after adjustment for confounders (P<0.001). Further sex-specific analysis found significant negative associations between NCCR and CMM in female either without or with one CMM component at baseline, which was attenuated in males but remained statistically significant among those with one basal CMM component. Notably, non-obese individuals with high NCCR levels had the lowest CMM risk compared to obese counterparts with low NCCR levels in both genders. Conclusion High NCCR was independently associated with reduced risk of CMM in middle-aged and older adults in China, particularly females.

Objective:To construct a failure mode and effects analysis(FMEA)evaluation model for medical devices to manage devices,so as to enhance management efficiency for medical devices.Methods:The FMEA was adopted to construct FMEA evaluation model for medical devices,so as to conduct comprehensive lifecycle management for medical devices.The process of management for equipment was optimized,and the operational risk of medical devices was reduced through failure mode(FM)analysis and the construction of management system for equipment.A total of 47 medical devices in clinical use of The First People's Hospital of Neijiang from January to December 2023 were included.In them,23 devices received conventional management mode during January and June 2023,and 24 devices received FMEA evaluation model(model management mode)during July and December 2023.For each group,2,000 patients'medical records were selected.The control effectiveness of infectious indicators,effect of cleaning and disinfection,and quality scores of infectious control for medical devices were compared between different management modes.A self-designed questionnaire was adopted to investigate the recognition scores of engineers who used and managed devices,operators,physicians,and department administrators for two kinds of management modes.Results:In 2,000 patients'medical records,who adopted model management mode,the infection rate of patients,and infection rate of aseptic surgical incision were respectively 0.15%and 0.05%,both were significantly lower than those in the conventional management mode(x2=5.420,8.358,P<0.05).The cleaning rate,and disinfection qualification rate of 24 medical devices,which adopted model management mode,were respectively 83.33%and 87.50%,all of which were significantly higher than these of conventional management mode(x2=8.080,6.741,P<0.05).The scores of standardized operation,rational use,disinfection and cleaning,and emergency intervention for medical devices in adopting model management mode were significantly higher than those in adopting conventional management mode(t=14.435,16.014,13.049,12.537,P<0.05).The recognition scores of engineers who used and managed devices,operators,physicians,and department administrators for adopting model management mode were significantly higher than those for adopting conventional management mode,and the differences were significant(t=12.219,12.147,17.437,13.420,P<0.05).Conclusion:The FMEA evaluation model for medical devices can real-time monitor the entire management process for medical devices,and reduce clinical infections,and ensure normal operation of devices,and improve clinically operational quality of them,and increase satisfaction of staffs in clinical departments.

Objective:To establish a rapid detection method based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS)for drug resistance of Carbapenem-resistant Enterobacteriaceae(CRE),so as to provide basis for enhancing clinically diagnostic effect.Methods:A total of 120 suspected CRE strains that were isolated from the clinical laboratory of Jiading District Central Hospital Affiliated to Shanghai University of Medicine&Health Sciences during October 2023 and September 2024 were collected,and the experimental detection of 44 strains was finally completed.The 44 suspected CRE bacterial strains were all from hospitalized patients.A rapid detection protocol based on the MALDI-TOF MS platform was initially established and improved,and experimental detection was carried out using the fully automatic rapid microbial mass spectrometry detection system(VITEK MS).The results of identification review and antimicrobial susceptibility test(AST)for VitEK-2 Compact strain was used as the reference standard.The screening results and detection efficacy of two kinds of detection methods were compared.Results:In the 44 suspected CRE strains,31 CRE strains were screened out by MALDI-TOF MS detection,and 31 CRE stains were screened out by VITEK-2 Compact recheck detection.In them,one strain of Enterobacter cloacae was confirmed as negativity by the MALDI-TOF MS test,but it was confirmed as CRE by the VITEK-2 Compact test.One strain of Klebsiella pneumoniae was confirmed as positivity by the MALDI-TOF MS test,but it was confirmed as mediator for carbapenem drugs by the VITEK-2 Compact test.The tested results of VITEK-2 Compact was used as standard,the results of four-grid table(2×2 contingency table)statistical method indicated that the sensitivity,specificity,accuracy rate and Youden index(R)of MALDI-TOF MS were respectively 96.7%,92.3%,100%and 89.1%.Conclusion:The rapid detection method based on the MALDI-TOF MS platform for CRE drug resistance has simple operation process and high accuracy rate,which can provide a basis for the application of targeted antibacterial drugs at early stage.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

BACKGROUND:Disruption of biological rhythms(circadian rhythms)is a typical problem associated with aging.Maintaining the normal function of biological rhythms may be a promising anti-aging strategy.Expression of nuclear factor erthroid 2-related factor 2(Nrf2)is biologically regulated.The glycogen synthase kinase 3(GSK3)system represents a"regulatory valve"that controls subtle oscillations in Nrf2 levels.Circadian changes in the transcript levels of antioxidant genes can influence the response of organisms to oxidative stress.However,the specific molecular mechanism of GSK3/Nrf2 in regulating organismal aging is still puzzling. OBJECTIVE:To search for the general pattern of GSK3/Nrf2-regulated biological rhythms in organismal aging by reviewing the literature in this field. METHODS:The bibliographic method was used to search,review and screen the relevant literature using the keywords of"glycogen synthase kinase 3,nuclear factor erthroid 2-related factor 2,biorhythms and aging"to lay a theoretical foundation for the analysis of the whole paper.Comparative analysis method,through reading and analyzing the obtained literature,was performed to compare the similarities and differences between the literature,thereby providing reasonable theoretical support for the argument.Further comparative analysis of the literature was conducted to clarify the relationship between the relevant indicators as well as the ideas for analysis throughout the text. RESULTS AND CONCLUSION:GSK3 can indirectly regulate Nrf2 expression through the regulation of rhythm genes.GSK3 and Nrf2 are components of anti-aging programs and are associated with biological rhythms.In addition,GSK3/Nrf2 is involved in several metabolic pathways,including those associated with age-related diseases(type 2 diabetes and cancer)and neurodegenerative diseases.