BACKGROUND AND AIM: Remnant cholesterol (remnant-C) mediates the progression of major adverse cardiovascular events. It is unclear whether remnant-C, and particularly cumulative exposure to remnant-C, is associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether remnant-C, not only baseline but cumulative exposure, can be used to independently evaluate the risk of NAFLD. METHODS: This study included 1 cohort totaling 21,958 subjects without NAFLD at baseline who underwent at least 2 repeated health checkups and 1 sub-cohort totaling 2,649 subjects restricted to those individuals with at least 4 examinations and no history of NAFLD until Exam 3. Cumulative remnant-C was calculated as a timeweighted model for each examination multiplied by the time between the 2 examinations divided the whole duration. Cox regression models were performed to estimate the association between baseline and cumulative exposure to remnant-C and incident NAFLD. RESULTS: After multivariable adjustment, compared with the quintile 1 of baseline remnant-C, individuals with higher quintiles demonstrated significantly higher risks for NAFLD (hazard ratio [HR] 1.48, 95%CI 1.31-1.67 for quintile 2; HR 2.07, 95%CI 1.85-2.33 for quintile 3; HR 2.55, 95%CI 2.27-2.88 for quintile 4). Similarly, high cumulative remnant-C quintiles were significantly associated with higher risks for NAFLD (HR 3.43, 95%CI 1.95-6.05 for quintile 2; HR 4.25, 95%CI 2.44-7.40 for quintile 3; HR 6.29, 95%CI 3.59-10.99 for quintile 4), compared with the quintile 1. CONCLUSION Elevated levels of baseline and cumulative remnant-C were independently associated with incident NAFLD. Monitoring immediate levels and longitudinal trends of remnant-C may need to be emphasized in adults as part of NAFLD prevention strategy.
Adult ; Humans ; Cohort Studies ; Non-alcoholic Fatty Liver Disease/etiology* ; Cholesterol ; Proportional Hazards Models ; Risk Factors

Objective This study aims to determine whether electroacupuncture regulates the phospholipase C(PLC)/inositol-1,4,5-trisphosphate(PLC/IP3)pathway in platelet-derived growth factor receptor α-positive(PDGFRα+)cells,thereby improving gastrointestinal motility disorders in functional dyspepsia(FD).Methods 40 SD rats were randomly divided into blank group,model group,electroacupuncture group,U73122(PLC inhibitor)group,and U73122+electroacupuncture group,with 8 rats in each group.Except for the blank group,all rats were subjected to multi-factor stress intervention to establish the FD model.After successful modeling,the U73122 group was given intraperitoneal injection of inhibitor,the electroacupuncture group was acupunctured at Zusanli and Taichong points,and the U73122+electroacupuncture group was injected with inhibitor 2 hours before acupunc-ture.Ten days later,gastrointestinal motility was tested;immunoblotting was used to detect the protein expression levels of PDGFRα,PLC,P-PLC,IP3;immunofluorescence was used to detect the average fluorescence density and co-localization expression of PDGFRα and PLC,IP3;electron microscope was used to observe the gap junction(GJ)situation in the gastric antrum area.Results After modeling,the gastrointestinal motility of rats was weakened,the protein expression levels of PDGFRα,PLC,and IP3 were significantly reduced,GJ widened,and cell morphol-ogy changed;compared with the model group,the gastrointestinal motility of rats in the electroacupuncture group,U73122 group,and U73122+electroacupuncture group was significantly improved,the expression levels of PDGFRα,PLC,P-PLC,IP3 increased,GJ was slightly tight,and cell morphology recovered;there was no significant difference in the expression levels of PDGFRα,PLC,P-PLC,IP3 in the gastric antrum of U73122 group and U73122+electroacupuncture group;PDGFRα,PLC,and IP3 had fluorescence co-localization.Conclusion Electroacupuncture can improve gastrointestinal dyskinesia in FD rats by activating the PLC/IP3 pathway in PDGFRα+cells.

The gut microbiota is a vast microbial ecosystem,specifically present in the organism and plays an important regulatory role in the body's health or disease state together with its metabolites.After spinal cord injury,the complex pathophysiology at the site of trauma makes axonal regeneration difficult,and the autonomic motor dysfunction induced by spinal cord injury disrupts gastrointestinal function and causes gut microbiota imbalance.The previous clinical outcomes of neurorepair strategies after spinal cord injury have not been ideal.The dysregulated gut microbiota and neuroinflammation after spinal cord injury are closely associated with the prognosis of the patients.The potential mechanisms by which the gut microbiota may influence the neuroinflammation after spinal cord injury may include the activation of gut-associated lymphoid tissue and disruption of the intestinal barrier by the imbalanced microbiota,and gut microbiota and its metabolites such as lipopolysaccharides(LPS),short chain fatty acids(SCFAs),5-hydroxytryptamine(5-HT),and tryptophan,as well as immune cells,inflammatory factors,and neurotransmitters the local inflammatory response in the spinal cord through the circulatory system.This paper revews the studies on the changes in gut microbiota after spinal cord injury and their effects on the spinal cord neuroinflammation,providing new targets and new ideas for improving the neuroinflammation after spinal cord injury.

Protein polypeptides are a class of bioactive substances that play a crucial role in maintaining the stability of various functions of the organism.Rapid and accurate detection of their levels could help in the diagnosis of diseases,the monitoring of drug therapy and the research and development of medicines,which is of great significance in the fields of clinical medicine,biology and pharmacy.Conventional protein polypeptides detection methods,such as Western blotting and enzyme-linked immunosorbent assay,still have problems like low sensitivity or difficulty in determining more than 1 analyte simultaneously.Liquid chromatography-mass spectrometry(LC-MS)has the advantages of specificity,sensitivity and high throughput.However,low ionization efficiency of macromolecules and strong biological matrix effects limit the feasibility of direct detection of protein polypeptides by LC-MS,which has led to the development of signal conversion and amplification strategies based on LC-MS technology.In this review,we summarized the research progress of sample pretreatment methods and signal conversion and amplification strategies for quantification of protein polypeptides in vivo based on LC-MS in recent years,providing a reference for developing specific high-sensitivity detection methods for low-abundance protein polypeptides in complex samples based on LC-MS technology.

Objective·To investigate the effects of the cancer-testis antigen 14(CT14)on embryonic and larval development in nematodes by using the model organism Caenorhabditis elegans(C.elegans),aiming to uncover its potential functions and mechanisms during development.Methods·Transgenic C.elegans strains were constructed by using microinjection for the inducible expression of human CT14(HsCT14),a truncated mutant of CT14(HsCT14?CIR)lacking CT14-specific intermediate region(CIR),and a green fluorescent protein(GFP)control.The impacts of full-length and truncated mutant CT14 on nematode embryonic and larval development were analyzed and compared.Additionally,transgenic C.elegans strains with inducible expression of CT14 from various primates,including the crab-eating macaque(Macaca fascicularis)and mouse lemur(Microcebus murinus),were also constructed to assess the effects on egg hatching and larval-to-adult transformation rates.The differential gene expression in nematode embryos induced by CT14 was analyzed by Smart-seq transcriptome sequencing,with further insights gained through KEGG(Kyoto Encyclopedia of Genes and Genomes)and GSEA(Gene Set Enrichment Analysis),to explore the involved biological processes and pathways.Results·The induced expression of HsCT14 and its truncated mutant HsCT14?CIR significantly reduced the hatching rate of nematode eggs,with a more pronounced effect observed in HsCT14-expressing strains.Differential interference contrast(DIC)microscopy imaging revealed significant morphological abnormalities in embryos expressing HsCT14 during the comma stage.Nematodes expressing HsCT14 or HsCT14?CIR exhibited developmental arrest in larvae and substantially lower larval-to-adult transformation rates compared to the GFP control.The impact was more pronounced in nematodes expressing HsCT14 than those with HsCT14?CIR.The expression of Macaca fascicularis CT14(MfCT14)exhibited significant effects on the hatching rate and adult transformation rate,similar to that of HsCT14,while the expression of Microcebus murinus CT14(MmCT14)displayed significantly reduced impact compared to HsCT14 and MfCT14.Smart-seq results indicated that CT14 expression affected various biological processes in nematode embryos,related to ATP-dependent chromatin remodeling and DNA replication.Conclusion·Ectopic expression of the cancer-testis antigen CT14 significantly disrupts both embryonic and larval developments in C.elegans,with the CIR sequence substantially enhancing this effect.It suggests that CT14 may play an important regulatory role in biological development by affecting gene expression in multiple pathways,including chromatin remodeling.

Objective:To investigate the DMD genetic variants of the Chinese population with Duchenne (DMD) and Becker muscular dystrophies (BMD).Methods:A cross-sectional study was conducted on 2 690 unrelated patients with DMD and BMD aged 0-18 who visited the Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from January 2005 to February 2022. The clinical data, such as gender, age, clinical manifestations, and address, were collected. Multiplex ligation-dependent probe amplification, next generation sequencing panel, Sanger sequencing, and PCR amplification were used to detect the variants of the DMD gene in the patients, whose clinical information and gene detection results were descriptively analyzed.Results:The 2 690 patients included 2 648 males and 42 females, with an age of 6.0 (4.0, 9.0) years. The serum creatine kinase increased in all patients. Pathogenic DMD gene variants were detected in the 2 618 patients, including 1 875 cases (71.6%) large deletions, 231 cases (8.8%) duplications, and 512 cases (19.6%) small variants. Among the deletion variants, the deletion of 3 exons was the most common, accounting for 15.4% (288/1 875); and hotspot deletion involved exons 45 to 50, accounting for 6.3% (119/1 875). Exon 2 was the most common type duplication region, accounting for 13.0% (30/231). Small variants were distributed in all 79 exons of the DMD gene, with no hotspots. In addition, the 46 small variants were previously unreported.Conclusion:Exon deletion is the most common type of DMD gene variant, followed by small variants and exon duplication.

African swine fever(ASF)is a virulent,hemorrhagic disease of swine caused by African swine fever virus(ASFV),which seriously affects the healthy development of Chinese pig indus-try.The genome of ASFV is large and encodes more than 165 proteins.Among them,the p54 pro-tein is encoded by the E183L gene,which has various functions such as participating in viral as-sembly,inducing apoptosis and inducing immune response.The conventional Chinese vaccine(C-strain)is a safe and effective attenuated vaccine developed by Chinese scientists.It can efficiently protect against attacks from various genotypes of classical swine fever virus(CSFV).The aim of this study was to investigate whether C-strain can express ASFV p54 protein serve as a delivery vector for ASF genetically engineered vaccines.An infectious clone of pHCLV-p54 was constructed by homologous recombination,the recombinant virus rHCLV-p54 was rescued by transfecting it into SK6 cells by blind passaging.Its genetic stability and growth curve were determined in vitro,while rabbits were immunized to evaluate its immunity effect.The results showed that the E183L gene remained genetically stable in the recombinant virus,indicating that the E183L gene could be stably inherited in recombinant viruses,but the inserted exogenous gene affected the replication of the C-strain.The results of the rabbit immunization test showed that the recombinant virus rHCLV-p54 was able to induce ASFV-specific antibodies.The above results indicated that we have successfully constructed a recombinant C-strain that stably expresses the ASFV p54 protein.In summary,the recombinant virus rHCLV-p54 has a good immunogenicity and is warranted for fur-ther evaluation as a vaccine candidate.

Objective To explore the feasibility and diagnostic value of ultra-fast scanning scheme based on deep learning-based reconstruction(DLR)for cervical MR examination.Methods Thirty-six subjects were prospectively enrolled and underwent both conventional scheme(scan time:6 min 14 s)and ultra-fast scheme(2 min)cervical spine MR scanning to acquire encompassing sagittal T1WI,sagittal adipose suppression T2WI and axial T2WI.The ultra-fast MRI were reconstructed using DLR method.The subjective and objective evaluations on imaging qualities of different MRIs were compared,along with the inter-observer agreement for diagnosing intervertebral disc degeneration and herniation.Results Compared with conventional MRI,artifacts in ultra-fast DLR images significantly reduced(P＜0.05).The subjective evaluation results of MRI had good agreement(all Kappa≥0.60).Compared with conventional MRI,the sagittal T1WI,T2WI and axial T2WI obtained with ultra-fast DLR showed significantly improved signal-to-noise ratio(SNR)of the spinal cord,cerebrospinal fluid(CSF)and vertebral body,as well as the spinal cord/CSF contrast(all P＜0.001).The Kappa value of 2 physicians for diagnosing intervertebral disc degeneration based on ultra-fast DLR and conventional scheme images was 0.94 and 1.00,respectively,of intervertebral disc herniation was 0.96 and 0.98,respectively.Conclusion Compared with conventional scanning scheme,using ultra-fast DLR scheme in cervical MR examination could shorten scanning time while achieve similar image quality and diagnostic accuracy.

Objective:To investigate the correlation between hearing loss and microvascular complications in diabetes.Methods:This cross-sectional study conducted the data from 572 patients with diabetes hospitalized in the Endocrinology Department of the General Hospital of Southern Theater Command from September 2022 to July 2023. All participants underwent electrical audiometry and acoustic immittance in the ENY department. Based on the audiometric results, participants were categorized into normal hearing group and hearing loss group. Additionally, 572 non-diabetic patients from the outpatient department were enrolled as the non-diabetic group. The general information and laboratory results were collected and compared using t test, rank sum test or χ2 test. Binary logistic regression analysis was used to evaluate the association of diabetic hearing loss with diabetic kidney disease(DKD), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN). Results:Among 572 patients with diabetes, 429 suffered from hearing loss and 143 were normal. χ2 test showed significant differences in combined DKD and DPN between two groups, but not in DR. Multivariate binary logistic regression analysis identified DKD and DPN as risk factors for hearing loss, but no correlation was found with DR. Conclusion:Diabetic patients with DKD or DPN should be monitored for potential hearing loss. Early screening and treatment are crucial to prevent severe hearing impairment.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous syestem (CNS) triggered by an autoimmune mechanism, which is the main cause of neurological disability in young people. In MS, a variety of glial cells participate in the pathogenesis and development of the disease, and oligodendrocytes (OL) and myelin cytes are destroyed by autoimmune mediated inflammation. Impaired OL production of oligodendrocyte progenitor cells (OPC) leads to persistent demyelination, myelin fragment accumulation and axonal injury, with clinical manifestation of CNS disability. Microglia (MG), which is involved in the inflammatory response and removal of myelin debris, plays a pivotal role in OPC differentiation and OL maturation, thereby directly or indirectly influencing the process of myelin regeneration. An interactive mechanism exists between these 2 components. The comprehension of the interrelationship between the 2 factors can provide enhanced insights into the pathogenesis of MS and facilitate the development of novel therapeutic strategies, thereby addressing pivotal scientific challenges encountered in clinical management of MS. Therefore, this review summarizes the dynamic changes of microglia in MS and its classic animal models, explores the internal relationship between MG and OL in this process, and focuses on the beneficial effects of targeted regulation of microglia, thereby promoting OPC differentiation and myelin regeneration, in order to provide a new research direction for MS treatment.